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In survival analysis sometimes the interest is not just on the failure time distribution function. It is common treatment comparisons as well as studying the effect of covariates in the response. This fact happens in engineering and clinical studies. Covariates effects are usually incorporated in the analysis by using a regression model. Moreover, in some real situations, covariates may be monitored and measured along the follow-up period. These covariates are known as time-dependent covariates. Analysis that include these covariates can be more reliable. Aalen proposed an additive risk model that is very attractive. This model has showed some practical advantages especially when the covariates effects varies in time. The main advantage of this model it is that through graphical analysis it is possible to verify changes in the time in the influence of each one of the covariates. That is, analyses with this model supply information detailed regarding the secular influence of each covariate. This model is presented in this paper in terms of time-dependent covariates. A real data set related to HIV patients and time to develop sinusitis is used to illustrate the fit of the additive Aalen model.En el análisis de supervivencia, a veces, el interés no es sólo la distribución del tiempo de fallo. Es habitual comparar los tiempos de supervivencia de dos o más grupos así como la verificación del efecto de covariables en la respuesta, especialmente en situaciones de ingeniería y en los estudios clínicos. La Los efectos de las covariables general se incorporan en el análisis mediante el uso de un modelo de regresión. Por otra parte, en algunas situaciones reales, las covariables pueden ser monitoreados y medidos a lo largo del período de seguimiento. Estas se denominan covariables dependientes del tiempo e incluirlas en el análisis puede proporcionar resultados más exactos. Aalen propuso un modelo de riesgo aditivo que tiene ventajas prácticas cuando las covariables son seguidas en el tiempo y sus valores pueden ser modificados durante el estudio. La principal ventaja de este modelo es que a través de análisis gráfico es posible verificar los cambios en el tiempo de la influencia de cada una de las covariables. Es decir, el análisis con este modelo proporciona información detallada acerca de la influencia temporal de cada covariable. Así, el modelo Aalen aditivo se presenta en este documento con el fin de mostrar su importancia en la presencia de covariables dependientes del tiempo. Una base de datos real de pacientes infectados por VIH y el tiempo para el desarrollo de la sinusitis se utiliza para ilustrar el ajuste del modelo aditivo de Aalen.Em estudos de sobrevivência, as vezes, o interesse não é apenas na distribuição do tempo de falha. É comum a comparação de tempos de sobrevivência de dois ou mais grupos bem como a verificação do efeito de covariáveis na resposta tanto em engenharia quanto, principalmente, em situações clínicas. A maneira mais eficiente de incorporar o efeito desses fatores no estudo é utilizar um modelo estatístico de regressão. Freqüentemente em estudos de sobrevivência o efeito das covariáveis de interesse pode variar ao longo dotempo de duração do estudo. Estas covariáveis são denominadas de dependentes do tempo e a inclusão delas na análise pode fornecer resultados mais precisos. Aalen propôs um modelo de risco aditivo que apresenta vantagens práticas quando as covariáveis são acompanhadas ao longo do tempo e os seus valores podem ser modificados durante o estudo. A principal vantagem desse modelo é que através de análise gráfica é possível verificar mudanças no tempo na influência de cada uma das covariáveis. Isto é, análises com este modelo fornecem informações detalhadas a respeito da influência temporal de cada covariável. Dessa forma o modelo aditivo de Aalen é apresentado neste trabalho com o objetivo de mostrar a sua importância na presença de covariáveis dependentes do tempo. Um banco de dados real envolvendo pacientes infectados pelo HIV e o tempo até o desenvolvimento de sinusite é utilizado para ilustrar o ajuste deste modelo.

Teniendo en cuenta una pedagogía crítica emancipadora (Jiménez Raya, Lamb & Vieira, 2007) enriquecida por enfoques multisensoriales (Arslan, 2009), se pretende en este artículo dar cuenta de prácticas verdaderamente interdisciplinarias y basadas en una filosofía de proyecto en el que alumnos de ELE en la Educación Básica (primer y tercer ciclos) llevan a cabo tareas de naturaleza plurilingüe y multicultural. En este estudio, hemos tratado de destacar las prácticas y estrategias emancipatorias que traducen aprendizajes que resultan significativos en un nivel multicultural y plurilingüe para los alumnos (Andrade & Araújo e Sá, 2003), contribuyendo al desarrollo de su conciencia crítica cultural (Byram et al, 2002). Buscando evidenciar una muestra de prácticas interdisciplinarias y multisensoriales (Arslan, 2009), relacionadas con el proyecto Pluri+Red y basadas en el uso de estrategias y materiales físicos o digitales (juegos didácticos, WebQuests, cuentos interactivos, etc.) que plantean retos a los estudiantes con el fin de provocar asombro y extrañeza, pero también cuestionamiento (Jiménez Raya, Lamb & Vieira, 2007), pretendemos que este estudio exploratorio demuestre las opciones y rutas tomadas hacia un único objetivo: formar a los futuros ciudadanos conscientes del mundo, capaces de intervenir y de formarse a lo largo de su vida.

Abstract Background Nanoemulsions have practical application in a multitude of commercial areas, such as the chemical, pharmaceutical and cosmetic industries. Cosmetic industries use rice bran oil in sunscreen formulations, anti ageing products and in treatments for skin diseases. The aim of this study was to create rice bran oil nanoemulsions using low energy emulsification methods and to evaluate their physical stability, irritation potential and moisturising activity on volunteers with normal and diseased skin types. Results The nanoemulsion developed by this phase diagram method was composed of 10% rice bran oil, 10% surfactants sorbitan oleate/PEG-30 castor oil, 0.05% antioxidant and 0.50% preservatives formulated in distilled water. The nanoemulsion was stable over the time course of this study. In vitro assays showed that this formulation has a low irritation potential, and when applied to human skin during in vivo studies, the nanoemulsion improved the skin's moisture and maintained normal skin pH values. Conclusion The results of irritation potential studies and in vivo assessments indicate that this nanoemulsion has potential to be a useful tool to treat skin diseases, such as atopic dermatitis and psoriasis.

