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Members of the parasitic copepod family Pennellidae are highly transformed ecto- or mesoparasites infecting a wide array of marine teleosts. Currently, this family contains more than 20 valid genera. The pennellid genus Cardiodectes Wilson, 1917 is currently known to contain 15 nominal species. Some pennellids exhibit a complex life cycle involving an intermediate host; it is known that planktonic pteropod molluscs are intermediate hosts for Cardiodectes. Pennellid mesoparasites can be detected by the conspicuous female egg-carrying trunk on the host external surface. The copepod cephalothorax is deeply embedded in the host muscle tissue. Members of Cardiodectes have been reported from several teleost families, mainly Myctophidae and Engraulidae. From the parasitological examination of a juvenile individual of a scarid teleost collected in a reef lagoon of Roatan Island, Honduras, Central America, several ovigerous female individuals of a mesoparasitic pennellid copepod were found; these specimens were recognized as representative of an undescribed species of Cardiodectes Wilson, 1917. The new species, C. roatanensis n. sp., differs from its known congeners in several respects, including the presence of neck lobes, paired posterior protuberances of the trunk, trunk shape and proportions, structure of cephalothorax lobes, cephalothorax relative size, and number of legs. The new species from Roatan is the second member of this copepod genus to be reported from the Caribbean region, after C. boxshalli Bellwood, 1981 from off Jamaica (Bellwood 1981). It is also the second report of Cardiodectes on a parrotfish.

GPNMB (glycoprotein nonmetastatic B) and other TFE3/TFEB transcriptional targets have been proposed as markers for microphthalmia (MiT) translocation renal cell carcinomas (tRCCs). We recently demonstrated that constitutive mTORC1 activation via TSC1/2 loss leads to increased activity of TFE3/TFEB, suggesting that the pathogenesis and molecular markers for tRCCs and TSC1/2-associated tumors may be overlapping. We examined GPNMB expression in human kidney and angiomyolipoma (AML) cell lines with TSC2 and/or TFE3/TFEB loss produced using CRISPR-Cas9 genome editing as well as in a mouse model of Tsc2 inactivation-driven renal tumorigenesis. Using an automated immunohistochemistry (IHC) assay for GPNMB, digital image analysis was employed to quantitatively score expression in clear cell RCC (ccRCC, n = 87), papillary RCC (papRCC, n = 53), chromophobe RCC (chRCC, n = 34), oncocytoma (n = 4), TFE3- or TFEB-driven tRCC (n = 56), eosinophilic solid and cystic RCC (ESC, n = 6), eosinophilic vacuolated tumor (EVT, n = 4), and low-grade oncocytic tumor (LOT, n = 3), as well as AML (n = 29) and perivascular epithelioid cell tumors (PEComas, n = 8). In cell lines, GPNMB was upregulated following TSC2 loss in a MiT/TFE- and mTORC1-dependent fashion. Renal tumors in Tsc2

This study leveraged a gene-protein assay to assess MYC and PTEN status at prostate cancer biopsy and examined the association with adverse outcomes after surgery. MYC gain and PTEN loss were simultaneously assessed by chromogenic in situ hybridization and immunohistochemistry, respectively, using 277 Grade Group 2 needle biopsies that were followed by prostatectomy. The maximal size of cribriform Gleason pattern 4 carcinoma (CRIB), the presence of intraductal carcinoma (IDC), and percentage of Gleason pattern 4 carcinoma at biopsy were also annotated. MYC gain or PTEN loss was present in 19% and 18% of biopsies, respectively, whereas both alterations were present in 9% of biopsies. Tumors with one or both alterations were significantly more likely to have non–organ-confined disease (NOCD) at radical prostatectomy. In logistic regression models, including clinical stage, tumor volume on biopsy, and presence of CRIB/IDC, cases with MYC gain and PTEN loss remained at higher risk for NOCD (odds ratio, 6.23; 95% CI, 1.74–24.55; P = 0.005). The area under the curve for a baseline model using CAPRA variables (age, prostate-specific antigen, percentage of core involvement, clinical stage) was increased from 0.68 to 0.69 with inclusion of CRIB/IDC status and to 0.75 with MYC/PTEN status. Dual MYC/PTEN status can be assessed in a single slide and is independently associated with increased risk of NOCD for Grade Group 2 biopsies.

The Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT) is a comprehensive instrument developed to accurately assess the main pretransplant psychosocial risk factors that may impact transplant outcomes.As neither established assessment procedures nor standardized tools designed to perform pretransplant psychosocial evaluation are currently available in Italy, the present study was designed to develop and preliminarily validate the Italian version of the SIPAT.First, our team developed the Italian version of the SIPAT, following standard forward-back translation procedures. Then, the Italian version of the SIPAT was retrospectively and blindly applied to 118 randomly selected transplant cases (40 heart, 40 lung, and 38 liver) by 2 independent examiners. Information about the patients' final transplant listing recommendation (i.e., listing vs. deferral) was independently collected from the respective transplant teams.The inter-rater reliability of the Italian version of the SIPAT scores was substantial (Cohen's kappa = 0.77; P 0.001). Moreover, the predictive value of the SIPAT ratings on the final transplant listing recommendation (i.e., listing vs. deferral) for each examiner was significant (both P 0.05).Current findings suggest that SIPAT is a promising and reliable instrument in its Italian version. Given these excellent psychometric characteristics, the use of the SIPAT as part of the pretransplant psychosocial evaluation in Italian medical settings is highly encouraged.

Background Suicide is a major public health concern in Brazil, with nearly 115,000 Brazilians dying by suicide in 2010–2019. As support for individuals at risk of suicide may come from the community, particularly family and friends, it is fundamental that evidence-based programs or resources to improve such support are in place when needed. This study aimed to culturally adapt the mental health first aid guidelines for assisting a person at risk of suicide used in English-speaking countries for Brazil. Methods A Delphi expert consensus study was conducted among a diverse range of Brazilian health professionals and individuals with lived experience of suicide (n = 60). A total of 161 items from the mental health first aid questionnaire used in English-speaking countries were translated and used in the Brazilian questionnaire. Participants were asked to rate the appropriateness of those items to the Brazilian culture and to recommend any new items when appropriate. Results Data were collected over two survey rounds. Consensus was achieved on 145 items. While 123 out of 161 items were adopted from the English guidelines, 22 new endorsed items were created from the expert panel comments. Conclusions Even though there were similarities among the Brazilian and English-language guidelines, the adapted guidelines incorporated actions that were specific to the Brazilian culture, such as new items emphasising the role of family and friends. Further research is warranted on dissemination and uptake of the guidelines in Brazil as well as research into incorporation of the guidelines into Mental Health First Aid (MHFA) training for Brazil.

Background The Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder scale (GAD-7) are self-report measures of major depressive disorder and generalised anxiety disorder. The primary aim of this study was to test for differential item functioning (DIF) on the PHQ-9 and GAD-7 items based on age, sex (males and females), and country. Method Data from nationally representative surveys in UK, Ireland, Spain, and Italy (combined N = 6,054) were used to fit confirmatory factor analytic and multiple-indictor multiple-causes models. Results Spain and Italy had higher latent variable means than the UK and Ireland for both anxiety and depression, but there was no evidence for differential items functioning. Conclusions The PHQ-9 and GAD-7 scores were found to be unidimensional, reliable, and largely free of DIF in data from four large nationally representative samples of the general population in the UK, Ireland, Italy and Spain.

