Induction of placental heme oxygenase-1 is protective against TNFα-induced cytotoxicity and promotes vessel relaxation

Background: Pregnancy is characterized by an inflammatory-like process and this may be exacerbated in preeclampsia. The heme oxygenase (HO) enzymes generate carbon monoxide (CO) that induces blood vessel relaxation and biliverdin that acts as an endogenous antioxidant. Materials and Methods: We examined the expression and localization of HO-1 and HO-2 in normal and preeclamptic placenta using reverse transcription polymerase chain reaction (RT-PCR), RNase protection assay, immunoblotting and immunohistochemistry. In addition, the effect of HO activation on tumor necrosis factor-alpha (TNF) induced placental damage and on feto-placental circulation was studied. Results: We provide the first evidence for the role of HO as an endogenous placental factor involved with cytoprotection and placental blood vessel relaxation. HO-1 was significantly higher at term, compared with first trimester placentae indicating its role in placental vascular development and regulation. HO-1 predominantly localized in the extravascular connective tissue that forms the perivascular contractile sheath around the developing blood vessels. HO-2 was localized in the capillaries, as well as the villous stroma, with weak staining of trophoblast. Induction of HO-1 caused a significant attenuation of TNF-mediated cellular damage in placental villous explants, as assessed by lactate dehydrogenase leakage (p 0.01). HO-1 protein was significantly reduced in placentae from pregnancies complicated with preeclampsia, compared with gestationally matched normal pregnancies. This suggests that the impairment of HO-1 activation may compromise the compensatory mechanism and predispose the placenta to cellular injury and subsequent maternal endothelial cell activation. Isometric contractility studies showed that hemin reduced vascular tension by 61% in U46619-preconstricted placental arteries. Hemininduced vessel relaxation and CO production was inhibited by HO inhibitor, tin protoporphyrin IX. Conclusions: Our findings establish HO-1 as an endogenous system that offers protection against cytotoxic damage in the placenta, identifies the HO-CO pathway to regulate feto-placental circulation and provides a new approach to study the disease of preeclampsia.

VaxiJen:a server for prediction of protective antigens, tumour antigens and subunit vaccines

Background - Vaccine development in the post-genomic era often begins with the in silico screening of genome information, with the most probable protective antigens being predicted rather than requiring causative microorganisms to be grown. Despite the obvious advantages of this approach – such as speed and cost efficiency – its success remains dependent on the accuracy of antigen prediction. Most approaches use sequence alignment to identify antigens. This is problematic for several reasons. Some proteins lack obvious sequence similarity, although they may share similar structures and biological properties. The antigenicity of a sequence may be encoded in a subtle and recondite manner not amendable to direct identification by sequence alignment. The discovery of truly novel antigens will be frustrated by their lack of similarity to antigens of known provenance. To overcome the limitations of alignment-dependent methods, we propose a new alignment-free approach for antigen prediction, which is based on auto cross covariance (ACC) transformation of protein sequences into uniform vectors of principal amino acid properties. Results - Bacterial, viral and tumour protein datasets were used to derive models for prediction of whole protein antigenicity. Every set consisted of 100 known antigens and 100 non-antigens. The derived models were tested by internal leave-one-out cross-validation and external validation using test sets. An additional five training sets for each class of antigens were used to test the stability of the discrimination between antigens and non-antigens. The models performed well in both validations showing prediction accuracy of 70% to 89%. The models were implemented in a server, which we call VaxiJen. Conclusion - VaxiJen is the first server for alignment-independent prediction of protective antigens. It was developed to allow antigen classification solely based on the physicochemical properties of proteins without recourse to sequence alignment. The server can be used on its own or in combination with alignment-based prediction methods.

Unravelling the theories of pre-eclampsia:Are the protective pathways the new paradigm?