Introduction: Peyronie's Disease (PD) is a condition characterized by the development of fibrous scar tissue causing penile curvature and often painful erections. From a sexual health perspective, PD is commonly researched in heterosexual men; however, there is a paucity of data assessing the impact that PD has on men who have sex with men (MSM) population. Objective: This prospective survey study sought to collect data on how PD affects MSM from a biopsychosocial and sexual perspective and compare this population's experience with non-MSM. Methods: An anonymous online survey was deemed IRB exempt and administered to the following online platforms: Reddit to include r/PeyroniesSupport, r/lgbtstudies, r/sex, and on Facebook to the Peyronie's Disease Support group in July 2023. Participants were asked demographic info, sexual orientation, type of sexual intercourse, family history of PD, history of trauma, immune disease, PD symptoms, partner and self-bother, degree of curvature, care seeking, medical interventions, impact on mental health, disease progression, as well as the Peyronie's Disease Questionnaire (PDQ) survey. Descriptive statistics were performed. Results: Thirty-six men completed the survey, nine being MSM (11.8% "men and others" and 14.7% "strictly men"). Reported sexual interactions included anal (50%), vaginal (77%), and oral (79%) intercourse. History of penile trauma occurred in 32% of respondents. None of the respondents reported a family history of PD, and two subjects disclosed autoimmune diseases. The most common symptoms, experienced by 91% of subjects, were "shortening and/or narrowing of the penis," followed by: erectile dysfunction (69%), difficulty with sexual intercourse (44%), painful erections (31%), and painful sexual intercourse or masturbation (28%). 85% of surveyed men and 100% of MSM stated PD negatively impacts their mental health. Assessment of partner satisfaction revealed women express greater disapproval (12%) compared to men (3%). The majority of men (91%) reported seeing a urologist with only 35% seeing one regularly and 50% being MSM. A negative experience with a urologist was reported in 40% of MSM and 20% of non-MSM. Degrees of reported curvature were: 77% with less than or equal to 45 degrees, 6% between 46-60 degrees, and 18% between 61-90 degrees. Greater than 60% and 27% were offered medical and surgical interventions, respectfully. 62% reported their PD has remained stable. Conclusions: In conclusion, the results of this survey suggest that PD may have a greater negative effect on mental health and experience with a urologist for MSM. However, non-MSM are more likely to experience partner disapproval. Overall, the characteristics of PD do not grossly vary between MSM and non-MSM but the psychosocial aspect may possess greater consequences for MSM. More data is needed on this understudied population affected by PD. Disclosure: No. [ABSTRACT FROM AUTHOR]

Competing Interests: 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Prostate cancer is one of the most prevalent malignancies affecting men worldwide. Despite advancements in understanding prostate anatomy and minimally invasive approaches to surgical treatment, surgery can have significant adverse effects on sexual function. Penile rehabilitation strategies have emerged as a promising approach to mitigate the impact of prostate cancer treatments on erectile function and improve quality of life. Several methods have been employed for penile rehabilitation, including pharmacotherapy, vacuum erection devices, intracavernous injections, and emerging novel techniques. Yet, there is no consensus on the exact programs or timing of initiation that should be utilized for optimal recovery after surgery. This review discusses various rehabilitation protocols and long-term outcomes and explores the cost-effectiveness of different interventions. Additionally, this review discusses the importance of a multidisciplinary approach to penile rehabilitation which includes patient education, counseling, and the selection of an appropriate rehabilitation strategy tailored to each individual's needs and preferences. Continued research and collaboration among healthcare professionals are essential to refine rehabilitation approaches and ensure optimal outcomes for patients with prostate cancer., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

The geographical range of schistosomiasis is affected by the ecology of schistosome parasites and their obligate host snails, including their response to temperature. Previous models predicted schistosomiasis' thermal optimum at 21.7°C, which is not compatible with the temperature in sub-Saharan Africa (SSA) regions where schistosomiasis is hyperendemic. We performed an extensive literature search for empirical data on the effect of temperature on physiological and epidemiological parameters regulating the free-living stages of S. mansoni and S. haematobium and their obligate host snails, i.e., Biomphalaria spp. and Bulinus spp., respectively. We derived nonlinear thermal responses fitted on these data to parameterize a mechanistic, process-based model of schistosomiasis. We then re-cast the basic reproduction number and the prevalence of schistosome infection as functions of temperature. We found that the thermal optima for transmission of S. mansoni and S. haematobium range between 23.1-27.3°C and 23.6-27.9°C (95% CI) respectively. We also found that the thermal optimum shifts toward higher temperatures as the human water contact rate increases with temperature. Our findings align with an extensive dataset of schistosomiasis prevalence in SSA. The refined nonlinear thermal-response model developed here suggests a more suitable current climate and a greater risk of increased transmission with future warming for more than half of the schistosomiasis suitable regions with mean annual temperature below the thermal optimum., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Aslan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The redox reactivity of iron is a double-edged sword for cell functions, being either essential or harmful depending on metal concentration and location. Deregulation of iron homeostasis is associated with several clinical conditions, including viral infections. Clinical studies as well as in silico, in vitro and in vivo models show direct effects of several viruses on iron levels. There is support for the strategy of iron chelation as an alternative therapy to inhibit infection and/or viral replication, on the rationale that iron is required for the synthesis of some viral proteins and genes. In addition, abnormal iron levels can affect signaling immune response. However, other studies report different effects of viral infections on iron homeostasis, depending on the class and genotype of the virus, therefore making it difficult to predict whether iron chelation would have any benefit. This review brings general aspects of the relationship between iron homeostasis and the nonspecific immune response to viral infections, along with its relevance to the progress or inhibition of the inflammatory process, in order to elucidate situations in which the use of iron chelators could be efficient as antivirals., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

