Multimodal pancreatic cancer detection using methylated DNA biomarkers in pancreatic juice and plasma CA 19-9: A prospective multicenter study.

BACKGROUND AND AIMS: In previous studies methylated DNA markers (MDMs) have been identified in pancreatic juice (PJ) for detecting pancreatic ductal adenocarcinoma (PDAC). In this prospective multicenter study, the sensitivity and specificity characteristics of this panel of PJ-MDMs was evaluated standalone and in combination with plasma CA 19-9. METHODS: Paired PJ and plasma were assayed from 88 biopsy-proven treatment naïve PDAC cases and 134 controls (normal pancreas: 53, chronic pancreatitis (CP): 23, intraductal papillary mucinous neoplasm (IPMN): 58). Bisulfite-converted DNA from buffered PJ was analyzed using long-probe quantitative amplified signal assay targeting 14 MDMs (NDRG4, BMP3, TBX15, C13orf18, PRKCB, CLEC11A, CD1D, ELMO1, IGF2BP1, RYR2, ADCY1, FER1L4, EMX1, and LRRC4) and a reference gene (methylated B3GALT6). Logistic regression was used to fit the previously identified 3-MDM PJ panel (FER1L4, C13orf18 and BMP3). Discrimination accuracy was summarized using area under the receiver operating characteristic curve (AUROC) with corresponding 95% confidence intervals. RESULTS: Methylated FER1L4 had the highest individual AUROC of 0.83 (95% CI: 0.78-0.89). The AUROC for the 3-MDM PJ + Plasma CA 19-9 model (0.95 (0.92-0.98))) was higher than both the 3-MDM PJ panel (0.87 (0.82-0.92)) and plasma CA 19-9 alone ((0.91 (0.87-0.96) (p=0.0002 and 0.0135, respectively). At a specificity of 88% (95% CI: 81-93%), the sensitivity of this model was 89% (80-94%) for all PDAC stages and 83% (64-94%) for stage I/II PDAC. CONCLUSION: A panel combining PJ-MDMs and plasma CA19-9 discriminates PDAC from both healthy and disease control groups with high accuracy. This provides support for combining pancreatic juice and blood-based biomarkers for enhancing diagnostic sensitivity and successful early PDAC detection.

Constitutional Mutation of PIK3CA: A Variant of Cowden Syndrome?

We present a family in which four individuals have been identified with the same likely pathogenic genetic alteration in the PIK3CA gene at the germinal level; specifically, c.1145G>A p.(Arg382Lys) missense type. The index case patient was diagnosed with multinodular goiter and breast cancer at 61 years old. Among the other three carrier relatives: one has been diagnosed with serous cystadenoma of the ovary and a thyroid nodule with no radiological suspicion of malignancy; the other two present multinodular goiter. Additionally, a sister of three of the carriers suffered from an ovarian teratoma, follicular thyroid carcinoma on multinodular goiter, and high-grade serous ovarian carcinoma. No direct mutation study was performed on her as she had died due to ovarian carcinoma. This finding suggests that the PIK3CA gene should be considered in Cowden-like families when no other gene mutations have been found. Furthermore, this report contributes to characterization of the clinical phenotype caused by mutations in PIK3CA, which may be shared with other hereditary breast and ovarian cancer syndromes.

Physiotherapy experiences of injured immigrant workers in Quebec: an intersectional perspective.

PURPOSE: Immigrant workers are more likely to suffer work-related injuries compared to native-born Canadians. Their physical rehabilitation usually involves physiotherapy. This study sought to better understand the experiences of injured immigrant workers receiving compensation and physiotherapy treatments. MATERIALS AND METHODS: We conducted a qualitative study using an interpretive descriptive methodology. Semi-structured interviews were completed with 10 compensated immigrant workers about the physiotherapy services they received. Transcripts were analyzed thematically and with an intersectional lens. RESULTS: Two major themes were identified: 1) complex pathways to physiotherapy, and 2) key pillars of physiotherapy experiences. The first theme demonstrates that a lack of familiarity with the health and compensation systems, delayed access to physiotherapy, and cumulative burdens complicate the care of immigrant workers. The second theme shows that moral/emotional support, pain relief, and the recognition of sociocultural beliefs and fears are key aspects to improving the experiences of care for these workers. CONCLUSIONS: This study offers new insights into physiotherapy in the context of a work injury, which may help physiotherapists adapt care to the complex needs of immigrant workers. The intersectional lens used in the analysis offers interesting ways of accounting for the multiple social identities of these workers.

