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1.
Psychol Trauma ; 12(3): 251-259, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31204813

RESUMO

OBJECTIVE: Although efforts to implement evidence-based psychotherapies (EBPs) require understanding how providers view and initiate these interventions, little is known regarding provider treatment selection in posttraumatic stress disorder (PTSD) care. The current study examines how specialty PTSD clinic providers within the Veterans Health Administration (VHA) describe reasons for selecting specific psychotherapies in PTSD treatment planning. METHOD: VHA psychotherapists in specialty PTSD care clinics completed a national online survey of treatment attitudes and practices, including an open-ended item inquiring about treatment selection. Thematic analysis was used to develop a framework describing factors in VHA providers' PTSD treatment selection. RESULTS: Of 250 survey participants, 219 provided description of their treatment selection process. Providers identified four domains of factors impacting treatment planning: (1) provider factors (e.g., training), (2) perceived characteristics of the intervention (e.g., structural features), (3) patient factors (e.g., characteristics of the patient and symptom presentation), and (4) organizational context (e.g., VHA policy). Assessment of appropriate treatments for an individual patient was described as resulting from interaction across these domains, particularly perceived fit between patient needs and specific treatments. CONCLUSIONS: Provider decision making has been understudied in implementation science. Although prior research has emphasized the role of organizational context in EBP reach, our findings suggest that other factors are salient when decisions are made at the level of the individual patient. Results suggest that increased attention to treatment selection and focused training in use of decision aids and shared decision making may have utility in increasing uptake, reach, and sustainment of EBPs among VHA PTSD specialty providers. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

2.
PLoS One ; 14(12): e0225181, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31805071

RESUMO

BACKGROUND: The spontaneous breathing trial (SBT) assesses the risk of weaning failure by evaluating some physiological responses to the massive venous return increase imposed by discontinuing positive pressure ventilation. This trial can be very demanding for some critically ill patients, inducing excessive physical and cardiovascular stress, including muscle fatigue, heart ischemia and eventually cardiac dysfunction. Extubation failure with emergency reintubation is a serious adverse consequence of a failed weaning process. Some data suggest that as many as 50% of patients that fail weaning do so because of cardiac dysfunction. Unfortunately, monitoring cardiovascular function at the time of the SBT is complex. The aim of our study was to explore if central venous pressure (CVP) changes were related to weaning failure after starting an SBT. We hypothesized that an early rise on CVP could signal a cardiac failure when handling a massive increase on venous return following a discontinuation of positive pressure ventilation. This CVP rise could identify a subset of patients at high risk for extubation failure. METHODS: Two-hundred and four mechanically ventilated patients in whom an SBT was decided were subjected to a monitoring protocol that included blinded assessment of CVP at baseline, and at 2 minutes after starting the trial (CVP-test). Weaning failure was defined as reintubation within 48-hours following extubation. Comparisons between two parametric or non-parametric variables were performed with student T test or Mann Whitney U test, respectively. A logistic multivariate regression was performed to determine the predictive value on extubation failure of usual clinical variables and CVP at 2-min after starting the SBT. RESULTS: One-hundred and sixty-five patients were extubated after the SBT, 11 of whom were reintubated within 48h. Absolute CVP values at 2-minutes, and the change from baseline (dCVP) were significantly higher in patients with extubation failure as compared to those successfully weaned. dCVP was an early predictor for reintubation (OR: 1.70 [1.31,2.19], p<0.001). CONCLUSIONS: An early rise in CVP after starting an SBT was associated with an increased risk of extubation failure. This might represent a warning signal not captured by usual SBT monitoring and could have relevant clinical implications.


Assuntos
Pressão Venosa Central/fisiologia , Estado Terminal , Desmame do Respirador/métodos , Adulto , Idoso , Extubação/métodos , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Medição de Risco
3.
Psychol Serv ; 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31599621

RESUMO

Funding is posited to affect evidence-based practice implementation, yet the complex interplay between financial matters and successful implementation is understudied. This study examined stakeholder perspectives on the impact of funding in evidence-based practice implementation. All participants were key stakeholders (e.g., clinicians, case managers, agency leaders; N = 41) involved in a trauma-focused cognitive-behavioral therapy implementation effort using a community-based learning collaborative model within the community's child welfare system. Semistructured interviews were conducted and qualitatively analyzed as part of a program evaluation of the implementation effort. Funding emerged as a key theme influencing implementation within this program evaluation from the perspective of all stakeholders. Thirty-four participants (83%) independently raised funding as an important factor affecting implementation outcomes across seven specific themes: (a) the impact of privatization, (b) turfism, (c) money as a primary implementation facilitator, (d) implementation costs impacting participation, (e) burden associated with funding evaluation efforts, (f) need for reimbursement practices to align with the use of trauma-informed treatment, and (g) a sense of shared mission to serve clients above money. Recommendations for addressing these challenges are provided. Future research should examine funding qualitatively and quantitatively across diverse communities and funding systems to improve understanding of the impact of funding on implementation and, ultimately, care provided to clients. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