This retrospective study evaluated the effect of combined periodontal-orthodontic treatment in terms of clinical, radiographic, and patient-reported outcomes in 40 stage IV periodontitis patients with advanced attachment loss and pathologic migration of anterior teeth. Full-mouth periodontal parameters were recorded at baseline (after diagnosis; T0), at the end of active periodontal therapy (APT; T1), at completion of orthodontic tooth movement (OTM; T2), and at the last supportive periodontal care (SPC) visit (T3). Radiographic analysis was performed at T0, T2, and T3. A total of 115 teeth were lost during APT, including 5 molars at T2 (used as orthodontic anchorage) and 10 premolars at T3 (due to root fracture). All anterior migrated teeth were in function at T3 (mean duration: 9.5 years). Significant mean probing pocket depth reduction (1.5 ± 1.1 mm) and attachment level gain (0.9 ± 1.0 mm) were observed after APT, whereas OTM and SPC were associated with furthering small changes. The alveolar bone level at T3 was slightly increased from T0 values. Patient-reported outcome measurements significantly improved in terms of esthetics and masticatory function. OTM should be considered an essential part of the comprehensive treatment plan to change the prognosis of severely compromised teeth in stage IV periodontitis patients.

The use of observational tools in psychological assessment has decreased in recent years, mainly due to its personnel and time costs, and researchers have not explored methodological innovations like adaptive algorithms in observational assessment. In the present study, we introduce the behavior-driven observation procedure to develop, test, and implement observational adaptive instruments. In Study 1, we use a preexisting observational checklist to evaluate nonverbal behaviors related to psychotic symptoms and to specify the adaptive algorithm’s model. We fit the model to observational data collected from 114 participants. The results support the model’s goodness of fit. In Study 2, we use the estimated model parameters to calibrate the adaptive procedure and test the algorithm for accuracy and efficiency in adaptively reconstructing 58 nonadaptively collected response patterns. The results show the algorithm’s good accuracy and efficiency, with a 40% average reduction in the number of administered items. In Study 3, we used real raters to test the adaptive checklist built with behavior-driven observation. The results indicate adequate intrarater agreement and good consistency of the observed response patterns. In conclusion, the results support the possibility of using behavior-driven observation to create accurate and affordable (in terms of resources) observational assessment tools.

Pathogenic mutations in homologous recombination (HR) DNA repair genes may be associated with increased tumor mutational burden and numbers of tumor-infiltrating lymphocytes (TIL). Though HR-deficient prostate tumors have been anecdotally associated with improved responses to immunotherapy, it is unclear whether HR mutations or HR deficiency (HRD) scores predict for increased T-cell densities in this cancer. We evaluated 17 primary prostate tumors from patients with pathogenic germline BRCA2 mutations (gBRCA2) and 21 primary prostate tumors from patients with pathogenic germline ATM (gATM) mutations, which were compared to 19 control tumors lacking HR gene mutations, as well as the TCGA prostate cancer cohort. HRD score was estimated by targeted sequencing (gBRCA2 and gATM) or by SNP microarray (TCGA). Tumor-associated T-cell densities were assessed using validated automated digital image analysis of CD8 and FOXP3 immunostaining (gBRCA2 or gATM) or by methylCIBERSORT (TCGA). CD8 + and FOXP3 + T-cell densities were significantly correlated with each other in gBRCA2 and gATM cases. There was no significant difference between CD8 + or FOXP3 + TIL densities in gBRCA2 or gATM cases compared to controls. In the TCGA cohort, HRD score was associated with predicted CD8 + and FOXP3 + TILs. Associations were also seen for HRD score and TIL density among the germline-mutated cases. In contrast to mismatch repair-deficient primary prostate tumors, cancers from germline BRCA2 or ATM mutation carriers do not appear to be associated with elevated TIL density. However, measures of genomic scarring, such as HRD score, may be associated with increased tumor-infiltrating T-cells.

Neuroendocrine prostate cancer (NEPC) is a rare but aggressive histologic variant of prostate cancer that responds poorly to androgen deprivation therapy. Hybrid NEPC-adenocarcinoma (AdCa) tumors are common, often eluding accurate pathologic diagnosis and requiring ancillary markers for classification. We recently performed an outlier-based meta-analysis across a number of independent gene expression microarray datasets to identify novel markers that differentiate NEPC from AdCa, including up-regulation of insulinoma-associated protein 1 (INSM1) and loss of Yes-associated protein 1 (YAP1). Here, using diverse cancer gene expression datasets, we show that Hippo pathway-related genes, including YAP1, are among the top down-regulated gene sets with expression of the neuroendocrine transcription factors, including INSM1. In prostate cancer cell lines, transgenic mouse models, and human prostate tumor cohorts, we confirm that YAP1 RNA and YAP1 protein expression are silenced in NEPC and demonstrate that the inverse correlation of INSM1 and YAP1 expression helps to distinguish AdCa from NEPC. Mechanistically, we find that YAP1 loss in NEPC may help to maintain INSM1 expression in prostate cancer cell lines and we further demonstrate that YAP1 silencing likely occurs epigenetically, via CpG hypermethylation near its transcriptional start site. Taken together, these data nominate two additional markers to distinguish NEPC from AdCa and add to data from other tumor types suggesting that Hippo signaling is tightly reciprocally regulated with neuroendocrine transcription factor expression. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Background PTEN is the most frequently lost tumor suppressor in primary prostate cancer (PCa) and its loss is associated with aggressive disease. However, the transcriptional changes associated with PTEN loss in PCa have not been described in detail. In this study, we highlight the transcriptional changes associated with PTEN loss in PCa. Methods Using a meta-analysis approach, we leveraged two large PCa cohorts with experimentally validated PTEN and ERG status by Immunohistochemistry (IHC), to derive a transcriptomic signature of PTEN loss, while also accounting for potential confounders due to ERG rearrangements. This signature was expanded to lncRNAs using the TCGA quantifications from the FC-R2 expression atlas. Results The signatures indicate a strong activation of both innate and adaptive immune systems upon PTEN loss, as well as an expected activation of cell-cycle genes. Moreover, we made use of our recently developed FC-R2 expression atlas to expand this signature to include many non-coding RNAs recently annotated by the FANTOM consortium. Highlighting potential novel lncRNAs associated with PTEN loss and PCa progression. Conclusion We created a PCa specific signature of the transcriptional landscape of PTEN loss that comprises both the coding and an extensive non-coding counterpart, highlighting potential new players in PCa progression. We also show that contrary to what is observed in other cancers, PTEN loss in PCa leads to increased activation of the immune system. These findings can help the development of new biomarkers and help guide therapy choices.

Objective: Driving under the influence (DUI) of alcohol recidivism may be a risk-taking behavior motivated by a change in decision-making capacity. Decision-making capacity has been investigated by...

The need for a liquid biopsy in non-small cell lung cancer (NSCLC) patients is rapidly increasing. We studied the relation between overall survival (OS) and the presence of four cancer biomarkers from a single blood draw in advanced NSCLC patients: EpCAM(high) circulating tumor cells (CTC), EpCAM(low) CTC, tumor-derived extracellular vesicles (tdEV) and cell-free circulating tumor DNA (ctDNA). EpCAM(high) CTC were detected with CellSearch, tdEV in the CellSearch images and EpCAM(low) CTC with filtration after CellSearch. ctDNA was isolated from plasma and mutations present in the primary tumor were tracked with deep sequencing methods. In 97 patients, 21% had >= 2 EpCAM(high) CTC, 15% had >= 2 EpCAM(low) CTC, 27% had >= 18 tdEV and 19% had ctDNA with >= 10% mutant allele frequency. Either one of these four biomarkers could be detected in 45% of the patients and all biomarkers were present in 2%. In 11 out of 16 patients (69%) mutations were detected in the ctDNA. Two or more unfavorable biomarkers were associated with poor OS. The presence of EpCAM(high) CTC and elevated levels of tdEV and ctDNA was associated with a poor OS; however, the presence of EpCAM(low) CTC was not. This single tube approach enables simultaneous analysis of multiple biomarkers to explore their potential as a liquid biopsy.

