Low Health Literacy, Lack of Knowledge, and Self-Control Hinder Healthy Lifestyles in Diverse Patients with Steatotic Liver Disease.

INTRODUCTION: In parallel with the obesity and diabetes epidemics, steatotic liver disease (SLD) has emerged as a major global public health concern. The mainstay of therapy is counseling on weight loss and increased exercise. However, such lifestyle modifications infrequently lead to success. We aimed to identify barriers to diet and lifestyle modification in patients with SLD. METHODS: Patients with SLD completed a 14-item questionnaire that assigned barriers to healthy eating to three categories: lack of knowledge, lack of self-control, and lack of time, with a higher summary score indicating more perceived barriers. We administered assessments of health literacy and physical activity. We analyzed the data using descriptive statistics and ordinal regression analysis. RESULTS: We included 151 participants with a median age of 64; 54% were female and 68.2% were Hispanic. Median BMI was 31.9 kg/m2. Most respondents, 68.2%, had low health literacy and were either underactive, 29.1% or sedentary, 23.2%. Lack of self-control was the strongest barrier to achieving a healthy lifestyle, followed by lack of knowledge. Lack of time was not significant barrier. Patients with the most significant barriers were more likely to have obesity, low health literacy, and be sedentary. DISCUSSION: Lack of self-control and knowledge are the greatest barriers to adopting a healthy lifestyle in patients with SLD. Future clinical interventions should integrate education that targets various health literacy levels with behavioral approaches to improve a sense of agency.

Identification of enteric viruses from raw water using fluoro-immuno-magnetic separation coupled to RT-PCR / Identificación de virus entéricos en aguas crudas usando separación inmuno-magnética acoplada a RT-PCR

Abstract | Introduction: Enteric viruses have been associated with the production of a variety of diseases transmitted by the fecal-oral route and carried through contaminated food and water. Given their structure and composition, they are highly resistant to environmental conditions and most of the chemical agents used in the purification processes. Therefore, the systematic monitoring of raw water is necessary to ensure its quality especially when it is used for producing drinking water for human consumption. Objective: We identified the presence of rotavirus and hepatitis A virus by means of the fluoro-immuno-magnetic separation technique (FIMS) in raw water taken from four purification plants and their water supplies in the department of Norte de Santander. Materials and methods: The viruses were captured and separated from the water samples using magnetic microparticles functionalized with monoclonal anti-Hepatitis A and anti-Rotavirus antibodies. Confocal microscopy was used to monitor the viral concentration process and transmission electron microscopy for the morphological visualization of the separated viruses. The reverse transcriptase-coupled polymerase chain reaction (RT-PCR) was applied to confirm the presence of pathogens. Results: The two enteric viruses were identified in the majority of the analyzed water samples including water supply sources. Conclusion: We determined that the FIMS technique together with RT-PCR is highly effective for the detection of viral pathogens in complex matrices such as raw water.

Resumen | Introducción. Los virus entéricos se asocian con una serie de enfermedades transmitidas por vía fecal-oral en alimentos o agua contaminada. Dada su estructura y composición, son muy resistentes a las condiciones ambientales y a la mayoría de los agentes químicos empleados en los procesos de potabilización, por lo cual es necesario un monitoreo sistemático del agua cruda para asegurar su calidad, máxime cuando se emplea como materia prima en la producción de agua potable para consumo humano. Objetivo. Determinar la presencia de rotavirus y del virus de la hepatitis A mediante la técnica de separación fluoro-inmuno-magnética en agua cruda procedente de cuatro plantas de potabilización y sus fuentes hídricas en el departamento de Norte de Santander. Materiales y métodos. Los virus fueron capturados y separados a partir de las muestras de agua, empleando micropartículas magnéticas funcionalizadas con anticuerpos monoclonales anti-hepatitis A y anti-rotavirus. Se empleó microscopía confocal para hacer el seguimiento del proceso de concentración viral y, microscopía electrónica de transmisión, para la visualización morfológica de los virus separados. La reacción en cadena de la polimerasa acoplada a transcriptasa inversa (RT-PCR) se utilizó para confirmar la presencia de los patógenos. Resultados. Los dos virus entéricos se detectaron en la mayoría de las muestras de agua analizadas, incluidas las de sus fuentes hídricas. Conclusión. La técnica de separación fluoro-inmuno-magnética acoplada a RT-PCR fue altamente efectiva en la detección de patógenos virales en matrices complejas como el agua cruda.

Deletion of ADORA2B from myeloid cells dampens lung fibrosis and pulmonary hypertension.

