An adenosine derivative prevents the alterations observed in metabolic syndrome in a rat model induced by a rich high-fat diet and sucrose supplementation.

Metabolic syndrome is a multifactorial disease with high prevalence worldwide. It is related to cardiovascular disease, diabetes, and obesity. Approximately 80% of patients with metabolic syndrome have some degree of fatty liver disease. An adenosine derivative (IFC-305) has been shown to exert protective effects in models of liver damage as well as on elements involved in central metabolism; therefore, here, we evaluated the effect of IFC-305 in an experimental model of metabolic syndrome in rats induced by a high-fat diet and 10% sucrose in drinking water for 18 weeks. We also determined changes in fatty acid uptake in the Huh-7 cell line. In the experimental model, increases in body mass, serum triglycerides and proinflammatory cytokines were induced in rats, and the adenosine derivative significantly prevented these changes. Interestingly, IFC-305 prevented alterations in glucose and insulin tolerance, enabling the regulation of glucose levels in the same way as in the control group. Histologically, the alterations, including mitochondrial morphological changes, observed in response to the high-fat diet were prevented by administration of the adenosine derivative. This compound exerted protective effects against metabolic syndrome, likely due to its action in metabolic regulation, such as in the regulation of glucose blood levels and hepatocyte fatty acid uptake.

Liver fibrotic development is reduced through inflammation prevention by an adenosine derivative compound.

BACKGROUND: Liver fibrosis is a global health problem, and studying its development provides important information to address its treatment. Here, we characterized the effects of an adenosine compound (IFC-305) on preventing fibrosis and liver inflammation. METHODS: We studied the impact of IFC-305 on a carbon tetrachloride-induced liver fibrosis model in Wistar male rats at 4, 6, and 8 weeks. The effects were characterized by liver tissue histology, macrophages identification by flow cytometry with CD163+/CD11b/c+ antibodies, hepatic and plasmatic cytokine levels employing MILLIPLEX MAP and ELISA, Col1a1 and Il6 gene expression by RTqPCR, lipoperoxidation by TBARS reaction, and reactive oxygen species using 2'-7'dichlorofluorescin diacetate. RESULTS: CCl4-induced liver fibrosis and inflammation were significantly reduced in rats treated with IFC-305 at 6 and 8 weeks. In addition, we observed diminished expression of Col1a1; a decrease in the inflammatory cytokines IL-1ß, IL-6, MCP-1, TNF-α, and IL-4 a; reduction in inflammatory macrophages; inhibition of lipoperoxidation; and ROS production in Kupffer cells. CONCLUSION: This study showed that IFC-305 can inhibit liver fibrosis establishment by regulating the immune response during CCl4-induced damage. The immunomodulatory action of IFC-305 supports its use as a potential therapeutic strategy for preventing liver fibrosis.

Rapid progression of myopia at onset during home confinement.

PURPOSE: To determine whether the myopic shift at myopia onset was faster than usual during home confinement associated with the COVID-19 pandemic. METHODS: Data on refractive error in consecutive children who presented for their first myopic spectacle prescription from September 2020 to May 2021 (new-onset myopia during the pandemic) were collected. Inclusion criteria were age 5-18 years and cycloplegic spherical equivalent in both eyes in the emmetropic range in the pre-pandemic years as recorded 1 year and 2 years before the actual visit. Annualized mean myopic shifts over the two previous periods were calculated. RESULTS: A total of 39 subjects (59% girls) were enrolled. Mean age at the visit after confinement was 10.79 ± 2.83 years. The mean refractive error for the right eyes in 2018 was +0.29 ± 0.56 D. The year after (2019), these children had a mean spherical equivalent of -0.12 ± 0.70 D. At the enrollment visit after myopia onset in the pandemic period, they had myopia of -1.33 ± 0.73 D. The mean annualized myopic shift for the right eyes was -0.37 ± 0.43 D before the pandemic and -1.12 ± 0.70 D during the pandemic period that included home confinement (P < 0·001 [Wilcoxon text]). CONCLUSIONS: Previous pre-pandemic prospective studies have reported myopic shift at onset of approximately -0.80 D. The period of strict pandemic home confinement saw higher rates of myopic shift.

