Concomitant Expression of CD39, CD69, and CD103 Identifies Antitumor CD8+ T cells in Breast Cancer Implications for Adoptive Cell Therapy.

BACKGROUND: In cancer, an effective immune response involves the action of several different cell types, among which CD8 T cells play a major role as they can specifically recognize and kill cancer cells via the release of cytotoxic molecules and cytokines, being of major importance for adoptive cell transfer (ACT) of ex vivo expanded tumor-infiltrating lymphocytes (TILs). The inflammation resulting from the tumor growth attracts both activated and bystander T cells. For an effective antitumor response, the T cell must express a specific group of chemokine receptors and integrins which include CD103, CD39, CD69, and CD25. These markers had already been analyzed in various cancers, not including breast cancer and their subsequent subtypes, until now. To analyze, the key receptors on ex vivo expanded tumor-infiltrating lymphocytes in luminal A and luminal B breast cancer (BC) subtypes. MATERIALS AND METHODS: We were successful in expanding TILs ex vivo using a standard TIL culture condition from a cohort study of 15 primary luminal A and luminal B breast cancer patients. Furthermore, we examined the expression of CD103, CD39, CD69, and CD25 biomarkers after the expansion by flow cytometry. RESULTS: We found that the information about the percentage of TILs obtainable after the ex vivo expansion is not associated to nor it is dependent on the heterogeneity of the TIL population before the expansion and does not differ by the molecular subtype (p>0.05). We also found that there is a major population of memory-resident antitumor CD8+CD103+CD39+ and CD8+CD103+CD69+ TILs present in the stroma after the expansion when compared to CD4 immunosubtypes (p<0.0001). Only the CD8+CD103+CD39+ subpopulation was related to BC subtype (0.0009). CONCLUSION: Evidence from our study suggests that CD8 TILs present in the stroma of luminal A and luminal B breast cancer patients can be quantified and phenotyped by flow cytometry and be further expanded ex vivo. The immuno-phenotyping of these markers may be targeted to improve the success of immunotherapeutic approaches, such as adoptive cellular therapy (ACT) in patients with BC.

Comparative Biomonitoring of Arsenic Exposure in Mothers and Their Neonates in Comarca Lagunera, Mexico.

Multiple comorbidities related to arsenic exposure through drinking water continue to be public problems worldwide, principally in chronically exposed populations, such as those in the Comarca Lagunera (CL), Mexico. In addition, this relationship could be exacerbated by an early life exposure through the placenta and later through breast milk. This study conducted a comparative analysis of arsenic levels in multiple biological samples from pregnant women and their neonates in the CL and the comparison region, Saltillo. Total arsenic levels in placenta, breast milk, blood, and urine were measured in pregnant women and their neonates from rural areas of seven municipalities of the CL using atomic absorption spectrophotometry with hydride generation methodology. The average concentrations of tAs in drinking water were 47.7 µg/L and 0.05 µg/L in the exposed and non-exposed areas, respectively. Mean levels of tAs were 7.80 µg/kg, 77.04 µg/g-Cr, and 4.30 µg/L in placenta, blood, urine, and breast milk, respectively, in mothers, and 107.92 µg/g-Cr in neonates in the exposed group, which were significantly higher than those in the non-exposed area. High levels of urinary arsenic in neonates were maintained 4 days after birth, demonstrating an early arsenic exposure route through the placenta and breast milk. In addition, our study suggested that breastfeeding may reduce arsenic exposure in infants in arsenic-contaminated areas. Further studies are necessary to follow up on comorbidities later in life in neonates and to provide interventions in this region.

Utility of transillumination and transparency renderings in 3D transthoracic imaging.