4.
Microb Pathog ; 128: 276-280, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30654009

RESUMO

BACKGROUND AND AIMS: Costa Rica is one of the countries with the highest incidence and mortality rates for gastric cancer. Helicobacter pylori infection rates are high in the whole country. We have previously shown that H. pylori CagA+ is significantly associated with atrophic gastritis (AG) of the antrum in a dyspeptic population. The aim of this work is to determine if other H. pylori virulence factors (vacA, dupA, oipA, iceA and babA2) are associated with atrophic gastritis (AG) or duodenal ulcer (DU). METHODS: The presence of virulence genes in Costa Rican H. pylori isolates was analyzed by PCR in 151 cultured strains from patients with dyspeptic symptoms. Endoscopic and histopathological diagnoses were available. Odds-ratio and 95% confidence intervals for AG patients vs. non-atrophic gastritis (NAG) or DU patients vs. no duodenal ulcer (NDU) patients were calculated. RESULTS: Amongst the studied isolates, 82% had the cagA+, 76.2% had the vacA s1m1, 97.0% had the oipA+, 21.0% had the icea1, 79.0% had the iceA2, 44.0% had the babA2+ and 76.0% the dupA+ genotypes. Infection with H pylori cagA+, dupA+, oipA+, iceA, babA2+, and vacA s1m1 genotypes was not associated with AG risk. The frequency of the dupA gene was 78.7 and 60.9% in isolates from patients with NDU and DU, respectively, and its presence was significantly associated with decreased risk of duodenal ulcer [odds-ratio: 0.33, p = 0.024, confidence interval 95% (0.11-0.85)]. CONCLUSION: H. pylori dupA genotype is inversely associated with DU risk in this population.


Assuntos
Proteínas de Bactérias/genética , Genes Bacterianos/genética , Genótipo , Helicobacter pylori/genética , Helicobacter pylori/isolamento & purificação , Fatores de Virulência/genética , Adesinas Bacterianas/genética , Antígenos de Bactérias/genética , Proteínas da Membrana Bacteriana Externa/genética , Costa Rica/epidemiologia , Úlcera Duodenal/epidemiologia , Úlcera Duodenal/etiologia , Úlcera Duodenal/microbiologia , Úlcera Duodenal/patologia , Feminino , Gastrite Atrófica/epidemiologia , Gastrite Atrófica/etiologia , Gastrite Atrófica/microbiologia , Gastrite Atrófica/patologia , Frequência do Gene , Estudos de Associação Genética , Infecções por Helicobacter/complicações , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Epidemiologia Molecular , Virulência/genética
5.
J Clin Endocrinol Metab ; 102(12): 4557-4567, 2017 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-29053802

RESUMO

Context: Maternal obesity in pregnancy has profound impacts on maternal metabolism and promotes placental nutrient transport, which may contribute to fetal overgrowth in these pregnancies. The fatty acid docosahexaenoic acid (DHA) has bioactive properties that may improve outcomes in obese pregnant women by modulating placental function. Objective: To determine the effects of DHA supplementation in obese pregnant women on maternal metabolism and placental function. Design: Pregnant women were supplemented with DHA or placebo. Maternal fasting blood was collected at 26 and 36 weeks' gestation, and placentas were collected at term. Setting: Academic health care institution. Subjects: Thirty-eight pregnant women with pregravid body mass index ≥30 kg/m2. Intervention: DHA (800 mg, algal oil) or placebo (corn/soy oil) daily from 26 weeks to term. Main Outcomes: DHA content of maternal erythrocyte and placental membranes, maternal fasting blood glucose, cytokines, metabolic hormones, and circulating lipids were determined. Insulin, mTOR, and inflammatory signaling were assessed in placental homogenates, and nutrient transport capacity was determined in isolated syncytiotrophoblast plasma membranes. Results: DHA supplementation increased erythrocyte (P < 0.0001) and placental membrane DHA levels (P < 0.0001) but did not influence maternal inflammatory status, insulin sensitivity, or lipids. DHA supplementation decreased placental inflammation, amino acid transporter expression, and activity (P < 0.01) and increased placental protein expression of fatty acid transporting protein 4 (P < 0.05). Conclusions: Maternal DHA supplementation in pregnancy decreases placental inflammation and differentially modulates placental nutrient transport capacity and may mitigate adverse effects of maternal obesity on placental function.


Assuntos
Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/uso terapêutico , Obesidade/tratamento farmacológico , Placenta/efeitos dos fármacos , Adulto , Glicemia/metabolismo , Proteínas de Transporte/metabolismo , Citocinas/sangue , Ácidos Docosa-Hexaenoicos/metabolismo , Ácidos Graxos/sangue , Feminino , Desenvolvimento Fetal/efeitos dos fármacos , Hormônios/sangue , Humanos , Recém-Nascido , Lipídeos/sangue , Obesidade/complicações , Placenta/metabolismo , Gravidez , Complicações na Gravidez , Adulto Jovem
6.
World J Biol Chem ; 8(1): 95-101, 2017 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-28289522