Comparative subcellular localization of NRF2 and KEAP1 during the hepatocellular carcinoma development in vivo.

The activation of Nuclear Factor, Erythroid 2 Like 2 - Kelch Like ECH Associated Protein 1 (NRF2-KEAP1) signaling pathway plays a critical dual role by either protecting or promoting the carcinogenesis process. However, its activation or nuclear translocation during hepatocellular carcinoma (HCC) progression has not been addressed yet. This study characterizes the subcellular localization of both NRF2 and KEAP1 during diethylnitrosamine-induced hepatocarcinogenesis in the rat. NRF2-KEAP1 pathway was continuously activated along with the increased expression of its target genes, namely Nqo1, Hmox1, Gclc, and Ptgr1. Similarly, the nuclear translocation of NRF2, MAF, and KEAP1 increased in HCC cells from weeks 12 to 22 during HCC progression. Likewise, colocalization of NRF2 with KEAP1 was higher in the cell nuclei of HCC neoplastic nodules than in surrounding cells. Moreover, immunofluorescence analyses revealed that the interaction of KEAP1 with filamentous Actin was disrupted in HCC cells. This disruption may be contributing to the release and nuclear translocation of NRF2 since the cortical actin cytoskeleton serves as anchoring of KEAP1. In conclusion, this evidence indicates that NRF2 is progressively activated and promotes the progression of experimental HCC.

Social Ecology of Hypertension Management Among Latinos Living in the U.S.-Mexico Border Region.

INTRODUCTION: While a growing body of research examines individual factors affecting the prevalence and management of hypertension among Latinos, less is known about how socioecological factors operate to determine health and affect implementation of interventions in rural communities. METHOD: We conducted eight focus groups to assess perceived risks and protective factors associated with managing hypertension among Latino adults and their family members living in two rural/frontier counties in the U.S.-Mexico border region. This analysis is part of a larger study, Corazon por la Vida (Heart for Life), which involved multiple data collection strategies to evaluate the effectiveness of a primary care and a promotora de salud intervention to manage hypertension. RESULTS: Of the 49 focus group participants, 70% were female and 30% were male, 39% were Spanish-only speakers, and 84% had hypertension. Participants' ages ranged between 18 and 75 years, and 63% reported annual incomes below $30,000. Drawing from a social-ecological framework to analyze focus group data, four major themes and subthemes emerged as factors facilitating or inhibiting disease management: (1) individual (emotional burdens, coping mechanisms), (2) social relationships (family as a source of support, family as a source of stress), (3) health system (trust/mistrust, patient-provider communication), and (4) environment (lack of access to safe exercise environment, lack of affordable food). CONCLUSION: Our findings are relevant to public health practitioners, researchers, and policymakers seeking to shift from individual level or single interventions aimed at improving treatment-modality adherence to multilevel or multiple interventions for rural Latino communities.

Reanimación cardiopulmonar en prono a propósito de un caso / Case report cardiopulmonary resuscitation in prone position

Prone position is necessary for some neurosurgical and othopedic procedures. Cardiopulmonary resuscitation (CPR) in prone position was first described by McNeil in 1989, since then several successful cases have been published. We report the case of a 72-year-old patient with history of stage IV breast cancer who presented acute spinal cord compression due to a vertebral fracture at T10 level. Surgical spinal cord decompression and posterior arthrodesis was performed. After three hours of surgery, cardiorespiratory arrest occur while patient was in prone position. Unestable spine and fixed head made turning the patient into supine position very difficult, consequently prone CPR manoeuvres were started with recovery of spontaneous circulation. In case of cardiorespiratory arrest in prone position, the intense fixation and the extent of the surgical incision make the change to supine a time-consuming and technically complex procedure. If cardiorespiratory arrest occurs in the prone position, CPR in the prone position might be reasonable.