The potential of low-frequency ultrasound (LFU) combined with nanotechnology-based formulations in improving skin tumors topical treatment was investigated. The impact of solid lipid nanoparticles (SLN) and hydrophilic nanogels as coupling media on LFU-induced skin localized transport regions (LTR) and the penetration of doxorubicin (DOX) in LFU-pretreated skin was evaluated. SLN were prepared by the microemulsion technique and liquid crystalline nanogels using Poloxamer. In vitro, the skin was pretreated with LFU until skin resistivity of ∼1 KΩ.cm 2 using the various coupling media followed by evaluation of DOX penetration from DOX-nanogel and SLN-DOX in skin layers. Squamous cell carcinoma (SCC) induced in mice was LFU-treated using the nanogel with the LFU tip placed 5 mm or 10 mm from the tumor surface, followed by DOX-nanogel application. LFU with nanogel coupling achieved larger LTR areas than LFU with SLN coupling. In LFU-pretreated skin, DOX-nanogel significantly improved drug penetration to the viable epidermis, while SLN-DOX hindered drug transport through LTR. In vivo, LFU-nanogel pretreatment with the 10 mm tip distance induced significant tumor inhibition and reduced tumor cell numbers and necrosis. These findings suggest the importance of optimizing nanoparticle-based formulations and LFU parameters for the clinical application of LFU technology in skin tumor treatment., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Resistance training (RT) effectively promotes functional independence after stroke., Objectives: To investigate the effect of lower limb RT on body structure and function (muscle strength, postural balance), activity (mobility, gait) and participation (quality of life, impact of stroke on self-perceived health) outcomes in individuals with chronic stroke., Methods: Six databases were searched from inception until September 2022 for randomized controlled trials comparing lower limb RT to a control intervention. The random-effects model was used in the meta-analyses. Effect sizes were reported as standardized mean differences (SMD). Quality of evidence was assessed using the GRADE approach., Results: Fourteen studies were included. Significant improvements were found in body structure and function after lower limb RT: knee extensors (paretic side - SMD: 1.27; very low evidence), knee flexors (paretic side - SMD: 0.51; very low evidence; non-paretic side - SMD: 0.52; low evidence), leg press (paretic side - SMD: 0.83; very low evidence) and global lower limb muscle strength (SMD: -1.47; low evidence). No improvement was found for knee extensors (p = 0.05) or leg press (p = 0.58) on the non-paretic side. No improvements were found in the activity domain after lower limb RT: mobility (p = 0.16) and gait (walking speed-usual: p = 0.17; walking speed-fast: p = 0.74). No improvements were found in the participation domain after lower limb RT: quality of life (p > 0.05), except the bodily pain dimension (SMD: 1.02; low evidence) or the impact of stroke on self-perceived health (p = 0.38)., Conclusion: Lower limb RT led to significant improvements in the body structure and function domain (knee extensors and flexors, leg press, global lower limb muscle strength) in individuals with chronic stroke. No improvements were found in the activity (mobility, gait [walking speed]) or participation (quality of life, impact of stroke on self-perceived health) domains., Prospero Registration Number: CRD42021272645., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Given the lack of advances in Oral Squamous Cell Carcinoma (OSCC) therapy in recent years, pharmacological strategies to block OSCC-related signaling pathways have gained prominence. The present study aimed to evaluate the therapeutic potential of Arsenic Trioxide (ATO) concerning its antitumoral effects and the inhibition of the Hedgehog (HH) pathway in OSCC. Initially, ATO cytotoxicity was assessed in a panel of cell lines. Cell viability, cell cycle, death patterns, and cell morphology were analyzed, as well as the effect of ATO on the expression of HH pathway components. After the cytotoxic assay, HSC3 cells were chosen for all in vitro assays. ATO increased apoptotic cell death and nuclear fragmentation in the sub-G1 cell cycle phase and promoted changes in cell morphology. In addition, the reduced expression of GLI1 indicated that ATO inhibits HH activity. The present study provides evidence of ATO as an effective cytotoxic drug for oral cancer treatment in vitro.

Metastasis is responsible for most breast cancer-related deaths; however, identifying the cellular determinants of metastasis has remained challenging. Here, we identified a minority population of immature THY1 + / VEGFA + tumor epithelial cells in human breast tumor biopsies that display angiogenic features and are marked by the expression of the oncogene, LMO2 . Higher abundance of LMO2 + basal cells correlated with tumor endothelial content and predicted poor distant recurrence-free survival in patients. Using MMTV-PyMT/Lmo2 CreERT2 mice, we demonstrated that Lmo2 lineage-traced cells integrate into the vasculature and have a higher propensity to metastasize. LMO2 knockdown in human breast tumors reduced lung metastasis by impairing intravasation, leading to a reduced frequency of circulating tumor cells. Mechanistically, we find that LMO2 binds to STAT3 and is required for STAT3 activation by tumor necrosis factor-α and interleukin-6. Collectively, our study identifies a population of metastasis-initiating cells with angiogenic features and establishes the LMO2-STAT3 signaling axis as a therapeutic target in breast cancer metastasis.

Environmental heterogeneity is a key component in explaining the megadiversity of tropical forests. Despite its importance, knowledge about local drivers of environmental heterogeneity remains a challenge for ecologists. In Neotropical forests, epiphytic tank bromeliads store large amounts of water and nutrients in the tree canopy, and their tank overflow may create nutrient-rich patches in the soil. However, the effects of this nutrient flux on environmental heterogeneity and plant community structure in the understory remain unexplored. In a Brazilian coastal sandy forest, we investigated the effects of the presence of epiphytic tank bromeliads on throughfall chemistry, soil chemistry, soil litter biomass, light, and seedling community structure. In the presence of epiphytic tank bromeliads, the throughfall nitrogen concentration increased twofold, the throughfall phosphorus concentration increased threefold, and the soil patches had a 3.96% higher pH, a 50% higher calcium concentration, and 11.88% less light. By altering the availability of soil resources and conditions, the presence of bromeliads partially shifted the available niche spaces for plant species and indirectly affected the structure of the seedling communities, decreasing their diversity, density, and biomass. For the first time, we showed that the presence of tank bromeliads in the canopy can create characteristic soil patches in the understory, affecting the structure of seedling communities via fertilization. Our results reveal a novel local driver of environmental heterogeneity, reinforcing and expanding the key role of tank bromeliads both in nutrient cycling and plant community structuring of Neotropical coastal sandy forests., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Obesity is a well-known risk factor for lower urinary tract disorders. Lifestyle plays an essential role in the etiology of the symptoms, negatively affecting self-esteem and quality of social, professional, and sexual life., Objectives: To assess the prevalence of lower urinary tract symptoms and urodynamic patterns in obese women and to compare to nonobese volunteers., Methods: Overactive bladder (OAB) questionaries (International Consultation on Incontinence Questionnaire [ICIQ]-OAB) and stress urinary incontinence (SUI) (ICIQ-short form) were applied to the participants. They underwent a physical exam and urodynamics except for the control group., Results: A total of 109 women completed the protocol and 20 were in the control group. The average age was 43.0 years, and the average body mass index was 45.12 ± 7.64 kg/m 2 and control was 44.5 years, and 29.95 ± 5.08 kg/m 2 . The OAB symptoms in the obese group were 31.20%, 55.95% higher than the control group (20.0%). The prevalence of SUI in the obese group was 20.20%, an increase of 34.53% compared with the control group (15.00%). The urodynamic study (UDS) showed that the morbidly obese women have a first sensation earlier than the obese or severely obese, as well as the first desire to void. The Valsalva leak point pressure of morbidly obese women was significantly higher than the others., Conclusion: Among obese women, either the prevalence of SUI or OAB is significantly higher than the nonobese female population. Regarding UDS, the pattern is similar to the clinic diagnostic. The grade of obesity is directly associated with an impairment of the patient's cystometric capacity., (© 2021 Wiley Periodicals LLC.)

Competing Interests: 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.