RESUMO

AIM: To report the results of the International Nosocomial Infection Control Consortium (INICC) study conducted in Quito, Ecuador. METHODS: A device-associated healthcare-acquired infection (DA-HAI) prospective surveillance study conducted from October 2013 to January 2015 in 2 adult intensive care units (ICUs) from 2 hospitals using the United States Centers for Disease Control/National Healthcare Safety Network (CDC/NHSN) definitions and INICC methods. RESULTS: We followed 776 ICU patients for 4818 bed-days. The central line-associated bloodstream infection (CLABSI) rate was 6.5 per 1000 central line (CL)-days, the ventilator-associated pneumonia (VAP) rate was 44.3 per 1000 mechanical ventilator (MV)-days, and the catheter-associated urinary tract infection (CAUTI) rate was 5.7 per 1000 urinary catheter (UC)-days. CLABSI and CAUTI rates in our ICUs were similar to INICC rates [4.9 (CLABSI) and 5.3 (CAUTI)] and higher than NHSN rates [0.8 (CLABSI) and 1.3 (CAUTI)] - although device use ratios for CL and UC were higher than INICC and CDC/NSHN's ratios. By contrast, despite the VAP rate was higher than INICC (16.5) and NHSN's rates (1.1), MV DUR was lower in our ICUs. Resistance of A. baumannii to imipenem and meropenem was 75.0%, and of Pseudomonas aeruginosa to ciprofloxacin and piperacillin-tazobactam was higher than 72.7%, all them higher than CDC/NHSN rates. Excess length of stay was 7.4 d for patients with CLABSI, 4.8 for patients with VAP and 9.2 for patients CAUTI. Excess crude mortality in ICUs was 30.9% for CLABSI, 14.5% for VAP and 17.6% for CAUTI. CONCLUSION: DA-HAI rates in our ICUs from Ecuador are higher than United States CDC/NSHN rates and similar to INICC international rates.

7.
Implement Sci ; 12(1): 32, 2017 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-28264720

RESUMO

BACKGROUND: Large-scale implementation of evidence-based psychotherapies (EBPs) such as cognitive processing therapy (CPT) for posttraumatic stress disorder can have a tremendous impact on mental and physical health, healthcare utilization, and quality of life. While many mental health systems (MHS) have invested heavily in programs to implement EBPs, few eligible patients receive EBPs in routine care settings, and clinicians do not appear to deliver the full treatment protocol to many of their patients. Emerging evidence suggests that when CPT and other EBPs are delivered at low levels of fidelity, clinical outcomes are negatively impacted. Thus, identifying strategies to improve and sustain the delivery of CPT and other EBPs is critical. Existing literature has suggested two competing strategies to promote sustainability. One emphasizes fidelity to the treatment protocol through ongoing consultation and fidelity monitoring. The other focuses on improving the fit and effectiveness of these treatments through appropriate adaptations to the treatment or the clinical setting through a process of data-driven, continuous quality improvement. Neither has been evaluated in terms of impact on sustained implementation. METHODS: To compare these approaches on the key sustainability outcomes and provide initial guidance on sustainability strategies, we propose a cluster randomized trial with mental health clinics (n = 32) in three diverse MHSs that have implemented CPT. Cohorts of clinicians and clinical managers will participate in 1 year of a fidelity oriented learning collaborative or 1 year of a continuous quality improvement-oriented learning collaborative. Patient-level PTSD symptom change, CPT fidelity and adaptation, penetration, and clinics' capacity to deliver EBP will be examined. Survey and interview data will also be collected to investigate multilevel influences on the success of the two learning collaborative strategies. This research will be conducted by a team of investigators with expertise in CPT implementation, mixed method research strategies, quality improvement, and implementation science, with input from stakeholders in each participating MHS. DISCUSSION: It will have broad implications for supporting ongoing delivery of EBPs in mental health and healthcare systems and settings. The resulting products have the potential to significantly improve efforts to ensure ongoing high quality implementation and consumer access to EBPs. TRIAL REGISTRATION: NCT02449421 . Registered 02/09/2015.


Assuntos
Terapia Cognitivo-Comportamental/métodos , Implementação de Plano de Saúde/métodos , Transtornos de Estresse Pós-Traumáticos/terapia , Canadá , Humanos , Texas , Estados Unidos , United States Department of Veterans Affairs , Veteranos
8.
JMIR Mhealth Uhealth ; 4(2): e41, 2016 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-27095507

RESUMO

BACKGROUND: There is significant potential for mobile health technology to improve health outcomes for patients with chronic diseases. However, there is a need for further development of mobile health technology that would help to improve the health of lower-income communities. OBJECTIVE: The study objective was to assess mobile phone and app usage among a culturally diverse patient population, and to determine whether patients would be interested in using mobile health technology to help manage their chronic diseases. METHODS: An observational study was conducted with patients of the Internal Medicine resident primary care clinics of Los Angeles County and University of Southern California (LAC+USC) Medical Center. Self-reported information regarding demographics, current mobile phone usage, current mobile health app and social media usage, barriers to using mobile phones or mobile health apps, and interest in using a mobile health app was collected. RESULTS: Ninety-one percent of patients owned a mobile phone, with 76% (169/223) of these reporting having a mobile phone with Internet capability. Fifty-seven percent of subjects used mobile apps on their mobile phones, and 32% (41/130) of these used mobile apps related to their health. Eighty-six percent (207/241) of respondents voiced interest in using a mobile app to improve their health, and 40% (88/221) stated they would use such an app daily. Patients stated they would find the mobile health app most useful for nutrition, exercise, and obtaining general information on medical conditions. CONCLUSIONS: Despite the fact that the majority of our primary care patients were of lower socioeconomic status, they utilized mobile phones with Internet and mobile app capabilities to a great extent. There was substantial interest among our patients in using mobile health technology to both manage chronic disease and improve overall health. Given that cultural, educational, and socioeconomic disparities strongly correlate with higher rates of chronic diseases such as obesity, diabetes and hypertension, access to culturally relevant mobile health tools may empower patients in these populations to improve health outcomes.