La posición de decúbito prono es necesaria para la realización de algunos procedimientos neuroquirúrgicos y traumatológicos. La reanimación cardiopulmonar (RCP) en prono fue descrita por primera vez por McNeil en 1989, desde entonces se han publicado varios casos de RCP en prono con buen resultado. Presentamos el caso de una paciente de 72 años con antecedentes de carcinoma de mama estadio IV que presenta síndrome de compresión medular por fractura patológica a nivel de T10. Se decide realizar descompresión medular y artrodesis por vía posterior. A las 3 horas de la cirugía se produjo parada cardiorrespiratoria en prono. Dada la inestabilidad espinal y la fijación de la paciente, el cambio a supino era complejo por lo que se iniciaron maniobras de RCP en prono con posterior recuperación de circulación espontánea. En caso de parda cardiorrespiratoria en prono, la intensa fijación y la extensión de la incisión quirúrgica hace que el cambio a supino consuma tiempo y sea técnicamente complejo. Si la PCR ocurre en prono, está justificado iniciar las maniobras de RCP en esta posición.

Wicca como fenómeno cultural entre los jóvenes cubanos / Wicca as a cultural phenomenon among young cubans

RESUMEN La Wicca, considerada una nueva corriente religiosa, se ha hecho presente entre grupos de adolescentes y jóvenes cubanos. Sin embargo, resulta desconocida para la mayoría de los profesionales sanitarios. Se realizó una revisión bibliográfica, con el objetivo de analizarla como fenómeno religioso-cultural a nivel mundial y en Cuba.

ABSTRACT Wicca, considered a new religious trend, has become present among groups of cuban adolescents and youth. However, it is unknown to most healthcare professionals. A bibliographic review was carried out, with the aim of analyzing it as a religious-cultural phenomenon worldwide and in Cuba.

Genome-wide 5-hydroxymethylcytosine (5hmC) emerges at early stage of in vitro differentiation of a putative hepatocyte progenitor.

A basic question linked to differential patterns of gene expression is how cells reach different fates despite using the same DNA template. Since 5-hydroxymethylcytosine (5hmC) emerged as an intermediate metabolite in active DNA demethylation, there have been increasing efforts to elucidate its function as a stable modification of the genome, including a role in establishing such tissue-specific patterns of expression. Recently we described TET1-mediated enrichment of 5hmC on the promoter region of the master regulator of hepatocyte identity, HNF4A, which precedes differentiation of liver adult progenitor cells in vitro. Here, we studied the genome-wide distribution of 5hmC at early in vitro differentiation of human hepatocyte-like cells. We found a global increase in 5hmC as well as a drop in 5-methylcytosine after one week of in vitro differentiation from bipotent progenitors, at a time when the liver transcript program is already established. 5hmC was overall higher at the bodies of overexpressed genes. Furthermore, by modifying the metabolic environment, an adenosine derivative prevents 5hmC enrichment and impairs the acquisition of hepatic identity markers. These results suggest that 5hmC could be a marker of cell identity, as well as a useful biomarker in conditions associated with cell de-differentiation such as liver malignancies.

Hydrodynamics-based liver transfection achieves gene silencing of CB1 using short hairpin RNA plasmid in cirrhotic rats.

BACKGROUND: There is a correlation between the endocannabinoid system and hepatic fibrosis based on the activation of CB1 and CB2 receptors; where CB1 has profibrogenic effects. Gene therapy with a plasmid carrying a shRNA for CB1 delivered by hydrodynamic injection has the advantage of hepatic tropism, avoiding possible undesirable effects of CB1 pharmacological inhibition. OBJECTIVE: To evaluate hydrodynamics-based liver transfection in an experimental model of liver cirrhosis of a plasmid with the sequence of a shRNA for CB1 and its antifibrogenic effects. METHODS: Three shRNA (21pb) were designed for blocking CB1 mRNA at positions 877, 1232 and 1501 (pshCB1-A, B, C). Sequences were cloned in the pENTR™/U6. Safety was evaluated monitoring CB1 expression in brain tissue. The silencing effect was determined in rat HSC primary culture and CCl4 cirrhosis model. Hydrodynamic injection in cirrhotic liver was through iliac vein and with a dose of 3mg/kg plasmid. Serum levels of liver enzymes, mRNA levels of TGF-ß1, Col IA1 and α-SMA and the percentage of fibrotic tissue were analyzed. RESULTS: Hydrodynamic injection allows efficient CB1 silencing in cirrhotic livers and pshCB1-B (position 1232) demonstrated the main CB1-silencing. Using this plasmid, mRNA level of fibrogenic molecules and fibrotic tissue considerably decrease in cirrhotic animals. Brain expression of CB1 remained unaltered. CONCLUSION: Hydrodynamics allows a hepatotropic and secure transfection in cirrhotic animals. The sequence of the shCB1-B carried in a plasmid or any other vector has the potential to be used as therapeutic strategy for liver fibrosis.

