Prevalence of Neutralizing Antibodies against Adeno-Associated Virus Serotypes 1, 2, and 9 in Non-Injected Latin American Patients with Heart Failure-ANVIAS Study.

Neutralizing antibody (NAb) activity against the viral capsid of adeno-associated viral (AAV) vectors decreases transduction efficiency, thus limiting transgene expression. Several reports have mentioned a variation in NAb prevalence according to age, AAV serotype, and, most importantly, geographic location. There are currently no reports specifically describing the anti-AAV NAb prevalence in Latin America. Here, we describe the prevalence of NAb against different serotypes of AAV vectors (AAV1, AAV2, and AAV9) in Colombian patients with heart failure (HF) (referred to as cases) and healthy individuals (referred to as controls). The levels of NAb were evaluated in serum samples of 60 subjects from each group using an in vitro inhibitory assay. The neutralizing titer was reported as the first dilution inhibiting ≥50% of the transgene signal, and the samples with neutralizing titers at ≥1:50 dilution were considered positive. The prevalence of NAb in the case and control groups were similar (AAV2: 43% and 45%, respectively; AAV1 33.3% in each group; AAV9: 20% and 23.2%, respectively). The presence of NAb for two or more of the serotypes analyzed was observed in 25% of the studied samples, with the largest amount in the positive samples for AAV1 (55-75%) and AAV9 (93%), suggesting serial exposures, cross-reactivity, or coinfection. Moreover, patients in the HF group exhibited more common combined seropositivity for NAb against AAV1 d AAV9 than those in the control group (91.6% vs. 35.7%, respectively; p = 0.003). Finally, exposure to toxins was significantly associated with the presence of NAb in all regression models. These results constitute the first report of the prevalence of NAb against AAV in Latin America, being the first step to implementing therapeutic strategies based on AAV vectors in this population in our region.

C-reactive protein, interleukin-6 and pre-eclampsia: large-scale evidence from the GenPE case-control study.

Multiple small studies have suggested that women with pre-eclampsia present elevated levels of C-reactive protein (CRP) and interleukin-6 (IL-6). However, little is known regarding the source of this CRP and IL-6 increase. Therefore, the aim of this study was to evaluate the relationship between CRP and IL-6 levels with pre-eclampsia considering different confounding factors. Using data from a large Colombian case-control study (3,590 cases of pre-eclampsia and 4,564 normotensive controls), CRP and IL-6 levels were measured in 914 cases and 1297 controls. The association between maternal serum levels of CRP and IL-6 with pre-eclampsia risk was evaluated using adjusted logistic regression models. Pre-eclampsia was defined as presence of blood pressure ≥140/90 mmHg and proteinuria ≥300mg/24 h (or ≥1 + dipstick). There was no evidence of association between high levels of CRP and IL-6 with pre-eclampsia after adjusting for the following factors: maternal and gestational age, ethnicity, place and year of recruitment, multiple-pregnancy, socio-economic position, smoking, and presence of infections during pregnancy. The adjusted OR for 1SD increase in log-CRP and log-IL-6 was 0.96 (95%CI 0.85, 1.08) and 1.09 (95%CI 0.97, 1.22), respectively. Although previous reports have suggested an association between high CRP and IL-6 levels with pre-eclampsia, sample size may lack the sufficient power to draw robust conclusions, and this association is likely to be explained by unaccounted biases. Our results, the largest case-control study reported up to date, demonstrate that there is not a causal association between elevated levels of CRP and IL-6 and the presence of pre-eclampsia.

Mobile phone text messaging to improve medication adherence in secondary prevention of cardiovascular disease.

