Deposition of collagen III and alterations in basement membrane integrity as candidate prognostic markers in prostate cancer.

The extracellular matrix surrounding the tumor undergoes changes in its organization during the metastasis process. The present study aims to quantify total collagen, collagen I (Col I) and collagen III (Col III), analyze the alignment of collagen fibers and assess the basement membrane integrity in samples from patients with metastatic and non-metastatic prostate cancer. Tissue samples from 60 patients were classified into groups based on prognostic parameters: better prognosis (n = 20), worse prognosis without metastasis (n = 23) and metastatic (n = 17). Picrosirius red with further analysis under polarizing microscope was used to quantify (with validation using immunohistochemistry) and analyze collagen alignment, and Periodic Acid Schiff staining was used to analyze the basement membrane integrity. The Col I/Col III ratio was found to be higher in the metastatic group than in the groups with better prognosis (p = 0.012) and worse prognosis without metastasis (p = 0.018). Basement membrane integrity constitution in malignant tumor tissue differed from that of adjacent non-tumor tissue (p < 0.001). Moreover, the worsening in the tumor tissue integrity was positively correlated with worse prognostic parameters. All in all, absence of Col III and basement membrane integrity might be indicators of poor prognosis in prostate cancer.

Perineuronal net in the extrinsic innervation of the distal colon of mice and its remodeling in ulcerative colitis.

The perineuronal net (PNN) is a well-described highly specialized extracellular matrix structure found in the central nervous system. Thus far, no reports of its presence or connection to pathological processes have been described in the peripheral nervous system. Our study demonstrates the presence of a PNN in the spinal afferent innervation of the distal colon of mice and characterizes structural and morphological alterations induced in an ulcerative colitis (UC) model. C57Bl/6 mice were given 3% dextran sulfate sodium (DSS) to induce acute or chronic UC. L6/S1 dorsal root ganglia (DRG) were collected. PNNs were labeled using fluorescein-conjugated Wisteria Floribunda (WFA) l lectin, and calcitonin gene-related peptide (CGRP) immunofluorescence was used to detect DRG neurons. Most DRG cell bodies and their extensions toward peripheral nerves were found surrounded by the PNN-like structure (WFA+), labeling neurons' cytoplasm and the pericellular surfaces. The amount of WFA+ neuronal cell bodies was increased in both acute and chronic UC, and the PNN-like structure around cell bodies was thicker in UC groups. In conclusion, a PNN-like structure around DRG neuronal cell bodies was described and found modulated by UC, as changes in quantity, morphology, and expression profile of the PNN were detected, suggesting a potential role in sensory neuron peripheral sensitization, possibly modulating the pain profile of ulcerative colitis.

Effects of dietary ß-glucans on the productive performance, blood parameters, and intestinal microbiota of angelfish (Pterophyllum scalare) juveniles.

Among the potential feed additives, ß-glucans are known to positively affect the growth performance, blood parameters, and intestinal microbiota of fish, even the ornamental species. Therefore, the present study evaluated the effects of the dietary supplementation of different Saccharomyces cerevisiae ß-glucans concentrations (0, 0.05, 0.1, and 0.2%) in juvenile angelfish (Pterophyllum scalare) over a 42-day period. Regarding growth performance, no effects were observed on most parameters. However, 0.2% ß-glucans supplementation produced higher condition factor values, indicating a better nutritional status. Furthermore, ß-glucans supplementation did not affect blood parameters. Regarding intestinal microbiota, ß-glucans supplementation increased the abundance of the potentially beneficial bacterial genus Phascolarctobacterium. The high abundance of bacteria from the phylum Bacteroidetes, which can degrade ß-glucans, may be attributed to the increased abundance of Phascolarctobacterium spp. In addition, 0.2% ß-glucans supplementation produced more operational taxonomic units and higher Sobs (observed species richness), indicating effects on the overall bacterial community structure. These results demonstrate the potential application of ß-glucans as a dietary supplement to improve the performance and modulate the intestinal microbiota of angelfish.

Paraoxonase 2 Deficiency Causes Mitochondrial Dysfunction in Retinal Pigment Epithelial Cells and Retinal Degeneration in Mice.