Pre-eclampsia is a vascular disorder of pregnancy where anti-angiogenic factors, systemic inflammation and oxidative stress predominate, but none can claim to cause pre-eclampsia. This review provides an alternative to the 'two-stage model' of pre-eclampsia in which abnormal spiral arteries modification leads to placental hypoxia, oxidative stress and aberrant maternal systemic inflammation. Very high maternal soluble fms-like tyrosine kinase-1 (sFlt-1 also known as sVEGFR) and very low placenta growth factor (PlGF) are unique to pre-eclampsia; however, abnormal spiral arteries and excessive inflammation are also prevalent in other placental disorders. Metaphorically speaking, pregnancy can be viewed as a car with an accelerator and brakes, where inflammation, oxidative stress and an imbalance in the angiogenic milieu act as the 'accelerator'. The 'braking system' includes the protective pathways of haem oxygenase 1 (also referred as Hmox1 or HO-1) and cystathionine-γ-lyase (also known as CSE or Cth), which generate carbon monoxide (CO) and hydrogen sulphide (H2S) respectively. The failure in these pathways (brakes) results in the pregnancy going out of control and the system crashing. Put simply, pre-eclampsia is an accelerator-brake defect disorder. CO and H2S hold great promise because of their unique ability to suppress the anti-angiogenic factors sFlt-1 and soluble endoglin as well as to promote PlGF and endothelial NOS activity. The key to finding a cure lies in the identification of cheap, safe and effective drugs that induce the braking system to keep the pregnancy vehicle on track past the finishing line.

In vitro protective effect and antioxidant mechanism of Resveratrol induced by Dapsone Hydroxylamine in human cells

Dapsone (DDS) hydroxylamine metabolites cause oxidative stress- linked adverse effects in patients, such as methemoglobin formation and DNA damage. This study evaluated the ameliorating effect of the antioxidant resveratrol (RSV) on DDS hydroxylamine (DDSNHOH) mediated toxicity in vitro using human erythrocytes and lymphocytes. The antioxidant mechanism was also studied using in-silico methods. In addition, RSV provided intracellular protection by inhibiting DNA damage in human lymphocytes induced by DDS-NHOH. However, whilst pretreatment with RSV (10-1000 μM significantly attenuated DDS-NHOH-induced methemoglobinemia, but it was not only significantly less effective than methylene blue (MET), but also post-treatment with RSV did not reverse methemoglobin formation, contrarily to that observed with MET. DDS-NHOH inhibited catalase (CAT) activity and reactive oxygen species (ROS) generation, but did not alter superoxide dismutase (SOD) activity in erythrocytes. Pretreatment with RSV did not alter these antioxidant enzymes activities in erythrocytes treated with DDS-NHOH. Theoretical calculations using density functional theory methods showed that DDS-NHOH has a pro-oxidant effect, whereas RSV and MET have antioxidant effect on ROS. The effect on methemoglobinemia reversion for MET was significantly higher than that of RSV. These data suggest that the pretreatment with resveratrol may decrease heme-iron oxidation and DNA damage through reduction of ROS generated in cells during DDS therapy.

Gender differences in the influence of protective factors, risk factors, and health risk behaviors on HIV risk behaviors among youth in South Florida

Adolescents engage in a range of risk behaviors during their transition from childhood to adulthood. Identifying and understanding interpersonal and socio-environmental factors that may influence risk-taking is imperative in order to meet the Healthy People 2020 goals of reducing the incidence of unintended pregnancies, HIV, and other sexually transmitted infections among youth. The purpose of this study was to investigate gender differences in the predictors of HIV risk behaviors among South Florida youth. More specifically, this study examined how protective factors, risk factors, and health risk behaviors, derived from a guiding framework using the Theory of Problem Behavior and Theory of Gender and Power, were associated with HIV risk behavior. A secondary analysis of 2009 Youth Risk Behavior Survey data sets from Miami-Dade, Broward, and Palm Beach school districts tested hypotheses for factors associated with HIV risk behaviors. The sample consisted of 5,869 high school students (mean age 16.1 years), with 69% identifying as Black or Hispanic. Logistic regression analyses revealed gender differences in the predictors of HIV risk behavior. An increase in the health risk behaviors was related to an increase in the odds that a student would engage in HIV risk behavior. An increase in risk factors was also found to significantly predict an increase in the odds of HIV risk behavior, but only in females. Also, the probability of participation in HIV risk behavior increased with grade level. Post-hoc analyses identified recent sexual activity (past 3 months) as the strongest predictor of condom nonuse and having four or more sexual partners for both genders. The strongest predictors of having sex under the influence of drugs/alcohol were alcohol use in both genders, marijuana use in females, and physical fighting in males. Gender differences in the predictors of unprotected sex, multiple sexual partners, and having sex under the influence were also found. Additional studies are warranted to understand the gender differences in predictors of HIV risk behavior among youth in order to better inform prevention programming and policy, as well as meet the national Healthy People 2020 goals.