Idiopathic pulmonary fibrosis (IPF) is a lethal, fibroproliferative disease. Pulmonary hypertension (PH) can develop secondary to IPF and increase mortality. Alternatively, activated macrophages (AAMs) contribute to the pathogenesis of both IPF and PH. Here we hypothesized that adenosine signaling through the ADORA2B on AAMs impacts the progression of these disorders and that conditional deletion of ADORA2B on myeloid cells would have a beneficial effect in a model of these diseases. Conditional knockout mice lacking ADORA2B on myeloid cells (Adora2B(f/f)-LysM(Cre)) were exposed to the fibrotic agent bleomycin (BLM; 0.035 U/g body weight, i.p.). At 14, 17, 21, 25, or 33 d after exposure, SpO2, bronchoalveolar lavage fluid (BALF), and histologic analyses were performed. On day 33, lung function and cardiovascular analyses were determined. Markers for AAM and mediators of fibrosis and PH were assessed. Adora2B(f/f)-LysM(Cre) mice presented with attenuated fibrosis, improved lung function, and no evidence of PH compared with control mice exposed to BLM. These findings were accompanied by reduced expression of CD206 and arginase-1, markers for AAMs. A 10-fold reduction in IL-6 and a 5-fold decrease in hyaluronan, both linked to lung fibrosis and PH, were also observed. These data suggest that activation of the ADORA2B on macrophages plays an active role in the pathogenesis of lung fibrosis and PH.

Human anti-Aß IgGs target conformational epitopes on synthetic dimer assemblies and the AD brain-derived peptide.

Soluble non-fibrillar assemblies of amyloid-beta (Aß) and aggregated tau protein are the proximate synaptotoxic species associated with Alzheimer's disease (AD). Anti-Aß immunotherapy is a promising and advanced therapeutic strategy, but the precise Aß species to target is not yet known. Previously, we and others have shown that natural human IgGs (NAbs) target diverse Aß conformers and have therapeutic potential. We now demonstrate that these antibodies bound with nM avidity to conformational epitopes on plate-immobilized synthetic Aß dimer assemblies, including synaptotoxic protofibrils, and targeted these conformers in solution. Importantly, NAbs also recognized Aß extracted from the water-soluble phase of human AD brain, including species that migrated on denaturing PAGE as SDS-stable dimers. The critical reliance on Aß's conformational state for NAb binding, and not a linear sequence epitope, was confirmed by the antibody's nM reactivity with plate-immobilized protofibrills, and weak uM binding to synthetic Aß monomers and peptide fragments. The antibody's lack of reactivity against a linear sequence epitope was confirmed by our ability to isolate anti-Aß NAbs from intravenous immunoglobulin using affinity matrices, immunoglobulin light chain fibrils and Cibacron blue, which had no sequence similarity with the peptide. These findings suggest that further investigations on the molecular basis and the therapeutic/diagnostic potential of anti-Aß NAbs are warranted.

The A2B adenosine receptor modulates pulmonary hypertension associated with interstitial lung disease.

Development of pulmonary hypertension is a common and deadly complication of interstitial lung disease. Little is known regarding the cellular and molecular mechanisms that lead to pulmonary hypertension in patients with interstitial lung disease, and effective treatment options are lacking. The purpose of this study was to examine the adenosine 2B receptor (A(2B)R) as a regulator of vascular remodeling and pulmonary hypertension secondary to pulmonary fibrosis. To accomplish this, cellular and molecular changes in vascular remodeling were monitored in mice exposed to bleomycin in conjunction with genetic removal of the A(2B)R or treatment with the A(2B)R antagonist GS-6201. Results demonstrated that GS-6201 treatment or genetic removal of the A(2B)R attenuated vascular remodeling and hypertension in our model. Furthermore, direct A(2B)R activation on vascular cells promoted interleukin-6 and endothelin-1 release. These studies identify a novel mechanism of disease progression to pulmonary hypertension and support the development of A(2B)R antagonists for the treatment of pulmonary hypertension secondary to interstitial lung disease.

Anestesia epidural para cesárea en anomalía de Ebstein / Epidural anesthesia for cesarean section in a patient with Ebstein's anomaly

La anomalía de Ebstein es un defecto congénito bastante raro, que consiste en la adherencia de las valvas septal y posterior de la tricúspide al miocardio, lo cual conlleva el desplazamiento apicaldel anillo tricuspídeo y la auricularización de parte del ventrículo derecho. Existen en la literatura pocos casos descritos de embarazo y anomalía de Ebstein. En el presente estudio se describe el manejo de una gestante con esta cardiopatía bajo anestesia epidural, siguiendo los principios básicos y actualizados del manejo anestésico con enfermedad cardiaca.

Ebstein’s anomaly is a rare congenital defect consisting of the adhesion of both the septal and posterior valves of the tricuspid valve to the myocardiumwhich produces an apical displacementof the tricuspid annulus and an atrialization of the right ventricle.There are few cases described in the literature of pregnancy and Ebstein’s anomaly. In this case report, the management of a pregnant patientwith this cardiac disease with epidural anesthesia is described following the current basic principles of the anesthetic management of pregnantwomen with cardiac disease.

Thymic and peripheral microenvironments differentially mediate development and maturation of iNKT cells by IL-15 transpresentation.

