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Nitric oxide (NO) is a molecule involved in plasticity across levels and systems. The role of NOergic pathways in stress-induced sensitization (SIS) of behavioral responses, in which a particular stressor triggers a state of hyper-responsiveness to other stressors after an incubation period, was assessed in adult zebrafish. In this model, adult zebrafish acutely exposed to a fear-inducing conspecific alarm substance (CAS) and left undisturbed for an incubation period show increased anxiety-like behavior 24 h after exposure. CAS increased forebrain glutamate immediately after stress and 30 min after stress, an effect that was accompanied by increased nitrite levels immediately after stress, 30 min after stress, 90 min after stress, and 24 h after stress. CAS also increased nitrite levels in the head kidney, where cortisol is produced in zebrafish. CAS-elicited nitrite responses in the forebrain 90 min (but not 30 min) after stress were prevented by a NOS-2 blocker. Blocking NOS-1 30 min after stress prevents SIS; blocking NOS-2 90 min after stress also prevents stress-induced sensitization, as does blocking calcium-activated potassium channels in this latter time window. Stress-induced sensitization is also prevented by blocking guanylate cyclase activation in both time windows, and cGMP-dependent channel activation in the second time window. These results suggest that different NO-related pathways converge at different time windows of the incubation period to induce stress-induced sensitization., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Soybean is a highly valuable commodity crop for Brazil's economy. However, it faces significant threats from the attack of a complex of lepidopteran pests, particularly Chrysodeixis includens (Walker) and Spodoptera frugiperda (J. E. Smith). These pests have been managed primarily using transgenic Bt soybeans, but limited knowledge exists about the resistance levels of Bt and non-Bt cultivars adapted to novel soybean-growing areas in Brazil, such as the Minas Gerais state. This study evaluated the resistance levels of Bt and non-Bt soybean cultivars to C. includens and S. frugiperda, and whether the Bt cultivars can differentially affect these pests across larval stages. No-choice bioassays were conducted using Bt (NS6010 IPRO and P97R50 IPRO) and non-Bt soybeans (UFLA 6301 RR, P96R90 RR, and ANsc 80111 RR) at V4-stage in the laboratory with neonate (24 h) and third-instar larvae. Larvae were fed leaf discs in Petri dishes, recording the mortality, leaf consumption, and weight gain after 7 days. There was high mortality of C. includens neonates on the Bt cultivars, but this trend was not observed for older larvae. For S. frugiperda neonates, there was high mortality on the Bt cultivar NS 6010 IPRO and non-Bt cultivar UFLA 6301 RR, but only the former was effective for older larvae. Although the Bt cultivars did not kill the third instars, antinutritional effects were found, such that leaf tissue consumed was not converted to larval weight gain. These findings are important for defining regional strategies of integrated and resistance management of C. includens and S. frugiperda in expanding regions of soybean cultivation in Brazil., (© 2024. Sociedade Entomológica do Brasil.)

COVID-19 is a systemic disease caused by the etiologic agent SARS-CoV-2, first reported in Hubei Province in Wuhan, China, in late 2019. The SARS-CoV-2 virus has evolved over time with distinct transmissibility subvariants from ancestral lineages. The clinical manifestations of the disease vary according to their severity and can range from asymptomatic to severe. Due to the rapid evolution to a pandemic, epidemiological studies have become essential to understand and effectively combat COVID-19, as the incidence and mortality of this disease vary between territories and populations. This study correlated epidemiological data on the incidence and mortality of COVID-19 with frequencies of important SNPs in GWAS studies associated with the susceptibility and mortality of this disease in different populations. Our results indicated significant correlations for 11 genetic variants (rs117169628, rs2547438, rs2271616, rs12610495, rs12046291, rs35705950, rs2176724, rs10774671, rs1073165, rs4804803 and rs7528026). Of these 11 variants, 7 (rs12046291, rs117169628, rs1073165, rs2547438, rs2271616, rs12610495 and rs35705950) were positively correlated with the incidence rate, these variants were more frequent in EUR populations, suggesting that this population is more susceptible to COVID-19. The rs2176724 variant was inversely related to incidence rates; therefore, the higher the frequency of the allele is, the lower the incidence rate. This variant was more frequent in the AFR population, which suggests a protective factor against SARS-CoV-2 infection in this population. The variants rs10774671, rs4804803, and rs7528026 showed a significant relationship with mortality rates. SNPs rs10774671 and rs4804803 were inversely related to mortality rates and are more frequently present in the AFR population. The rs7528026 variant, which is more frequent in the AMR population, was positively related to mortality rates. The study has the potential to identify and correlate the genetic profile with epidemiological data, identify populations that are more susceptible to severe forms of COVID-19, and relate them to incidence and mortality.

Breast cancer (BCa) is the most common cancer and leading cause of cancer death among women globally. This can be explained by the genetic factor of this disease. This article aims to correlate the epidemiological data, worldwide incidence, and mortality of BCa with the Single-Nucleotide Polymorphisms (SNPs) associated with the susceptibility and severity in different populations. Two hundred and forty genetic variants associated with BCa susceptibility/severity were selected from the literature through Genome-Wide Association Studies (GWAS). The allele frequencies were obtained from the 1000 Genomes Project, and the epidemiological data were obtained from the World Health Organization (WHO). The BCa incidence, mortality rates, and allele frequencies of the variants were evaluated using Pearson's correlation. Our study demonstrated that 11 SNPs (rs3817578, rs4843437, rs3754934, rs61764370, rs780092, rs2290203, rs10411161, rs6001930, rs16886165, rs8051542 and rs4973768) were significantly correlated with the epidemiological data in different ethnic groups. Seven polymorphisms (rs3817578, rs3754934, rs780092, rs2290203, rs10411161, rs6001930 and rs16886165) were inversely correlated with the incidence rate and four polymorphisms (rs4843437, rs61764370, rs8051542 and rs4973768) were directly correlated with the incidence rate. African and South-East Asian populations have a lower risk of developing BCa when evaluated in terms of genetic factors since they possess variants characterized as protective, as their higher incidence is associated with a lower frequency of BCa cases. The genetic variants investigated here are likely to predispose individuals to BCa. The genetic study described here is promising for implementing personalized strategies to screen for breast cancer in diverse populations.

Condition monitoring of synchronous generators through non-invasive methods is widely requested by maintenance teams for not interfering the machine operation. Among the techniques used, external magnetic field monitoring is a recent strategy with great potential for detecting incipient faults. In this context, this paper proposes the application of a simple strategy with low computational cost to process data of external magnetic field time derivative signals for the purposes of condition monitoring and fault detection in synchronous machines. The information of interest is extracted from changes in the magnetic signature of the synchronous generator, obtained from frequency spectra of monitored signals using induction magnetic field sensors. The process forms a set of time series that reflects constructive and operational characteristics of the machine. The Shewhart control chart method is applied for anomaly detection in these time series, allowing the detection of changes in the machine magnetic signature. This method is employed in an algorithm for continuous condition monitoring of synchronous generators, presenting as output a global change indicator for the multivariable problem associated with magnetic signature monitoring. Correlation matrices are used to improve the algorithm response, filtering series with similar variation patterns associated with detected events. The proposed method is validated through tests on an experimental bench that allows the controlled imposition of faults in a synchronous generator. The proposed global change indicator allows the automatic detection of stator and rotor faults with the machine synchronized with the commercial power grid. The proposed methodology is also applied on data obtained from an equipment installed in a 305 MVA synchronous generator of a hydroelectric power plant where the evolution of an incipient fault, i.e., a mechanical vibration fault, has been detected.