Purpose: Nonobstructive azoospermia (NOA) is associated with intrinsic testicular defects that severely impair sperm production. Although NOA invariably leads to infertility, focal sperm production may exist in the testicles of affected patients, which can be retrieved and used for intracytoplasmic sperm injection (ICSI) to generate healthy offspring. However, geographic locations of testicular sperm producing-areas are uncertain, making microsurgical-guided sperm retrieval (microdissection testicular sperm extraction; micro-TESE) an attractive method to identify and retrieve sperm in patients with NOA due to spermatogenic failure. Given the widespread use of micro-TESE, its effectiveness in harvesting sperm and related potential complications need to be clarified., Methods: We queried PubMed/MEDLINE for studies published in English, from inception to May 2021, concerning the effect of micro-TESE on sperm retrieval rate (SRR), complication rate and ICSI pregnancy rate-using retrieved testicular sperm in subfertile couples where the male had NOA., Results: We found 116 articles, including 70 original papers, 32 review articles, and 14 systematic reviews. The evidence accounted for 4895 patients. Micro-TESE retrieved sperm in 46.6% of men with NOA, but SRRs varied considerably (18.4-70.8%) and were mainly related to the treated population characteristics. Concerning the general population of NOA patients who have not undergone previous sperm retrieval (naïve population), the SRR by micro-TESE was 46.8% (1833 of 3914 patients; range 20-70.8%; 28 studies). In studies reporting SR by micro-TESE for men who had failed percutaneous testicular sperm aspiration or non-microsurgical testicular sperm extraction, the SRR was 39.1% (127 of 325 patients; range 18.4-57.1%; 4 studies). Data on adverse events indicated that micro-TESE was associated with low (~ 3%) short-term postoperative complication rates. The fertilizing ability of testicular sperm retrieved by micro-TESE and used for ICSI was adequate (~ 57%), whereas clinical pregnancy and live birth were obtained in 39% and 24% of couples who had an embryo transfer, respectively. The health of the resulting children seems reassuring, but the evidence is limited. The procedure increases sperm retrieval success compared to non-microsurgical retrieval methods, particularly in men with Sertoli cell-only testicular histopathology., Conclusion: We concluded that micro-TESE is an effective and safe method to retrieve sperm from men with NOA-related infertility, with potential advantages over non-microsurgical methods. Nevertheless, high-quality, head-to-head comparative randomized controlled trials by sperm retrieval method, focusing on SRR, live birth rate and assessing long-term adverse events and health of children conceived using testicular sperm from NOA patients are lacking. Therefore, further research is required to determine the full clinical implications of micro-TESE in male infertility treatment., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Hepatosplenic schistosomiasis mansoni (HS) is associated with thrombocytopenia. Accurate platelet counts are required for identification and management of HS patients. EDTA-dependent pseudothrombocytopenia (EDTA-PTCP) is an in vitro phenomenon of anticoagulant-activated platelet agglutination resulting in low platelet counts by automated methods. The prevalence of EDTA-PCTP in schistosomiasis is unknown and only one case has been described. Our aims were to determine the prevalence of EDTA-PTCP in HS and evaluate alternative methods to overcome this analytical error., Methods: Blood samples from 56 HS patients and 56 healthy volunteers were collected, and platelet counts were obtained using standard microscopy and automated (electric impedance) methods. Automated platelet counts and the presence of platelet clumps in blood smears were evaluated in samples collected in EDTA or sodium citrate tubes 20 and 180 min after blood collection., Results: EDTA-PTCP was more frequent in HS patients than healthy volunteers (8.92% vs 0.00%, p<0.0285). Platelet clumps and PTCP were also observed in samples collected in sodium citrate tubes, refuting its use as an alternative method., Conclusions: Automated platelet counts in blood samples from HS patients should be performed right after blood collection in EDTA tubes and verified by manual counts in blood smears., (© The Author(s) 2021. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Introduction and Hypothesis: There is a great interest in avoiding mesh usage in vaginal surgeries. We propose using the autologous rectus fascia to repair apical vaginal prolapse in a similar way it has been successfully used in urinary stress incontinence surgery. This study aims to demonstrate the technique of sacrospinous hysteropexy using autologous rectus fascia for apical pelvic organ prolapse (POP) treatment., Methods: We present a video of a 63-year-old female with stage IV pelvic organ prolapse and urinary obstruction. A rectus fascia sling of approximately 90 × 10 mm was harvested through a Pfannenstiel incision. It was used in vaginal surgery to suspend the cervix and fix the apical POP., Results: The patient resumed her usual activities after 1 week and waited 2 months to resume physical activities and sexual intercourse. She is satisfied at 6 months follow-up, without complications or prolapse recurrence., Conclusion: The sacrospinous hysteropexy using autologous rectus fascia is a feasible technique with excellent results and low risk of complication. Further studies are required to compare POP repair using autologous rectus fascia and polypropylene meshes., (© 2021. The International Urogynecological Association.)

Schistosomiasis is a major public health problem in tropical areas of the world. Health-related quality of life (HRQOL) measurement is being widely used to evaluate the impact of a disease or treatment in several aspects of daily life. However, few studies evaluated the impact of severe forms of schistosomiasis on HRQOL of affected individuals and compared them to healthy controls with a similar socio-demographic background. Our aims were to evaluate the HRQOL in patients with hepatosplenic schistosomiasis (HS) and schistosomal myeloradiculopathy (SMR) and healthy volunteers (HV) and determine if clinical complications of the disease are associated with HRQOL scores. We interviewed and evaluated the HRQOL in 49 patients with HS, 22 patients with SMR, and 26 HV from an outpatient clinic of the Federal University of Minas Gerais University Hospital using the WHOQOL-BREF questionnaire. SMR and HS patients had a significantly lower overall quality of life score when comparing with the HV control group ( p = 0.003 and p = 0.005, respectively). Multivariate ordinal regression model adjusted for sex, age, and educational level indicated that HS and SMR patients have three and five times more chances of having a lower quality of life than healthy volunteers (Odds Ratio 3.13 and 5.04, respectively). There was no association between complications of HS disease and quality of life scores. In contrast, worse quality of life was observed in SMR patients that presented back or leg pain, leg paresthesia, and bladder dysfunction. In conclusion, HS and SMR significantly impact the overall quality of life of the affected individuals, reinforcing the importance of efforts to control and eradicate this debilitating disease and suggesting that multidisciplinary clinical management of schistosomiasis patients would be more appropriate and could potentially improve patient's quality of life., Competing Interests: 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 © 2021 Roriz, Pereira, Vaz de Melo Trindade, Caporali and Lambertucci.)