BACKGROUND: Worldwide at least 100 million people are thought to have prevalent cardiovascular disease (CVD). This population has a five times greater chance of suffering a recurrent cardiovascular event than people without known CVD. Secondary CVD prevention is defined as action aimed to reduce the probability of recurrence of such events. Drug interventions have been shown to be cost-effective in reducing this risk and are recommended in international guidelines. However, adherence to recommended treatments remains sub-optimal. In order to influence non-adherence, there is a need to develop scalable and cost-effective behaviour-change interventions. OBJECTIVES: To assess the effects of mobile phone text messaging in patients with established arterial occlusive events on adherence to treatment, fatal and non-fatal cardiovascular events, and adverse effects. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, the Conference Proceedings Citation Index - Science on Web of Science on 7 November 2016, and two clinical trial registers on 12 November 2016. We contacted authors of included studies for missing information and searched reference lists of relevant papers. We applied no language or date restrictions. SELECTION CRITERIA: We included randomised trials with at least 50% of the participants with established arterial occlusive events. We included trials investigating interventions using short message service (SMS) or multimedia messaging service (MMS) with the aim to improve adherence to medication for the secondary prevention of cardiovascular events. Eligible comparators were no intervention or other modes of communication. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. In addition, we attempted to contact all authors on how the SMS were developed. MAIN RESULTS: We included seven trials (reported in 13 reports) with 1310 participants randomised. Follow-up ranged from one month to 12 months. Due to heterogeneity in the methods, population and outcome measures, we were unable to conduct meta-analysis on these studies. All seven studies reported on adherence, but using different methods and scales. Six out of seven trials showed a beneficial effect of mobile phone text messaging for medication adherence. Dale 2015a, reported significantly greater medication adherence score in the intervention group (Mean Difference (MD) 0.58, 95% confidence interval (CI) 0.19 to 0.97; 123 participants randomised) at six months. Khonsari 2015 reported less adherence in the control group (Relative Risk (RR) 4.09, 95% CI 1.82 to 9.18; 62 participants randomised) at eight weeks. Pandey 2014 (34 participants randomised) assessed medication adherence through self-reported logs with 90% adherence in the intervention group compared to 70% in the control group at 12 months. Park 2014a (90 participants randomised) reported a greater increase of the medication adherence score in the control group, but also measured adherence with an event monitoring system for a number of medications with adherence levels ranging from 84.1% adherence to 86.2% in the intervention group and 79.7% to 85.7% in the control group at 30 days. Quilici 2013, reported reduced odds of non-adherence in the intervention group (Odds Ratio (OR) 0.43, 95% CI 0.22 to 0.86, 521 participants randomised) at 30 days. Fang 2016, reported that participants given SMS alone had reduced odds of being non-adherent compared to telephone reminders (OR 0.40 95% CI 0.18 to 0.63; 280 patients randomised). Kamal 2015 reported higher levels of adherence in the intervention arm (adjusted MD 0.54, 95% CI 0.22 to 0.85; 200 participants randomised). Khonsari 2015 was the only study to report fatal cardiovascular events and only reported two events, both in the control arm. No study reported on the other primary outcomes. No study reported repetitive thumb injury or road traffic crashes or other adverse events that were related to the intervention.Four authors replied to our questionnaire on SMS development. No study reported examining causes of non-adherence or provided SMS tailored to individual patient characteristics.The included studies were small, heterogeneous and included participants recruited directly after acute events. All studies were assessed as having high risk of bias across at least one domain. Most of the studies came from high-income countries, with two studies conducted in an upper middle-income country (China, Malaysia), and one study from a lower middle-income country (Pakistan). The quality of the evidence was found to be very low. There was no obvious conflicts of interest from authors, although only two declared their funding. AUTHORS' CONCLUSIONS: While the results of this systematic review are promising, there is insufficient evidence to draw conclusions on the effectiveness of text message-based interventions for adherence to medications for secondary prevention of CVD. Sufficiently powered, high-quality randomised trials are needed, particularly in low- and middle-income countries.

Time-Dependent Risk for Recurrence in Survivors of Major Adverse Cardiovascular Events.