Injured immigrant workers are at a heightened risk of experiencing impacts on both their physical and mental well-being.Rehabilitation professionals should be supported with resources and training to facilitate timely access to care for immigrant workers, including education on the health and compensation systems.Healthcare institutions should ensure that rehabilitation professionals have the tools and support to develop culturally sensitive approaches that address systemic and sociocultural barriers faced by immigrant workers.

Screening for advanced liver disease incorporating the use of transitional elastography in primary care. / Detección de enfermedad hepática avanzada incorporando el uso de la elastografía de transición en atención primaria.

OBJECTIVES: To describe the proportion of patients with liver fibrosis in at-risk populations in primary care (PC). To know the agreement between FIB-4 and transitional elastography (TE), interobserver agreement between PC and hospital care (HC) in TE, and associated risk Factors (RF). METHODS: Observational, descriptive, cross-sectional study in ≥16 years of age with RF for chronic liver disease. Sex and age, RF (alteration of liver tests [LT], metabolic syndrome, diabetes, obesity, alcohol consumption, hepatic steatosis), and FIB-4, controlled attenuation parameter and TE in PC and in HC, were collected. According to a consensus algorithm, vibration-controlled TE was performed in PC in patients with FIB-4≥1,3, and those with measurement ≥8kPa were referred to HC. RESULTS: 326 patients were studied. 71% were not referred to HC, due to liver stiffness <8kPa. 83 of the 95 derivations did TE in HC. 45 (54%) had TE ≥8, and 25 (30%) ≥12. The proportion of patients with stiffness ≥8kPa was 13,8% (45/326) and ≥12kPa, 7,6% (25/326). The predictive values of the FIB-4 were low. The interobserver correlation coefficient between TE in PC and HC was 0,433. Variables associated with TE ≥8 in PC: LT alteration, diabetes and steatosis. With TE ≥12: LT alteration, diabetes and obesity. PREDICTOR VARIABLES: LT alteration and obesity. CONCLUSIONS: The study supports the sequential performance of serum indices and TE as a screening for fibrosis in the at-risk population in PC, which allows a reduction in the percentage of patients referred to AH, and a better stratification of risk patients.

Occurrence of marine plastic litter and plasticizers from touristic beaches of Arauco Gulf in Central Chile.

Marine plastic litter (MPL) was collected from beaches (n = 3) of the Arauco Gulf in central Chile in spring 2021 and summer 2022. MPL was analyzed for physical and chemical characteristics, and plasticizers were also screened using FTIR-ATR. Three hundred seventeen plastic items with an accumulated weight of 226.8 g were found. MPL densities ranged from 0.4 to 17.1 items m-2. Significant differences (p < 0.05) between seasons were observed for Arauco and Maule beaches, being ∼ten times higher in summer compared to spring. Solid pieces were the predominant shape, macroplastics were the most abundant (>2.5 cm), and white and blue colors were dominant. Polypropylene (52 %) and polyethylene (31 %) were the predominant polymers. Plasticizers (n = 3) were detected in the MPL in the study area (dioctyl phthalate, polybutene, and alpha-methylstyrene) for the first time. This study contributes new information related to MPL in coastal areas of central Chile and their chemical composition.

How to Assess Oral Narrative Skills of Children and Adolescents with Intellectual Disabilities: A Systematic Review.