Gastrointestinal (GI) cancers are a set of diverse diseases affecting many parts/ organs. The five most frequent GI cancer types are esophageal, gastric cancer (GC), liver cancer, pancreatic cancer, and colorectal cancer (CRC); together, they give rise to 5 million new cases and cause the death of 3.5 million people annually. We provide information about molecular changes crucial to tumorigenesis and the behavior and prognosis. During the formation of cancer cells, the genomic changes are microsatellite instability with multiple chromosomal arrangements in GC and CRC. The genomically stable subtype is observed in GC and pancreatic cancer. Besides these genomic subtypes, CRC has epigenetic modification (hypermethylation) associated with a poor prognosis. The pathway information highlights the functions shared by GI cancers such as apoptosis; focal adhesion; and the p21-activated kinase, phosphoinositide 3-kinase/Akt, transforming growth factor beta, and Toll-like receptor signaling pathways. These pathways show survival, cell proliferation, and cell motility. In addition, the immune response and inflammation are also essential elements in the shared functions. We also retrieved information on protein-protein interaction from the STRING database, and found that proteins Akt1, catenin beta 1 (CTNNB1), E1A binding protein P300, tumor protein p53 (TP53), and TP53 binding protein 1 (TP53BP1) are central nodes in the network. The protein expression of these genes is associated with overall survival in some GI cancers. The low TP53BP1 expression in CRC, high EP300 expression in esophageal cancer, and increased expression of Akt1/TP53 or low CTNNB1 expression in GC are associated with a poor prognosis. The Kaplan Meier plotter database also confirmed the association between expression of the five central genes and GC survival rates. In conclusion, GI cancers are very diverse at the molecular level. However, the shared mutations and protein pathways might be used to understand better and reveal diagnostic/prognostic or drug targets., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Trypanosoma cruzi, the etiological agent of Chagas disease (CD), is a heterogeneous species with high genetic and phenotypic diversity. MASP is the second largest multigene family of T. cruzi. The high degree of polymorphism of the family associated with its location at the surface of infective forms of T. cruzi suggests that MASP participates in mechanisms of host-parasite interaction. In this work, MASP members were divided into 7 subgroups based on protein sequence similarity, and one representative member from each subgroup was chosen to be expressed recombinantly. Immunogenicity of recombinant MASP proteins (rMASP) was investigated using different sera panels from T. cruzi infected mice. To mimic a natural condition in which different MASP members are expressed at the same time in the parasite population, a multiplex bead-based flow cytometry assay was also standardized. Results showed that rMASPs are poorly recognized by sera from mice infected with Colombiana strain, whereas sera from mice infected with CL Brener and Y display high reactivity against the majority of rMASPs tested. Flow cytometry showed that MASP recognition profile changes 10 days after infection. Also, multiplex assay suggests that MASP M1 and M2 are more immunogenic than the other MASP members evaluated that may play an immunodominant role during infection., Competing Interests: Conflict of interest statement The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

Redoxome is the network of redox reactions and redox active species (ReAS) that affect the homeostasis of cells and tissues. Due to the intense and constant interaction with external agents, the human skin has a robust redox signalling framework with specific pathways and magnitudes. The establishment of the skin redoxome concept is key to expanding knowledge of skin disorders and establishing better strategies for their prevention and treatment. This review starts with its definition and progress to propose how the master redox regulators are maintained and activated in the different conditions experienced by the skin and how the lack of redox regulation is involved in the accumulation of several oxidation end products that are correlated with various skin disorders., (© 2021 European Academy of Dermatology and Venereology.)

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the main pathogens that cause infections in diabetic individuals. In this paper, we report the outcomes of our investigation on the intradermal application of antimicrobial photodynamic therapy (PDT) with curcumin in an infection induced by MRSA ATCC 43300 strain in the ear of mice with Type 1 Diabetes Mellitus (T1DM). A solution containing 100 μg of curcumin was photoactivated ex vivo with a LED light (450 nm) delivering a fluency of 13.5 J/cm 3 . This solution was administered in the ear intradermally, at the same inoculum site as the MRSA ATCC 43300 strain (PDT Group). This study also included the use of two control groups (both infected): One was treated with saline and the other was treated with non-photoactivated curcumin. The animals were euthanized 24 h after these treatments and samples of draining lymph node and treated ear were collected for examination. The PDT group showed lower bacterial load in the draining lymph node when compared to the saline and curcumin groups (p-value <0.05) 24 h after treatment. In addition to bacterial load, the PDT group presented a higher concentration of nitrates and nitrites in the draining lymph node when compared to the saline and curcumin groups (p-value <0.001). Examining the infectious site, despite apparently having similar inflammatory cell recruitment compared with the control groups, the PDT group showed a profile with less intense activity in the myeloperoxidase expression when compared to the saline group (p-value <0.001). Additionally, the detected concentration of cytokines such as IL-1β, IL-12, and IL-10 was significantly lower in the PDT group when compared to the saline group (p-value <0.01; p-value <0.05; p-value <0.05, respectively), thus presenting a less intense inflammatory response during infection resolution. Our pilot study showed for the first time the therapeutic potential of PDT using curcumin when administered intradermally in the treatment of infections caused by S. aureus in mice with T1DM., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objectives: To analyse the factors associated with length of stay (LOS) and death in nasogastric/nasoenteric tube (NG/NET)-fed patients., Design: A cross-sectional multicentre study., Method: Data collection took place from October 2017-April 2019, and the sample consisted of 365 participants from seven Brazilian hospitals. Demographic, clinical and therapeutic data were collected from the patients' medical records. Data analysis was performed using bivariate and multivariate tests, considering a significance level of p<.05., Results: Most patients were male, older adults, with high risk of death and highly dependent on nursing care. The LOS was associated with age, patient care complexity and length of NG/NET use. Death was associated with patient age. In the multivariate analysis, patients highly dependent on nursing care, and intensive and semi-intensive care had a greater chance of dying when compared with patients receiving minimal care. Screening for factors affecting LOS and death is important to plan effective nursing care., (© 2021 The Authors. Nursing Open published by John Wiley & Sons Ltd.)

Background: COVID-19 has stroke Brazil harshly, deaths by COVID-19 in Brazil represent almost 13% of the total deaths by COVID-19 in the world, even though Brazilian population represents only 2.6% of the world population. Our aim in this study was to evaluate death and intubation outcomes and risk factors associated with COVID-19, and treatment options focusing on diabetes patients and the use of metformin pre-admission and during hospitalization., Methods: In this Brazilian single-center study we evaluated 1170 patients hospitalized due to COVID-19. Diabetes patients (n = 188) were divided based on their use of pre-hospital and in-hospital metformin (non-met-group and met-group)., Results: In the total cohort most comorbidities were risk factors for orotracheal intubation and death. The use of chloroquine/hydroxychloroquine was significantly associated with increased death and intubation risk in uni- and multivariate analysis. Diabetes patients showed worst clinical feature compared with non-diabetes patients. In-hospital non-met-group had increased mortality (20.5%) compared to met-group (3.5%) (p = 0.0002) and univariable cox proportion hazard regression indicated in-hospital metformin reduced mortality (HR = 0.325, p = 0.035). Patients that used pre-hospital metformin showed lower severity parameters at hospital admission. (met-group: 2.45 ± 2.5; non-met-group: 4.25 ± 3.4). In all the groups older patients showed more severe clinical conditions and high risk of death and intubation., Conclusion: Even though this is a single-center study, results from other reports have shown a similar trend, indicating that patients that used metformin during hospitalization have a better prognosis and reduced risk of death., (© 2021. The Author(s).)