9.
Placenta ; 40: 60-6, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27016784

RESUMO

BACKGROUND: Obese and overweight women are more likely to deliver a large infant or an infant with increased adiposity, however the underlying mechanisms are not well established. We tested the hypothesis that placental capacity to transport fatty acid is increased in overweight/obese women. METHODS: Pregnant women with body mass index (BMI) ranging from 18.4 to 54.3 kg/m(2) and with uncomplicated term pregnancies were recruited for collection of blood samples and placental tissue. Maternal and fetal levels of non-esterified fatty acids (NEFAs) were measured in plasma. The expression and localization of CD36/fatty acid translocase (FAT), fatty acid transport protein (FATP)2, and FATP4 was determined in fixed placental tissue and in isolated syncytiotrophoblast plasma membranes from normal and high BMI mothers. RESULTS: Maternal and fetal plasma NEFA levels did not correlate (n = 42). FATP2 and FATP4 expressions were higher in the basal plasma membrane (BPM) compared to the microvillous membrane (P < 0.001; n = 7) per unit membrane protein. BPM expression of FATP2 correlated with maternal BMI (P < 0.01; n = 30); there was no association between CD36/FAT or FATP4 expression and maternal BMI. CONCLUSION: The polarization of FATPs to the BPM will facilitate fatty acid transfer across the placenta. In overweight/obese pregnancies, the increased FATP2 expression could contribute to increased fatty acid delivery to the fetus and while we have no direct data we speculate that this could lead accelerated fetal growth or increased fat deposition.


Assuntos
Antígenos CD36/metabolismo , Coenzima A Ligases/metabolismo , Proteínas de Transporte de Ácido Graxo/metabolismo , Obesidade/metabolismo , Complicações na Gravidez/metabolismo , Adulto , Índice de Massa Corporal , Ácidos Graxos/sangue , Feminino , Humanos , Gravidez
10.
Reprod Biol Endocrinol ; 13: 57, 2015 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-26050671

RESUMO

BACKGROUND: System L transporters LAT1 (SLC7A5) and LAT2 (SLC7A8) mediate the uptake of large, neutral amino acids in the human placenta. Many System L substrates are essential amino acids, thus representing crucial nutrients for the growing fetus. Both LAT isoforms are expressed in the human placenta, but the relative contribution of LAT1 and LAT2 to placental System L transport and their subcellular localisation are not well established. Moreover, the influence of maternal body mass index (BMI) on placental System L amino acid transport is poorly understood. Therefore the aims of this study were to determine: i) the relative contribution of the LAT isoforms to System L transport activity in primary human trophoblast (PHT) cells isolated from term placenta; ii) the subcellular localisation of LAT transporters in human placenta; and iii) placental expression and activity of System L transporters in response to maternal overweight/obesity. METHODS: System L mediated leucine uptake was measured in PHT cells after treatment with si-RNA targeting LAT1 and/or LAT2. The localisation of LAT isoforms was studied in isolated microvillous plasma membranes (MVM) and basal membranes (BM) by Western blot analysis. Results were confirmed by immunohistochemistry in sections of human term placenta. Expression and activity System L transporters was measured in isolated MVM from women with varying pre-pregnancy BMI. RESULTS: Both LAT1 and LAT2 isoforms contribute to System L transport activity in primary trophoblast cells from human term placenta. LAT1 and LAT2 transporters are highly expressed in the MVM of the syncytiotrophoblast layer at term. LAT2 is also localised in the basal membrane and in endothelial cells lining the fetal capillaries. Measurements in isolated MVM vesicles indicate that System L transporter expression and activity is not influenced by maternal BMI. CONCLUSIONS: LAT1 and LAT2 are present and functional in the syncytiotrophoblast MVM, whereas LAT2 is also expressed in the BM and in the fetal capillary endothelium. In contrast to placental System A and beta amino acid transporters, MVM System L activity is unaffected by maternal overweight/obesity.