Background Molecular subtyping of urothelial cancer (UC) has significantly advanced the understanding of bladder tumor heterogeneity and development of prognostic and predictive biomarkers. Evolving evidence across cancers strongly suggests that tumor immunoediting has a profound impact on the behaviour of cancer cells and their adaptation to the co-evolving microenvironment and response to treatment. In alignment with these concepts, recent immune checkpoint blockade (ICB) therapies in UC have demonstrated the predictive potential of mutations in the DNA damage repair (DDR) genes. A comprehensive understanding of DDR gene inactivation associated expression of immune regulatory genes could thus aid in expansion of current immunotherapies and predictive biomarkers for the design of patient-tailored combination treatments. Methods We investigated pre-treatment tumor transcriptomic profiles of the five recently described molecular subtypes of muscle invasive urothelial cancer (MIUC; n = 408) from The Cancer Genome Atlas, to determine subtype specific immune cell abundance, expression of 67 immune regulatory genes, and association with DDR gene inactivation (via mutation, copy number alteration) profiles. Results Analysis using CIBERSORT immune cell abundance determination tool showed significant differences in immune cell profiles and abundance between MIUC subtypes. Expression patterns of a selected panel of 67 genes including both immune stimulatory and inhibitory genes, showed significant associations with subtypes, and DDR gene mutation status. Conclusion Findings from our study provide compelling evidence for co-expression of multiple immune checkpoint genes including, PD-1, PD-L1, IDO1, TIGIT, TIM-3, TGFB1, LAG3, and others, that potentially contribute to compensatory immune evasion in bladder tumors. Our findings also emphasize the urgent need for biomarker discovery approaches that combine molecular subtype, DDR gene mutation status, tumor immune landscape classification, and immune checkpoint gene expression to increase the number of patients responding to immunotherapies. Electronic supplementary material The online version of this article (10.1186/s40425-019-0619-8) contains supplementary material, which is available to authorized users.

Background Harmful use of alcohol is highly prevalent around the world and results in a large disease burden. Most people who meet the criteria for an alcohol use disorder do not receive treatment. Those in a person’s social network can be useful in recognizing a problem and encouraging the person to seek treatment. However, many people lack the knowledge and skills to do this effectively. This study reports on the cultural adaptation for Brazil of the 2009 English-language mental health first aid guidelines for helping someone with problem drinking. Methods A Delphi expert consensus study with two expert panels, one comprising health professionals with experience in the treatment of problem drinking and the other comprising people with lived experience was conducted. Participants rated the importance of actions to be taken to help a person with problem drinking. Results Over two rounds, 60 participants (30 professionals and 30 people with lived experience) rated 197 items. A total of 166 items were included in the final guidelines. Conclusions While there were many similarities with the English-language guidelines for high-income countries, the guidelines also incorporate actions of importance for Brazil, including compulsory treatment and different approaches to dealing with people with problem drinking. Further research is necessary to assess their impact.

When a radiological and nuclear (R/N) emergency occurs, the categorization of individuals into those who are unaffected and those requiring medical intervention is a high priority. At times, a professional dosimeter is not available and therefore some common belongings may be used as fortuitous dosimeters. The preparation of these objects for the measurement should be such as to give the most accurate and precise results. This paper focused on the Photo-Stimulated Luminescence (PSL) response of salty crackers confronts the problem of sample preparation (mass, grain size), dose response and signal stability. The dose response was determined for doses up to 5 Gy, which allowed the calculation of the limit of detection. Additionally, the signal stability was investigated for samples irradiated with 0.3 and 3 Gy. The observed decrease of the signal does not prevent the detection in the dose range typical for R/N emergency. The main dosimetric characteristics were investigated by using two different models of PSL readers equipped with single (infrared) or double (infrared, blue light) stimulation. The results indicated that the limit of detection can be improved by applying blue light stimulation. Moreover, strong correlation of the measurements performed in the two different instruments, as well as the rapidity of the analysis and the simplicity of the operations, suggest that this method can be suitable for a rapid radiation triage of a large number of civilians in a mass casualty event. The study was simultaneously conducted by two laboratories (Ruder Bošković Institute, RBI, Croatia and Istituto Superiore di Sanità, ISS, Italy) involved in the BioPhyMeTRE project (grant No. G5684) supported by NATO Science for Peace and Security Programme.

Despite the severe psychological impact of the COVID-19 pandemic, some individuals do not develop high levels of psychological distress and can be termed resilient. Using the ecological resilience model, we examined factors promoting or hindering resilience in the COVID-19 pandemic. Of the 1034 participants (49.9±16.2 years; females 51.2%) from Italian general population, 70% displayed resilient outcomes and 30% reported moderate-severe anxiety and/or depression. A binary regression model revealed that factors promoting resilience were mostly psychological (e.g., trait resilience, conscientiousness) together with social distancing. Conversely, factors hindering resilience included COVID-19-anxiety, COVID-19-related PTSD symptoms, intolerance of uncertainty, loneliness, living with children, higher education, and living in regions where the virus was starting to spread. In conclusion, the ecological resilience model in the COVID-19 pandemic explained 64% of the variance and identified factors promoting or hindering resilient outcomes. Critically, these findings can inform psychological interventions supporting individuals by strengthening factors associated with resilience.

Black men die more often of prostate cancer yet, interestingly, may derive greater survival benefits from immune-based treatment with sipuleucel-T. Since no signatures of immune-responsiveness exist for prostate cancer, we explored race-based immune-profiles to identify vulnerabilities. Here we show in multiple independent cohorts comprised of over 1,300 patient samples annotated with either self-identified race or genetic ancestry, prostate tumors from Black men or men of African ancestry have increases in plasma cell infiltrate and augmented markers of NK cell activity and IgG expression. These findings are associated with improved recurrence-free survival following surgery and nominate plasma cells as drivers of prostate cancer immune-responsiveness., A recent report suggested Black men with prostate cancer were more responsive to immunotherapy. Here, the authors analysed prostate cancer gene expression profiles and show tumours from Black men and men with African ancestry have an increased proportion of plasma cells compared to those of White men and this correlates with improved outcome following treatment.

Objective: To compare dental arch relationships in children with unilateral cleft lip and palate (UCLP) between two surgical techniques for repair of cleft lip/palate and two ages of palate repair. Settings and Sample: Dental models were taken for a group of 448 subjects at a mean age of 7 years and were evaluated by means of the Goslon Yardstick. The patients studied consisted of an initial group of 673 infants with complete UCLP randomized into 8 study groups according to lip repair procedures (Millard versus Spina techniques); palate repair procedures (von Langenbeck versus Furlow techniques); and palate repair timing (early: 9 to 12 months versus late: 15-18 months). Methods: Four surgeons performed all surgeries. Dependent variables included the following: lip repair technique, palate repair technique, age at time of palate repair and surgeon; with sex as an independent variable. The data were analysed using a general linear model (P < .05). Results: There were no significant differences for occlusal index scores as a function of lip or palate surgical technique, palatal repair timing and sex. Significant differences were found for occlusal index scores as a function of the surgeon. Conclusion: Dental arch relationships were not influenced by lip and palatal repair techniques or patient age at palatal repair. The surgeon was the major factor that influenced the dental arch relationship outcome. info:eu-repo/semantics/publishedVersion

Previous research has addressed the study of the well-being structure focusing on the separability among hedonic and eudaimonic dimensions by means of latent variable approaches. Diener’s tripartite model of Subjective Well-Being has often been identified with hedonic well-being, while flourishing (i.e., positive functioning) has been classified as a proxy for eudaimonic well-being. Instead of pursuing a theory-driven approach, the structure of well-being dimensions can be retrieved by means of network psychometrics that is a highly informative, data-driven approach that allows the model structure to spontaneously emerge from the relationships among indicators. Furthermore, we propose a strength centrality decomposition that is able to summarize the influence of a specific indicator within its dimension and between the other dimensions. Contrary to the theoretical conjecture that the separability among well-being dimensions can be grounded on a hedonic and eudaimonic distinction, our results point to a categorization of the Diener’s well-being indicators based on the type of information they convey, that is global evaluation of life satisfaction, positive and negative affective experiences, and perceived positive functioning in life.