Although AMD is a complex disease, oxidative stress is a crucial contributor to its development, especially in view of the higher oxygen demand of the retina. Paraoxonase 2 (PON2) is a ubiquitously and constitutively expressed antioxidant protein that is found intracellularly associated with mitochondrial membranes and modulates mitochondrial ROS production and function. The contribution of PON2 to AMD has not been studied to date. In this study, we examined the role of PON2 in AMD utilizing both in vitro and in vivo models of AMD with emphasis on mitochondrial function. Mitochondrial localization and regulation of PON2 following oxidative stress were determined in human primary cultured retinal pigment epithelium (hRPE) cells. PON2 was knocked down in RPE cells using siRNA and mitochondrial bioenergetics were measured. To investigate the function of PON2 in the retina, WT and PON2-deficient mice were administered NaIO3 (20 mg/kg) intravenously; fundus imaging, optical coherence tomography (OCT), electroretinography (ERG) were conducted; and retinal thickness and cell death were measured and quantified. In hRPE, mitochondrial localization of PON2 increased markedly with stress. Moreover, a time-dependent regulation of PON2 was observed following oxidative stress, with an initial significant increase in expression followed by a significant decrease. Mitochondrial bioenergetic parameters (basal respiration, ATP production, spare respiratory capacity, and maximal respiration) showed a significant decrease with oxidative stress, which was further exacerbated in the absence of PON2. NaIO3 treatment caused significant retinal degeneration, retinal thinning, and reduced rod and cone function in PON2-deficient mice when compared to WT mice. The apoptotic cells and active caspase 3 significantly increased in PON2-deficient mice treated with NaIO3, when compared to WT mice. Our investigation demonstrates that deficiency of PON2 results in RPE mitochondrial dysfunction and a decline in retinal function. These findings imply that PON2 may have a beneficial role in retinal pathophysiology and is worthy of further investigation.

The robot eyes don't have it. The presence of eyes on collaborative robots yields marginally higher user trust but lower performance.

Eye gaze is a prominent feature of human social lives, but little is known on whether fitting eyes on machines makes humans trust them more. In this study we compared subjective and objective markers of human trust when collaborating with eyed and non-eyed robots of the same type. We used virtual reality scenes in which we manipulated distance and the presence of eyes on a robot's display during simple collaboration scenes. We found that while collaboration with eyed cobots resulted in slightly higher subjective trust ratings, the objective markers such as pupil size and task completion time indicated it was in fact less comfortable to collaborate with eyed robots. These findings are in line with recent suggestions that anthropomorphism may be actually a detrimental feature of collaborative robots. These findings also show the complex relationship between human objective and subjective markers of trust when collaborating with artificial agents.

Differential benefits of physical training associated or not with l-arginine supplementation in rats with metabolic syndrome: Evaluation of cardiovascular, autonomic and metabolic parameters.

Metabolic syndrome (MetS) is characterized by endocrine-metabolic and cardiac alterations that increase the risk of cardiovascular disease, dyslipidemia, and type-2 diabetes mellitus. Dietary supplementation with l-Arginine (L-Arg) is beneficial for fat loss, while chronic aerobic exercise has several benefits in reversing cardiovascular, autonomic, and metabolic dysfunctions caused by obesity. However, the association between these two approaches has not yet been described. This study aimed to evaluate the possible benefits of physical training, with or without l-Arg-supplementation, on cardiovascular, autonomic, and metabolic parameters in rats with MetS, which was induced by the subcutaneous administration of monosodium glutamate at 4 mg g-1day-1 in rats from the first to fifth day of life. Physical training on a treadmill and supplementation with l-Arg-in adulthood were carried out concomitantly for 8 weeks. After this, the animals underwent femoral artery catheterization to record their cardiovascular parameters and autonomic modulation. Organs and blood were removed to measure levels of nitrite, glucose, and hepatic steatosis. In adult rats with MetS, supplementation with l-Arg-in combination with physical training reduced hypertension, tachycardia, adipose tissue mass, free fatty acids, and hepatic steatosis. Supplementation with l-Arg-and physical training separately was beneficial in reducing several aspects of MetS, but a combination of both was especially effective in reducing adipose tissue and hepatic steatosis. Together, the two therapies can form a good strategy to combat MetS.