Assuntos
Sistema L de Transporte de Aminoácidos/metabolismo , Sobrepeso/metabolismo , Placenta/metabolismo , Trofoblastos/metabolismo , Adulto , Sistema L de Transporte de Aminoácidos/genética , Feminino , Humanos , Obesidade/genética , Obesidade/metabolismo , Sobrepeso/genética , Gravidez , Nascimento a Termo/metabolismo
11.
Am J Obstet Gynecol ; 212(2): 227.e1-7, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25132463

RESUMO

OBJECTIVE: Obese women are at increased risk to deliver a large infant, however, the underlying mechanisms are poorly understood. Fetal glucose availability is critically dependent on placental transfer and is linked to fetal growth by regulating the release of fetal growth hormones such as insulin. We hypothesized that (1) umbilical vein glucose and insulin levels and (2) placental glucose transporter (GLUT) expression and activity are positively correlated with early pregnancy maternal body mass index and infant birthweight. STUDY DESIGN: Subjects in this prospective observational cohort study were nondiabetic predominantly Hispanic women delivered at term. Fasting maternal and umbilical vein glucose and insulin concentrations were determined in 29 women with varying early pregnancy body mass index (range, 18.0-54.3) who delivered infants with birthweights ranging from 2800-4402 g. We isolated syncytiotrophoblast microvillous and basal plasma membranes from 33 placentas and determined the expression of GLUT-1 and -9 (Western blot) and glucose uptake (radiolabeled glucose). RESULTS: Birthweight was positively correlated with umbilical vein glucose and insulin and maternal body mass index. Umbilical vein glucose levels were positively correlated with placental weight and maternal body mass index, but not with maternal fasting glucose. Basal plasma membranes GLUT-1 expression was positively correlated with birthweight. In contrast, syncytiotrophoblast microvillous GLUT-1 and -9, basal plasma membranes GLUT-9 expression and syncytiotrophoblast microvillous and basal plasma membranes glucose transport activity were not correlated with birthweight. CONCLUSION: Because maternal fasting glucose levels and placental glucose transport capacity were not increased in obese women delivering larger infants, we speculate that increased placental size promotes glucose delivery to these fetuses.


Assuntos
Peso ao Nascer/fisiologia , Glicemia/metabolismo , Proteínas Facilitadoras de Transporte de Glucose/metabolismo , Transportador de Glucose Tipo 1/metabolismo , Insulina/sangue , Obesidade/sangue , Placenta/metabolismo , Complicações na Gravidez/sangue , Adulto , Índice de Massa Corporal , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Macrossomia Fetal/sangue , Macrossomia Fetal/metabolismo , Humanos , Recém-Nascido , Masculino , Troca Materno-Fetal/fisiologia , Obesidade/metabolismo , Tamanho do Órgão , Placentação , Gravidez , Complicações na Gravidez/metabolismo , Estudos Prospectivos , Trofoblastos/metabolismo , Veias Umbilicais
12.
BMJ Open Diabetes Res Care ; 2(1): e000010, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25452858

RESUMO

OBJECTIVE: Gestational diabetes mellitus (GDM) is more common in pregnancies complicated by obesity and both diseases increase the risk for fetal overgrowth and long-term adverse health consequences for the mother and child. Previous studies have linked low maternal serum adiponectin to GDM in normal and overweight women. We hypothesized that lower adiponectin, in particular the high-molecular-weight form, and insulin-like growth factor I (IGF-I) and its binding protein (IGFBP-1) are associated with GDM in pregnant obese Hispanic women. METHODS: 72 obese, predominantly Hispanic (92%), women were recruited at 24-28 weeks of gestation. Adiposity was assessed, fasting serum samples were collected, and glucose, insulin, triglyceride, cholesterol levels, adipokines, and hormones associated with obesity and insulin resistance were measured. 30 women had been recently diagnosed with GDM. RESULTS: Gestational weeks, body mass index, triceps skinfold thickness, mid-arm circumference, serum leptin, IGF-I, tumor necrosis factor α, and interleukin-6 did not differ in the two groups. Obese women with GDM had significantly higher fasting glucose, A1C, triglycerides, very-low-density lipoprotein cholesterol and lower high-density lipoprotein cholesterol, adiponectin, and IGFBP-1 compared to obese women without GDM. Homeostasis model assessment of insulin resistance was positively correlated to IGF-I and negatively correlated to adiponectin. CONCLUSIONS: Obese pregnant women with recently diagnosed GDM had a significantly exacerbated metabolic profile, low serum adiponectin and IGFBP-1 levels at 24-28 weeks of gestation, as compared to women with obesity alone. Because low adiponectin is well established to cause insulin resistance and decreased IGFBP-1 indicates increased IGF-I bioavailability, we propose that these changes are mechanistically linked to the development of GDM in obese Hispanic women.

13.
Gut Microbes ; 5(4): 517-21, 2014 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-25137097

RESUMO

Helicobacter pylori infects a significant proportion of the world population and it is associated with pathologies which include chronic atrophic gastritis, peptic ulcer, and gastric neoplasias such as gastric adenocarcinoma and MALT lymphoma. Costa Rica has a high prevalence of the infection and an elevated incidence of gastric cancer and its associated mortality. The global population structure for H. pylori has been established using a MLST scheme. The population structure of the strains of H. pylori circulating in Costa Rica is currently unknown. We characterized the geographical origin of 24 H. pylori isolates from Costa Rican patients. We identified 142 new alleles for the genes included in the scheme and in eight of the 24 isolates from Costa Rican patients, all seven alleles sequenced were described for the first time. Twenty-one isolates from Costa Rican patients group with hpEurope strains and the remaining three isolates grouped with hspWAfrica isolates (Bayesian posterior probability values above 0.70, P = 0.05, after 2 000 000 generations). The obtained result in the MLST analysis was not unexpected and reflects the genetic composition of the Costa Rican population.