The pathogenesis of schistosomiasis and the mechanism of disease regression after Praziquantel pharmacotherapy are not fully elucidated. Schistosoma mansoni egg antigens directly stimulate the expression of the profibrogenic molecule osteopontin (OPN), and systemic OPN levels strongly correlate with disease severity, suggesting its use as a potential morbidity biomarker. In this study, we investigated the impact of Praziquantel use on systemic OPN levels and on liver collagen deposition in chronic murine schistosomiasis. Praziquantel treatment significantly reduced systemic OPN levels and liver collagen deposition, indicating that OPN could be a reliable tool for monitoring PZQ efficacy and fibrosis regression in murine schistosomiasis., (Copyright © 2021 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.)

Background: People with diabetes mellitus, especially insulin-dependent diabetic patients, are a risk group for staphylococcal infections. Asymptomatic infection with Staphylococcus aureus is common and favors dissemination of the microorganism, rendering these individuals a source of infection. This study aimed to characterize the resistance profile, clonal profile and sequence type, as well as to analyze the prevalence and risk factors for nasal and oropharyngeal carriage of methicillin-susceptible (MSSA) and methicillin-resistant S. aureus (MRSA) isolated from insulin-dependent diabetic individuals in the city of Botucatu, SP, Brazil., Methods: Staphylococcus aureus was collected from the nasopharynx and oropharynx of 312 community-dwelling insulin-dependent diabetic individuals over a period of 3 years (October 2015 to December 2018). The isolates were characterized by susceptibility profiling, detection of the mecA gene, SCCmec typing, and molecular typing by PFGE and MLST. The risk factors associated with S. aureus and MRSA carriage were determined by logistic regression analysis., Results: The overall prevalence of colonization with S. aureus and MRSA was 30.4% and 4.8%, respectively. Fifteen of the 112 S. aureus isolates carried the mecA gene; SCCmec type IV was identified in 10 isolates, SCCmec type I in three, and SCCmec type II in two. Among the 15 resistant isolates (MRSA), four were susceptible to oxacillin/cefoxitin by the disc diffusion method and one MSSA isolate was resistant to sulfamethoxazole/trimethoprim. The analysis of risk factors revealed a protective effect of age and lung disease, while lower-extremity ulcers were a risk factor for S. aureus. For MRSA, only male gender was significantly associated as a risk factor in multivariate analysis. Clonal profile analysis demonstrated the formation of clusters among MRSA isolates from different patients, with the identification of ST5-IV, ST5-I, and ST8-IV. Isolates carrying ST398 were identified among MSSA and MRSA (ST398-IV)., Conclusion: Our findings reinforce the importance of epidemiological studies of S. aureus carriage, especially in populations at high risk of infections such as diabetics. The data suggest widespread dissemination of MRSA in the population of insulin-dependent diabetic patients studied, as well as the emergence of important lineages among these individuals.

The purpose of this study was to evaluate the expression of Hedgehog (HH) signaling molecules (SHH and GLI-1) by cancer-associated fibroblasts (CAF) in oral squamous cell carcinoma (OSCC). Immunohistochemistry was used to detect molecular HH signaling and CAF-related protein expression, including α-SMA and S100A4, in 70 samples of human OSCC. The colocalization of α-SMA and S100A4 with SHH was also evaluated by double-staining. In vitro study was performed using primary normal oral fibroblast (NOF) and CAF through immunofluorescence and Western Blot for CAF-proteins, SHH, and GLI-1. Forty-five cases (64.28%) were positive for α-SMA exclusively in tumor stroma, and S100A4 was identified in the cytoplasm of CAFs in 94.28% (n = 66) of the cases. With respect to stromal cells, 64 (91.43%) OSCC cases were positive for SHH, and 31 were positive for GLI-1 (44.29%); positive correlations were found between SHH and α-SMA (p < 0.0001, φ = 0.51), as well as between SHH and S100A4 (p = 0.087, φ = 0.94). Protein expression of SHH and GLI-1 was observed in primary CAFs and NOFs. Although SHH was found to be localized in the cellular cytoplasm of both cell types, GLI-1 was present only in the nuclei of CAF. Our results indicate that CAFs are not only potential sources of HH ligands in tumor stroma, but may also respond to HH signaling through nuclear GLI-1 activation. We further observed that elevated SHH expression by OSCC cells was associated with higher CAF density, reinforcing the chemoattractant role played by these molecules.

Oral Squamous Cell Carcinoma (OSCC) presents an important challenge for the health systems worldwide. Thus, unraveling the biological mechanisms involved in OSCC pathogenesis is essential to the discovery of new drugs with anticancer potential. The Hedgehog (HH) pathway has shown promising results as a therapeutic target both in vitro and in vivo. This study aimed to investigate the effects of vismodegib and itraconazole on the expression of Hedgehog (HH) genes (PTCH1, SMO, and GLI1), cell cycle and cell death in OSCC cells. Alamar Blue assay was used to assess the cytotoxicity of vismodegib and itraconazole in a panel of oral cancer cell lines, including CAL27. The expression of HH signaling components after treatment with vismodegib and itraconazole, at concentrations of 25 or 50 μg/ml was evaluated by qPCR. Cell cycle and apoptosis were evaluated by flow cytometry after 72 h treatment with 50 μg/ml of vismodegib or itraconazole. HH signaling was activated in OSCC cell lines CAL27, SCC4, SCC9, and HSC3. Vismodegib and itraconazole significantly reduced CAL27 cell viability after 48 h of treatment. Gene expression of PTCH1, SMO, and GLI1 decreased in response to 24 h of treatment with vismodegib or itraconazole. Furthermore, CAL27 cells exhibited alterations in morphology, cell size, and cellular granularity. An increase in the DNA fragmentation was observed after treatment and both inhibitors induced apoptosis after 72 h. In conclusion, SMO inhibitors vismodegib and itraconazole demonstrably reduced the expression of HH genes in CAL27 OSCC cell line. In addition, treatment with vismodegib and itraconazole reduced cellular viability and altered the morphology of CAL27 cells, and also induced apoptosis., (Copyright © 2020 Freitas, Dias, Vidal, Valverde, Gomes Alves Costa, Damasceno, Sales, Siquara da Rocha, dos Reis, Soares, Coletta, Pereira, Bezerra and Gurgel Rocha.)