Transillumination (TI) is a new 3D rendering tool that uses a freely movable virtual light source to enhance depth, contours, and image detail. The TI model was recently modified to allow the operator adjust the degree of transparency of both cardiac and extra-cardiac structures. While the addition of transparency was shown to significantly improve quality in 3D transesophageal imaging, this has not yet been shown for transthoracic (TTE) imaging. We prospectively studied 35 patients who underwent clinically indicated TTE with standard 3D acquisition, as well as TI with and without transparency. Six experienced echocardiographers were shown images of all three display types in random order. Each image was scored independently using a Likert Scale while assessing each of the following aspects: ability to identify anatomy or pathology, depth perception, degree of anatomic detail, and border delineation. All experts perceived an incremental value of the transparency mode, compared to TI without transparency and standard 3D rendering, in terms of ability to identify anatomy or pathology (4.15 ± 0.97 vs. 3.88 ± 0.99 vs. 2.52 ± 1.41, p < 0.01), depth perception (4.33 ± 0.78 vs. 3.88 ± 0.82 vs. 2.29 ± 1.07, p < 0.01), degree of anatomic detail (4.08 ± 1.0 vs. 3.89 ± 0.79 vs. 2.31 ± 1.08, p < 0.01), and border delineation (4.44 ± 0.80 vs. 3.90 ± 0.78 vs. 2.42 ± 1.13, p < 0.01). Compared to standard 3D and TI renderings of TTE images, the addition of transparency significantly improves both image quality and diagnostic confidence.

Cranial bone regeneration with collagen type I and polyvinylpyrrolidone (Fibroquel®) combined with hyaluronic acid in Wistar rats: morphological study / Regeneración ósea craneal con colágeno tipo I y polivinilpirrolidona (Fibroquel®) combinado con ácido hialurónico en ratas Wistar: estudio morfológico

SUMMARY: The purpose of this study was to evaluate by morphological methods, if a mixture of Fibroquel® and hyaluronic acid implanted in an animal model of cranial bone injury could promote bone regeneration. 12 Wistar rats were divided in three groups, control group, bone injury without treatment and bone injury with treatment. After experimental period, bone samples were taken and stained with H & E, Masson trichrome, PAS-D, immunohistochemistry with anti-PCNA monoclonal antibody and applied a semiquantitative morphometric method. Treatment group showed extensive areas of collagen fibers in contact with normal bone tissue, areas of normal histology, PAS positive material and less cellular proliferation. We demonstrated for the first time that a mixture of Fibroquel® and hyaluronic acid implanted in an animal model of cranial bone injury promotes bone regeneration.

RESUMEN: El propósito de este estudio fue evaluar por métodos morfológicos, si una mezcla de Fibroquel® y ácido hialurónico implantado en un modelo animal de lesión del hueso craneal podría promover la regeneración ósea. Se dividieron 12 ratas Wistar en tres grupos, grupo control, lesión ósea sin tratamiento y lesión ósea con tratamiento. Después del período experimental, se tomaron muestras de hueso y se tiñeron con H & E, tricrómico de Masson, PAS-D, inmunohistoquímica con anticuerpo monoclonal anti-PCNA y se aplicó un método morfométrico semicuantitativo. El grupo de tratamiento mostró áreas extensas de fibras de colágeno en contacto con tejido óseo normal, áreas de histología normal, material PAS positivo y menor proliferación celular. Demostramos por primera vez que una mezcla de Fibroquel® y ácido hialurónico implantado en un modelo animal de lesión del hueso craneal promueve la regeneración ósea.

Transgenerational effects in DNA methylation, genotoxicity and reproductive phenotype by chronic arsenic exposure.

An emerging concern is the influences of early life exposure to environmental toxicants on offspring characteristics in later life. Since recent evidence suggests a transgenerational transference of aberrant phenotypes from exposed-parents to non-exposed offspring related to adult-onset diseases including reproductive phenotype. The transgenerational potential of arsenic a well know genotoxic and epigenetic modifier agent has not been assessed in mammals until now. In this experimental study, we evaluated the transgenerational effects of arsenic in a rat model with chronic exposure to arsenic. Rats chronically exposed to arsenic in drinking water (1 mg As2O3/mL) (F0) were mated to produce the arsenic lineage (F1, F2, and F3). The arsenic toxic effects on were evaluated over the four generations by analyzing the DNA methylation percentage, genotoxicity in WBC and physical and reproductive parameters, including sperm quality parameters and histopathological evaluation of the gonads. Chronic exposure to arsenic caused genotoxic damage (F0-F3) different methylation patterns, alterations in physical and reproductive parameters, aberrant morphology in the ovaries (F0 and F1) and testicles (F1-F3), and a decrease in the quality of sperm (F0-F3, except F2). Parental chronic arsenic exposure causes transgenerational genotoxicity and changes in global DNA methylation which might be associated with reproductive defects in rats. Combined with recent studies reveal that disturbances in the early life of an individual can affect the health of later generations.