Phosphatase and tensin homolog (PTEN) loss is associated with adverse outcomes in prostate cancer and has clinical potential as a prognostic biomarker. The objective of this work was to develop an artificial intelligence (AI) system for automated detection and localization of PTEN loss on immunohistochemically (IHC) stained sections. PTEN loss was assessed using IHC in two prostate tissue microarrays (TMA) (internal cohort, n = 272 and external cohort, n = 129 patients). TMA cores were visually scored for PTEN loss by pathologists and, if present, spatially annotated. Cores from each patient within the internal TMA cohort were split into 90% cross-validation (N = 2048) and 10% hold-out testing (N = 224) sets. ResNet-101 architecture was used to train core-based classification using a multi-resolution ensemble approach (×5, ×10, and ×20). For spatial annotations, single resolution pixel-based classification was trained from patches extracted at ×20 resolution, interpolated to ×40 resolution, and applied in a sliding-window fashion. A final AI-based prediction model was created from combining multi-resolution and pixel-based models. Performance was evaluated in 428 cores of external cohort. From both cohorts, a total of 2700 cores were studied, with a frequency of PTEN loss of 14.5% in internal (180/1239) and external 13.5% (43/319) cancer cores. The final AI-based prediction of PTEN status demonstrated 98.1% accuracy (95.0% sensitivity, 98.4% specificity; median dice score = 0.811) in internal cohort cross-validation set and 99.1% accuracy (100% sensitivity, 99.0% specificity; median dice score = 0.804) in internal cohort test set. Overall core-based classification in the external cohort was significantly improved in the external cohort (area under the curve = 0.964, 90.6% sensitivity, 95.7% specificity) when further trained (fine-tuned) using 15% of cohort data (19/124 patients). These results demonstrate a robust and fully automated method for detection and localization of PTEN loss in prostate cancer tissue samples. AI-based algorithms have potential to streamline sample assessment in research and clinical laboratories.

Immunotherapy has improved patient survival in many types of cancer, but for prostate cancer, initial results with immunotherapy have been disappointing. Prostate cancer is considered an immunologically excluded or cold tumor, unable to generate an effective T-cell response against cancer cells. However, a small but significant percentage of patients do respond to immunotherapy, suggesting that some specific molecular subtypes of this tumor may have a better response to checkpoint inhibitors. Recent findings suggest that, in addition to their function as cancer genes, somatic mutations of PTEN, TP53, RB1, CDK12, and DNA repair, or specific activation of regulatory pathways, such as ETS or MYC, may also facilitate immune evasion of the host response against cancer. This review presents an update of recent discoveries about the role that the common somatic mutations can play in changing the tumor microenvironment and immune response against prostate cancer. We describe how detailed molecular genetic analyses of the tumor microenvironment of prostate cancer using mouse models and human tumors are providing new insights into the cell types and pathways mediating immune responses. These analyses are helping researchers to design drug combinations that are more likely to target the molecular and immunological pathways that underlie treatment failure.

Background and objectives Previous research has provided insufficient evidence on the factorial validity of the negative cognitive style questionnaires, which is a problem for the validity of the total score's computation. In Study 1, we focused on the relationship between internality and the other dimensions of negative cognitive style. In Study 2, we explored the predictive validity of negative cognitive style for negative interpretation bias. Methods In Study 1, 770 participants completed the Cognitive Style Questionnaire – Short Form (CSQ-SF). In Study 2, from a prescreening data collection (N = 300) we selected participants with low (N = 40) and high (N = 32) cognitive vulnerability to depression who were primed with negative mood induction and who completed a generative interpretation task. Results In Study 1, a confirmatory factor analysis (CFA) indicated that the best fitting model for the CSQ-SF was a bifactor model without the internality dimension. In Study 2, a CFA replicated the factorial structure of Study 1 and individuals with a high negative cognitive style exhibited a negative interpretation bias after controlling for depressive symptoms. Limitations The university-age sample limited the generalizability of our results to different populations, and the lack of longitudinal data prevented us from discussing further implications on the relationship between the negative interpretation bias and negative cognitive style in predicting depression. Conclusions Together, the results of our two studies support the construct validity of the CSQ-SF and recommend the use of a composite score of negative cognitive style without internality.

OBJECTIVES: With evidence of benefits of pediatric palliative care (PPC) integration, we sought to characterize subspecialty PPC referral patterns and end of life (EOL) care in pediatric advanced heart disease (AHD). METHODS: In this retrospective cohort study, we compared inpatient pediatric ( RESULTS: Of 3409 early-epoch admissions, there were 110 deaths; the late epoch had 99 deaths in 4032 admissions. In the early epoch, 45 patients (1.3% admissions, 17% deaths) were referred for PPC, compared with 146 late-epoch patients (3.6% admissions, 58% deaths). Most deaths (186 [89%]) occurred in the cardiac ICU after discontinuation of life-sustaining therapy (138 [66%]). Medical therapies included ventilation (189 [90%]), inotropes (184 [88%]), cardiopulmonary resuscitation (68 [33%]), or mechanical circulatory support (67 [32%]), with no temporal difference observed. PPC involvement was associated with decreased mechanical circulatory support, ventilation, inotropes, or cardiopulmonary resuscitation at EOL, and children were more likely to be awake and be receiving enteral feeds. PPC involvement increased advance care planning, with lower hospital charges on day of death and 7 days before (respective differences $5058 [P = .02] and $25 634 [P = .02]). CONCLUSIONS: Pediatric AHD deaths are associated with high medical intensity; however, children with PPC consultation experienced substantially less invasive interventions at EOL. Further study is warranted to explore these findings and how palliative care principles can be better integrated into care.

Background Phosphatase and tensin homolog (PTEN) loss has long been associated with adverse findings in early prostate cancer. Studies to date have yet to employ quantitative methods (qPTEN) for measuring of prognostically relevant amounts of PTEN loss in postsurgical settings and demonstrate its clinical application. Methods PTEN protein levels were measured by immunohistochemistry in radical prostatectomy samples from training (n = 410) and validation (n = 272) cohorts. PTEN loss was quantified per cancer cell and per tissue microarray core. Thresholds for identifying clinically relevant PTEN loss were determined using log-rank statistics in the training cohort. Univariate (Kaplan-Meier) and multivariate (Cox proportional hazards) analyses on various subpopulations were performed to assess biochemical recurrence-free survival (BRFS) and were independently validated. All statistical tests were two-sided. Results PTEN loss in more than 65% cancer cells was most clinically relevant and had statistically significant association with reduced BRFS in training (hazard ratio [HR] = 2.48, 95% confidence interval [CI] = 1.59 to 3.87; P Conclusions Compared with previous qualitative approaches, qPTEN improves risk stratification of postradical prostatectomy patients and may be considered as a complementary tool to guide disease management after surgery.

Background Low skin-related quality of life (QoL) is usually associated with low levels of self-confidence and self-esteem and with high levels of anxiety and depression symptoms. The way patients cope with a physical disease impacts significantly on their psychosocial adjustment to the disorder and on their emotional functioning. Objectives To explore how coping strategies, skin-related QoL, psychological distress and self-esteem interact in a sample of individuals with neurofibromatosis type 1 (NF1). Methods Seventy-two adult patients with NF1 completed the following questionnaires: Coping Orientation to Problem Experiences (COPE), Skindex-29, Padua Skin-Related QoL questionnaire (PSRQ), State-Trait Anxiety Inventory-X2 form (STAI-X2), Depression Questionnaire (DQ) and Rosenberg Self-Esteem Scale (RSES). The k-modes algorithm was used to identify clusters of patients based on four variables: sex, NF1 severity, number and distribution of cutaneous neurofibromas. Individuals in different clusters were compared with regard to their scores; correlations between scores were analysed within each cluster. Results Two main clusters were identified: individuals in Cluster 1 had a larger number and more widespread distribution of neurofibromas compared with Cluster 2. Patients in Cluster 1 scored higher only on several PSRQ and Skindex-29 scales. Among patients in Cluster 1, the COPE 'avoidance strategies' scale was significantly correlated with the PSRQ 'physical distress and impairments' scale, the Skindex-29 'physical symptoms' and 'functioning' scales, the STAI-X2, the DQ and the RSES. Conclusions Patients with major skin involvement have reduced skin-related QoL. Among them, current findings tentatively suggest that the higher the use of dysfunctional coping, the more impaired are QoL, psychological distress and self-esteem. What's already known about this topic? Neurofibromatosis type 1 (NF1) can affect the quality of life (QoL) in adolescent and adult patients. Low skin-related QoL is usually associated with low levels of self-confidence and self-esteem and with high levels of anxiety and depression symptoms. Questionnaires evaluating skin-related QoL, anxiety, depression, self-esteem and coping are available. What does this study add? Patients with a large number and a widespread distribution of cutaneous neurofibromas have reduced skin-related QoL compared with patients with minor skin involvement. The newly developed Padua Skin-Related QoL questionnaire allows the simultaneous evaluation of discomfort and comfort skin-related QoL dimensions in patients with NF1. Among patients with major skin involvement, the higher the use of dysfunctional coping, the more impaired are skin-related QoL, psychological distress and self-esteem. Our data suggest that patients with NF1 with major skin involvement who endorse dysfunctional beliefs about their own coping abilities might benefit from psychological counselling and coping skills treatments aiming to both improve perceived self-efficacy and learn more adaptive coping strategies.