Invariant NKT (iNKT) cells are an innate type of T cells, which respond rapidly on activation. iNKT cells acquire these innate-like abilities during development; however, the signals driving development and functional maturation remain only partially understood. Because interleukin-15 (IL-15) is crucial for iNKT development and is delivered by transpresentation, we set out to identify the cell types providing IL-15 to developing iNKT cells and determine their role at the various states of development and maturation. We report here that transpresentation of IL-15 by parenchymal cells was crucial for generating normal number of iNKTs in the thymus, whereas both hematopoietic and parenchymal cells regulated iNKT cell numbers in the periphery, particularly in the liver. Specifically, dendritic cells contributed to peripheral iNKT cell numbers by up-regulating Bcl-2 expression and promoting extrathymic iNKT cell ex-pansion and their homeostatic proliferation. Whether IL-15 affects functional maturation of iNKT cells was also examined. In IL-15Rα(-/-) mice, CD44(High)NK1.1(+) iNKT cells displayed decreased T-bet expression and in response to α-galactosylceramide, had deficient interferon-γ expression. Such defects could be reversed by exogenous IL-15 signals. Overall, these studies identify stage-specific functions of IL-15, which are determined by the tissue microenvironment and elucidate the importance of IL-15 in functional maturation.

Trans-presentation of IL-15 by intestinal epithelial cells drives development of CD8alphaalpha IELs.

IL-15 is crucial for the development of intestinal intraepithelial lymphocytes (IEL) and delivery is mediated by a unique mechanism known as trans-presentation. Parenchymal cells have a major role in the trans-presentation of IL-15 to IELs, but the specific identity of this cell type is unknown. To investigate whether the intestinal epithelial cells (IEC) are the parenchymal cell type involved, a mouse model that expresses IL-15Ralpha exclusively by the IECs (Villin/IL-15Ralpha Tg) was generated. Exclusive expression of IL-15Ralpha by the IECs restored all the deficiencies in the CD8alphaalpha(+)TCRalphabeta(+)and CD8alphaalpha(+)TCRgammadelta(+) subsets that exist in the absence of IL-15Ralpha. Interestingly, most of the IEL recovery was due to the preferential increase in Thy1(low) IELs, which compose a majority of the IEL population. The differentiation of Thy1(high)CD4(-)CD8(-) thymocytes into Thy1(-)CD8alphaalpha IELs was found to require IL-15Ralpha expression specifically by IECs and thus, provides evidence that differentiation of Thy1(low) IELs is one function of trans-presentation of IL-15 in the intestines. In addition to effects in IEL differentiation, trans-presentation of IL-15 by IECs also resulted in an increase in IEL numbers that was accompanied by increases in Bcl-2, but not proliferation. Collectively, this study demonstrates that trans-presentation of IL-15 by IECs alone is completely sufficient to direct the IL-15-mediated development of CD8alphaalpha(+) T cell populations within the IEL compartment, which now includes a newly identified role of IL-15 in the differentiation of Thy1(low) IELs.

Regulation of inflammatory responses by IL-17F.

Although interleukin (IL) 17 has been extensively characterized, the function of IL-17F, which has an expression pattern regulated similarly to IL-17, is poorly understood. We show that like IL-17, IL-17F regulates proinflammatory gene expression in vitro, and this requires IL-17 receptor A, tumor necrosis factor receptor-associated factor 6, and Act1. In vivo, overexpression of IL-17F in lung epithelium led to infiltration of lymphocytes and macrophages and mucus hyperplasia, similar to observations made in IL-17 transgenic mice. To further understand the function of IL-17F, we generated and analyzed mice deficient in IL-17F or IL-17. IL-17, but not IL-17F, was required for the initiation of experimental autoimmune encephalomyelitis. Mice deficient in IL-17F, but not IL-17, had defective airway neutrophilia in response to allergen challenge. Moreover, in an asthma model, although IL-17 deficiency reduced T helper type 2 responses, IL-17F-deficient mice displayed enhanced type 2 cytokine production and eosinophil function. In addition, IL-17F deficiency resulted in reduced colitis caused by dextran sulfate sodium, whereas IL-17 knockout mice developed more severe disease. Our results thus demonstrate that IL-17F is an important regulator of inflammatory responses that seems to function differently than IL-17 in immune responses and diseases.

Bim/Bcl-2 balance is critical for maintaining naive and memory T cell homeostasis.

We examined the role of the antiapoptotic molecule Bcl-2 in combating the proapoptotic molecule Bim in control of naive and memory T cell homeostasis using Bcl-2(-/-) mice that were additionally deficient in one or both alleles of Bim. Naive T cells were significantly decreased in Bim(+/-)Bcl-2(-/-) mice, but were largely restored in Bim(-/-)Bcl-2(-/-) mice. Similarly, a synthetic Bcl-2 inhibitor killed wild-type, but not Bim(-/-), T cells. Further, T cells from Bim(+/-)Bcl-2(-/-) mice died rapidly ex vivo and were refractory to cytokine-driven survival in vitro. In vivo, naive CD8(+) T cells required Bcl-2 to combat Bim to maintain peripheral survival, whereas naive CD4(+) T cells did not. In contrast, Bim(+/-)Bcl-2(-/-) mice generated relatively normal numbers of memory T cells after lymphocytic choriomeningitis virus infection. Accumulation of memory T cells in Bim(+/-)Bcl-2(-/-) mice was likely caused by their increased proliferative renewal because of the lymphopenic environment of the mice. Collectively, these data demonstrate a critical role for a balance between Bim and Bcl-2 in controlling homeostasis of naive and memory T cells.