INTRODUCTION: The prevalence of the population with a history of an occlusive cardiovascular event has been increasing in recent years, which means that a large number of patients will have a higher risk of presenting a fatal recurrence. The aim is to determine variables associated with time-to-recurrent cardiovascular events and analyze how changes in low-density lipoprotein cholesterol (LDL-C) levels during follow-up may be associated with this time-to-event. MATERIALS AND METHODS: This is a prospective observational cohort study of 727 adults with a history of at least one occlusive cardiovascular event recruited at a referral hospital in northeastern Colombia. Data from a follow-up period of a maximum of 33 months (median 26 months) (one death) were used to define how clinical and sociodemographic variables impact the recurrence of major adverse cardiovascular events (MACE). Analyses were performed based on proportional hazard models and time-dependent hazard models. RESULTS: Upon enrollment, 215 (30%) of the participants reported experiencing their most recent cardiovascular event within the preceding year. After two years, the recurrence rate was 12.38% (90/727). The risk of recurrence before two years was 3.9% (95% CI 2.7-5.6). In the multiple models, the presence of severe depression gives a Hazard Ratio of 8.25 (95% CI 2.98-22.86) and LDL ≥120 md/dl Hazard Ratio of 2.12 (95% CI 1.2 -3.9). It was found that LDL >120 mg/dl maintained over time increases the chances of recurrence by 1.7% (Hazard Ratio: 1.017, 95% CI 0.008-0.025). CONCLUSIONS: The present study allows us to identify a profile of patients who should be treated promptly in an interdisciplinary manner to avoid recurrences of coronary events.

Efficacy of vitamin D supplementation in reducing body mass index and lipid profile in healthy young adults in Colombia: a pilot randomised controlled clinical trial.

The objective of the present study was to evaluate the efficacy of oral administration of vitamin D supplementation in reducing BMI and lipid profile in adolescents and young adults from a cohort in Bucaramanga, Colombia. One hundred and one young adults were randomly assigned to one of two doses of vitamin D [1000 international units (IU) or 200 IU] administered daily for 15 weeks. The primary outcomes were serum 25(OH)D levels, BMI and lipid profile. The secondary outcomes were waist-hip ratio, skinfolds and fasting blood glucose. We found a mean ± sd plasma concentration of 25-hydroxyvitamin D [25(OH)D] was 25⋅0 ± 7⋅0 ng/ml at baseline, and after 15 weeks, it increased to 31⋅0 ± 10⋅0 ng/ml in the participants who received a daily dose of 1000 IU, (P < 0⋅0001). For the participants in the control group (200 IU), it went from 26⋅0 ± 8⋅0 ng/ml to 29⋅0 ± 8⋅0 ng/ml (P = 0⋅002). There were no differences between groups in body mass index. There was a statistically significant decrease in LDL-cholesterol between the intervention group v. the control group (mean difference -11⋅50 mg/dl (95 % CI -21⋅86 to -1⋅15; P = 0⋅030). The conclusions of the present study were two different doses of vitamin D supplementation (200 IU v. 1000 IU) produced changes in serum 25(OH)D levels over 15 weeks of administration in healthy young adults. No significant changes were found in the body mass index when the effect of the treatments was compared. A significant reduction in LDL-cholesterol was found when comparing the two intervention groups. Trial registration: NCT04377386.

Uric acid and risk of pre-eclampsia: results from a large case-control study and meta-analysis of prospective studies.

To quantify the association between maternal uric acid levels and pre-eclampsia risk in a large collection of primigravid women. A case-control study (1365 cases of pre-eclampsia and 1886 normotensive controls) was conducted. Pre-eclampsia was defined as blood pressure ≥ 140/90 mmHg and proteinuria ≥ 300 mg/24 h. Sub-outcome analysis included early, intermediate, and late pre-eclampsia. Multivariable analysis for pre-eclampsia and its sub-outcomes was conducted using binary and multinomial logistic regression, respectively. Additionally, a systematic review and meta-analysis of cohort studies measuring uric acid levels < 20 weeks of gestation was performed to rule out reverse causation. There was a positive linear association between increasing uric acid levels and presence of pre-eclampsia. Adjusted odds ratio of pre-eclampsia was 1.21 (95%CI 1.11-1.33) for every one standard deviation increase in uric acid levels. No differences in the magnitude of association were observed between early and late pre-eclampsia. Three studies with uric acid measured < 20 weeks' gestation were identified, with a pooled OR for pre-eclampsia of 1.46 (95%CI 1.22-1.75) for a top vs. bottom quartile comparison. Maternal uric acid levels are associated with risk of pre-eclampsia. Mendelian randomisation studies would be helpful to further explore the causal role of uric acid in pre-eclampsia.