Mutations inPTENactivate the phosphoinositide 3-kinase (PI3K) signalling network, leading to many of the characteristic phenotypic changes of cancer. However, the primary effects of this gene on oncogenesis through control of the PI3K–AKT–mammalian target of rapamycin (mTOR) pathway might not be the only avenue by which PTEN affects tumour progression. PTEN has been shown to regulate the antiviral interferon network and thus alter how cancer cells communicate with and are targeted by immune cells. An active, T cell-infiltrated microenvironment is critical for immunotherapy success, which is also influenced by mutations in DNA damage repair pathways and the overall mutational burden of the tumour. As PTEN has a role in the maintenance of genomic integrity, it is likely that a loss of PTEN affects the immune response at two different levels and might therefore be instrumental in mediating failed responses to immunotherapy. In this review, we summarise findings that demonstrate how the loss of PTEN function elicits specific changes in the immune response in several types of cancer. We also discuss ongoing clinical trials that illustrate the potential utility of PTEN as a predictive biomarker for immune checkpoint blockade therapies.

To analyze the impact and severity of chronic obstructive pulmonary disease (COPD) on pulmonary function and postoperative clinical outcome based on the Global Initiative for Obstructive Lung Disease criteria in patients undergoing off-pump coronary artery bypass grafting (CABG).Patients were allocated into 3 groups according to presence and severity of COPD: no or mild COPD (n = 144); moderate COPD (n = 77); and severe COPD (n = 30). Spirometry values were obtained preoperatively and on postoperative days (PODs) 2 and 5. The incidences of pneumonia and reintubation, time of mechanical ventilation, and length of postoperative hospital stay were recorded.Significant impairment in pulmonary function was observed in all groups on PODs 2 and 5 (P .001). However, postoperative pulmonary dysfunction was significantly higher in the moderate and severe COPD groups compared with the no or mild COPD group (P .05). On multivariable analysis, severe COPD was associated with an elevated risk for composite outcomes (odds ratio, 1.37; 95% confidence interval, 1.20-1.57; P .001). A preoperative forced expiratory volume in 1 second (FEVMore severe COPD was associated with greater impairment in pulmonary function and worse clinical outcomes after off-pump CABG surgery. A preoperative FEV

Made available in DSpace on 2018-12-11T17:22:29Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-08-29 Background: Lymph node metastasis is one of the most important prognostic factors in head and neck squamous cell carcinomas (HNSCCs) and critical for delineating their treatment. However, clinical and histological criteria for the diagnosis of nodal status remain limited. In the present study, we aimed to characterize the proteomic profile of lymph node metastasis from HNSCC patients. Methods: In the present study, we used one- and two-dimensional electrophoresis and mass spectrometry analysis to characterize the proteomic profile of lymph node metastasis from HNSCC. Results: Comparison of metastatic and non-metastatic lymph nodes showed 52 differentially expressed proteins associated with neoplastic development and progression. The results reinforced the idea that tumors from different anatomical subsites have dissimilar behaviors, which may be influenced by micro-environmental factor including the lymphatic network. The expression pattern of heat shock proteins and glycolytic enzymes also suggested an effect of the lymph node environment in controlling tumor growth or in metabolic reprogramming of the metastatic cell. Our study, for the first time, provided direct evidence of annexin A1 overexpression in lymph node metastasis of head and neck cancer, adding information that may be useful for diagnosing aggressive disease. Conclusions: In brief, this study contributed to our understanding of the metastatic phenotype of HNSCC and provided potential targets for diagnostic in this group of carcinomas. Departamento de Biologia Molecular Faculdade de Medicina (FAMERP), Av. Brigadeiro Faria Lima, 5416, Vila São Pedro Departamento de Biologia Instituto de Biociências Letras e Ciências Exatas (IBILCE) Universidade Estadual Paulista (UNESP), R. Cristóvão Colombo, 2265 Instituto Do Câncer de São Paulo Octavio Frias de Oliveira - ICESP, Av. Dr. Arnaldo, 251 - Cerqueira César Faculdade Ceres (Faceres), Av. Anísio Haddad, 6751 Departamento de Estomatologia Faculdade de Odontologia Universidade de São Paulo, Av. Prof. Lineu Prestes, 2227 Instituto Do Câncer Arnaldo Vieira de Carvalho, R. Dr Cesário Mota Jr, 112 Departamento de Cirurgia de Cabeça e Pescoço Hospital Heliópolis, R. Cônego Xavier, 276 Departamento de Análises Clínicas Toxicológicas e Bromatológicas Faculdade de Ciências Farmacêuticas Universidade de São Paulo, Avenida do Café, s/n Departamento de Genética e Biologia Evolutiva Instituto de Biociências Universidade de São Paulo, R. do Matão, 321 Departamento de Biologia Instituto de Biociências Letras e Ciências Exatas (IBILCE) Universidade Estadual Paulista (UNESP), R. Cristóvão Colombo, 2265

Purpose: The aim of this study is to evaluate the walked distance and physiological responses during incremental shuttle walk test in patients with different degrees of adolescent idiopathic scoliosis (AIS). Methods: We evaluated 20 healthy teenagers and 46 patients with AIS; they were divided into 2 groups: AIS > 45° and AIS Results: Patients with AIS > 45° presented significant reduced incremental shuttle walked distance compared with the AIS P = .001) and expiratory volume in the first second (P = .005) compared with control group. Moderate correlations between forced vital capacity (r = −.506) and tidal volume (r = −.476) with scoliosis angles were found. Conclusions: The incremental shuttle walk test was capable of identifying reduced functional capacity in patients with different degrees of AIS. Moreover, the severity of spinal curvature may exert influence on ventilatory and metabolic variables.

The effects of low levels of blood alcohol concentration (BAC) on motorcyclist performance are still not fully comprehended. The great majority of the studies are, in fact, focused on car driving. So far, it is known that even BAC levels below the legal limit negatively affect riding motor skills correlated with crash rate. In the present study, we used a moped riding simulator to investigate the effects of low alcohol dosages (under the limits established in Italy, and in most European countries) on the defensive riding ability of light drinkers, particularly focusing on the degree of danger characterizing their riding performance. We recruited 24 participants through a double-blind, random distribution, balanced, cross-over design. We administered moderate amounts of alcohol to participants during two sessions of moped riding simulation. The results showed that even though BAC levels were always below (mean value: 0.03 g/dL) the limit allowed by Italian traffic law (0.05 g/dL), alcohol induced a reduction in safe riding behaviors, as indicated by the greater amount of hazardous scenes faced with dangerous riding behaviors when participants were under the influence of alcohol than when they were sober. Moreover, low BAC levels had a greater detrimental influence when a certain amount of learning had already been achieved by the participants (i.e., in the last experimental session). The results suggest that the effect of a low dose of alcohol interacts with participants’ self-confidence.