Background: The prevalence of sexual dysfunction is high in postmenopausal women and pelvic floor muscle training (PFMT) could improve sexual function during this period., Aim: To assess the effect of a PFMT protocol on sexual function in postmenopausal women and to investigate the effect of this protocol on pelvic floor muscle function., Methods: This is an assessor blinded randomized controlled trial including 77 postmenopausal women. The study was registered in ReBEC Trial: RBR-3s3ff7. The intervention group (n = 40) received an intensive supervised PFMT protocol during 12 weeks and the control group (n = 37) received no intervention., Outcomes: The primary outcome of the study was assessed by the Female Sexual Function Index (FSFI) questionnaire and the secondary outcome was the evaluation of pelvic floor muscle function performed by digital palpation using the modified Oxford scale at baseline and after 12 weeks., Results: No difference between groups was found in the FSFI domains and total score at baseline and in the second evaluation after 12 weeks. However, after 12 weeks, a higher percentage of women without sexual dysfunction was found in the intervention group (95% CI = 27.97-72.03) when compared to the control group (95% CI = 7.13-92.87). No difference was found between groups in relation to the pelvic floor muscle function at the baseline (P = .2) and after 12 weeks (P = .06)., Clinical Implications: PFMT is a conservative intervention that can lead women to have less sexual dysfunction., Strengths & Limitations: The protocol provided a reduced number of women with sexual dysfunction, the strength of this research is the study design and the limitation is to have used only one tool to assess sexual function although it is a validated questionnaire., Conclusion: PFMT decreases sexual dysfunction in postmenopausal women. MM Franco, CC Pena, LM de Freitas, et al. Pelvic Floor Muscle Training Effect in Sexual Function in Postmenopausal Women: A Randomized Controlled Trial. J Sex Med 2021;18:1236-1244., (Copyright © 2021 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Based on the antimicrobial activity of bothropstoxin-I (BthTX-I) and on the premise that a C-terminal peptide of Lys49 myotoxin can reproduce the antimicrobial activity of the parent protein, we aimed to study the mechanism of action of a peptide derived from the C-terminal region of the myotoxin BthTX-I [(p-BthTX-I) 2 , sequence: KKYRYHLKPFCKK, disulfide-linked dimer] against Gram-positive and Gram-negative bacteria. Fluorescence quenching technique showed that the carboxyfluorescein labeled-peptide [CF-(p-BthTX-I) 2 ] when incubated with E. coli displayed a superior penetration activity than when incubated with S. aureus. Cell death induced by the peptide (p-BthTX-I) 2 showed a loss of membrane integrity in E. coli and S. aureus; however, the mechanisms of cell death were different, characterized by the presence of necrosis-like and apoptosis-like deaths, respectively. Scanning electron microscopy studies in E. coli and S. aureus showed morphological changes in the cells, with superficial deformities, appearance of wrinkles and bubbles, and formation of vesicles. Our results demonstrate that the mechanism of action of the peptide (p-BthTX-I) 2 is different in Gram-negative (E. coli) and Gram-positive (S. aureus) bacteria. Knowledge of the mechanism of action of these peptides is important, since they are promising prototypes for new antimicrobial drugs., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Viruses are associated with several human diseases that infect a large number of individuals, hence directly affecting global health and economy. Owing to the lack of efficient vaccines, antiviral therapy and emerging resistance strains, many viruses are considered as a potential threat to public health. Therefore, researches have been developed to identify new drug candidates for future treatments. Among them, antiviral research based on natural molecules is a promising approach. Phospholipases A 2 (PLA 2 s) isolated from snake venom have shown significant antiviral activity against some viruses such as Dengue virus, Human Immunodeficiency virus, Hepatitis C virus and Yellow fever virus, and have emerged as an attractive alternative strategy for the development of novel antiviral therapy. Thus, this review provides an overview of remarkable findings involving PLA 2 s from snake venom that possess antiviral activity, and discusses the mechanisms of action mediated by PLA 2 s against different stages of virus replication cycle. Additionally, molecular docking simulations were performed by interacting between phospholipids from Dengue virus envelope and PLA 2 s from Bothrops asper snake venom. Studies on snake venom PLA 2 s highlight the potential use of these proteins for the development of broad-spectrum antiviral drugs., (Copyright © 2020. Published by Elsevier B.V.)

Contagious agalactia (CA) is a serious disease notifiable to the World Organisation for Animal Health (OIE) causing severe economic losses to sheep and goat producers worldwide. Mycoplasma agalactiae, considered as its main etiological agent, inflicts a variety of symptoms in infected animals, including keratoconjunctivitis, mastitis, arthritis, ankylosis, abortions, stillbirths and granular vulvovaginitis. Despite its significance, developing a successful vaccine remains elusive, mostly due to the lack of knowledge about M. agalactiae's pathogenicity factors and pathogenic mechanisms, including its "core" antigens. The aim of this study was to identify, characterize and express antigenic proteins of M. agalactiae as potential vaccine candidates. Predicted proteins of type strain PG2 were analyzed using bioinformatic algorithms to assess their cellular localization and to identify their linear and conformational epitopes for B cells. Out of a total of 156 predicted membrane proteins, three were shortlisted as potential antigenic surface proteins, namely [MAG&#95;1560 (WP&#95;011949336.1), MAG&#95;6130 (WP&#95;011949770.1) and P40 (WP&#95;011949418.1)]. These proteins were expressed in recombinant Escherichia coli strains. Purified proteins were evaluated for their antigenicity using Western blot and ELISA using sera of M. agalactiae-naturally infected and non-infected sheep and goats. All 3 proteins were specifically recognized by the tested sera of M. agalactiae-infected animals. Also, specific rabbit antisera raised against each of these 3 proteins confirm their membrane localization using TritonX-114 phase partioning, Western and colony immunoblotting. In conclusion, our study successfully identified P40 (as proof of concept and validation) and two novel antigenic M. agalactiae proteins as potential candidates for developing effective CA vaccines., (Copyright © 2020 Elsevier B.V. All rights reserved.)