Children and adolescents with intellectual disabilities (ID) often encounter difficulties with narrative skills. Yet, there is a lack of research focusing on how to assess these skills in this population. This study offers an overview of the tools used for assessing oral narrative skills in children and adolescents with ID, addressing key questions about common assessment tools, their characteristics, and reported evidence. A systematic review was conducted of the literature published between 2010 and 2023 in the PsycINFO, ERIC, Education, and Psychology databases. An initial 1176 studies were reviewed by abstract, of which 485 were read in full text, leading to the selection and analysis of 22 studies. Most of the identified tools involve analyzing language samples obtained using wordless picture story books. Three common tools are emphasized. Studies have primarily identified inter-rater reliability and test-criterion evidence for validity. The main tools and their characteristics are discussed in depth to aid readers in discerning suitable options for research or practical applications. The importance of reporting diverse sources of evidence for validity and reliability within this population is highlighted.

A Pioneer Tool to Reduce Restrictive Practices toward People with Intellectual and Developmental Disabilities.

Reducing restrictive practices toward individuals with intellectual and developmental disabilities is a globally recognized imperative and human rights priority. This paper presents a novel tool called LibRe for assessing and reducing restrictive practices. This tool involved an instrumental multistage design and collaboration between professionals, individuals with disabilities, family members, and experts from different fields. It addresses diverse restrictive practices in five key domains: physical or mechanical, chemical or pharmacological, structural, relational, and practices related to contexts and supports. It addresses practices that are pertinent to the Spanish context and that existing tools have not covered. Embedded as a step within an organizational approach, LibRe fosters organizational transformation and provides resources to achieve outcomes within reduction plans for restrictive practices. In total, 156 teams comprising 585 professionals, 64 people with disabilities, and 44 family members responded to the tool. In terms of evidence for internal structure validity, the oblique five-factor model exhibited an adequate fit through confirmatory factor analysis, along with satisfactory reliability indices, according to ordinal alpha and omega. Users positively appraised the tool's usefulness and identified its strengths and challenges. Although further research is needed, preliminary evidence frames LibRe as a useful resource for practice and research.

Marine litter pollution in a subantarctic beach of the Strait of Magellan, Punta Arenas, Chile.

This study assessed the presence of marine litter along the beach of the city of Punta Arenas, Chile. The sampling period coincided with the COVID-19 pandemic. A total of 239 plastic waste items were identified out of a total of 638 litter items. The Clean Coast Index reported within this study ranged from Clean (CCI 2-5) to Extremely dirty (CCI >20), especially near the port. The majority of litter items has been classified as originating from varied origins, as it is not possible to pinpoint a precise origin in most items. The results indicate that the predominant plastic litter in Punta Arenas is PVC. The results are discussed in relation to the sources and composition of the residues, the morpho dynamics of the coast, and the CCI is compared with other locations around the globe.

Novel flame retardants detected in marine plastic litter in coastal areas in Central Chile.

Flame retardants (FRs) are released throughout the plastic life cycle, potentially impacting the environment, biodiversity, and human health. This study analyzed novel flame retardants (NFR) in marine plastic litter (MPL) from six coastal areas in central Chile in November 2017. Target chemicals (n = 19) were analyzed using ultrasonic extraction with hexane, gas chromatography, and mass spectrometry (GC-MS). From all nineteen NFRs analyzed, only ten (53 %) were routinely detected. BTBPE (1,2-bis(2,4,6-tribromophenoxy) ethane) showed the highest concentrations at the Bellavista site (618 to 424,000 pg g-1), and HBB (Hexabromobiphenyl), banned since 1970, was detected in Coliumo (2630 to 13,700 pg g-1). These results show emerging transport patterns and underscore the critical need for enhanced waste management practices for MPL in coastal regions to prevent adverse impacts on marine biodiversity.

A Myeloid-Specific Lack of IL-4Rα Prevents the Development of Alternatively Activated Macrophages and Enhances Immunity to Experimental Cysticercosis.