*Adoption status: A risk factor or protective factor for children of divorced families

This study examined two competitive hypotheses: the double jeopardy hypothesis and the buffering effect hypothesis on whether parental divorce affects adopted children and non-adopted children similarly or differently. The double jeopardy hypothesis suggests that when adopted children experience their parents' divorce, they perform worse because they carry two risk factors, adoption status and parental divorce, while their non-adopted counterparts carry only the risk factor of their parents' divorce. The buffering effect hypothesis suggests that, being adopted children, their previous experiences of parental loss help them better deal with the later loss of their parents' divorce so their adoption status is a protective factor rather than a risk factor. ^ Secondary analyses of a nation-wide data set were executed using different statistical methods such as ANOVA and Chi-square on different outcome variables. The results indicated that there was no evidence supporting the double-jeopardy hypothesis. That is, adopted children from divorced families did not perform significantly worse than the non-adopted children from divorced families on any outcome variable. The results also indicated that there was only weak evidence supporting the buffering effect hypothesis. The general conclusion based on the results from most of the outcome variables suggest that adopted children from divorced families do not perform differently than the biological children from divorced families. ^

Factors surgical team members perceive influence choices of wearing or not wearing personal protective equipment during operative /invasive procedures

Exposure to certain bloodborne pathogens can prematurely end a person’s life. Healthcare workers (HCWs), especially those who are members of surgical teams, are at increased risk of exposure to these pathogens. The proper use of personal protective equipment (PPE) during operative/invasive procedures reduces that risk. Despite this, some HCWs fail to consistently use PPE as required by federal regulation, accrediting agencies, hospital policy, and professional association standards. The purpose of this mixed methods survey study was to (a) examine factors surgical team members perceive influence choices of wearing or not wearing PPE during operative/invasive procedures and (b) determine what would influence consistent use of PPE by surgical team members. Using an ex post facto, non-experimental design, the memberships of five professional associations whose members comprise surgical teams were invited to complete a mixed methods survey study. The primary research question for the study was: What differences (perceptual and demographic) exist between surgical team members that influence their choices of wearing or not wearing PPE during operative/invasive procedures? Four principal differences were found between surgical team members. Functional (i.e., profession or role based) differences exist between the groups. Age and experience (i.e., time in profession) differences exist among members of the groups. Finally, being a nurse anesthetist influences the use of risk assessment to determine the level of PPE to use. Four common themes emerged across all groups informing the two study purposes. Those themes were: availability, education, leadership, and performance. Subsidiary research questions examined the influence of previous accidental exposure to blood or body fluids, federal regulations, hospital policy and procedure, leaders’ attitudes, and patients’ needs on the use of PPE. Each of these was found to strongly influence surgical team members and their use of PPE during operative/invasive procedures. Implications based on the findings affect organizational policy, purchasing and distribution decisions, curriculum design and instruction, leader behavior, and finally partnership with PPE manufacturers. Surgical team members must balance their innate need to care for patients with their need to protect themselves. Results of this study will help team members, leaders, and educators achieve this balance.

Acculturation and Diabetes Self-management of Cuban Americans: Is Age a Protective Factor?

Migration to the United States has been linked to obesity and poor diet quality. We investigated the relationship among diabetes self-management, diet, age and acculturation factors for 182 Cuban-Americans (Females = 110, Males = 72) with type 2 diabetes recruited from a randomized mailing list in South Florida. Inadequate glycemic control (β = 0.257), BMI (β = 0.251), total fat intake (β = 0.251), and smoking (β = 0.200), were positively associated, while understanding of overall diabetes care (β = -0.165), was negatively associated with migration (N = 162, adj.R2 = 0.286, F = 14.65, p < 0.001). These associations suggest that effective diabetes education targeting acculturation issues is lacking.