Background: Prostatic xanthoma is a lesion of unknown cause that is often an incidental finding in patients undergoing needle biopsy or transurethral resection. To the best of our knowledge, we report on a unique case of a pure xanthoma without benign prostatic hyperplasia of the prostate in a patient with lower urinary tract symptoms manifested after kidney transplantation., Methods: A 62-year-old man was submitted for a kidney transplant in April 2018. He had no urinary complaints previous to the transplant. Since July 2019, he had complained of lower urinary tract symptoms. In October 2019, he had acute urinary retention being submitted to a transurethral resection of an estimated 47 g prostate. All measures of cholesterol, high-density lipoproteins (HDL), and low-density lipoproteins (LDL) were within the normal range-except triglycerides, which were mildly elevated in 2 measures., Results: The pathologic examination of the resected prostate showed pure xanthoma without benign prostatic hyperplasia. A similar lesion with a xanthomatous cell component is verruciform xanthoma. It is a rare benign lesion of unknown etiology not associated with underlying disorders of lipid metabolism that has been reported in patients with bone marrow, kidney, and liver transplant., Conclusions: We report a unique case of prostate enlargement caused by pure xanthoma in a patient with renal transplant. In absence of any apparent infection, normal cholesterol measures, and appearance of symptoms after the transplant and considering the morphologic similarity with verruciform xanthoma, a lesion also reported in transplanted patients, we speculate that the pathogenesis of the lesion in this particular patient may be related to immunosuppression., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: To promptly identify mental suffering in low-risk prostate cancer (LRPC) patients, vulnerable to over- and undertreatment, we evaluated the correlation of rapid emotional thermometers (ET) with multidimensional validated structured questionnaires., Methods: At diagnosis, consecutive LRPC patients underwent five ET domains: emotional suffering, anxiety, depression (DT), revolt and need for help and multidimensional questionnaires: beck anxiety inventory (BAI), beck depression inventory (BDI), beck hopelessness scale, SF36 (physical functioning PF, role limitations due to physical health RP, bodily pain BP, general health perceptions GH, vitality VT, social functioning SF, role limitations due to emotional problems RE and general mental health MH), international index of erectile function and international prostate symptom score (IPSS)., Results: Among 30 included patients, mean age 67.4 y (52-74), 20 days after the diagnosis (15-30), mean time to obtain ET 27 s (15-57) and all questionnaires 36.7 min (31-49), ETs showed moderate/strong Spearman correlation among themselves. DT domain displayed the best correlation to most of the multidimensional validated structured questionnaires: moderate to BDI, SF-36 (PF, GH, VT, SF, RE, MH) and IPSS and strong to BAI., Conclusion: DT revealed the best correlation to validated structured questionnaires of diverse dimensions with clear potential for quick screening of patients with psychological suffering and in need of further evaluation and support.

We investigate a six-species class of May-Leonard models leading to the formation of two types of competing spatial domains, each one inhabited by three species with their own internal cyclic rock-paper-scissors dynamics. We study the resulting population dynamics using stochastic numerical simulations in two-dimensional space. We find that as three-species domains shrink, there is an increasing probability of extinction of two of the species inhabiting the domain, with the consequent creation of one-species domains. We determine the critical initial radius beyond which these one-species spatial domains are expected to expand. We further show that a transient scaling regime, with a slower average growth rate of the characteristic length scale L of the spatial domains with time t, takes place before the transition to a standard L∝t^{1/2} scaling law, resulting in an extended period of coexistence.

In chronic schistosomiasis, liver fibrosis is linked to portal hypertension, which is a condition associated with high mortality and morbidity. High mobility group box 1 (HMGB1) was originally described as a nuclear protein that functions as a structural co-factor in transcriptional regulation. However, HMGB1 can also be secreted into the extracellular milieu under appropriate signal stimulation. Extracellular HMGB1 acts as a multifunctional cytokine that contributes to infection, injury, inflammation, and immune responses by binding to specific cell-surface receptors. HMGB1 is involved in fibrotic diseases. From a clinical perspective, HMGB1 inhibition may represent a promising therapeutic approach for treating tissue fibrosis. In this study, we demonstrate elevated levels of HMGB1 in the sera in experimental mice or in patients with schistosomiasis. Using immunohistochemistry, we demonstrated that HMGB1 trafficking in the hepatocytes of mice suffering from acute schistosomiasis was inhibited by Glycyrrhizin, a well-known HMGB1 direct inhibitor, as well as by DIC, a novel and potential anti-HMGB1 compound. HMGB1 inhibition led to significant downregulation of IL-6, IL4, IL-5, IL-13, IL-17A, which are involved in the exacerbation of the immune response and liver fibrogenesis. Importantly, infected mice that were treated with DIC or GZR to inhibit HMGB1 pro-inflammatory activity showed a significant increase in survival and a reduction of over 50% in the area of liver fibrosis. Taken together, our findings indicate that HMGB1 is a key mediator of schistosomotic granuloma formation and liver fibrosis and may represent an outstanding target for the treatment of schistosomiasis.

Aims: Streptococcus agalactiae, commonly known as group B Streptococcus (GBS), has been recognised as a worldwide causative pathogenic agent of neonatal sepsis, meningitis and pneumonia. To better understand the behaviour of S. agalactiae in pregnant women from a hospital from the North of Portugal, retrospective analyses were performed to describe epidemiological, clinical and microbiological characteristics of the isolates obtained., Methods: Based on laboratorial records and the hospital's patient files, a 6-year retrospective study was performed to analyse S. agalactiae isolates from screened pregnant women between 35 and 37 weeks of gestation and hospitalised neonates from pregnant women between 24 and 41 weeks of gestation admitted in Hospital Pedro Hispano. Serotype characterisation was also performed in 67 GBS strains., Results: In 6692 pregnant women between 35 and 37 weeks of gestation screened between 2011 and 2016, a total of 1377 S. agalactiae isolates (21%) were found. A high percentage (40%) of unknown colonisation status among hospitalised neonates from pregnant women between 24 and 41 weeks of gestations was also found. The incidence of neonatal sepsis was 8.7 (95% CI 7.0 to 10.8) cases per 1000 live births. Regarding serotype characterisation, serotype III (22.4%) was the most frequent, followed by serotype Ia (19.4%) and serotypes Ib and V (both with 17.9%)., Conclusion: High epidemiological values of GBS colonisation and incidence were found in this study. In Portugal studies on the epidemiology and behaviour of S. agalactiae remain limited, reinforcing the importance and need for S. agalactiae screening across the country., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