To determine the role that the IL-4/IL13 receptor plays in the development of alternatively activated macrophages (AAM or M2) and their role in the regulation of immunity to the extraintestinal phase of the helminth parasite Taenia crassiceps, we followed the infection in a mouse strain lacking the IL-4Rα gene (IL-4Rα-/-) and in the macrophage/neutrophil-specific IL-4Rα-deficient mouse strain (LysMcreIL-4Rα-/lox or cre/LoxP). While 100% of T. crassiceps-infected IL-4Rα+/+ (WT) mice harbored large parasite loads, more than 50% of th eIL-4Rα-/- mice resolved the infection. Approximately 88% of the LysMcreIL-4Rα-/lox mice displayed a sterilizing immunity to the infection. The remaining few infected cre/LoxP mice displayed the lowest number of larvae in their peritoneal cavity. The inability of the WT mice to control the infection was associated with antigen-specific Th2-type responses with higher levels of IgG1, IL-4, IL-13, and total IgE, reduced NO production, and increased arginase activity. In contrast, IL-4Rα-/- semi-resistant mice showed a Th1/Th2 combined response. Furthermore, macrophages from the WT mice displayed higher transcripts for Arginase-1 and RELM-α, as well as increased expression of PD-L2 with robust suppressive activity over anti-CD3/CD28 stimulated T cells; all of these features are associated with the AAM or M2 macrophage phenotype. In contrast, both the IL-4Rα-/- and LysMcreIL-4Rα-/lox mice did not fully develop AAM or display suppressive activity over CD3/CD28 stimulated T cells, reducing PDL2 expression. Additionally, T-CD8+ but no T-CD4+ cells showed a suppressive phenotype with increased Tim-3 and PD1 expression in WT and IL-4Rα-/-, which were absent in T. crassiceps-infected LysMcreIL-4Rα-/lox mice. These findings demonstrate a critical role for the IL-4 signaling pathway in sustaining AAM and its suppressive activity during cysticercosis, suggesting a pivotal role for AAM in favoring susceptibility to T. crassiceps infection. Thus, the absence of these suppressor cells is one of the leading mechanisms to control experimental cysticercosis successfully.

Reading Lessons Planning With Students With Intellectual and Developmental Disabilities in Mind: Needs-Based Assessment Proposal.

This study addresses the need to reinforce the reading learning of students with intellectual and developmental disabilities (IDD) in general education classrooms. A standardized way of assessing support needs in reading (SNr) from the teachers' perspective is proposed. The objectives were (i) to develop an instrument and evaluate its properties and (ii) to preliminarily assess the support needs in reading of students with IDD. Participants were 86 Chilean elementary school teachers who responded about the support needs of their own students. The instrument assesses three dimensions (i.e., representation, engagement, and action and expression). Analyses showed excellent preliminary evidence of validity and reliability. Preliminarily identified support needs suggest that students need more support in representation. Practical and research implications are discussed.

Plastic debris, persistent organic pollutants and their toxicity impacts in coastal areas in Central Chile.

The chemical components of plastic wastes have made their disposal a major economic, social, and environmental problem worldwide. This study evaluated the acute toxicity and genotoxicity of marine plastic debris on the beaches of Concepción Bay, Central Chile, taken during three periods (spring, summer, and winter). An integrated approach was used, including chemical and toxicological data, using the Microtox® test with Vibrio fischeri and SOS chromotest with Escherichia coli and concentrations of polychlorinated biphenyls (PCBs), Organochlorine Pesticides (OCPs) and polybrominated diphenyl ethers (PBDEs). The results presented here exclusively include the novel data obtained from the winter campaign, revealing high concentrations of PBDEs (238 ± 521 ng g-1). In addition, the genotoxicity and acute toxicity tests were sensitive for most of the samples studied. This investigation is the first attempt to analyse the toxicity of plastic debris in coastal areas along the Chilean coast.

Metabolic Unhealthiness is Associated With Increased Risk of Critical COVID-19 Pneumonia and Inpatient Mortality in Hospitalized Patients with Obesity or Overweight.