Assuntos
Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/classificação , Helicobacter pylori/genética , Análise por Conglomerados , Costa Rica/epidemiologia , DNA Bacteriano/química , DNA Bacteriano/genética , Genótipo , Helicobacter pylori/isolamento & purificação , Humanos , Epidemiologia Molecular , Tipagem de Sequências Multilocus
14.
Biol Reprod ; 90(6): 129, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24759787

RESUMO

Obese pregnant women have increased levels of proinflammatory cytokines in maternal circulation and placental tissues. However, the pathways contributing to placental inflammation in obesity are largely unknown. We tested the hypothesis that maternal body mass index (BMI) was associated with elevated proinflammatory cytokines in maternal and fetal circulations and increased activation of placental inflammatory pathways. A total of 60 women of varying pre-/early pregnancy BMI, undergoing delivery by Cesarean section at term, were studied. Maternal and fetal (cord) plasma were collected for analysis of insulin, leptin, IL-1beta, IL-6, IL-8, monocyte chemoattractant protein (MCP) 1, and TNFalpha by multiplex ELISA. Activation of the inflammatory pathways in the placenta was investigated by measuring the phosphorylated and total protein expression of p38-mitogen-activated protein kinase (MAPK), c-Jun-N-terminal kinase (JNK)-MAPK, signal transducer-activated transcription factor (STAT) 3, caspase-1, IL-1beta, IkappaB-alpha protein, and p65 DNA-binding activity. To determine the link between activated placental inflammatory pathways and elevated maternal cytokines, cultured primary human trophoblast (PHT) cells were treated with physiological concentrations of insulin, MCP-1, and TNFalpha, and inflammatory signaling analyzed by Western blot. Maternal BMI was positively correlated with maternal insulin, leptin, MCP-1, and TNFalpha, whereas only fetal leptin was increased with BMI. Placental phosphorylation of p38-MAPK and STAT3, and the expression of IL-1beta protein, were increased with maternal BMI; phosphorylation of p38-MAPK was also correlated with birth weight. In contrast, placental NFkappaB, JNK and caspase-1 signaling, and fetal cytokine levels were unaffected by maternal BMI. In PHT cells, p38-MAPK was activated by MCP-1 and TNFalpha, whereas STAT3 phosphorylation was increased following TNFalpha treatment. Maternal BMI is associated with elevated maternal cytokines and activation of placental p38-MAPK and STAT3 inflammatory pathways, without changes in fetal systemic inflammatory profile. Activation of p38-MAPK by MCP-1 and TNFalpha, and STAT3 by TNFalpha, suggests a link between elevated proinflammatory cytokines in maternal plasma and activation of placental inflammatory pathways. We suggest that inflammatory processes associated with elevated maternal BMI may influence fetal growth by altering placental function.


Assuntos
Índice de Massa Corporal , Imunidade Inata/imunologia , Inflamação/imunologia , Obesidade/imunologia , Placenta/imunologia , Efeitos Tardios da Exposição Pré-Natal/imunologia , Adolescente , Adulto , Caspase 10/metabolismo , Células Cultivadas , Citocinas/imunologia , Citocinas/metabolismo , Feminino , Humanos , Recém-Nascido , Inflamação/complicações , Inflamação/patologia , Interleucina-1beta/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Sistema de Sinalização das MAP Quinases/imunologia , Masculino , NF-kappa B/metabolismo , Obesidade/complicações , Obesidade/patologia , Placenta/citologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/etiologia , Efeitos Tardios da Exposição Pré-Natal/patologia , Fator de Transcrição STAT3/metabolismo , Trofoblastos/citologia , Trofoblastos/imunologia , Adulto Jovem , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
15.
Arch Med Res ; 44(6): 467-74, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24051039

RESUMO

BACKGROUND AND AIMS: Costa Rica has among the highest incidence and mortality rates for gastric cancer worldwide. The reasons for this are largely unknown. Polymorphisms of inflammatory response genes including genes encoding heat shock proteins (HSP) have been shown to be associated with the risk of gastric cancer in some populations. This study addresses the possible association between the HSP70-2 +1267 and HSP70-Hom +2437 polymorphisms and the risk of developing gastric cancer in a high-risk population in Costa Rica. METHODS: DNA from 39 individuals diagnosed with gastric cancer, 79 healthy controls, 55 individuals with chronic gastritis and 52 individuals with duodenal ulcer was genotyped for the polymorphisms HSP70-2 +1267 and HSP70-Hom +2437 by RFLP. Logistic regression analysis was used to determine possible associations with the diagnoses and lineal regression analysis to determine associations with blood pepsinogen (PGs) levels as measured by serology. RESULTS: The GA genotype of HSP70-2 was associated with increased risk of gastric cancer (OR = 3.42; 95% CI = 1.27-9.21; p = 0.015) and duodenal ulcer (OR = 2.57; 95% CI = 1.03-6.36; p = 0.042) as compared to the GG genotype. Persons with C carrier genotypes of HSP70-Hom were significantly less susceptible to gastric cancer than those with the TT genotype (OR = 0.29; 95% CI = 0.09-0.87; p = 0.027). The C carrier genotype was associated with lower PGI concentrations but none of the polymorphisms were associated with PGI/PGII. CONCLUSIONS: Polymorphisms of HSP70 genes are associated with the development of gastric cancer and duodenal ulcers in a population at high risk for gastric cancer in Costa Rica.