This study aimed to evaluate the effect of the continuous irradiation with low intensity (continuous mode) and fractioned irradiation with high intensity (fractionated mode), keeping the same dose of light by using Light Emitting Diode (LEDs) with wavelength emission centered at 450 and at 660 nm, using methylene blue (MB), chlorin-e6 (Ce 6 ) and curcumin (CUR) as photosensitizers (PSs) against planktonic phase of E. faecalis. Cell viability was assessed by counting colonies forming per mL (CFU/mL), and the quantification of reactive species was performed by fluorescence with the photodegradation rate evaluated by measurements of absorbance of PSs at different times. The results revealed that MB-mediated PDT was efficient to achieve total microbial load reduction in both irradiation modes, but in fractional mode it was possible to use a lower light dose. Using Ce 6 , a total bacterial reduction was observed when fractional light was used, but at the same light dose, there was no reduction in the continuous irradiation mode. CUR-mediated PDT under continuous irradiation mode promoted the total microbial load reduction. However, for fractional mode, a higher concentration of CUR was required to completely reduce E. faecalis cell viability. Our results suggest that the biological response to PDT is variable depending on the irradiation mode and on the photosensitizer. Therefore, these studies indicate that the irradiation mode, intensity and the specific PSs should be taken into account for the development of clinical protocols for PDT., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Orofacial pain is clinically challenging, having therapeutic failures and side effects. This study evaluated the antinociceptive activities of the CTK 01512-2 toxin, the TRPA1 channel antagonist, and the selective inhibitor of the N-type voltage-gated calcium channels (N-type VGCC), in different pain models., Materials and Methods: The trigeminal ganglia were stimulated in vitro with capsaicin. The in vivo models received subcutaneous (sc) injections of formalin into the upper lip of the rats, Freund's Complete Adjuvant (FCA) into the temporomandibular joint (TMJ), and infraorbital nerve constrictions (IONC). CTK 01512-2 at concentrations of 30, 100, and 300 pmol/site, intrathecally (ith), and MVIIA at 10, 30, and 100 pmol/site in the formalin test, guided the doses for the models. The glutamate levels in the CSF of the rats that were submitted to IONC were analyzed., Results: CTK 01512-2 decreased the nociceptive behavior in the inflammatory phase of the formalin test (65.94 ± 7.35%) and MVIIA in the neurogenic phase (81.23 ± 3.36%). CTK 01512-2 reduced facial grooming with FCA in the TMJ (96.7 ± 1.6%), and in the IONC neuropathy model, it decreased heat hyperalgesia (100%) and cold hyperalgesia (81.61 ± 9.02%). The levels of glutamate in the trigeminal ganglia in vitro (81.40 ± 8.59%) and in the CSF in vivo (70.0 ± 9.2%) were reduced., Conclusions: The roles of TRPA1 in pain transduction and the performance of CTK 01512-2 in the inhibition of the N-type VGCCs were reinforced. This dual activity may represent an advantage in clinical treatments.

Leishmaniasis is a parasitic infection transmitted by the bite of infected female sandflies. It principally affects the skin, and the frequency of mucosal involvement is about 5% to 20%. Considering the rarity of leishmaniasis affecting the upper aerodigestive tract mucosa, we evaluated the characteristics of mucocutaneous leishmaniasis and mucosal leishmaniasis and the diagnostic difficulty when the parasites are scarce in tissue samples. The clinical, histopathological, histochemical, immunohistochemical, and molecular features of 17 cases of mucocutaneous leishmaniasis and mucosal leishmaniasis were assessed. Mucosal disease was principally found in the soft palate, oropharynx, and nose, manifesting mainly as a solitary ulcer. In hematoxylin and eosin-stained sections, 10 cases revealed abundant amastigotes within the macrophages. Giemsa staining was not shown to be helpful to confirm the diagnosis in 6 cases with scarce or nondetectable amastigotes. Immunohistochemistry (IHC) showed high sensitivity by positive staining in 14 out of 17 cases (82.3%). Polymerase chain reaction was shown to be more sensitive than IHC with 13 out of 14 (92.8%) positive cases, including the 3 IHC negative cases; however, this technique is not available in many endemic regions. In summary, we suggest that the IHC is a simple technique with rapid results and relatively low cost, when compared with other laboratorial procedures; thus, IHC is a helpful tool that should be implemented in the routine diagnosis of leishmania.

Breast cancer is a serious public health problem that causes thousands of deaths annually. Chemotherapy continues to play a central role in the management of breast cancer but is associated with extreme off-target toxicity. Therefore, treatments that directly target the tumor and display reduced susceptibility to resistance could improve the outcome and quality of life for patients suffering from this disease. Photodynamic therapy is a targeted treatment based on the use of light to activate a photosensitizer (PS) that then interacts with molecular oxygen and other biochemical substrates to generate cytotoxic levels of Reactive Oxygen Species. Currently approved PS also tends to have poor aqueous solubility that can cause problems when delivered intravenously. In order to circumvent this limitation, in this manuscript, we evaluate the potential of a phthalocyanine-loaded nanostructured lipid carrier (NLC) functionalized with folic acid (FA). To prepare the FA labelled NLC, the polymer PF127 was first esterified with FA and emulsified with an oil phase containing polyoxyethylene 40 stearate, capric/caprylic acid triglycerides, ethoxylated hydrogenated castor oil 40 and the PS zinc phthalocyanine. The resulting PS loaded FA-NLC had a hydrodynamic diameter of 180 nm and were stable in suspension for >90 days. Interestingly, the amount of singlet oxygen generated upon light activation for the PS loaded FA-NLC was substantially higher than the free PS, yet at a lower PS concentration. The PS was released from the NLC in a sustained manner with 4.13 ± 0.58% and 27.7 ± 3.16% after 30 min and 7 days, respectively. Finally, cytotoxicity assays showed that NLC in the concentrations of 09.1 μM of PS present non-toxic with >80 ± 6.8% viable and after 90 s of the light-exposed the results show a statistically significant decrease in cell viability (57 ± 4%). The results obtained allow us to conclude that the functionalized NLC incorporated with PS associated with the PDT technique have characteristics that make them potential candidates for the alternative treatment of breast cancer., (Published by Elsevier B.V.)

Food safety and quality management play a pivotal role in the dairy industry. Milk is a highly nutritious food that also provides an excellent medium for growth of pathogenic microorganisms. Thus, dairy industry focuses most of their processes and costs on keeping contamination levels as low as possible. Thermal processes for microbial decontamination may be effective; however, they cannot provide excellent organoleptic, nutritional, and decontamination properties simultaneously. In this scenario, microbial inactivation by exposure to blue light is a promising alternative method in the food industry due to its intrinsic antimicrobial properties free of any thermal effect. Therefore, this study aimed to determine the inactivation kinetics induced by blue light (λ = 413 nm) against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Salmonella Typhimurium, and Mycobacterium fortuitum cells suspended in whole milk or saline solution. We also performed a series of optic spectroscopies to investigate possible degradation of milk components. All species were sensitive to photoinactivation suspended either in saline solution or milk. Inactivation kinetics differs significantly depending on the suspension medium and each species is differently affected. All bacterial species tested presented more than 5 log 10 of inactivation within less than 2 h of irradiation (720 J/cm 2 ). Infrared spectroscopy did not reveal any significant alteration in any of the milk constituents (e.g., sugars, proteins, and lipids). Riboflavin (vitamin B 2 ) was the only significantly degraded constituent found. Therefore, we conclude that microbial inactivation performed by blue light presents extraordinary potential for processes in the dairy industry., (Copyright © 2020 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Background: Although the pancreatic ductal adenocarcinoma (PDAC) presents high mortality and metastatic potential, there is a lack of effective therapies and a low survival rate for this disease. This PDAC scenario urges new strategies for diagnosis, drug targets, and treatment., Methods: We performed a gene expression microarray meta-analysis of the tumor against normal tissues in order to identify differentially expressed genes (DEG) shared among all datasets, named core-genes (CG). We confirmed the CG protein expression in pancreatic tissue through The Human Protein Atlas. It was selected five genes with the highest area under the curve (AUC) among these proteins with expression confirmed in the tumor group to train an artificial neural network (ANN) to classify samples., Results: This microarray included 461 tumor and 187 normal samples. We identified a CG composed of 40 genes, 39 upregulated, and one downregulated. The upregulated CG included proteins and extracellular matrix receptors linked to actin cytoskeleton reorganization. With the Human Protein Atlas, we verified that fourteen genes of the CG are translated, with high or medium expression in most of the pancreatic tumor samples. To train our ANN, we selected the best genes (AHNAK2, KRT19, LAMB3, LAMC2, and S100P) to classify the samples based on AUC using mRNA expression. The network classified tumor samples with an f1-score of 0.83 for the normal samples and 0.88 for the PDAC samples, with an average of 0.86. The PDAC-ANN could classify the test samples with a sensitivity of 87.6 and specificity of 83.1., Conclusion: The gene expression meta-analysis and confirmation of the protein expression allow us to select five genes highly expressed PDAC samples. We could build a python script to classify the samples based on RNA expression. This software can be useful in the PDAC diagnosis.