Background and aims Being metabolically unhealthy (MU) is defined as having either hypertension, hyperlipidemia, type 2 diabetes mellitus/pre-diabetes, or fatty liver disease. We aimed to determine if MU was associated with severe COVID-19 pneumonia (severe disease). Methods We performed a single-center retrospective study between March 2020 and August 2021 for patients with overweight or obesity hospitalized with COVID-19 pneumonia. Logistic regression analysis was utilized to derive a risk score for severe disease. The accuracy of the model was assessed using the area under the receiver operating characteristic curve (AUROCC) and bootstrap resampling. Results A total of 334 of 450 patients hospitalized with COVID-19 pneumonia (74.2%) were MU. Patients who were MU had higher in-hospital mortality (10.5% vs. 2.6%) and longer length of hospitalization (median 6 vs. 4 days). MU was not associated with severe disease, p=0.311. On multivariable analysis, older age, male sex, and Asian race were associated with severe disease. Not being vaccinated was associated with doubled odds of severe disease. The AUROCC of the final model was 0.66 (95% CI: 0.60 to 0.71). The risk score at the lowest quintile had a 33.1% to 65.5% predicted risk and a 58.7% observed risk of severe disease, whereas, at the highest quintile, there was an 85.7% to 97.7% predicted risk and an 89.7% observed risk of severe disease. Conclusion Being MU was not a predictor of severe disease, even though mortality was higher despite having higher rates of vaccination. This risk score may help to predict severe disease in hospitalized patients with obesity or overweight. External validation is recommended.

Development and Validation of Standardized Quality of Life Measures for Persons with IDD.

The implications of the individual quality of life (QoL) model of Schalock and Verdugo have made it the most cited QoL model in the field of disability. The QoL model is understood as a conceptual and applied framework for action that allows the materialization of the rights of persons with disabilities through the multidimensional assessment of these persons using QoL indicators, and the development of actions guided by these values and supported by evidence. The purpose of this work is to present the foundations of this model and offer a step-by-step guide to developing standardized QoL assessment instruments and providing evidence that supports their use to implement the model in practice. This paper explores relevant topics such as: (a) the need to identify critical population groups and contexts; (b) the identification of QoL indicators for said groups and contexts; (c) the development of items focused on the assessment of personal outcomes; (d) provision to the items of validity evidence based on content and pilot measure design and (e) validation process to gather evidence that supports the uses of the instrument. Last, a framework that allows using the evidence on personal outcomes as disaggregated and aggregated data at different levels of the social system is presented, thus highlighting the role of the model as a change agent regarding individuals, organizations and schools, and public policy.

Endoscopic Sleeve Gastroplasty: A Practice Pattern Survey.

PURPOSE: Obesity is a complex, chronic disease that is strongly associated with complications which cost the US healthcare system billions of dollars per year. Endoscopic sleeve gastroplasty (ESG) has emerged as a safe and effective procedure for treatment of obesity, but without practice guidelines there are likely to be variations practice. We sought to describe current practice patterns amongst endoscopists who perform ESG to help define areas of focus for future research and guideline development. METHODS: We conducted an anonymous cross-sectional survey to examine practice patterns related to ESG. The survey was organized in 5 sections: Endoscopic Practice, Training, and Resources; Pre-ESG Evaluation and Payment Model; Perioperative/Operative Period; Post-operative Period; and Endobariatric Practice Other Than ESG. RESULTS: A variety of exclusion criteria were reported by physicians performing ESG. Most respondents (n = 21/32, 65.6%) would not perform ESG for BMI under 27, and 40.6% (n = 13/32) would not perform ESG on patients with BMI over 50. The majority of respondents (74.2%, n = 23/31) reported ESG was not covered in their region, and most reported patients covered residual costs (67.7%, n = 21/31). CONCLUSIONS: We found significant variability with respect to practice setting, exclusion criteria, pre-procedural evaluation, and medication use. Without guidelines for the selection of patients or standards for pre- and post-ESG care, substantial barriers to coverage will remain, and ESG will remain limited to those who can meet out-of-pocket costs. Larger studies are needed to confirm our findings, and future research should be focused on establishing patient selection criteria and standards in practices to provide guidance for endobariatric programs.

Environmental signature and health risk assessment of polybrominated diphenyl ethers (PBDEs) emitted from a landfill fire in Santiago de Chile.