Assuntos
Úlcera Duodenal/epidemiologia , Úlcera Duodenal/genética , Proteínas de Choque Térmico HSP70/genética , Polimorfismo de Nucleotídeo Único , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/genética , Idoso , Estudos de Casos e Controles , Costa Rica/epidemiologia , Úlcera Duodenal/metabolismo , Feminino , Mucosa Gástrica/metabolismo , Gastrite Atrófica/epidemiologia , Gastrite Atrófica/genética , Predisposição Genética para Doença , Genótipo , Infecções por Helicobacter/epidemiologia , Helicobacter pylori , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Pepsinogênio A/sangue , Pepsinogênio C/sangue , Análise de Regressão , Neoplasias Gástricas/metabolismo
16.
J Lipid Res ; 54(3): 725-33, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23275648

RESUMO

Obese women have an increased risk to deliver large babies. However, the mechanisms underlying fetal overgrowth in these pregnancies are not well understood. Obese pregnant women typically have elevated circulating lipid levels. We tested the hypothesis that fatty acids stimulate placental amino acid transport, mediated via toll-like receptor 4 (TLR4) and mammalian target of rapamycin (mTOR) signaling pathways. Circulating NEFA levels and placental TLR4 expression were assessed in women with varying prepregnancy body mass index (BMI). The effects of oleic acid on system A and system L amino acid transport, and on the activation of the mTOR (4EBP1, S6K1, rpS6), TLR4 (IĸB, JNK, p38 MAPK), and STAT3 signaling pathways were determined in cultured primary human trophoblast cells. Maternal circulating NEFAs (n = 33), but not placental TLR4 mRNA expression (n = 16), correlated positively with BMI (P < 0.05). Oleic acid increased trophoblast JNK and STAT3 phosphorylation (P < 0.05), whereas mTOR activity was unaffected. Furthermore, oleic acid doubled trophoblast system A activity (P < 0.05), without affecting system L activity. siRNA-mediated silencing of TLR4 expression prevented the stimulatory effect of oleic acid on system A activity. Our data suggest that maternal fatty acids can increase placental nutrient transport via TLR4, thereby potentially affecting fetal growth.


Assuntos
Ácido Oleico/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Trofoblastos/efeitos dos fármacos , Trofoblastos/metabolismo , Adulto , Aminoácidos/metabolismo , Transporte Biológico/efeitos dos fármacos , Transporte Biológico/genética , Índice de Massa Corporal , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Ácidos Graxos não Esterificados , Feminino , Humanos , Técnicas In Vitro , Gravidez , RNA Interferente Pequeno , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Serina-Treonina Quinases TOR/genética , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo
17.
Neurocirugia (Astur) ; 23(4): 170-4, 2012 Jul.
Artigo em Espanhol | MEDLINE | ID: mdl-22728121

RESUMO

OBJECTIVE: We present a case report of symptomatic compression of the right sciatic nerve notch, secondary to piriformis muscle endometriosis, as well as a literature review. MATERIAL AND METHODS: We report the case of a 29-year-old woman with 2-year evolution of right chronic sciatica. During the first year, symptoms were episodic and associated with menstruation. During the second year, sciatica was constant and associated with gait disorder due to sciatic musculature weakness. Mononeuropathy was proved by a neurophysiological study, with MRI and PET studies revealing a mass in the sciatic notch and regional pathological increase in metabolic activity. Surgical treatment was performed in order to release the nerve and obtain a histological sample. RESULTS: The patient was treated by a transgluteal approach, with external neurolysis of the sciatic nerve and resection of an old-blood cyst at the level of the piriformis muscle. This was subsequently reported as endometriosis by histological examination. The sciatica was resolved after surgery. CONCLUSIONS: Extrapelvic sciatic nerve compression by adjacent endometriosis is very infrequent. Muscle denervation and lack of a histological diagnosis led to surgical exploration of the compression area in order to release the nerve, resect the cause of compression and obtain a definitive diagnosis. The procedure improved all symptoms.