Definition of Scenarios for Modern Power Systems with a High Renewable Energy Share.

Recent environmental policies have led academic, industrial, and governmental stakeholders to plan scenarios with a high share of renewable energy sources (RES), to ensure that future energy systems, composed mostly of RES, can remain stable, match the demand during seasonal variations and are economically feasible. This article considers different energy scenarios to obtain various options in terms of size, generation technologies, and grid configuration. The scenarios are studied in the POSYTYF project and are quantified through an optimization-based algorithm, where the test grids topologies are based on specific locations in Europe, and real data related to the availability of RES, as well as the demand. Different RES technologies are considered to meet requirements of grid integration of renewables at different horizons of time, up to 100% in the most futuristic case. The optimization algorithm is applied to three scenarios. It is shown that solar photovoltaic (PV) and wind can provide the renewable backbone, but they lack flexibility to achieve a very high share in the energy mix. Solar thermal and pumped hydro become important to cover the last range of integration, as they provide high flexibility, which is crucial for high share, but they are expensive for low share.

A Platform for Data-Centric, Continuous Epidemiological Analyses (EpiGraphHub): Descriptive Analysis.

BACKGROUND: Guaranteeing durability, provenance, accessibility, and trust in open data sets can be challenging for researchers and organizations that rely on public repositories of data critical for epidemiology and other health analytics. The required data repositories are often difficult to locate and may require conversion to a standard data format. Data-hosting websites may also change or become unavailable without warning. A single change to the rules in one repository can hinder updating a public dashboard reliant on data pulled from external sources. These concerns are particularly challenging at the international level, because policies on systems aimed at harmonizing health and related data are typically dictated by national governments to serve their individual needs. OBJECTIVE: In this paper, we introduce a comprehensive public health data platform, EpiGraphHub, that aims to provide a single interoperable repository for open health and related data. METHODS: The platform, curated by the international research community, allows secure local integration of sensitive data while facilitating the development of data-driven applications and reports for decision-makers. Its main components include centrally managed databases with fine-grained access control to data, fully automated and documented data collection and transformation, and a powerful web-based data exploration and visualization tool. RESULTS: EpiGraphHub is already being used for hosting a growing collection of open data sets and for automating epidemiological analyses based on them. The project has also released an open-source software library with the analytical methods used in the platform. CONCLUSIONS: The platform is fully open source and open to external users. It is in active development with the goal of maximizing its value for large-scale public health studies.

Kaurenoic Acid Reduces Ongoing Chronic Constriction Injury-Induced Neuropathic Pain: Nitric Oxide Silencing of Dorsal Root Ganglia Neurons.

Kaurenoic acid (KA) is a diterpene extracted from Sphagneticola trilobata (L.) Pruski. KA presents analgesic properties. However, the analgesic activity and mechanisms of action of KA in neuropathic pain have not been investigated so far; thus, we addressed these points in the present study. A mouse model of neuropathic pain was induced by chronic constriction injury (CCI) of the sciatic nerve. Acute (at the 7th-day post-CCI surgery) and prolonged (from 7-14th days post-CCI surgery) KA post-treatment inhibited CCI-induced mechanical hyperalgesia at all evaluated time points, as per the electronic version of von Frey filaments. The underlying mechanism of KA was dependent on activating the NO/cGMP/PKG/ATP-sensitive potassium channel signaling pathway since L-NAME, ODQ, KT5823, and glibenclamide abolished KA analgesia. KA reduced the activation of primary afferent sensory neurons, as observed by a reduction in CCI-triggered colocalization of pNF-κB and NeuN in DRG neurons. KA treatment also increased the expression of neuronal nitric oxide synthase (nNOS) at the protein level as well as the intracellular levels of NO in DRG neurons. Therefore, our results provide evidence that KA inhibits CCI neuropathic pain by activating a neuronal analgesic mechanism that depends on nNOS production of NO to silence the nociceptive signaling that generates analgesia.