Polybrominated diphenyl ethers (PBDEs) have been used as flame retardants in building materials, electronics, furnishings, vehicles, airplanes, plastics, polyurethane foams, and textiles for many years. Currently, the primary commercial mixtures, penta-, octa-, and deca-BDE, are globally restricted. Still, products containing PBDEs are expected to impact waste management and the environment for many years. In January 2016, an open fire in the Santa Marta landfill close to Santiago de Chile affected the city and surroundings. The fire caused several acute health effects and an increase in emergency hospitalizations. We measured PBDE levels in the areas affected by the fire in the air (gaseous and particulate) and soil, and PBDE emissions were estimated using a dispersion model. The results showed an increase in PBDE concentrations by a factor of 2-4 one day after the start of the fire. However, PBDE concentrations measured after the fire in PM10 and the gas phase were considered low compared to other regions. Interestingly, PBDEs' patterns differed across the sites; however, BDE209 was the dominant congener for all environmental matrices. A preliminary risk assessment was conducted using the daily exposure dose (DED) by air inhalation estimation. The results showed low DED values for adults and children and suggested no direct health risk due to PBDE exposure. This study brings new data useful for future solid waste management initiatives in the country.

ACG Clinical Guideline: Diagnosis and Management of Biliary Strictures.

A biliary stricture is an abnormal narrowing in the ductal drainage system of the liver that can result in clinically and physiologically relevant obstruction to the flow of bile. The most common and ominous etiology is malignancy, underscoring the importance of a high index of suspicion in the evaluation of this condition. The goals of care in patients with a biliary stricture are confirming or excluding malignancy (diagnosis) and reestablishing flow of bile to the duodenum (drainage); the approach to diagnosis and drainage varies according to anatomic location (extrahepatic vs perihilar). For extrahepatic strictures, endoscopic ultrasound-guided tissue acquisition is highly accurate and has become the diagnostic mainstay. In contrast, the diagnosis of perihilar strictures remains a challenge. Similarly, the drainage of extrahepatic strictures tends to be more straightforward and safer and less controversial than that of perihilar strictures. Recent evidence has provided some clarity in multiple important areas pertaining to biliary strictures, whereas several remaining controversies require additional research. The goal of this guideline is to provide practicing clinicians with the most evidence-based guidance on the approach to patients with extrahepatic and perihilar strictures, focusing on diagnosis and drainage.

Outcomes and Trends of Endoscopic Bariatric Therapies (EBT) Among Minority Populations.

INTRODUCTION: Endoscopic bariatric therapies (EBT) have emerged as effective options for weight loss. While the benefits of EBT have been documented, data regarding such therapies among minority populations remains scant. We aim to investigate EBT trends and outcomes in minority populations. METHODS: Data were extracted from the 2015 to 2019 Metabolic and Bariatric Surgery Accreditation and Quality Improvement Project (MBSAQIP) databases. Intragastric balloon (IGB) and endoscopic sleeve gastroplasty (ESG) cases were identified, and procedure volume assessed by year and race/ethnicity. Measures of interest included year-to-year mortality, surgical complications, and 30-day adverse outcomes. RESULTS: Of 966,646 cases in the MBSAQIP databases, 5209 (0.54%) IGB and ESG cases were included. 10.7% were black, and 81.6% were female patients. Compared to white patients, black and Hispanic patients were younger (p < 0.01) with a higher body mass index (p < 0.001). Mortality (0.03% vs. 0% vs. 0%, p = 0.99), reoperation (1.1% vs. 0.8% vs. 0.6%, p = 0.30), and reintervention (3.9% vs. 3.2% vs. 2.3%, p = 0.09) rates were similar between racial/ethnic cohorts. All complications were similar between racial/ethnic cohorts, except a higher rate of venous thromboembolism, in Hispanic (1.04%, p < 0.01) compared to black (0.18%) and white (0.21%) patients. IGB and ESG were predominantly performed in white and Hispanic patients, respectively. ESG was associated with a higher leak (0.6% vs. 0.02%, p < 0.01) and venous thromboembolism (VTE) (1.0% vs. 0.12%, p < 0.01) rate. CONCLUSION: While EBTs have increased annually, they are performed less in black patients. Future studies are needed to identify access barriers for black patients. They are safely performed with similar outcomes in racial/ethnic cohorts, except for a higher VTE rate in Hispanic patients.