Dysfunctional breathing (DB) is a respiratory condition characterized by irregular breathing patterns that occur either in the absence of concurrent diseases or secondary to cardiopulmonary diseases. Although the primary symptom is often dyspnea or “air hunger”, DB is also associated with nonrespiratory symptoms such as dizziness and palpitations. DB has been identified across all ages. Its prevalence among adults in primary care in the United Kingdom is approximately 9.5%. In addition, among individuals with asthma, a positive diagnosis of DB is found in a third of women and a fifth of men. Although DB has been investigated for decades, it remains poorly understood because of a paucity of high-quality clinical trials and validated outcome measures specific to this population. Accordingly, DB is often underdiagnosed or misdiagnosed, given the similarity of its associated symptoms (dyspnea, tachycardia, and dizziness) to those of other common cardiopulmonary diseases such as COPD and asthma. The high rates of misdiagnosis of DB suggest that health care professionals do not fully understand this condition and may therefore fail to provide patients with an appropriate treatment. Given the multifarious, psychophysiological nature of DB, a holistic, multidimensional assessment would seem the most appropriate way to enhance understanding and diagnostic accuracy. The present narrative review was developed as a means of summarizing the available evidence about DB, as well as improving understanding of the condition by researchers and practitioners. RESUMO A disfunção respiratória (DR) é um quadro respiratório caracterizado por padrões respiratórios irregulares que ocorrem na ausência de doenças concomitantes ou secundariamente a doenças cardiopulmonares. Embora o principal sintoma seja frequentemente dispneia ou “fome por ar”, a DR também está associada a sintomas não respiratórios, como vertigem e palpitações. A DR pode ser identificada em todas as idades. Sua prevalência entre adultos na atenção primária no Reino Unido é de aproximadamente 9,5%. Além disso, entre indivíduos com asma, um diagnóstico positivo de DR é encontrado em um terço das mulheres e um quinto dos homens. Embora a DR tenha sido investigada por décadas, ela permanece pouco compreendida devido a uma escassez de ensaios clínicos de alta qualidade e de variáveis de desfecho validadas especificamente para essa população. Assim, a DR é frequentemente subdiagnosticada ou diagnosticada incorretamente, devido à similaridade de seus sintomas associados (dispneia, taquicardia e vertigem) aos de outras doenças cardiopulmonares comuns, como DPOC e asma. As altas taxas de diagnóstico incorreto de DR sugerem que os profissionais de saúde não entendam completamente esse quadro e possam, portanto, não fornecer aos pacientes um tratamento adequado. Dada à natureza multifatorial e psicofisiológica da DR, uma avaliação holística e multidimensional parece ser a maneira mais apropriada de melhorar a compreensão e a precisão do diagnóstico. A presente revisão foi desenvolvida como um meio de resumir as evidências disponíveis sobre DB, bem como de melhorar a compreensão do quadro por pesquisadores e profissionais.

Glioblastomas represent a challenging problem with an extremely poor survival rate. Since these tumour cells have a highly invasive character, an effective surgical resection as well as chemotherapy and radiotherapy is very difficult. Convection-enhanced delivery (CED), a technique that consists in the injection of a therapeutic agent directly into the parenchyma, has shown encouraging results. Its efficacy depends on the ability to predict, in the pre-operative phase, the distribution of the drug inside the tumour. This paper proposes a method to compute a fundamental parameter for CED modelling outcomes, the hydraulic permeability, in three brain structures. Therefore, a bidimensional brain-like structure was built out of the main geometrical features of the white matter: axon diameter distribution extrapolated from electron microscopy images, extracellular space (ECS) volume fraction and ECS width. The axons were randomly allocated inside a defined border, and the ECS volume fraction as well as the ECS width maintained in a physiological range. To achieve this result, an outward packing method coupled with a disc shrinking technique was implemented. The fluid flow through the axons was computed by solving Navier–Stokes equations within the computational fluid dynamics solver ANSYS. From the fluid and pressure fields, an homogenisation technique allowed establishing the optimal representative volume element (RVE) size. The hydraulic permeability computed on the RVE was found in good agreement with experimental data from the literature.

Glioblastoma multiforme treatment is a challenging task in clinical oncology. Convection- enhanced delivery (CED) is showing encouraging but still suboptimal results due to drug leakages. Numerical models can predict drug distribution within the brain, but require retrieving brain physical properties, such as the axon diameter distribution (ADD), through axon architecture analysis. The goal of this work was to provide an automatic, accurate and fast method for axon segmentation in electronic microscopy images based on fully convolutional neural network (FCNN) as to allow automatic ADD computation. The segmentation was performed using a residual FCNN inspired by U-Net and Resnet. The FCNN training was performed exploiting mini-batch gradient descent and the Adam optimizer. The Dice coefficient was chosen as loss function. The proposed segmentation method achieved results comparable with already existing methods for axon segmentation in terms of Information Theoretic Scoring ( $$0.98\%$$ ) with a faster training (5 h on the deployed GPU) and without requiring heavy post-processing (testing time was 0.2 s with a non-optimized code). The ADDs computed from the segmented and ground-truth images were statistically equivalent. The algorithm proposed in this work allowed fast and accurate axon segmentation and ADD computation, showing promising performance for brain microstructure analysis for CED delivery optimization.

BACKGROUND: In a randomized, controlled trial that compared liraglutide, a glucagon-like peptide 1 analogue, with placebo in patients with type 2 diabetes and high cardiovascular risk who were receiving usual care, we found that liraglutide resulted in lower risks of the primary end point (nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes) and death. However, the long-term effects of liraglutide on renal outcomes in patients with type 2 diabetes are unknown. METHODS: We report the prespecified secondary renal outcomes of that randomized, controlled trial in which patients were assigned to receive liraglutide or placebo. The secondary renal outcome was a composite of new-onset persistent macroalbuminuria, persistent doubling of the serum creatinine level, end-stage renal disease, or death due to renal disease. The risk of renal outcomes was determined with the use of time-to-event analyses with an intention-to-treat approach. Changes in the estimated glomerular filtration rate and albuminuria were also analyzed. RESULTS: A total of 9340 patients underwent randomization, and the median follow-up of the patients was 3.84 years. The renal outcome occurred in fewer participants in the liraglutide group than in the placebo group (268 of 4668 patients vs. 337 of 4672; hazard ratio, 0.78; 95% confidence interval [CI], 0.67 to 0.92; P=0.003). This result was driven primarily by the new onset of persistent macroalbuminuria, which occurred in fewer participants in the liraglutide group than in the placebo group (161 vs. 215 patients; hazard ratio, 0.74; 95% CI, 0.60 to 0.91; P=0.004). The rates of renal adverse events were similar in the liraglutide group and the placebo group (15.1 events and 16.5 events per 1000 patient-years), including the rate of acute kidney injury (7.1 and 6.2 events per 1000 patient-years, respectively). CONCLUSIONS: This prespecified secondary analysis shows that, when added to usual care, liraglutide resulted in lower rates of the development and progression of diabetic kidney disease than placebo. (Funded by Novo Nordisk and the National Institutes of Health; LEADER ClinicalTrials.gov number, NCT01179048 .).