Diminished S-adenosylmethionine biosynthesis and its metabolism in a model of hepatocellular carcinoma is recuperated by an adenosine derivative.

S-adenosylmethionine (SAM), biosynthesis from methionine and ATP, is markedly decreased in hepatocellularular carcinoma (HCC) for a diminution in ATP levels, and the down regulation of the liver specific MAT1a enzyme. Its metabolic activity is very important in the transmethylation reactions, the methionine cycle, the biosynthesis of glutathione (GSH) and the polyamine pathway, which are markedly affected in the HCC. The chemo-preventive effect of IFC305 in HCC induced by DEN, and the increase of ATP and SAM in CCl4-induced cirrhosis have been previously demonstrated. The aim of this work was to test whether this chemo-preventive effect is mediated by the induction of SAM biosynthesis and its metabolic flow. SAM hepatic levels and the methionine cycle were recovered with IFC305 treatment, restoring transmethylation and transsulfuration activities. IFC305 treatment, increased MAT1a levels and decrease MAT2a levels through modulation of their post-transcriptional regulation. This occurred through the binding of the AUF1 (binding factor 1 AU-rich sites) and HuR (human antigen R) ribonucleoproteins to Mat1a and Mat2a messenger RNAs, which maintained their nuclear localization. Finally, the compound inhibited the polyamine pathway favoring the recuperation of the normal methionine and one carbon cycle recuperating the metabolic flow of methionine, which probably facilitated its HCC chemo-preventive effect.

Differential Expression of Striatal ΔFosB mRNA and FosB mRNA After Different Levodopa Treatment Regimens in a Rat Model of Parkinson's Disease.

Levodopa-induced dyskinesia (LID) is the main side effect associated with levodopa treatment and represents the biggest challenge for Parkinson's disease therapy. While the overexpression of ΔFosB transcription factor is related to the development of LID, few studies have been undertaken on fosB gene transcriptional regulation induced by levodopa in vivo. The aim of this study is to evaluate the expression of ΔFosB mRNA and FosB mRNA in the striatum after acute, chronic, and subchronic levodopa treatment in rats with unilateral 6-OHDA-lesion in the medial forebrain bundle. qRT-PCR was used to compare the levels of ΔFosB and FosB mRNA expression in the dopamine-denervated striatum following levodopa treatment. While the results obtained after a single levodopa dose indicate a significant increase of ∆FosB mRNA expression in the striatum 1 h post-injection, the levels returned to baseline values after 24 h. After subchronic levodopa treatment, the levels of ∆FosB and FosB mRNA expression were lower 1 h post-administration of levodopa in comparison with acute effect. However, after chronic levodopa treatment, ∆FosB mRNA expression in the striatum persisted in dyskinetic rats only, and positive correlation was found between the levels of ∆FosB mRNA expression 1 h after levodopa administration and the level of dyskinetic severity. In summary, acute levodopa treatment led to highly increased levels of ∆FosB mRNA expression in the striatum. While repeated administration induced a partial desensitization of the fosB gene in the striatum, it did not suppress its activity completely, which could explain why dyskinesia appears after chronic levodopa treatment.