Colonic motility adjustments in acute and chronic DSS-induced colitis.

AIMS: Inflammatory bowel disease is recurrent inflammation that affects the gastrointestinal tract causing changes in intestinal motility. The evolution of these changes is not completely understood. The aim of this study was to evaluate anatomical and functional changes in the colon during the development of acute and chronic DSS-induced ulcerative colitis (UC) in C57Bl/6 mice. MATERIALS AND METHODS: Mice were relocated into 5 groups: control (GC) and groups exposed to DSS 3 % for 2 (DSS2d), 5 (DSS5d) and 7 DSS7d) days (acute UC) or 3 cycles (DSS3C; Chronic UC). Mice were monitored daily. After euthanasia, colonic tissue was assessed with histological, immunofluorescence and colon manometry methods. KEY FINDINGS: Ulcerative Colitis is a chronic disease characterized by overt inflammation of the colon. Here we investigate whether the morphological changes caused by UC in the colonic wall, in tuft cells and in enteric neurons also promote any alteration in colonic motility patterns. UC Promotes thickening in the colonic wall, fibrosis, reduction in the number of tuft cells and consequently goblet cells also, without promoting neuronal death however there is a change in the chemical code of myenteric neurons. All of these morphological changes were responsible for causing a change in colonic contractions, colonic migration motor complex, total time of gastrointestinal transit and therefore promoting dysmotility. Further studies stimulating a hyperplasia of tuft cells may be the way to try to keep the colonic epithelium healthy, reducing the damage caused by UC. SIGNIFICANCE: Increasing disease pathology of DSS-induced UC induces structural and neuroanatomical changes and driven damage to cholinergic neurons causes colonic dysmotility, including increase of cholinergic myenteric neurons, followed by variations in the motility pattern of different regions of the colon that taking together characterize colonic dysmotility.

A traveling SARS-CoV-2 laboratory as part of a pandemic response among vulnerable Brazilian populations.

BACKGROUND: Brazil has been dramatically hit by the SARS-CoV-2 pandemic and is a world leader in COVID-19 morbidity and mortality. Additionally, the largest country of Latin America has been a continuous source of SARS-CoV-2 variants and shows extraordinary variability of the pandemic strains probably related to the country´s outstanding position as a Latin American economical and transportation hub. Not all regions of the country show sufficient infrastructure for SARS-CoV-2 diagnosis and genotyping which can negatively impact the pandemic response. METHODS: Due to this reason and to disburden the diagnostic system of the inner São Paulo State, the Butantan Institute established the Mobile Laboratory (in Portuguese: LabMovel) for SARS-CoV-2 testing which started a trip of the most important "hotspots" of the most populous Brazilian region. The LabMovel initiated in two important cities of the State: Aparecida do Norte (an important religious center) and the Baixada Santista region which incorporates the port of Santos, the busiest in Latin America. The LabMovel was fully equipped with an automatized system for SARS-CoV-2 diagnosis and sequencing/genotyping. It also integrated the laboratory systems for patient records and results divulgation including in the Federal Brazilian Healthcare System. RESULTS: Currently,16,678 samples were tested, among them 1,217 from Aparecida and 4,564 from Baixada Santista. We tracked the delta introductio in the tested regions with its high diversification. The established mobile SARS-CoV-2 laboratory had a major impact on the Public Health System of the included cities including timely delivery of the results to the healthcare agents and the Federal Healthcare system, evaluation of the vaccination status of the positive individuals in the background of exponential vaccination process in Brazil and scientific and technological divulgation of the fieldwork to the most vulnerable populations. CONCLUSIONS: The SARS-CoV-2 pandemic has demonstrated worldwide the importance of science to fight against this viral agent and the LabMovel shows that it is possible to integrate researchers, clinicians, healthcare workers and patients to take rapid actions that can in fact mitigate this and other epidemiological situations.

SOCS2 protects against chemical-induced hepatocellular carcinoma progression by modulating inflammation and cell proliferation in the liver.