Factors Surgical Team Members Perceive Influence Choices of Wearing or not Wearing Personal Protective Equipment During Operative/Invasive Procedures

Exposure to certain bloodborne pathogens can prematurely end a person’s life. Healthcare workers (HCWs), especially those who are members of surgical teams, are at increased risk of exposure to these pathogens. The proper use of personal protective equipment (PPE) during operative/invasive procedures reduces that risk. Despite this, some HCWs fail to consistently use PPE as required by federal regulation, accrediting agencies, hospital policy, and professional association standards. The purpose of this mixed methods survey study was to (a) examine factors surgical team members perceive influence choices of wearing or not wearing PPE during operative/invasive procedures and (b) determine what would influence consistent use of PPE by surgical team members. Using an ex post facto, non-experimental design, the memberships of five professional associations whose members comprise surgical teams were invited to complete a mixed methods survey study. The primary research question for the study was: What differences (perceptual and demographic) exist between surgical team members that influence their choices of wearing or not wearing PPE during operative/invasive procedures? Four principal differences were found between surgical team members. Functional (i.e., profession or role based) differences exist between the groups. Age and experience (i.e., time in profession) differences exist among members of the groups. Finally, being a nurse anesthetist influences the use of risk assessment to determine the level of PPE to use. Four common themes emerged across all groups informing the two study purposes. Those themes were: availability, education, leadership, and performance. Subsidiary research questions examined the influence of previous accidental exposure to blood or body fluids, federal regulations, hospital policy and procedure, leaders’ attitudes, and patients’ needs on the use of PPE. Each of these was found to strongly influence surgical team members and their use of PPE during operative/invasive procedures. Implications based on the findings affect organizational policy, purchasing and distribution decisions, curriculum design and instruction, leader behavior, and finally partnership with PPE manufacturers. Surgical team members must balance their innate need to care for patients with their need to protect themselves. Results of this study will help team members, leaders, and educators achieve this balance.

Risk and protective factors in the mental health of adolescents living with HIV in Namibia

"Introducción": A pesar de que el 90% de los adolescentes con VIH en el mundo viven en África subsahariana, pocos estudios han examinado el impacto que tiene el hecho de estar infectados por VIH sobre su salud mental en este región. Además, los adolescentes con VIH en contextos de escasos recursos se enfrentan con factores de riesgo adicionales, como la pobreza, la falta de apoyo social y el estigma relacionado con el VIH. Este estudio examina la salud mental de los adolescentes que viven con el VIH en Namibia, un país con una de las prevalencias de VIH más altas del mundo. El estudio examina si estos adolescentes muestran mayores problemas de salud mental respecto a un grupo de comparación de la comunidad. Asimismo, el estudio evalúa los factores que predicen problemas de salud mental con el fin de identificar las potenciales áreas de intervención que permitan mejorar dichos problemas. Métodos: En una fase piloto, se organizan grupos de discusión con 34 adolescentes y entrevistas con ocho informantes clave para explorar las percepciones locales sobre los problemas de salud mental, así como sus factores de riesgo y factores de proteccion. Dado que las propiedades psicométricas del instrumento seleccionado para medir salud mental, el cuestionario Strengths and Difficulties Questionnaire/ Cuestionario de Capacidades y Dificultades (SDQ), nunca habían sido exploradas antes en Namibia, se decidió administrarlo a 236 participantes con edades comprendidas entre 12 y 18 años en una fase piloto cuantitativa...

Editor's choice Regional trade agreements and export competitiveness: the uncertain path of Nicaragua’s apparel exports under CAFTA

The Central American Free Trade Agreement (CAFTA) has been a mixed blessing for economic development. While exports to the US economy have increased, dependency may hinder economic growth if countries do not diversify or upgrade before temporary provisions expire. This article evaluates the impact of the temporary Tariff Preference Levels (TPLs) granted to Nicaragua under CAFTA and the consequences of TPL expiration. Using trade statistics, country- and firm-level data from Nicaragua’s National Free Zones Commission (CNZF) and data from field research, we estimate Nicaragua’s apparel sector will contract as much as 30–40% after TPLs expire. Our analysis underscores how rules of origin and firm nationality affect where and how companies do business, and in so doing, often constrain sustainable export growth.

Parental Criminal Justice Involvement and Children's Involvement With Child Protective Services: Do Adult Drug Treatment Courts Prevent Child Maltreatment?