Metabolic and genetic markers' associations with elevated levels of alanine aminotransferase in adolescents.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), the most common chronic liver disease in adolescents, is a feature of metabolic syndrome (MetS). Obesity and insulin resistance (IR) are risk factors for NAFLD, as well as inflammation-related genetic markers. The relationship between metabolic or inflammation-related genetic markers and alanine aminotransferase (ALT) is not fully understood. We examined the relationship of MetS, metabolic and inflammation-related genetic markers with elevated ALT in adolescents. METHODS: A total of 674 adolescents participated in a cross-sectional study in Guadalajara, Mexico. Elevated ALT (>40 IU/L), a surrogate marker of NAFLD, and MetS (International Diabetes Federation definition) were evaluated. Obesity, IR, lipids, C-reactive protein (CRP) and genetic markers (TNFA-308G>A, CRP+1444C>T, IL1RN and IL6-597/-572/-174 haplotype) were evaluated. Multivariate logistic regression was performed. RESULTS: Elevated ALT was observed in 3% and 14.1% (total and obese, respectively) of the adolescents. Obesity (odds ratio [OR], 5.86; 95% confidence interval [95% CI], 1.16-25.89), insulin (OR, 8.51; 95% CI, 2.61-27.71), IR (OR, 9.10; 95% CI, 2.82-29.38), total cholesterol (TC) (OR, 3.67; 95% CI, 1.25-10.72), low-density lipoprotein-cholesterol (LDL-C) (OR, 3.06; 95% CI, 1.06-8.33), non-high-density lipoprotein-cholesterol (HDL-C) (OR, 3.88; 95% CI, 1.27-11.90) and IL1RN (OR, 4.64; 95% CI, 1.10-19.53) were associated with elevated ALT. Among males, ≥2 MetS criteria were associated with elevated ALT (OR, 4.22; 95% CI, 1.14-15.71). CONCLUSIONS: Obesity, insulin, IR, high TC, high LDL-C, high non-HDL-C and IL1RN polymorphism were associated with elevated ALT. Among males, ≥2 MetS criteria were associated with elevated ALT. There is an urgent need to reduce obesity and IR in adolescents to prevent NAFLD.

Inflammation is regulated by the adenosine derivative molecule, IFC-305, during reversion of cirrhosis in a CCl4 rat model.

Cirrhosis is a liver pathology originated by hepatocytes, Kupffer and hepatic stellate cells interactions and transformations. This pathology is associated with inflammation and fibrosis, originated by molecular signals secreted by immunological and parenchymal cells, such as cytokines and chemokines, like IL-1ß, IL-6, TNF-α or MCP-1, driven by Kupffer cells signals. As part of inflammation resolution, the same activated Kupffer cells contribute to anti-inflammatory effects with IL-10 and MMP-9 secretion. In a Wistar rat model, cirrhosis induced with CCl4 is characterized by increased inflammatory cytokines, IL-6, IL-1ß, MCP-1, and TNF-α, in plasma and liver tissue. The IFC-305 compound, an adenosine derivative salt, reverses the cirrhosis in this model, suggesting that immune mechanisms related to inflammation should be explored. The IFC-305 reduced inflammatory cytokines, supporting the anti-inflammatory effects induced by the elevation of IL-10, as well as the reduction of M1 inflammatory macrophages (CD11b/c+/CD163+) and the increase of M2 anti-inflammatory macrophages (HIS36+/CD11b+), measured by flow cytometry. Furthermore, the IFC-305 enhances the metabolic activity of arginase and moderates the inducible nitric oxide synthetase, evaluated through biochemical and immunohistochemical methods. These results contribute to understand the function of the IFC-305, which modulates the immune response in the Wistar rat model of CCl4-induced cirrhosis and support the hepatic protective action through an anti-inflammatory effect, mainly mediated by Kupffer cells.

Methylation of FOXP3 TSDR Underlies the Impaired Suppressive Function of Tregs from Long-term Belatacept-Treated Kidney Transplant Patients.

Regulatory T cells (Tregs) are considered key players in the prevention of allograft rejection in transplanted patients. Belatacept (BLT) is an effective alternative to calcineurin inhibitors that appears to preserve graft survival and function; however, the impact of this drug in the homeostasis of Tregs in transplanted patients remains controversial. Here, we analyzed the phenotype, function, and the epigenetic status of the Treg-specific demethylated region (TSDR) in FOXP3 of circulating Tregs from long-term kidney transplant patients under BLT or Cyclosporine A treatment. We found a significant reduction in the proportion of CD4+CD25hiCD127lo/-FOXP3+ T cells in all patients compared to healthy individual (controls). Interestingly, only BLT-treated patients displayed an enrichment of the CD45RA+ "naïve" Tregs, while the expression of Helios, a marker used to identify stable FOXP3+ thymic Tregs remained unaffected. Functional analysis demonstrated that Tregs from transplanted patients displayed a significant reduction in their suppressive capacity compared to Tregs from controls, which is associated with decreased levels of FOXP3 and CD25. Analysis of the methylation status of the FOXP3 gene showed that BLT treatment results in methylation of CpG islands within the TSDR, which could be associated with the impaired Treg suppression function. Our data indicate that analysis of circulating Tregs cannot be used as a marker for assessing tolerance toward the allograft in long-term kidney transplant patients. Trial registration number IM103008.