Hepatocellular carcinoma (HCC) is one of the most prevalent and lethal cancers worldwide, but the precise intracellular mechanisms underlying the progression of this inflammation associated cancer are not well established. SOCS2 protein plays an important role in the carcinogenesis of different tumors by regulating cytokine signalling through the JAK/STAT axis. However, its role in HCC is unclear. Here, we investigate the role of SOCS2 in HCC progression and its potential as HCC biomarker. The effects of SOCS2 in HCC progression were evaluated in an experimental model of diethylnitrosamine (DEN)-induced HCC in C57BL/6 and SOCS2 deficient mice, in cultured hepatic cells, and in liver samples from HCC patients. Mice lacking SOCS2 showed higher liver tumor burden with increased malignancy grade, inflammation, fibrosis, and proliferation than their controls. Protein and gene expression analysis reported higher pSTAT5 and pSTAT3 activation, upregulation of different proteins involved in survival and proliferation, and increased levels of proinflammatory and pro-tumoral mediators in the absence of SOCS2. Clinically relevant, downregulated expression of SOCS2 was found in neoplasia from HCC patients compared to healthy liver tissue, correlating with the malignancy grade. In summary, our data show that lack of SOCS2 increases susceptibility to chemical-induced HCC and suggest the tumor suppressor role of this protein by regulating the oncogenic and inflammatory responses mediated by STAT5 and STAT3 in the liver. Hence, SOCS2 emerges as an attractive target molecule and potential biomarker to deepen in the study of HCC treatment.

Anatomy and Imaging of Accessory Liver Lobes: What Radiologists Should Know.

Although the liver may present a range of congenital anomalies, often involving shape irregularities or the number of lobules, less common variations include the presence of accessory liver lobes (ALL), consisting of a supernumerary lobe of normal hepatic parenchyma in continuity with the liver. This paper reviews the embryology, frequency, anatomy, and types of ALL. Furthermore, we describe computed tomography and magnetic resonance imaging findings in a range of such cases, including those simulating disease or presenting with complications. Knowledge about ALL may facilitate imaging interpretation of such alterations, avoiding inappropriate additional work-up and unnecessary interventions.

Community intervention programs for sex offenders: A systematic review.

Sexual violence is a phenomenon that negatively impacts the victims' physical and psychological health and well-being. Sex offenders tend not to take responsibility for their actions, have difficulties in emotion regulation and impulse control, paraphilias or other disorders, so they are a difficult group to treat. In addition, the available psychological treatment programs tend to have inconsistent and, sometimes, undesirable results. This systematic review aimed to analyse the recidivism rates of sex offenders treated in community settings. According to the PRISMA guidelines, a systematic search in three databases, EBSCOhost, PubMed, and Web of Science, and a manual search was performed. A total of 319 empirical studies using quantitative methodologies were identified, 27 of which were selected for full-text analysis. In the end, 15 studies were included, published between 1996 and 2020. The objectives, intervention approach, instruments used, and the main results and conclusions were extracted from each study. The studies explored different types of sex offenders, such as: violent sex offenders (e.g., rapists), child abusers, and child abusers with pedophilia (and/or other paraphilias). Results showed that most of the programs had a cognitive-behavioral approach (n = 13). Overall, the interventions appear to be effective in reducing recidivism rates, and some of them led to improvements in other outcomes, such as cognitive distortions, accepting responsibility, victim awareness and empathy, emotional regulation, and offense supportive attitudes. Limitations and implications for future studies were discussed.

COVID-19 in Switzerland real-time epidemiological analyses powered by EpiGraphHub.

Here we present the design and results of an analytical pipeline for COVID-19 data for Switzerland. It is applied to openly available data from the beginning of the epidemic in 2020 to the present day (august 2022). We analyzed the spatio-temporal patterns of the spread of SARS-CoV2 throughout the country, applying Bayesian inference to estimate population prevalence and hospitalization ratio. We also developed forecasting models to characterize the transmission dynamics for all the country's cantons taking into account their spatial correlations in COVID incidence. The two-week forecasts of new daily hospitalizations showed good accuracy, as reported herein. These analyses' raw data and live results are available on the open-source EpiGraphHub platform to support further studies.

Influx of radioactive gas in norm occurrences in Northeastern Brazil.