Effect of Antioxidants in the Treatment of COPD Patients: Scoping Review.

Chronic obstructive pulmonary disease (COPD) is a common, preventable, treatable lung disease characterized by persistent respiratory symptoms and airflow limitation and multiorgan impact. This affects the nutritional status of patients and requires multidimensional interventions including nutritional interventions according to individual metabolic needs. Our scoping review determined the effects of antioxidants in the treatment of COPD patients and their role in the decrease in the probability of exacerbations, hospital readmissions, and changes in lung function. The sources MEDLINE, LILACS, and Google Scholar were consulted and 19 studies were selected. The most indicated antioxidants are N-Acetylcysteine, vitamins E and D, and Zinc. Other antioxidants from plants or fruits extracts are also being investigated. The beneficial effect of antioxidants in stable or exacerbated patients is not clear, but theoretical and biological arguments of benefit justify lines of research that specify the impact on reducing oxidative stress and negative effects in COPD.

Frequency of eNOS polymorphisms in the Colombian general population.

BACKGROUND: Nitric oxide (NO) synthesized by endothelial cells is known to be a potent vasodilator. It has been suggested that polymorphisms in endothelial nitric oxide synthase (eNOS) can affect the response of the vascular endothelium to increased oxidative stress. The objective of the present study was to determine the presence of G894T (rs1799983), intron-4 (27-bp TR) and -T786C (rs2070744) polymorphisms in the eNOS gene among the Colombian general population. RESULTS: Genotype and allele frequencies showed significant differences in their distribution. White, black and mixed populations were in HW equilibrium for the variants in 27-bp TR- and rs1799983, but the black population was in HW disequilibrium for rs2070744 (p < 0.001). Allele "T" of rs1799983 polymorphisms was more common in the white population (26,5%) than the others, while allele "C" of rs2070744 polymorphisms had a similar frequency in all populations, and the allele 4a from 27-bp TR was more frequent in the black population (26,2%) than the others. Similar differences were found when genotypes were analyzed. CONCLUSION: The findings suggest that there is a substantial difference in the distribution of eNOS polymorphisms between different ethnic groups. These results could aid the understanding of inter-ethnic differences in NO bioavailability, cardiovascular risk, and response to drugs.

Prevalence of vitamin D status and its association with overweight or obesity in a population of Colombian children and adolescents.

The present study aimed to estimate the prevalence of 25-OH-D status (insufficiency and deficiency) in children and adolescents residing in Bucaramanga, Colombia and to determine its association with excess weight. A case-control study was nested in the SIMBA II cohort in children and adolescents between the ages of 11 and 20 years old. Cases were defined as those children and adolescents with overweight or obesity. The control group was composed of children and adolescents from the same population sample with similar sociodemographic and economic characteristics but without overweight or obesity diagnosis. 25-hydroxyvitamin D (25-OH-D) was quantified in serum using a chemiluminescent microparticle immunoassay. Logistic regression models were used to assess the association between vitamin D status and overweight or obesity adjusted for the main confounding variables. A total of 494 children and adolescents cases were 138 (52⋅17% boys and 47⋅83% girls; median age 16⋅0 [Q1 15; Q3 18]). The median BMI S-Score minors age in the cases was 1⋅36 [Q1 1⋅06; Q3 2⋅00] and BMI (kg/m2) 28⋅0 [Q1 26⋅2; Q3 30⋅8]. The prevalence of vitamin D in the cases was deficiency 16⋅67%, insufficiency 57⋅25%, sufficiency 26⋅09. 25-OH-D insufficiency was associated with overweight or obesity after adjusting for the main confounding variables (OR 1⋅73; 95% CI 1⋅05-2⋅84). Our study concludes that the 25-OH-D insufficiency is common in children and adolescents in Bucaramanga, Colombia, and it was associated with overweight or obesity.