Aims: To assess women's self-perception of their pelvic floor muscle (PFM) contraction and its agreement with an assessed PFM contraction. Further, to assess a possible correlation between women's self-perception and reports of urinary incontinence (UI) and between PFM contraction and severity of UI., Methods: A cross-sectional observational study including 82 women. The study was conducted in a basic healthcare unit in Brazil. PFM contraction was assessed by a physiotherapist and estimated by women using the Modified Oxford Scale (MOS). UI symptoms were assessed using a validated questionnaire (ICIQ-UI-SF). A descriptive analysis of the data was performed. The weighted κ coefficient, Spearman's correlation coefficient, and Fisher's exact test were used to analyze data., Results: Eighty-two women with a mean age of 46.83 (±17.94) were analyzed. The majority (98.8%) believed they were able to voluntarily contract their PFM, but only 33% correctly estimated their PFM considering the examiner assessment as reference. No agreement (κ = 0.139, P = .087) was found between the examiner's classification and the women's estimation of their PFM contraction. Women's self-perception did not correlate with the ICIQ-IU-SF (r's = .011, P = .922). A moderate negative correlation was found between the assessed PFM contraction and the ICIQ-UI-SF score (r's = -.406, P = .00)., Conclusion: Most of the women did not show an accurate self-perception of PFM contraction. No correlation between women's self-perception and the ICIQ-UI-SF score was found, but a negative correlation was found between the assessed PFM contraction and the ICIQ-UI-SF score., (© 2019 Wiley Periodicals, Inc.)

The neural system plays an important role in understanding some features of animals. Anatomical complexity correlates with the increase of functional capacity. Xenarthrans include anteaters (Vermilingua), armadillos (Cingulata) and sloths (Folivora). This group is the base of eutherian mammals, and understanding the anatomy of its neural system could provide data for functional and evolutionary interpretations. The gross anatomy of the xenarthran brain is recorded. Four extant families of Pilosa and two families of Cingulata were sampled. Usual dissection procedures were used, and the brains were analysed macroscopically. The brain of two-toed sloth, three-toed sloth, six-banded armadillo, giant anteater and collared anteater are gyrencephalic. Pygmy anteater, nine-banded armadillo, great long-nosed armadillo, southern naked-tailed armadillo and giant armadillo are lissencephalic. In most species, the rhinal fissure presents two segments, rostral and caudal (except in Vermilingua and three-toed sloth). The diencephalon and brainstem present similar anatomy. The cerebellum is wide and presents four lobes (rostral, central, caudal and floccular). Its average volume is 12.16% (Folivora), 14.26% (Vermilingua) and 18.61% (Cingulata). Among these groups, there is a statistical difference between Folivora/Cingulata concerning the cerebellum average. The general pattern of the brain of the xenarthrans is similar to that of other mammals., (© 2019 Blackwell Verlag GmbH.)

Glioblastoma (GBM) is the most common and malignant type of primary brain tumor, showing rapid development and resistance to therapies. On average, patients survive 14.6 months after diagnosis and less than 5% survive five years or more. Several pieces of evidence have suggested that the DNA damage signaling and repair activities are directly correlated with GBM phenotype and exhibit opposite functions in cancer establishment and progression. The functions of these pathways appear to present a dual role in tumorigenesis and cancer progression. Activation and/or overexpression of ATRX, ATM and RAD51 genes were extensively characterized as barriers for GBM initiation, but paradoxically the exacerbated activity of these genes was further associated with cancer progression to more aggressive stages. Excessive amounts of other DNA repair proteins, namely HJURP, EXO1, NEIL3, BRCA2, and BRIP, have also been connected to proliferative competence, resistance and poor prognosis. This scenario suggests that these networks help tumor cells to manage replicative stress and treatment-induced damage, diminishing genome instability and conferring therapy resistance. Finally, in this review we address promising new drugs and therapeutic approaches with potential to improve patient survival. However, despite all technological advances, the prognosis is still dismal and further research is needed to dissect such complex mechanisms.

Introduction and Hypothesis: There seems to be little knowledge about pelvic floor muscles (PFMs) in the general population; however, literature confirming this assertion is scarce, especially in developing countries. The present study hypothesized a low level of knowledge about PFMs in a sample of Brazilian women and a positive relationship between that knowledge and the ability to contract the PFMs, strength, and urinary continence., Methods: This was a cross-sectional study including 133 women. A questionnaire assessing knowledge about PFMs and the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-UI-SF) were applied. Vaginal palpation and manometry were used to assess PFM condition. Pearson's correlation coefficient was used to test the association between PFM knowledge and continuous variables, and Fisher's exact test was used to compare the women's PFM knowledge with the categorical variables., Results: A low level of PFM knowledge was observed in this sample, with a mean total score of 0.48 (±0.97). Vaginal manometry peak, mean, and duration values were 39.1 cmH 2 O (±23.7), 25.5 cmH 2 O (±16.1), and 21.1 s (±20.8) respectively. The ICIQ-UI-SF mean score was 7.1 (± 6.8). There were weak correlations between PFM knowledge and age (r -0.2044/ p = 0.01), and parity (r -0.19568/p = 0.02). PFM knowledge was higher among women with higher education levels (p = 0.0012) and those who had previously performed PFM training (p <0.001)., Conclusion: The participants showed a low level of PFM knowledge. No relationship between PFM knowledge and ability to contract or prevalence of UI was observed.

The self-produced extracellular polymeric matrix of biofilms renders them difficult to eliminate once they are established. This makes the inhibition of biofilm formation key to successful treatment of biofilm infection. Antimicrobial photodynamic therapy (aPDT) and antimicrobial peptides offer a new approach as antibiofilm strategies. In this study sub-lethal doses of aPDT (with chlorin-e6 (Ce6-PDT) or methylene blue (MB-PDT)) and the peptides AU (aurein 1.2 monomer) or (AU) 2 K (aurein 1.2 C-terminal dimer) were combined to evaluate their ability to prevent biofilm development by Enterococcus faecalis . Biofilm formation was assessed by resazurin reduction, confocal microscopy, and infrared spectroscopy. All treatments successfully prevented biofilm development. The (AU) 2 K dimer had a stronger effect, both alone and combined with aPDT, while the monomer AU had significant activity when combined with Ce6-PDT. Additionally, it is shown that the peptides bind to the lipoteichoic acid of the E. faecalis cell wall, pointing to a possible key mechanism of biofilm inhibition.