Improved Delineation of Cardiac Pathology Using a Novel Three-Dimensional Echocardiographic Tissue Transparency Tool.

BACKGROUND: Accurate visualization of cardiac valves and lesions by three-dimensional (3D) echocardiography is integral for optimal guidance of structural procedures and appropriate selection of closure devices. A new 3D rendering tool known as transillumination (TI), which integrates a virtual light source into the data set, was recently reported to effectively enhance depth perception and orifice definition. We hypothesized that adding the ability to adjust transparency to this tool would result in improved visualization and delineation of anatomy and pathology and improved localization of regurgitant jets compared with TI without transparency and standard 3D rendering. METHODS: We prospectively studied 30 patients with a spectrum of structural heart disease who underwent 3D transesophageal imaging (EPIQ system, Philips) with standard acquisition and TI with and without the transparency feature. Six experienced cardiologists and sonographers were shown randomized images of all three display types in a blinded fashion. Each image was scored independently by all experts using a Likert scale from 1 to 5, while assessing each of the following aspects: (1) ability to recognize anatomy, (2) ability to identify pathology, including regurgitant jet origin, (3) depth perception, and (4) quality of border delineation. RESULTS: TI images with transparency were successfully obtained in all cases. All experts perceived an incremental value of the transparency mode, compared with TI without transparency and standard 3D rendering, in terms of ability to recognize anatomy (respective scores: 4.5 ± 1.1 vs 4.1 ± 1.1 vs 3.6 ± 1.1, P < .05), ability to identify pathology (4.1 ± 1.1 vs 3.9 ± 1.2 vs 3.3 ± 1, P < .05), depth perception (4.6 ± 0.7 vs 4.1 ± 0.8 vs 3.2 ± 1.0, P < .05), and border delineation (4.6 ± 0.8 vs 4.1 ± 1.0 vs 3.1 ± 1.1, P < .05). CONCLUSIONS: The addition of the transparency mode to TI rendering significantly improves the diagnostic and clinical utility of 3D echocardiography and has the potential to markedly enhance echocardiographic guidance of cardiac structural interventions.

Permanent pacemaker implantation in complete congenital fetal atrioventricular (AV) block: a case report / Implantación de marcapasos permanente en bloqueo atrioventricular (AV) fetal congénito completo: reporte de caso

Abstract: One of the most common pathologies attributed to lupus neonatal refers to atrioventricular (AV) congenital block, which diagnosis can be made between 16 and 30 weeks of gestation due to persistent fetal bradycardia. The development of this disease is mostly related to maternal anti-Ro/SSA and anti-Smith autoantibodies. Currently, there are a number of alternatives for prenatal and postnatal treatment, with some controversy about their viability. The placement of a permanent pacemaker is presented as one of the most appropriate procedures currently, even with the risks awarded. This case report describes the placement of a permanent pacemaker to a two-month-old newborn with high maternal contents of anti-Ro/SSA and anti-Smith nuclear autoantibodies, with a favorable outcome.(AU)

Resumen: Una de las patologías más comunes atribuidas al lupus neonatal se refiere al bloqueo congénito atrioventricular (AV), diagnóstico que se puede realizar entre 16 y 30 semanas de gestación debido a bradicardia fetal persistente. El desarrollo de esta enfermedad se relaciona principalmente con los anticuerpos anti-Ro/SSA materno y anti-Smith. Actualmente, existen varias alternativas para el tratamiento prenatal y postnatal, con cierta controversia sobre su viabilidad. La colocación de un marcapasos permanente se presenta como uno de los procedimientos más adecuados actualmente, incluso con los riesgos adjudicados. Este relato de caso describe la colocación de un marcapasos permanente en un recién nacido de dos meses con alto contenido materno de autoanticuerpos anti-Ro/SSA y anti-Smith, con un resultado favorable.(AU)

From Classroom to Capitol: Building Advocacy Capacity Through State-Level Advocacy Experiences.