The present study was designed to evaluate possible adverse effects of different dosages of avermectins (abamectin and a combination of ivermectin + abamectin) administered subcutaneously in calves less than one month of age. Clinical as well as biochemical parameters of blood and cerebrospinal fluid (CSF) were evaluated for animals subjected to various treatments. Thirty-five calves were divided into seven groups of five animals each: T01 (control), T02 (abamectin 200 μg/kg), T03 (abamectin 400 μg/kg), T04 (abamectin 600 μg/kg), T05 (ivermectin 450 μg/kg + abamectin 250 μg/kg), T06 (ivermectin 900 μg/kg + abamectin 500 μg/kg) and T07 (ivermectin 1350 μg/kg + abamectin 750 μg/kg). Cerebrospinal fluid and blood samples were collected on day zero (treatment day) and on days 1, 7 and 14 following treatment. The biochemical parameters measured in blood samples were total protein and the AST, GGT and alkaline phosphatase enzymes. In CSF samples, color, aspects, pH, density, cellularity, total proteins, glucose and the CK, ALT and LDH enzymes were evaluated. No neurological toxicity or biochemical changes in the CSF or blood that could be correlated to administration of tested products were observed in this study. Though it is well known that abamectin may lead to intoxication in bovines less than four months of age, based on data from the present study, no adverse clinical effects to the CSF or blood were observed in calves <30 days old that had received up to 600 μg/kg abamectin formulations and up to 1350 μg/kg ivermectin +750 μg/kg abamectin associations. It is possible that the level and activity of the multiple drug resistance gene (MDR1 - ABCB1) present in the calves may have influenced the results obtained in this study. Future studies should be carried out., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The present study sought to evaluate and compare the immunoexpression of proteins minichromosome maintenance (MCM) 3 and Ki-67 in oral squamous cell carcinoma (OSCC) to assess the potential of these proteins as markers of cellular proliferation. Twenty-eight cases of OSCC, 9 of tumor-free resection margins (TM), and 4 of non-neoplastic oral mucosa (NNM) were subjected to immunohistochemistry to detect the expression of proteins MCM3 and Ki-67. All OSCCs demonstrated positivity for both proteins. In these tumors, greater MCM3 immunoreactivity was observed in comparison with Ki-67, whereas TMs and NNMs exhibited greater Ki-67 expression compared with MCM3. The immunoexpression of Ki-67 seemed to be influenced by the inflammatory process, particularly in TM and NNM. Our findings indicate that although both MCM3 and Ki-67 represent reliable markers of cellular proliferation in OSCC, as MCM3 expression does not appear to be influenced by external factors, this protein may emerge as a novel marker of cellular proliferation in these types of tumors.

We previously showed that luminous fungi share a common mechanism in bioluminescence, and identified hispidin as a luciferin precursor in Neonothopanus nambi mycelium. Here we showed the presence of hispidin as a bioluminescent active compound at 25-1000 pmol g -1 in the fruiting bodies of Mycena chlorophos, Omphalotus japonicus, and Neonothopanus gardneri. These results suggest that luminous mushrooms contain hispidin as a luciferin precursor. We also found that non-luminous "young" fruiting bodies exhibited luminescence by hispidin treatment. Furthermore, we observed a gradual luminescence enhancement of the cell-free fruiting body extract by the addition of hispidin biosynthetic components, namely caffeic acid, ATP and malonyl-CoA. These findings suggest that continuous weak glow of luminous mushrooms is regulated by slow recycling biosynthesis of hispidin.

Aim: To evaluate the therapeutic effects of bone marrow-derived CD11b + CD14 + monocytes in a murine model of chronic liver damage., Methods: Chronic liver damage was induced in C57BL/6 mice by administration of carbon tetrachloride and ethanol for 6 mo. Bone marrow-derived monocytes isolated by immunomagnetic separation were used for therapy. The cell transplantation effects were evaluated by morphometry, biochemical assessment, immunohistochemistry and enzyme-linked immunosorbent assay., Results: CD11b + CD14 + monocyte therapy significantly reduced liver fibrosis and increased hepatic glutathione levels. Levels of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin (IL)-6 and IL-1β, in addition to pro-fibrotic factors, such as IL-13, transforming growth factor-β1 and tissue inhibitor of metalloproteinase-1 also decreased, while IL-10 and matrix metalloproteinase-9 increased in the monocyte-treated group. CD11b + CD14 + monocyte transplantation caused significant changes in the hepatic expression of α-smooth muscle actin and osteopontin., Conclusion: Monocyte therapy is capable of bringing about improvement of liver fibrosis by reducing oxidative stress and inflammation, as well as increasing anti-fibrogenic factors., Competing Interests: Conflict-of-interest statement: The authors declare that they have no actual or potential conflicts of interest regarding this manuscript.

Introduction:: Thrombocytopenia is commonly found in patients living in highly endemic areas for Schistosoma mansoni. Recently, different degrees of liver steatosis have also been associated with low platelet counts worldwide. We investigated the association of platelet counts with hepatosplenic schistosomiasis and with liver steatosis in an area of low prevalence of schistosomiasis in Brazil., Method:: Pains, a city in the state of Minas Gerais, Brazil, had a population of 8,307 inhabitants and a schistosomiasis prevalence of 8%. Four micro-areas comprising 1,045 inhabitants were selected for this study. Blood sample was collected and a complete blood count (CBC) was performed. Eighty-seven (87) patients had low platelet counts (group 1 - 8.3%) and 94 volunteers presenting normal CBC were randomized (group 2 - 8.9%). They underwent clinical and ultrasound examinations. Liver steatosis was determined as either present or absent using abdominal ultrasound. A spleen > 12 cm in length, measured by ultrasound (US), was considered to be increased. Data collected were analyzed using SPSS software version 19.0., Results:: Twenty-two patients (22/25.3%) in group 1 had liver steatosis compared with 11 volunteers (11.7%) in group 2 (p=0.02). Hepatosplenic schistosomiasis was diagnosed in two patients (p>0.05)., Conclusion:: Thrombocytopenia was not a good marker of hepatosplenic schistosomiasis mansoni in a low prevalence area in Brazil. Liver steatosis was associated with thrombocytopenia in our study.