Introduction: Hospitalised patients with nasogastric/nasoenteric tube (NGT/NET) are at constant risk of incidents; therefore, healthcare professionals need to routinely monitor risks and adopt strategies for patient safety and quality of care., Aim: This study aimed to evaluate the NGT/NET-related incidents in hospitalised patients and associated factors., Methods: This is a multicentre study, with a prospective cohort design. Data will be collected at the general medical ward of seven Brazilian hospitals in the north, northeast, southeast and south. The sample will consist of 391 patients that require an NGT/NET during hospitalisation. Three different methods will be used to identify the incidents: (1) healthcare professionals and patients/caregivers will be required to report any NGT/NET-related incidents; (2) researchers will visit the wards to get information about the incidents with healthcare professionals and patients/caregivers; (3) the researchers will review the medical records looking for information on the occurrence of any NGT/NET-related incidents. Demographic, clinical and therapeutic details will be obtained from the medical records and will be registered in an electronic data collection tool developed for the purposes of this study. The complexity of patients will be assessed by the Patient Classification System, and the severity of comorbid diseases will be assessed through the Charlson Comorbidity Index., Implication for Practice: The results may encourage the use of evidence effectively to influence the scientific foundation for clinical practice and the development of evidence-based policies that will prevent, manage and eliminate complications caused by NGT/NET-related incidents, and improve the quality and safety of care provided to hospitalised patients., Ethics and Dissemination: The study has been approved by the Research Ethics Committee. Detailed information about the study can be provided by the principal investigator. The findings will be reported through academic journals, seminar and conference presentations, social media, print media, the internet and community/stakeholder engagement activities., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Comparative genomic analysis of strains may help us to better understand the wide diversity of their genetic profiles. The aim of this study was to analyse the genomic features of the resistome and virulome of Brazilian first methicillin-resistant Staphylococcus aureus (MRSA) isolates and their relationship to other Brazilian and international MRSA strains., Methodology: The whole genomes of three MRSA strains previously isolated in Vitória da Conquista were sequenced, assembled, annotated and compared with other MRSA genomes. A phylogenetic tree was constructed and the pan-genome and accessory and core genomes were constructed. The resistomes and virulomes of all strains were identified.Results/Key findings. Phylogenetic analysis of all 49 strains indicated different clones showing high similarity. The pan-genome of the analysed strains consisted of 4484 genes, with 31 % comprising the gene portion of the core genome, 47 % comprising the accessory genome and 22 % being singletons. Most strains showed at least one gene related to virulence factors associated with immune system evasion, followed by enterotoxins. The strains showed multiresistance, with the most recurrent genes conferring resistance to beta-lactams, fluoroquinolones, aminoglycosides and macrolides., Conclusions: Our comparative genomic analysis showed that there is no pattern of virulence gene distribution among the clones analysed in the different regions. The Brazilian strains showed similarity with clones from several continents.

The rock cavy (Kerodon rupestris) is a crepuscular Hystricomorpha rodent that has been used in comparative analysis of retinal targets, but its retinal organization remains to be investigated. In order to better characterize its visual system, the present study analyzed neurochemical features related to the topographic organization of catecholaminergic cells and ganglion cells, as well the distribution of calcium-binding proteins in the outer and inner retina. Retinal sections and/or wholemounts were processed using tyrosine hydroxylase (TH), GABA, calbindin, parvalbumin and calretinin immunohistochemistry or Nissl staining. Two types of TH-immunoreactive (TH-IR) cells were found which differ in soma size, dendritic arborization, intensity of TH immunoreactivity and stratification pattern in the inner plexiform layer. The topographic distribution of all TH-IR cells defines a visual streak along the horizontal meridian in the superior retina. The ganglion cells are also distributed in a visual streak and the visual acuity estimated considering their peak density is 4.13 cycles/degree. A subset of TH-IR cells express GABA or calbindin. Calretinin is abundant in most of retinal layers and coexists with calbindin in horizontal cells. Parvalbumin is less abundant and expressed by presumed amacrine cells in the INL and some ganglion cells in the GCL. The topographic distribution of TH-IR cells and ganglion cells in the rock cavy retina indicate a suitable adaptation for using a broad extension of its inferior visual field in aspects that involve resolution, adjustment to ambient light intensity and movement detection without specialized eye movements., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Photodynamic therapy has emerged as an alternative treatment for cutaneous leishmaniasis, and compounds with photocatalytic behavior are promising candidates to develop new therapeutic strategies for the treatment of this parasitic disease. Titanium dioxide TiO 2 is a semiconductor ceramic material that shows excellent photocatalytic and antimicrobial activity under Ultraviolet irradiation. Due to the harmful effects of UV radiation, many efforts have been made in order to enhance both photocatalytic and antimicrobial properties of TiO 2 in the visible region of the spectrum by doping or through modifications in the route of synthesis. Herein, Fe-, Zn-, or Pt- doped TiO 2 nanostructures were synthesized by solution-combustion route. The obtained compounds presented aggregates of 100 nm, formed by particles smaller than 20 nm. Doping compounds shift the absorption spectrum towards the visible region, allowing production of reactive oxygen species in the presence of oxygen and molecular water when the system is irradiated in the visible spectrum. The Pt (EC 50  = 18.2 ± 0.8 μg/mL) and Zn (EC 50  = 16.4 ± 0.3 μg/mL) -doped TiO 2 presented the higher antileishmanial activities under visible irradiation and their application as photosensitizers in photodynamic therapy (PDT) strategies for the treatment of cutaneous leishmaniasis should be considered., (Copyright © 2018 Elsevier B.V. All rights reserved.)

In the past few years, the World Health Organization has been warning that the post-antibiotic era is an increasingly real threat. The rising and disseminated resistance to antibiotics made mandatory the search for new drugs and/or alternative therapies that are able to eliminate resistant microorganisms and impair the development of new forms of resistance. In this context, antimicrobial photodynamic therapy (aPDT) and helical cationic antimicrobial peptides (AMP) are highlighted for the treatment of localized infections. This study aimed to combine the AMP aurein 1.2 to aPDT using Enterococcus faecalis as a model strain. Our results demonstrate that the combination of aPDT with aurein 1.2 proved to be a feasible alternative capable of completely eliminating E. faecalis employing low concentrations of both PS and AMP, in comparison with the individual therapies. Aurein 1.2 is capable of enhancing the aPDT activity whenever mediated by methylene blue or chlorin-e6, but not by curcumin, revealing a PS-dependent mechanism. The combined treatment was also effective against different strains; noteworthy, it completely eliminated a vancomycin-resistant strain of Enterococcus faecium. Our results suggest that this combined protocol must be exploited for clinical applications in localized infections as an alternative to antibiotics.

The prevalence profile of periodontal pathogens in dental plaque can vary as a function of the detection method; however, the sampling technique may also play a role in determining dental plaque microbial profiles. We sought to determine the bacterial composition comparing two sampling methods, one well stablished and a new one proposed here. In this study, a ligature-induced periodontitis model was used in 30 rats. Twenty-seven days later, ligatures were removed and microbiological samples were obtained directly from the ligatures as well as from the periodontal pockets using absorbent paper points. Microbial analysis was performed using DNA probes to a panel of 40 periodontal species in the checkerboard assay. The bacterial composition patterns were similar for both sampling methods. However, detection levels for all species were markedly higher for ligatures compared with paper points. Ligature samples provided more bacterial counts than paper points, suggesting that the technique for induction of periodontitis could also be applied for sampling in rats. Our findings may be helpful in designing studies of induced periodontal disease-associated microbiota.