This commentary provides insight from Community Health Education and Master of Public Health students on the benefits of participating in a state-level Advocacy Experience and provides a theoretical framework for increased advocacy intention among students as a result of participating in a state-level Advocacy Experience. Providing students the opportunity to translate what they learn about advocacy in the classroom into advocacy in action with policy makers is vital to the career development of our future health education professionals and is key to increasing advocacy capacity within our profession. This article builds on previous work from emerging public health professionals highlighting the role of policy advocacy in professional development and provides additional perspectives from the next generation of health education specialists.

A novel combined electrochemical-magnetic method for water treatment.

Electrocoagulation (EC) is a wastewater treatment process in which aqueous pollutants can be removed by adsorption, entrapment, precipitation or coalescence during a coagulation step produced by electrochemically generated metallic species. When using Fe as the sacrificial electrode, Fe(2+) and Fe(3+) ions are formed. As Fe(3+) species are paramagnetic, this property can in principle be used to facilitate their removal through the application of a magnetic field. In the present work we present a proof-of-concept for a combined electrochemical-magnetic method for pollutant removal. For this approach, the amounts of Fe(2+) and Fe(3+) produced in an EC cell at various voltages were measured by spectroscopic methods to confirm that Fe(3+) species predominate (up to 84%). The effectiveness of the presence of a magnetic field in the precipitation of coagulants from a suspension was confirmed by monitoring the turbidity change versus time with and without exposure to a magnetic field, up to a 30% improvement.

Structured interruptions of highly active antiretroviral therapy in cycles of 4 weeks off/12 weeks on therapy in children having a chronically undetectable viral load cause progressively smaller viral rebounds.

OBJECTIVES: To evaluate the viral, immune and clinical impact of a structured treatment interruption (STI) program of highly active antiretroviral therapy (HAART) in three cycles of 4 weeks off/12 weeks on therapy in a cohort of children with HIV infection under chronic viral control. METHODS: Using a single-group time series experimentation design and following informed consent, the HAART of children with HIV and a chronically undetectable viral load (VL) was discontinued for 4 weeks and then restarted and continued for 12 weeks for a total of three cycles. The VL, CD4+/CD8+ lymphocytes, and clinical status were evaluated at the end of each STI and at 6 and 12 weeks after HAART was resumed. RESULTS: Four children with a median age of 10.3 years (range 6.5-11.2 years) were included in the study. Their clinical immune categories were: A1 (n=2), A2 (n=1), and B3 (n=1). Treatment of all four patients was with zidovudine (AZT)+lamivudine (3TC)+ritonavir (RTV). At the end of the first STI, VL was a median 214000 copies/ml (range 27400-616000), corresponding to 5.3 log(10) (range 4.4-5.8). At the end of the second STI, VL was a median 72400 copies/ml (range 17800-126000) or 4.7 log(10) (range 4.2-5.1), which corresponds to a rebound 0.6 log(10) lower than the first. At the end of the third STI, VL was a median 28200 copies/ml (range 5370-140000) or 4.45 log(10) (range 3.7-5.1), a rebound 0.85 log(10) lower than the first. All rebounds were followed by a decrease in the VL to undetectable levels during the treatment periods. CD8+ T lymphocyte counts increased during viral rebounds and an initial decrease in CD4+ T lymphocyte counts was followed by a tendency to increase even exceeding CD8+ T cell counts. Only one event of transitory severe immunosuppression occurred. There were no symptoms related to the HIV infection. CONCLUSIONS: The STI of HAART in cycles of 4 weeks off/12 weeks on therapy in children with chronically undetectable VL can cause progressively lower viral rebounds followed by a decrease to undetectable levels, with a low risk of severe immunosuppression and without the occurrence of symptoms related to HIV.