BACKGROUND: In light of evidence showing reduced criminal recidivism and cost savings, adult drug treatment courts have grown in popularity. However, the potential spillover benefits to family members are understudied. OBJECTIVES: To examine: (1) the overlap between parents who were convicted of a substance-related offense and their children's involvement with child protective services (CPS); and (2) whether parental participation in an adult drug treatment court program reduces children's risk for CPS involvement. METHODS: Administrative data from North Carolina courts, birth records, and social services were linked at the child level. First, children of parents convicted of a substance-related offense were matched to (a) children of parents convicted of a nonsubstance-related offense and (b) those not convicted of any offense. Second, we compared children of parents who completed a DTC program with children of parents who were referred but did not enroll, who enrolled for <90 days but did not complete, and who enrolled for 90+ days but did not complete. Multivariate logistic regression was used to model group differences in the odds of being reported to CPS in the 1 to 3 years following parental criminal conviction or, alternatively, being referred to a DTC program. RESULTS: Children of parents convicted of a substance-related offense were at greater risk of CPS involvement than children whose parents were not convicted of any charge, but DTC participation did not mitigate this risk. Conclusion/Importance: The role of specialty courts as a strategy for reducing children's risk of maltreatment should be further explored.

Bullying Involvement and Adolescent Substance Use: A Study of Multilevel Risk and Protective Factors

Bullying, frequent drunkenness, and frequent cannabis use are significant health-risk behaviours among youth. While many studies have demonstrated that bullying involvement may initiate a developmental pathway to both types of frequent substance use, there is a limited understanding of the connection between these behaviours. The presence of risk and protective factors within youths’ relationships and within their neighbourhoods may alter the associations between bullying involvement and both types of frequent substance use. A systemic approach is needed to assess the complex, social environments in which youth are embedded. The current thesis consists of two studies that examined the associations between bullying and both types of frequent substance use within the context of youths’ social environments. In Study 1, multilevel modeling was used to examine the associations between bullying and frequent substance use within the context of individual and neighbourhood risk factors. Our results indicated that the risk factors associated with both frequent drunkenness and frequent cannabis use exist at both levels, with neighbourhoods altering the association of individual risk factors. Moreover, bullying was a unique risk factor associated with both types of frequent substance use, whereas indirect associations were observed for victimization. Study 2 used a similar methodology to examine the association between bullying and both types of frequent substance use within the context of individual and neighbourhood protective factors. Once again, our results indicated that the protective factors associated with both types of frequent substance use exist at multiple levels, and that neighbourhoods altered the association of individual protective factors. Additionally, positive relationship characteristics interacted with the link between bullying and both types of frequent substance use. Together, these findings clarify the nature of the bullying-substance use link and emphasize the need to study adolescent development in context.

Attenuation of monocyte chemotaxis--a novel anti-inflammatory mechanism of action for the cardio-protective hormone B-type natriuretic peptide

B-type natriuretic peptide (BNP) is a prognostic and diagnostic marker for heart failure (HF). An anti-inflammatory, cardio-protective role for BNP was proposed. In cardiovascular diseases including pressure overload-induced HF, perivascular inflammation and cardiac fibrosis are, in part, mediated by monocyte chemoattractant protein (MCP)1-driven monocyte migration. We aimed to determine the role of BNP in monocyte motility to MCP1. A functional BNP receptor, natriuretic peptide receptor-A (NPRA) was identified in human monocytes. BNP treatment inhibited MCP1-induced THP1 (monocytic leukemia cells) and primary monocyte chemotaxis (70 and 50 %, respectively). BNP did not interfere with MCP1 receptor expression or with calcium. BNP inhibited activation of the cytoskeletal protein RhoA in MCP1-stimulated THP1 (70 %). Finally, BNP failed to inhibit MCP1-directed motility of monocytes from patients with hypertension (n = 10) and HF (n = 6) suggesting attenuation of this anti-inflammatory mechanism in chronic heart disease. We provide novel evidence for a direct role of BNP/NPRA in opposing human monocyte migration and support a role for BNP as a cardio-protective hormone up-regulated as part of an adaptive compensatory response to combat excess inflammation.