BACKGROUND Accumulating evidence shows that tumor cell-specific genomic changes can influence the cross talk between cancer cells and the surrounding tumor microenvironment (TME). Loss of the PTEN tumor suppressor gene is observed in 20% to 30% of prostate cancers (PCa) when first detected and the rate increases with PCa progression and advanced disease. Recent findings implicate a role for PTEN in cellular type I interferon response and immunosuppression in PCa. However, the way that PTEN inactivation alters antitumor immune response in PCa is poorly understood. MATERIALS AND METHODS To investigate the changes associated with PTEN loss and an immunosuppressive TME in PCa, we used CIBERSORT to estimate the relative abundance of 22 immune-cell types from 741 primary and 96 metastatic tumors. Our in silico findings were then validated by immunohistochemical analysis of immune cells and IDO1 and PDL1 checkpoint proteins in a cohort of 94 radical prostatectomy specimens. RESULTS FoxP3+ T regulatory cells (Tregs) were significantly increased in PTEN-deficient PCa in all three public domain cohorts. Loss of PTEN in bone metastases was associated with lower CD8+ T-cell abundance, but in liver metastasis, FoxP3+ Tregs were present at higher levels. PTEN-deficient lymph node metastasis had a distinct profile, with high levels of CD8+ T cells. Moreover, we found that metastatic PCa presents higher abundance of FoxP3+ Treg when compared to primary lesions. Since PTEN-deficient tumors are likely to be immunosuppressed as a consequence of increased FoxP3+ Tregs, we then evaluated the localization and expression of IDO1, PDL1 immune checkpoints, and the corresponding density of FoxP3+ Treg and CD8+ T cells using our validation cohort (n = 94). We found that IDO1 protein expression and FoxP3+ Treg density were higher in neoplastic glands compared with benign adjacent tissue. Moreover, higher densities of FoxP3+ Treg cells in both stromal (P = 0.04) and tumor (P = 0.006) compartments were observed in PTEN-deficient tumors compared to tumors that retained PTEN activity. Similarly, IDO1 protein expression was significantly increased in the tumor glands of PTEN-deficient PCa (P < 0.0001). Spearman correlation analysis showed that IDO1 expression was significantly associated with FoxP3+ Treg and CD8+ T-cell density (P < 0.01). CONCLUSIONS Our findings imply that PTEN deficiency is linked to an immunosuppressive state in PCa with distinct changes in the frequency of immune cell types in tumors from different metastatic sites. Our data suggest that determining PTEN status may also help guide the selection of patients for future immunotherapy trials in localized and metastatic PCa.

The present study aimed to isolate and genotype strains of T. gondii from pigs slaughtered for human consumption in South Brazil. Blood and tissues (heart, diaphragm, liver, tongue, and masseter) from 400 animals were collected at two slaughterhouses. Sera were obtained, and antibodies against T. gondii were detected by both indirect fluorescence antibody test (IFAT) and modified agglutination test (MAT). The tissues of animals that tested positive in MAT, IFAT, or both (cut-off ≥ 64) were bioassayed. Twenty-six (6.5%) of the 400 animals were positive by serology. A total of 18 (69.2%) out of those 26 were positive in the mouse bioassay. The isolates were characterized by using 10 PCR-RFLP genetic markers. Fourteen isolates were fully genotyped, and four isolates were genotyped using nine of the 10 markers. All isolates belonged to ToxoDB PCR-RFLP genotype #206. The present study reports on genotype #206 in pigs for the first time, and it confirms the atypical nature of the Brazilian T. gondii isolates. Additionally, even with low levels of antibodies detected in pig herds, pork presents a T. gondii infection risk for humans.

Patients affected by glioblastomas have a very low survival rate. Emerging techniques, such as convection enhanced delivery (CED), need complex numerical models to be effective; furthermore, the estimation of the main parameters to be used to instruct constitutive laws in simulations represents a major challenge. This work proposes a new method to compute tortuosity, a key parameter for drug diffusion in fibrous tissue, starting from a model which incorporates the main white matter geometrical features. It is shown that tortuosity increases from 1.35 to 1.85 as the extracellular space width decreases. The results are in good agreement with experimental data reported in the literature.

AIMS Cardio50 is a project of active risk identification and cardiovascular prevention implemented in an Italian cohort of healthy people aged 50. METHODS A total of 3127 individuals were invited for a screening visit with lifestyle interview and registration of BMI, blood pressure (BP), glucose, cholesterol and classified into groups: A (normal), B (abnormal lifestyle, normal parameters), C (at least one abnormal parameter). People in group C were offered a free blood test and a specialistic medical visit to investigate the suspect of hypertension, dyslipidemia or dysglycemia. Those in groups B and C were scheduled for a follow-up visit after 4-6 months and finally readdressed to the general practitioner. RESULTS A total of 2325 invited individuals attended the screening visit: 18% were classified in group A, 32% in B, 42% in C, 8% met exclusion criteria and were not classifiable. In group C, 86% attended to the cardiologist visit, 76% had dyslipidemia, 35% hypertension, 1% diabetes, 14% impaired fasting glycemia, 19% obesity, 21% metabolic syndrome; 21% were smokers, 11% at risk of alcoholism. At follow-up, we appreciated a decrease in BP in group C individuals. After lifestyle intervention, physical activity increased, whereas metabolic syndrome, impaired fasting glucose and risky drinking decreased. CONCLUSION The current project is coherent with modern strategies based on multifactorial actions. After the intervention, we observed an early reduction in BP and some improvements in lifestyle. This simple and low-technology program allowed us to detect and treat large numbers of individuals at high risk for cardiovascular events.

BACKGROUND: No specific quality-of-life scale for stroke patients has previously been translated and evaluated for reproducibility, for use in the Portuguese language. Internationally, the instrument for this purpose is the Stroke Impact Scale 2.0 (SIS). Use of of SIS enables comprehensive analysis on the impact of mild and moderate stroke on patients’ lives. The aims here were to translate SIS into Portuguese, adapt it culturally, evaluate its reproducibility and correlate it with SF-36 among stroke patients. DESIGN AND SETTING: Translation and validation study. METHODS: The process of initial and retrograde translation was performed, in addition to cultural adaptation to the Brazilian language and culture. SIS was applied to 40 patients, who answered the questions three times. On the first day, the scale was applied twice by two independent researchers (to evaluate interobserver reproducibility). Fifteen days later, the scale was applied for a third time by another researcher (intraobserver reproducibility). The intraclass correlation coefficient (ICC) was used to measure the reproducibility of the SIS scale. RESULTS: The reproducibility of the whole scale was very good (ICC: 0.73 to 0.99). Intraobserver reproducibility in all domains was also very good (ICC: 0.85 to 0.95). Comparison of SIS with SF-36 showed that the domains of strength, mobility and activities of daily living (ADLs) correlated moderately with the functional capacity domain, as did the ADL domain with general health status. The other correlations were weak. The depression domain showed a moderate negative correlation with the memory and communication domains. CONCLUSION: The translation of the SIS 2.0 scale was easy to understand and it had good reproducibility among stroke patients.

ObjectiveRecently it has been demonstrated that constitutively activated signal transducer and activator of transcription 1 (STAT1) gene expression may act as a biomarker of ovarian cancer chemotherapy response. In this study, our objective was to validate the use of STAT1 immunohistochemistry as a prognostic biomarker for disease outcome using a cohort derived from Latin America.MethodsWe evaluated a cohort of Brazilian high-grade serous ovarian cancer, comprising 65 patients with outcome data covering more than 5 years to determine the prognostic and predictive value of STAT1 expression levels. High-grade serous ovarian cancer tumors were used to construct a tissue microarray. Exploratory analyses were conducted on clinical, histopathological, and STAT1 expression data that included descriptive statistics and Pearson correlative analyses. Survival curves for disease-free survival and overall survival were obtained by the Kaplan-Meier method, and the significance of homogeneity between the classes was assessed by log-rank statistics (Mantel-Cox).ResultsHigh expression of STAT1 in tumors was significantly associated with improved disease-free survival (P = 0.0256) and overall survival (P = 0.0193). Proportional hazards regression analysis showed STAT1 expression had an independent effect on both disease-free survival (P = 0.0358) and overall survival (P = 0.0469).ConclusionsThese findings from a Brazilian cohort of patients with ovarian cancer reinforce the association of high STAT1 expression with better response to chemotherapy, providing additional validation of this protein as both a prognostic and predictive biomarker. Collectively, these results together with other recently published studies increase the feasibility of using the STAT1 pathway for the development of novel immunomodulator drugs that could enhance response to treatment.