Residuos de plaguicidas organofosforados y carbamatos en aguas subterráneas de bebida en las zonas rurales de Plottier y Senillosa, Patagonia Norte, Argentina / Organophosphate and carbamate pesticide residues in drinking groundwater in the rural areas of Plottier and Senillosa, North Patagonia, Argentina

Plottier y Senillosa son dos localidades contiguas que forman parte del área de producción agrícola del Alto Valle de Río Negro y Neuquén, Patagonia Norte. Entre los plaguicidas más utilizados predominan las familias de neonicotinoides, carbamatos y organofosforados. El conocimiento de los niveles de estos compuestos en aguas superficiales y subterráneas se ha convertido en un tema de interés social debido a su posible impacto en el ambiente y la salud. El objetivo del presente trabajo fue determinar niveles de residuos de plaguicidas en agua subterránea utilizada para bebida en zonas rurales de Plottier y Senillosa. Se analizaron carbamatos: propoxur, carbofuran, pirimicarb, carbaril y organofosforados: clorpirifos, dimetoato, metidation, fenaminfos, triazofos, fosmet y metil azinfos, por cromatografía gaseosa (GC), en seis sitios de muestreo, durante la época de aplicación y no aplicación de insecticidas. No se detectaron residuos de los plaguicidas estudiados por el método analítico utilizado. El límite de detección fue 0,010 µg/L para organofosforados y 0,030 µg/L para carbamatos. Estos resultados indican que las buenas prácticas agrícolas aplicadas en la zona así como las características fsicoquímicas del suelo, su espesor y el contenido de materia orgánica y las propiedades fsicoquímicas de los plaguicidas estudiados son factores que contribuyen favorablemente a la calidad del agua de bebida de la población rural.

Plottier and Senillosa are two adjoining towns that belong to the agricultural production area of Upper Valley, Río Negro and Neuquén, North Patagonia. Among the most widely used pesticides, neonicotinoids, carbamates and organophosphates are predominant. The levels of these compounds in surface and groundwater have become a topic of public concern, since the possible impact on health and environment. The aim of this study was the determination of pesticide residue levels in drinking ground-water in the rural areas of Plottier and Senillosa. Carbamates: propoxur, carbofuran, pirimicarb, carbaryl and organophosphate: chlorpyrifos, dimethoate, methidathion, fenaminfos, triazophos, phosmet, azinphos methyl, were analyzed by GC in six sampling sites during insecticide application and non-application season. No pesticide residues were detected by the analytical method used. The detection limit for organophosphates was 0.010 µg/L and 0.030 µg/L for carbamates. These results indicate that good agricultural practices, the physicochemical characteristics of the soil, its thickness, the content of organic matter and the physicochemical properties of pesticides studied are factors that positively contribute to the drinking water quality in the rural population.

The Influence of a Mexican Cultural Immersion Experience on Personal and Professional Healthcare Practices.

The purpose of this study was to understand the influence of a cultural immersion experience on personal and professional healthcare practices of occupational therapists. The experience, a 10-day course in Oaxaca, Mexico, exposed participants to alternative and complementary medicine through interactive sessions with Mexican indigenous traditional healers. The literature indicates that cultural immersion experiences can increase the perceived cultural effectiveness of healthcare professionals. Three focus groups were conducted with eight occupational therapists and two occupational therapy fieldwork students who had participated in the course. Themes were coded based on responses to each question by two graduate students and a qualitative researcher. Four major themes emerged regarding the influence of a cultural immersion experience on personal and professional healthcare practices of occupational therapists: (1) Natural Remedies; (2) Mind, Body, Spirit Connection; (3) Increased Openness; and (4) Challenges of Integrating Traditional and Western Medicine. The themes derived from this study confirmed the advantages of a cultural immersion experience on both the personal and professional views and practices of occupational therapists. Cultural immersion courses can assist occupational therapists to better understand different cultural views of health, disability and healing in order to provide quality occupational therapy care in a multicultural society. Copyright © 2016 John Wiley & Sons, Ltd.