Radon and progeny are potentially relevant in radioecological studies, as they contribute more than half of the exposure to environmental radiation. The investigation of 222Rn in internal environments of municipalities of Paraíba and Rio Grande do Norte in Brazil was carried out using passive dosimetry with α Espec-222, installed in environments selected by the history of natural radiative occurrences. The monitoring time was eight months to consider seasonal influence. Concentrations from 26.91 to 316.35 Bq m-3 were obtained, with a maximum effective dose of almost 8 mSv y-1. The influence on households exceeds, by almost 31%, the average obtained for occupational environments. The municipalities of Paraíba presented higher results for Rn, with an average of almost 176 Bq m-3 and an effective dose greater than 4 mSv y-1. The application of individual occupancy factors for home and work environments made it possible to combine the dosimetric models, making the scenario closer to the real exposure of individuals who work and reside in the same municipality, with a dosimetric response of 21.45% lower than the model used worldwide. The different scenarios applied allowed expanding the radiometry of the environments, generating a database that precedes studies of environmental and radioecological impacts, strengthening security and enabling new works to interpret public health problems in search of joint and shared solutions.

Lethal destructive sinusopathy due to amphotericin B-resistant Aspergillus flavus: A case report.

BACKGROUND: The prevalence of pulmonary aspergillosis and the importance of its early diagnosis are recognized. However, non-pulmonary involvement, including the sinuses region, is not frequently reported, and an infection in this area can affect all paranasal sinuses (pansinusopathy), being a rare pathology that affects immunocompromised hosts. Recent studies have highlighted the occurrence of Aspergillus flavus resistant to antifungal therapy. Therefore, a nasal sinus infection by resistant Aspergillus strains in immunocompromised patients may be linked to a high risk of lethality. CASE REPORT: We are reporting a resistant A. flavus infection in an allogeneic hematopoietic stem cell transplant recipient with episodes of febrile neutropenia, and prolonged use of various antibacterial drugs and antifungal prophylaxis. The patient underwent brain magnetic resonance, which showed the presence of pansinusopathy, and presented necrosis in the left nasal region. Direct microscopic examination of a sample taken from the nasal mucosa revealed the presence of septate hyphae and conidiophores resembling those of A. flavus, that species being the identification achieved with MALDI-TOF MS. Antifungigram was performed by microdilution in broth (EUCAST-E.DEF. 9.3.2) and E-test, and resistance to amphotericin B was shown in both tests. The patient died after septic shock and hemorrhage. CONCLUSIONS: Invasive fungal infections due to amphotericin-B resistant A. flavus may lead to the death of the patient due to an ineffective therapeutic management. Therefore, antifungal susceptibility testing are of utmost importance for administering the proper treatment.

Vaginal cancer: Why should we care? Anatomy, staging and in-depth imaging-based review of vaginal malignancies focusing on MRI and PET/CT.

Vaginal cancer often poses a challenge for clinical and radiological diagnosis, and its risk factors, progression, and treatment are still poorly established. Although vaginal malignancies are rare, even globally, their rates have increased due to the increased access to healthcare and the evolution of screening measures and diagnostic methods. Because the vaginal cavity is a virtual space, it can harbor lesions that often go unnoticed and, not infrequently, diagnosed belatedly. MRI and, more recently, PET/CT are part of the imaging armamentarium that have already been incorporated into the clinical staging and management of gynecological tumors, allowing excellent morphological characterization of the lesion, its topography and relationship with adjacent structures for the investigation of disease dissemination, overcoming limitations of clinical methods, such as speculum examination, usually restricted to observation only of the superficial characteristics of these lesions. Some vaginal neoplasms have characteristic MRI patterns, which, combined with expert knowledge of anatomy, allow identification of local macroscopic details (such as the mucosal, submucosal, and muscle layers). Furthermore, the application of PET/CT, already well established for identifying systemic disease, has a large impact on patient prognosis. The objective of this work is to review the epidemiological aspects of primary vaginal cancers and the imaging patterns of their main histological subtypes based on MRI and PET/CT, with a brief discussion of the local anatomy, oncological staging, and treatment.