Introduction:: The Kato-Katz technique is the standard diagnostic test for Schistosoma mansoni infection in rural areas. However, the utility of this method is severely limited by the day-to-day variability in host egg excretion in the stool. In high-transmission areas, the point-of-care circulating cathodic antigen (POC-CCA) urine assay has proven to be a reliable test. However, investigations of the reliability of the POC-CCA assay in low-transmission regions are under way. This study aimed to evaluate the sensitivity and specificity of the POC-CCA assay and the morbidity of schistosomiasis in a low-endemic area in Brazil., Methods:: Pains City is a low-transmission zone for schistosomiasis. A total of 300 subjects aged 7-76 years were randomly selected for the POC-CCA cassette test. For S. mansoni diagnosis, three stool samples on six slides were compared with one urine sample for each subject. The sensitivity and specificity in the absence of a gold standard were calculated using latent class analysis. Clinical examinations and abdominal ultrasounds were performed in 181 volunteers to evaluate morbidity associated with schistosomiasis., Results:: The sensitivity and specificity of the Kato-Katz technique were 25.6% and 94.6%, respectively. By contrast, the sensitivity and specificity of the POC-CCA assay were 68.1% and 72.8%, respectively. Hepatosplenic schistosomiasis was diagnosed in two patients (1.1%)., Conclusions:: Overall, the POC-CCA urine assay proved to be a useful test for diagnosing S. mansoni in a low-endemic area in Brazil. Severe clinical forms of schistosomiasis can be present even in such low-endemic areas.

Bioluminescent fungi are spread throughout the globe, but details on their mechanism of light emission are still scarce. Usually, the process involves three key components: an oxidizable luciferin substrate, a luciferase enzyme, and a light emitter, typically oxidized luciferin, and called oxyluciferin. We report the structure of fungal oxyluciferin, investigate the mechanism of fungal bioluminescence, and describe the use of simple synthetic α-pyrones as luciferins to produce multicolor enzymatic chemiluminescence. A high-energy endoperoxide is proposed as an intermediate of the oxidation of the native luciferin to the oxyluciferin, which is a pyruvic acid adduct of caffeic acid. Luciferase promiscuity allows the use of simple α-pyrones as chemiluminescent substrates.

Low frequency ultrasound (LFU) enhances skin permeability via the formation of heterogeneous localized transport regions (LTRs). In this work, hydrogels with different zeta potentials were used as the coupling medium for LFU to investigate their contribution to LTR patterns and to the skin penetration of two model drugs, calcein and doxorubicin (DOX). When hydrogels were used, LTRs covering at least a 3-fold greater skin area were observed compared to those resulting from traditional LFU treatment and sodium lauryl sulfate. More LTRs resulted in an enhancement of calcein skin permeation. The zeta potential of the hydrogels affected the skin penetration of the positively charged DOX; the cationic coupling medium decreased the DOX recovered from the viable epidermis by 2.8-fold, whereas the anionic coupling medium increased the DOX accumulation in the stratum corneum by 4.4-fold. Therefore, LFU/hydrogel treatment increases LTRs areas and can target ionized drugs to specific skin layers depending on the zeta potential of the coupling medium.

Schistosomiasis is a major cause of fibrosis and portal hypertension. The reason 4-10% of infected subjects develops hepatosplenic schistosomiasis remains unclear. Chronically infected male CBA/J mice reproduce the dichotomic forms of human schistosomiasis. Most mice (80%) develop moderate splenomegaly syndrome (similar to hepatointestinal disease in humans) and 20% present severe hypersplenomegaly syndrome (analogous to human hepatosplenic disease). We demonstrated that the profibrogenic molecule osteopontin discriminates between mice with severe and mild disease and could be a novel morbidity biomarker in murine and human schistosomiasis. Failure to downregulate osteopontin during the chronic phase may explain why hepatosplenic subjects develop severe fibrosis., (Copyright © 2016. Published by Elsevier Ltd.)

Background: Symptomatic acute schistosomiasis mansoni is a systemic hypersensitivity reaction against the migrating schistosomula and mature eggs after a primary infection. The mechanisms involved in the pathogenesis of acute schistosomiasis are not fully elucidated. Osteopontin has been implicated in granulomatous reactions and in acute hepatic injury. Our aims were to evaluate if osteopontin plays a role in acute Schistosoma mansoni infection in both human and experimentally infected mice and if circulating OPN levels could be a novel biomarker of this infection., Methodology/principal Findings: Serum/plasma osteopontin levels were measured by ELISA in patients with acute (n = 28), hepatointestinal (n = 26), hepatosplenic (n = 39) schistosomiasis and in uninfected controls (n = 21). Liver osteopontin was assessed by immunohistochemistry in needle biopsies of 5 patients. Sera and hepatic osteopontin were quantified in the murine model of schistosomiasis mansoni during acute (7 and 8 weeks post infection, n = 10) and chronic (30 weeks post infection, n = 8) phase. Circulating osteopontin levels are increased in patients with acute schistosomiasis (p = 0.0001). The highest levels of OPN were observed during the peak of clinical symptoms (7-11 weeks post infection), returning to baseline level once the granulomas were modulated (>12 weeks post infection). The plasma levels in acute schistosomiasis were even higher than in hepatosplenic patients. The murine model mirrored the human disease. Macrophages were the major source of OPN in human and murine acute schistosomiasis, while the ductular reaction maintains OPN production in hepatosplenic disease. Soluble egg antigens from S. mansoni induced OPN expression in primary human kupffer cells., Conclusions/significance: S. mansoni egg antigens induce the production of OPN by macrophages in the necrotic-exudative granulomas characteristic of acute schistosomiasis mansoni. Circulating OPN levels are upregulated in human and murine acute schistosomiasis and could be a non-invasive biomarker of this form of disease., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: One of the authors (RPW) is an employee of Thermo Fisher Scientific and own stocks of that company.

Background: There are currently several electrocardiographic algorithms to locate the accessory pathway (AP) in patients with Wolff-Parkinson-White (WPW) syndrome., Objective: To compare the ability of electrocardiographic algorithms in identifying the location of the AP in patients with WPW pattern referred for ablation., Methods: Observational, cross-sectional, retrospective study with 111 patients with WPW syndrome referred for AP ablation. The electrocardiogram (ECG) obtained prior to the ablation was analyzed by an experienced observer who consecutively applied seven algorithms to identify non-invasively the AP. We then compared the location estimated with this assessment with that obtained in the electrophysiological study and calculated the agreement rates., Results: Among the APs, 59 (53.15%) were distributed around the mitral annulus and the remaining 52 (46.85%) were located around the tricuspid annulus. The overall absolute accuracy of the algorithms evaluated varied between 27% and 47%, increasing to between 40% and 76% when we included adjacent locations. The absolute agreement rate by AP location was 2.00-52.20% for septal APs (n = 51), increasing to 5.90-90.20% when considering adjacent locations; 7.70-69.20% for right APs (n = 13), increasing to 42.90-100% when considering adjacent locations; and 21.70-54.50% for left APs (n = 47), increasing to 50-87% when considering adjacent locations., Conclusion: The agreement rates observed for the analyzed scores indicated a low discriminative ability of the ECG in locating the AP in patients with WPW., Competing Interests: Potential Conflict of Interest No potential conflict of interest relevant to this article was reported.