Bacterial resistance to available antibiotics nowadays is a global threat leading researchers around the world to study new treatment modalities for infections. Antimicrobial photodynamic therapy (aPDT) has been considered an effective and promising therapeutic alternative in this scenario. Briefly, this therapy is based on the activation of a non-toxic photosensitizing agent, known as photosensitizer (PS), by light at a specific wavelength generating cytotoxic singlet oxygen and free radicals. Virtually all studies related to aPDT involve a huge screening to identify ideal PS concentration and light dose combinations, a laborious and time-consuming process that is hardly disclosed in the literature. Herein, we describe an antimicrobial Photodynamic Therapy (aPDT) study against Enterococcus faecalis and Propionibacterium acnes employing methylene blue, chlorin-e6 or curcumin as PS. Similarities and discrepancies between the two bacterial species were pointed out in an attempt to speed up and facilitate futures studies against those clinical relevant strains. Susceptibility tests were performed by the broth microdilution method. Our results demonstrate that aPDT mediated by the three above-mentioned PS was effective in eliminating both gram-positive bacteria, although P. acnes showed remarkably higher susceptibility to aPDT when compared to E. faecalis. PS uptake assays revealed that P. acnes is 80 times more efficient than E. faecalis in internalizing all three PS molecules. Our results evidence that the cell wall structure is not a limiting feature when predicting bacterial susceptibility to aPDT treatment., (Copyright © 2017. Published by Elsevier B.V.)

Infection by Leishmania protozoan parasites can cause a variety of disease outcomes in humans and other mammals, from single self-healing cutaneous lesions to a visceral dissemination of the parasite. The correlation between chronic lesions and ecto-nucleotidase enzymes activity on the surface of the parasite is addressed here using damage caused in epithelial cells by nitric oxide. In order to explore the role of purinergic metabolism in lesion formation and the outcome of the infection, we implemented a cellular automata/lattice gas model involving major immune characters (Th1 and Th2 cells, IFN-γ, IL-4, IL-12, adenosine-Ado-, NO) and parasite players for the dynamic analysis of the disease progress. The model were analyzed using partial ranking correlation coefficient (PRCC) to indicate the components that most influence the disease progression. Results show that low Ado inhibition rate over Th-cells is shared by L. major and L. braziliensis , while in L. amazonensis infection the Ado inhibition rate over Th-cells reaches 30%. IL-4 inhibition rate over Th-cell priming to Th1 independent of IL-12 are exclusive of L. major . The lesion size and progression showed agreement with published biological data and the model was able to simulate cutaneous leishmaniasis outcomes. The sensitivity analysis suggested that Ado inhibition rate over Th-cells followed by Leishmania survival probability were the most important characteristics of the process, with PRCC of 0.89 and 0.77 respectively. The simulations also showed a non-linear relationship between Ado inhibition rate over Th-cells and lesion size measured as number of dead epithelial cells. In conclusion, this model can be a useful tool for the quantitative understanding of the immune response in leishmaniasis.

Background: One of the main mechanisms of microbial resistance is given by efflux pumps, which reduce the effectiveness of antimicrobials by decreasing their intracellular concentration., Objective and Methods: Considering that efflux pump inhibitors are promising adjuvant molecules for antibiotics in infections, in this study, using XTT test and colony forming unit (CFU) counting, we evaluated the association between the pump inhibitor verapamil (VP) and the antimicrobial photodynamic therapy (aPDT) mediated by methylene blue (MB) in biofilms of Escherichia coli and Staphylococcus aureus to optimize the bacterial reduction., Results: By applying 44 J/cm 2 , 215 μg/mL of VP, and 200 μg/mL of MB, we obtained 80% of metabolism reduction and 3.4 log 10 CFU/mL decrease for E. coli. Biofilm of S. aureus presented 80% of metabolism reduction and 3.65 log 10 CFU/mL decrease when 22 J/cm 2 , 312 μg/mL of VP, and 200 μg/mL of MB was used. Applying 200 μg/mL of MB, the E. coli biofilm required a higher dose of light, while the S. aureus biofilm required a higher concentration of VP to obtain the same reduction., Conclusions: The VP optimized the efficiency of aPDT and showed no toxicity when used alone in both strains, proving that inhibiting efflux pumps in combination with aPDT has great potential for clinical application.

We report here the draft genome sequences of two community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strains, C18 and C80, isolated from healthy children from day care centers. To our knowledge, these are the first draft genome sequences of CA-MRSA ST398/CC398/Scc mec V and CA-MRSA ST5/CC5/Scc mec IVa isolated from healthy children in Brazil., (Copyright © 2017 de Carvalho et al.)

Here, we report the draft genome sequence of Staphylococcus aureus strain LC33, isolated from human breast milk in Brazil. This microorganism has been typed as ST1/t127/sccmecV. To our knowledge, this is the first draft genome sequence of a methicillin-resistant S. aureus strain isolated from human breast milk., (Copyright © 2017 de Almeida et al.)

Background: Photodynamic therapy (PDT) has proven to be a promising alternative to current cancer treatments, especially if combined with conventional approaches. The technique is based on the administration of a non-toxic photosensitizing agent to the patient with subsequent localized exposure to a light source of a specific wavelength, resulting in a cytotoxic response to oxidative damage. The present study intended to evaluate in vitro the type of induced death and the genotoxic and mutagenic effects of PDT alone and associated with cisplatin., Methods: We used the cell lines SiHa (ATCC® HTB35™), C-33 A (ATCC® HTB31™) and HaCaT cells, all available at Dr. Christiane Soares' Lab. Photosensitizers were Photogem (PGPDT) and methylene blue (MBPDT), alone or combined with cisplatin. Cell death was accessed through Hoechst and Propidium iodide staining and caspase-3 activity. Genotoxicity and mutagenicity were accessed via flow cytometry with anti-gama-H2AX and micronuclei assay, respectively. Data were analyzed by one-way ANOVA with Tukey's posthoc test., Results: Both MBPDT and PGPDT induced caspase-independent death, but MBPDT induced the morphology of typical necrosis, while PGPDT induced morphological alterations most similar to apoptosis. Cisplatin predominantly induced apoptosis, and the combined therapy induced variable rates of apoptosis- or necrosis-like phenotypes according to the cell line, but the percentage of dead cells was always higher than with monotherapies. MBPDT, either as monotherapy or in combination with cisplatin, was the unique therapy to induce significant damage to DNA (double strand breaks) in the three cell lines evaluated. However, there was no mutagenic potential observed for the damage induced by MBPDT, since the few cells that survived the treatment have lost their clonogenic capacity., Conclusions: Our results elicit the potential of combined therapy in diminishing the toxicity of antineoplastic drugs. Ultimately, photodynamic therapy mediated by either methylene blue or Photogem as monotherapy or in combination with cisplatin has low mutagenic potential, which supports its safe use in clinical practice for the treatment of cervical cancer.

Background: Helicobacter pylori ( H. pylori ) infection affects about 50% of the world population and its association with environmental factors and host properties is involved in gastric carcinogenesis. The study aimed to estimate the prevalence of H. pylori in samples of gastric mucosa biopsies, correlate the presence of the bacteria in the sample with the variables age, sex and origin, to identify the types of lesions found in patients with H. pylori , and to evaluate the association of the lesions with the region of the gastric mucosa., Methods: A cross-sectional, retrospective study was carried out in Aracaju, Sergipe, Brazil, from January 2013 to December 2015. A total of 45,206 gastric mucosal biopsies were obtained from patients submitted to upper gastrointestinal endoscopy. Of the reports evaluated, 12,909 met the inclusion criteria since they presented the patient's demographic data as well as the histopathological characteristics of gastric mucosal regions and positivity for H. pylori . Data were analyzed by IBM SPSS Statistic 20 and subjected to descriptive analyses (categorical variables) and inferential (Pearson's Qui-square and linear association tests) and multiple correspondence analyses. Significance level adopted 5%., Results: Of the total of 12,909 (28.6%) reports evaluated, 67% (8,647) came from urban areas and 64.5% (8,320) were female. The mean age (standard deviation (SD)) was 43 years, ranging from 8 to 100 years, prevailing between 21 and 60 years. Among the types of gastric mucosa analyzed, 95.5% (12,322) were of the antral mucosa. The absence of glandular atrophy, the mild infection intensity for H. pylori , the absence of metaplasia, the presence of foveolar hyperplasia and lymphoid follicles were statistically significant (P < 0.001) in this region. In the fundic region, the evidence of fibrinoleucocytic crust and lymphoid follicles was significant (P < 0.001). There was no evidence of associated ulcerated lesions or significant relationship with intestinal metaplasia in the antral mucosa, whereas the fundic mucosa had a strong association with lymphoid follicles. The prevalence of active H. pylori infection in this study was 30.93%., Conclusion: Detection rate of H. pylori and its association with acute and chronic inflammation should be taken into account. The antral region has shown higher incidence and the presence of H. pylori was strongly associated with foveolar hyperplasia and lymphoid follicles.