The nonverbal behavior (NVB) of people diagnosed with schizophrenia consistently interacts with their symptoms during the assessment. Previous studies frequently observed such an interaction when a prevalence of negative symptoms occurred. Nonetheless, a list of NVBs linked to negative symptoms needs to be defined. Furthermore, a list of items that can exhaustively assess such NVBs is still needed. The present study aims to introduce both lists by using the Formal Psychological Assessment. A deep analysis was performed on both the scientific literature and the DSM-5 for constructing the set of nonverbal behaviors; similarly, an initial list of 138 items investigating the behaviors was obtained from instruments used to assess schizophrenia. The Formal Psychological Assessment was then applied to reduce the preliminary list. A final list of 23 items necessary and sufficient to investigate the NVBs emerged. The list also allowed us to analyze specific relations among items. The present study shows how it is possible to deepen a patient's negative symptomatology, starting with the relations between items and the NVBs they investigate. Finally, this study examines the advantages and clinical implications of defining an assessment tool based on the found list of items.

The methodologies for the construction of a knowledge structure mainly refer to the query to experts, the skill maps, and the data-driven approaches. This last method is of growing interest in recent literature. In this paper, an iterative procedure for building a skill map from a set of data is introduced. This procedure is based on the minimization of the distance between the knowledge structure delineated by a given skill map and the data. The accuracy of the proposed method is tested through a number of simulation studies where the amount of noise in the data is manipulated as well as the kind of structure to be reconstructed. Results show that the procedure is accurate and that its performance tends to be sufficiently stable even with high error rates. The procedure is compared to two already-existing methodologies to derive knowledge structures from a set of data. The use of the corrected Akaike Information Criterion (AICc) as a stopping criterion of the iterative reconstruction procedure is tested against the app criterion introduced by Schrepp. Moreover, two empirical applications on clinical data are reported, and their results show the applicability of the procedure.

To evaluate if the Incremental Shuttle Walking Test (ISWT) requires maximal effort in healthy subjects of different ages.Cross-sectional.University-based research laboratory.331 healthy subjects separated into six groups according to age: G1, 18 to 28 years; G2, 29 to 39 years; G3, 40 to 50 years; G4, 51 to 61 years; G5, 62 to 72 years and; G6, 73 to 83 years.Two ISWTs were performed and participants were permitted to run and to exceed 12 levels during the test, if necessary. Heart rate (HR) and symptoms of dyspnoea and fatigue were recorded before and after the test, and the percentage of age-predicted maximal HR (HRmax) was calculated. Maximal effort was defined as HRmax90% of age-predicted HRmax.Almost 31% of the subjects exceeded 12 levels in the ISWT. At the end of the test, all groups presented a median [interquartile range] HR greater than 90% of HRmax (G1: 100 [95 to 104]; G2: 100 [96 to 105]; G3: 103 [97 to 108]; G4: 99 [91 to 106]; G5: 96 [87 to 106] and G6: 96 [91 to 109]% HRmax). Regarding symptoms, all groups showed higher values after the test (P0.05). A multiple logistic regression analysis identified female gender, older age and a lower HR before the test as determinants of not achieving 90% of HRmax at the end of the test.The ISWT requires maximal effort in healthy individuals, but for that it is necessary to extend the test beyond twelve levels. Female gender, older age and lower heart rate before the test are the determinants of not reaching maximal effort.

BACKGROUND: The revised foot function index (FFI-R) is used to evaluate the functionality of patients with conditions that affect the feet. The objective here was to produce the Brazilian Portuguese version of this index. DESIGN AND SETTING: Translation and validation study conducted at the Federal University of São Paulo, Brazil. METHODS: The translation and cultural adaptation process involved translation by two independent translators, analysis by an expert committee, back translation into the original language, analysis by the expert committee again and a pretest. The Portuguese-language version was administered to 35 individuals with plantar fasciitis and metatarsalgia to determine their level of understanding of the assessment tool. RESULTS: Changes were made to the terms and expressions of some original items to achieve cultural equivalence. Terms not understood by more than 10% of the sample were altered based on the suggestions of the patients themselves. CONCLUSION: The translation and cultural adaptation of the FFI-R for the Portuguese language were completed and the Brazilian version was obtained.

This study analyzes the relationship between salivary cortisol and testosterone levels and performance in track and field athletes. In addition, we analyzed the influence of status among athletes (measured based on previous athletic achievement) on hormone levels. Nineteen members of the Austrian track and field team (eleven males, eight females, 25.9 ± 3.9 years of age, 74.9 ± 20.1 kg, and 179.3 ± 10 cm) participated in this study. Data was collected during the European Games in Baku. Athletes delivered saliva samples at various time-points including morning samples and samples directly before and after the competition. Scoring points of the International Association of Athletics Federation were used as an individual measure of relative performance. We found that performance was negatively correlated with rise in testosterone concentrations in the last 24 h prior to the competition. A similar trend was found for cortisol levels, but only when the three least competitive athletes were removed from analysis. Pre-competition cortisol levels were significantly increased compared to measurements 24 h earlier. No effect of status on cortisol or testosterone increase in the same timeframe was found. We conclude that the tournament represented a stressor and that excessive endocrine response was associated with reduced performance.

Yellow fever virus (YFV) replication is highly dependent on host cell factors. YFV NS4B is reported to be involved in viral replication and immune evasion. Here interactions between NS4B and human proteins were determined using a GST pull-down assay and analyzed using 1-DE and LC-MS/MS. We present a total of 207 proteins confirmed using Scaffold 3 Software. Cyclophilin A (CypA), a protein that has been shown to be necessary for the positive regulation of flavivirus replication, was identified as a possible NS4B partner. 59 proteins were found to be significantly increased when compared with a negative control, and CypA exhibited the greatest difference, with a 22-fold change. Fisher's exact test was significant for 58 proteins, and the p value of CypA was the most significant (0.000000019). The Ingenuity Systems software identified 16 pathways, and this analysis indicated sirolimus, an mTOR pathway inhibitor, as a potential inhibitor of CypA. Immunofluorescence and viral plaque assays showed a significant reduction in YFV replication using sirolimus and cyclosporine A (CsA) as inhibitors. Furthermore, YFV replication was strongly inhibited in cells treated with both inhibitors using reporter BHK-21-rep-YFV17D-LucNeoIres cells. Taken together, these data suggest that CypA-NS4B interaction regulates YFV replication. Finally, we present the first evidence that YFV inhibition may depend on NS4B-CypA interaction.

Objective: To evaluate the lung function and clinical outcome in severe chronic obstructive pulmonary disease in patients undergoing off-pump coronary artery bypass grafting with left internal thoracic artery graft, comparing the pleural drain insertion in the intercostal versus subxyphoid region. Methods: A randomized controlled trial. Chronic obstructive pulmonary disease patients were randomized into two groups according pleural drain site: II group (n=27) - pleural drain in intercostal space; SI group (n=29) - pleural drain in the subxyphoid region. Spirometry values (Forced Vital Capacity - and Forced expiratory volume in 1 second) were obtained on preoperative and 1, 3 and 5 postoperative days. Chest x-ray from preoperative until postoperative day 5 (POD5) was performed for monitoring respiratory events, such as atelectasis and pleural effusion. Pulmonary shunt fraction and pain score was evaluate preoperatively and on postoperative day 1. Results: In both groups there was a significant decrease of the spirometry values (Forced Vital Capacity and Forced expiratory volume in 1 second) until POD5 (P

Extraintestinal pathogenicEscherichia coli(ExPEC) is one of the main etiological agents of bloodstream infections caused by Gram-negative bacilli. In the present study, 20E. coliisolates from human hemocultures were characterized to identify genetic features associated with virulence (pathogenicity islands markers, phylogenetic group, virulence genes, plasmid profiles, and conjugative plasmids) and these results were compared with commensal isolates. The most prevalent pathogenicity island, in strains from hemoculture, were PAI IV536, described by many researchers as a stable island in enterobacteria. Among virulence genes,iutA gene was found more frequently and this gene enconding the aerobactin siderophore receptor. According to the phylogenetic classification, group B2 was the most commonly found. Additionally, through plasmid analysis, 14 isolates showed plasmids and 3 of these were shown to be conjugative. Although in stool samples of healthy people the presence of commensal strains is common, human intestinal tract may serve as a reservoir for ExPEC.