Assuntos
Endometriose , Ciática , Feminino , Humanos , Imagem por Ressonância Magnética , Síndromes de Compressão Nervosa , Nervo Isquiático
18.
J Neuroimmune Pharmacol ; 6(4): 617-25, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21547539

RESUMO

Endogenous neuropeptide orphanin FQ/nociceptin (OFQ/N) and its receptor, nociceptin orphanin FQ peptide receptor (NOPr), play a modulatory role throughout the body including nociceptive sensitivity, motor function, spatial learning, and the immune system. NOPr is an inhibitory G protein coupled receptor (GPCR) that modulates expression and release of inflammatory mediators from immune cells and in the CNS. Inhibitory GPCRs have been shown to activate the immune and central nervous system regulator, nuclear factor kappa B (NFκB), whose family consists of several subunits. When activated, NFκB translocates to the nucleus and can modify transcription. To determine if OFQ/N modulates NFκB activity, SH-SY5Y human neuroblastoma cells were treated with OFQ/N and assessed for changes in nuclear accumulation, DNA binding, and transcriptional activation. For the first time, we show that OFQ/N increases the nuclear accumulation (1.9-2.8-fold) and the DNA binding of NFκB (2.9-fold) by 2 h as determined by immunoblotting and electromobility shift assay, respectively. OFQ/N induction of NFκB binding to DNA is protein kinase C-dependent and NOPr-specific. OFQ/N stimulated binding of both NFκB p50 and p65 subunits to their consensus binding site on DNA. OFQ/N also induces transcriptional activation of an NFκB reporter gene 2.2-fold by 2 h with an EC(50) of 6.3 nM. This activation of NFκB by OFQ/N suggests a likely mechanism for its modulation of the central nervous and immune systems.


Assuntos
Ativação Enzimática/fisiologia , NF-kappa B/metabolismo , Neuroimunomodulação/fisiologia , Peptídeos Opioides/metabolismo , Western Blotting , Linhagem Celular , Núcleo Celular/metabolismo , Ensaio de Desvio de Mobilidade Eletroforética , Humanos , Transfecção
19.
J Virol ; 85(13): 6502-12, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21507981

RESUMO

Transforming growth factor beta 1 (TGF-ß1) signal transduction has been implicated in many second-messenger pathways, including the NF-κB pathway. We provide evidence of a novel TGF-ß1-mediated pathway that leads to extracellular signal-regulated kinase (ERK) 1/2 phosphorylation, which in turn induces expression of an Epstein-Barr virus (EBV) protein, ZEBRA, that is responsible for the induction of the viral lytic cycle. This pathway includes two unexpected steps, both of which are required to control ERK 1/2 phosphorylation: first, a quick and transient activation of NF-κB, and second, downregulation of inducible nitric oxide synthase (iNOS) activity that requires the participation of NF-κB activity. Although necessary, NF-κB alone is not sufficient to produce downregulation of iNOS, suggesting that another uncharacterized event(s) is involved in this pathway. Dissection of the steps involved in the switch from the EBV latent cycle to the lytic cycle will be important to understand how virus-host relationships modulate the innate immune system.


Assuntos
Regulação para Baixo , Herpesvirus Humano 4/fisiologia , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Ativação Viral , Linfócitos B/virologia , Linhagem Celular , Linhagem Celular Transformada , Regulação da Expressão Gênica , Regulação Viral da Expressão Gênica , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/metabolismo , Humanos , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , NF-kappa B/genética , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/genética , Transativadores/genética , Transativadores/metabolismo
20.
Diabetes Educ ; 36(4): 586-94, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20538970

RESUMO

PURPOSE: The purpose of this study was to conduct a diabetes education program delivered by community health workers (CHWs) in community settings and to evaluate its effectiveness in improving glycemic control and self-management skills in Hispanics/Latinos with type 2 diabetes. METHODS: Trained CHWs recruited Hispanic/Latino community residents with self-reported type 2 diabetes, implemented intervention in nonclinical locations, and collected data on diabetes knowledge, self-care behaviors, self-efficacy, depression, A1C, weight, and blood pressure. Classes applied participatory techniques and were delivered in 2-hour group sessions over 10 weeks. Two focus groups collected qualitative postintervention data. RESULTS: Seventy participants enrolled, and 47 completed pretest and posttest data. Improvements were significant for A1C (P = .001) and systolic blood pressure (P = .006). Other positive outcomes were diabetes knowledge, physical activity, spacing carbohydrates, following a healthy eating plan, and eating fruits and vegetables. Improved behaviors also included foot care, glucose self-monitoring, and medication adherence. Depressive symptoms showed a positive trend in intent-to-treat analysis (P = .07), but self-efficacy did not change significantly (P = .142). Qualitative information reported an increase in participants' perceived competence in self-care and a positive influence of CHWs in participants' compliance with the program. CONCLUSIONS: A diabetes self-management education program for Hispanics/Latinos led by CHWs can be implemented in community settings and may effectively improve behavioral skills and glycemic control.


Assuntos
Diabetes Mellitus/psicologia , Hispano-Americanos , Educação de Pacientes como Assunto , Poder Psicológico , Autocuidado/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Agentes Comunitários de Saúde , Diabetes Mellitus/sangue , Diabetes Mellitus/reabilitação , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/psicologia , Diabetes Mellitus Tipo 2/reabilitação , Feminino , Hemoglobina A Glicada/análise , Humanos , Masculino , Pessoa de Meia-Idade , Autocuidado/psicologia , Ensino/métodos
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