Chagas disease, caused by the Trypanosoma cruzi, has a wide distribution in South America, and its main method of control is the elimination of triatomines. It is presented here the geographic distribution and the rate of natural infection by T. cruzi of triatomines collected and evaluated from 2008 to 2013 in southwest of Bahia. Triatomines were captured in the intradomiciliary and peridomiciliary areas of five cities located in the southwest of Bahia state, identified, and analyzed for the presence of trypanosomatids in their feces. During the study period the number of patients suspected for acute Chagas disease was recovered from the Notifiable Diseases Information System (SINAN). 8966 triatomines were captured and identified as belonging to eight species. Twenty-six presented themselves infected, being Triatoma sordida the most abundant and with the highest percentage of infection by T. cruzi. Tremedal was the city with the highest number of cases of acute Chagas' disease reported to SINAN. All cities showed triatomines infected with T. cruzi, so there is considerable risk of vectorial transmission of Chagas disease in the southwestern Bahia state, evidencing the need for vector transmission control programs and preventive surveillance measures.

Antimicrobial photodynamic therapy (aPDT) is increasingly being explored for treatment of periodontitis. Here, we investigated the effect of aPDT on human dental plaque bacteria in suspensions and biofilms in vitro using methylene blue (MB)-loaded poly(lactic-co-glycolic) (PLGA) nanoparticles (MB-NP) and red light at 660 nm. The effect of MB-NP-based aPDT was also evaluated in a clinical pilot study with 10 adult human subjects with chronic periodontitis. Dental plaque samples from human subjects were exposed to aPDT-in planktonic and biofilm phases-with MB or MB-NP (25 µg/mL) at 20 J/cm² in vitro. Patients were treated either with ultrasonic scaling and scaling and root planing (US + SRP) or ultrasonic scaling + SRP + aPDT with MB-NP (25 µg/mL and 20 J/cm²) in a split-mouth design. In biofilms, MB-NP eliminated approximately 25% more bacteria than free MB. The clinical study demonstrated the safety of aPDT. Both groups showed similar improvements of clinical parameters one month following treatments. However, at three months ultrasonic SRP + aPDT showed a greater effect (28.82%) on gingival bleeding index (GBI) compared to ultrasonic SRP. The utilization of PLGA nanoparticles encapsulated with MB may be a promising adjunct in antimicrobial periodontal treatment.

The occurrence of a variety of pathogens resistant to current antibiotics remains the major problem in medical care, especially when bacterial infections are established as biofilms. In this study, we propose the use of photodynamic therapy (PDT) as a monotherapy and associated with antibiotic as an alternative treatment. The aim of this study was to analyze the effects of PDT mediated by methylene blue (MB) on Staphylococcus aureus (ATCC 25923) and Escherichia coli (ATCC 25922) in both biofilm and planktonic phases. Several concentrations of MB and light doses were tested. The bactericidal effects of PDT as a monotherapy did not increase with the concentration of photosensitizer, but were light dose-dependent. In addition, bacteria in biofilms were less affected than cells in the planktonic phase. Although not concentration-dependent, the disruption effect of PDT on biofilms was clearly illustrated by scanning electron microscopy (SEM). We also carried out experiments that evaluated the synergistic effect of photodynamic therapy and the antibiotic ciprofloxacin. The best results were obtained after combination treatment of photodynamic therapy followed by ciprofloxacin on biofilms, which increased bacterial reduction on biofilms, resulting in a 5.4 log reduction for S. aureus biofilm and approximately 7 log for E. coli biofilm., (Copyright © 2016. Published by Elsevier B.V.)

Photodynamic therapy (PDT) is a promising alternative approach for improved cancer treatment. In PDT, a photosensitizer (PS) is administered that can be activated by light of a specific wavelength, which causes selective damage to the tumor and its surrounding vasculature. The success of PDT is limited by the difficulty in administering photosensitizers (PSs) with low water solubility, which compromises the clinical use of several molecules. Incorporation of PSs in nanostructured drug delivery systems, such as polymeric nanoparticles (PNPs), solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), gold nanoparticles (AuNPs), hydrogels, liposomes, liquid crystals, dendrimers, and cyclodextrin is a potential strategy to overcome this difficulty. Additionally, nanotechnology-based drug delivery systems may improve the transcytosis of a PS across epithelial and endothelial barriers and afford the simultaneous co-delivery of two or more drugs. Based on this, the application of nanotechnology in medicine may offer numerous exciting possibilities in cancer treatment and improve the efficacy of available therapeutics. Therefore, the aim of this paper is to review nanotechnology-based drug delivery systems for photodynamic therapy of cancer.

Cervical cancer is a neoplasia primarily caused by Human papillomavirus (HPV) infection. Current treatment modalities involve cisplatin, a potent chemotherapeutic agent with severe adverse effects. Photodynamic therapy (PDT) is a promising modality for the treatment of cancer and infections, which has been associated with innovative therapeutic approaches, especially for the treatment of neoplasias. This study aimed to investigate the anticancer potential of PDT mediated by methylene blue (MB) or Photogem (PG) individually and combined with cisplatin in vitro. SiHa, C-33 A and HaCaT cells were incubated with MB, PG and/or cisplatin and received no further treatment or were irradiated with a 630 or a 660 nm LED light source at energy densities varying according to the photosensitizer (PS). The MTT assay was employed to assess cell viability. Both PS were effective in reducing cell viability with the cytotoxicity being dependent on the light dose. When compared to PDT groups, cisplatin was less effective. The cell viability of the combined therapy groups was significantly lower compared to monotherapies. The sequence of treatments (PDT+cisplatin/cisplatin+PDT) was important and had different results when varying the PS, but combination therapy resulted in an enhanced anticancer effect regardless of treatment protocol., (Copyright © 2014 Elsevier B.V. All rights reserved.)

The purpose of this study was to evaluate the neuromuscular efficiency of the vastus medialis obliquus and postural balance in high-performance soccer athletes after anterior cruciate ligament (ACL) reconstruction, compared to the uninvolved leg. A cross-sectional study was conducted with 22 male professional soccer players after ACL reconstruction (4-12 months postoperatively). The athletes were submitted to functional rehabilitation with an accelerated protocol on the soccer team. They were evaluated using isokinetic dynamometer, surface electromyography and electronic baropodometer. There was no decrease or difference between neuromuscular efficiency of the VMO when comparing both the limbs after ACL reconstruction in the professional soccer athletes under treatment. The same result was found in postural balance. It can be concluded that the NME of the VMO in the involved member and postural balance were successfully re-established after the reconstruction procedure of the ACL in the sample group studied.