B-esterase determination and organophosphate insecticide inhibitory effects in JEG-3 trophoblasts.

The placenta and trophoblasts express several B-esterases. This family includes acethylcholinesterase (AChE), carboxylesterase (CES) and butyrylcholinesterase (BChE), which are important targets of organophosphate insecticide (OP) toxicity. To better understand OP effects on trophoblasts, B-esterase basal activity and kinetic behavior were studied in JEG-3 choriocarcinoma cell cultures. Effects of the OP azinphos-methyl (Am) and chlorpyrifos (Cp) on cellular enzyme activity were also evaluated. JEG-3 cells showed measurable activity levels of AChE and CES, while BChE was undetected. Recorded Km for AChE and CES were 0.33 and 0.26 mM respectively. Native gel electrophoresis and RT-PCR analysis demonstrated CES1 and CES2 isoform expression. Cells exposed for 4 and 24 h to the OP Am or Cp, showed a differential CES and AChE inhibition profiles. Am inhibited CES and AChE at 4 h treatment while Cp showed the highest inhibition profile at 24 h. Interestingly, both insecticides differentially affected CES1 and CES2 activities. Results demonstrated that JEG-3 trophoblasts express AChE, CES1 and CES2. B-esterase enzymes were inhibited by in vitro OP exposure, indicating that JEG-3 cells metabolization capabilities include phase I enzymes, able to bioactivate OP. In addition, since CES enzymes are important for medicinal drug activation/deactivation, OP exposure may interfere with trophoblast CES metabolization, probably being relevant in a co-exposure scenario during pregnancy.

[Myelophthisis and kasabach merrit syndrome as initial manifestation of splenic angiosarcoma].

Primary splenic angiosarcoma is an extremely agressive and rare neoplasm. Manifestations as bone marrow invasion and coagulation disorders have been reported isolatedly. A 26 years-old woman presented with abdominal pain; several anemia and thrombocytopenia associated to leukoerythroblastic reaction were found in the laboratory. Consumpion coagulopathy signs and microangiopathy as schistocytes, prolonged prothrombine time, decreased fibrinogen and increased D dimer were also present. Imaging findings included a lobulated, enlarged spleen, with spontanously hyperdense areas, and heterogeneous nodules with intense, irregular enhancement after contrast administration. There were hepatic and pulmonary metastases, as well as bone lesions with conspicuous vessels. Clinical features of Kasabach-Merrit syndrome and imaging vascular neoplasm characteristics suggest a primary splenic angiosarcoma. Splenectomy and bone marrow biopsy confirmed the diagnosis of primary splenic angiosarcoma in metastatic stage.

New Mexico Community Health Councils: Documenting Contributions to Systems Changes.

CONTEXT: Coalition research has shifted from delineating structures and processes to identifying intermediate, systems changes (e.g., changes in policies) that contribute to longterm community health improvement. OBJECTIVE: The University of New Mexico, the New Mexico Department of Health, and community health councils entered a multiyear participatory evaluation process to answer: What actions did health councils take that led to improving health through intermediate, systems changes? DESIGN: The evaluation system was created over several phases through an iterative, participatory process. Data were collected for councils' health priority areas (e.g., substance abuse) from 2009 to 2011. PARTICIPANTS: Twenty-three community health councils participated. MAIN OUTCOME MEASURES: Intermediate systems changes were measured: 1) networking and partnering, 2) joint planning of strategies, programs, and services, 3) leveraging resources, and 4) policy initiatives. RESULTS: Health councils reported data for each intermediate outcome by health priority area. Data showed councils identified local public health priorities and addressed those priorities through strengthening networks and partnerships, which lead to the creation and enhancement of strategies, services, and programs. Data also showed councils influenced policies in several ways (e.g., developing policy, identifying new policy, or sponsoring informational forums). Additionally, data showed councils leveraged $1.10 for every dollar invested by the state. When funding was suspended in July 2010, data showed dramatic decreases in activity levels from 2010 to 2011. CONCLUSIONS: The data demonstrate the feasibility and utility of an Internet-based system designed to gather intermediate systems changes evaluation data. This process is a model for similar efforts to capture common outcomes across diverse coalitions and partnerships.