Potential Role of Antioxidants as Adjunctive Therapy in Chagas Disease.

Chagas disease (CD) is one of the most important neglected tropical diseases in the American continent. Host-derived nitroxidative stress in response to Trypanosoma cruzi infection can induce tissue damage contributing to the progression of Chagas disease. Antioxidant supplementation has been suggested as adjuvant therapy to current treatment. In this article, we synthesize and discuss the current evidence regarding the use of antioxidants as adjunctive compounds to fight harmful reactive oxygen species and lower the tissue oxidative damage during progression of chronic Chagas disease. Several antioxidants evaluated in recent studies have shown potential benefits for the control of oxidative stress in the host's tissues. Melatonin, resveratrol, the combination of vitamin C/vitamin E (vitC/vitE) or curcumin/benznidazole, and mitochondria-targeted antioxidants seem to be beneficial in reducing plasma and cardiac levels of lipid peroxidation products. Nevertheless, further research is needed to validate beneficial effects of antioxidant therapies in Chagas disease.

Family history of pre-eclampsia and cardiovascular disease as risk factors for pre-eclampsia: the GenPE case-control study.

Objective: To determine whether family history of pre-eclampsia and cardiovascular disease is consistently associated with the occurrence of pre-eclampsia sub-phenotypes and fetal growth restriction (FGR).Material and Methods: We conducted a case-control study in which cases of pre-eclampsia and healthy pregnant controls were recruited at the time of delivery from eight Colombian cities between 2000 and 2012. Odds of pre-eclampsia among women with a positive family history of pre-eclampsia or cardiovascular disease were compared to women without affected relatives (logistic regression modeling and multinomial logistic regression model [Ajusted]).Results: A total of 3510 pre-eclampsia cases and 4512 controls with data on family history of pre-eclampsia were included in analyses. A subsample of 3086 cases and 3888 controls also provided information on family history of cardiovascular disease. Women whose mothers had pre-eclampsia had 3.38 (95% CI 2.89, 3.96) higher odds than those who did not, and having an affected sister increased pre-eclampsia odds by 2.43 (95% CI 2.02, 2.93). The effect of having both mother and sister affected with pre-eclampsia was stronger than the two independent risk factors (OR 4.17 [95% CI 2.60, 6.69]). Women with parental history of cardiovascular disease also had an increased risk of pre-eclampsia (OR 1.58 [95% CI 1.24, 2.01]).Conclusions: Family history of pre-eclampsia increased the risk of PE. The impact of family history of cardiovascular disease on pre-eclampsia was more conservative, but serves to support the hypothesis that pre-eclampsia may reflect the premature exposure of underlying cardiovascular dysfunction, precipitated by the stress test of pregnancy.

Efficacy of oral Vitamin D supplementation in reducing body mass index and lipid profile in adolescents and young adults in Colombia: A pilot clinical trial protocol nested in the SIMBA cohort.

BACKGROUND: In recent years, the role of vitamin D (VD) as a protective factor in cardiovascular disease has been recognized. Thus, there is a need to study the effect of vitamin D supplementation in the control of different cardiovascular risk factors and metabolic syndrome, especially in young populations where few studies have been conducted. METHODS: Pilot study of a randomized, parallel two-arm, triple-blind clinical controlled trial in 150 adolescents and young adults in the city of Bucaramanga-Colombia. The intervention group will receive 1000 IU of VD and the control group 200 IU of VD daily for 15 weeks. The main outcomes are: serum calcifediol levels (25(OH) D), body mass index and lipid profile; secondary outcomes are complementary to the previous ones (skin folds, waist-hip ratio). Other variables will be analyzed such as assessment of dietary intake, physical activity, sun exposure, cigarette and tobacco consumption and compliance with VD supplementation. DISCUSSION: This study is innovative since there is little evidence from clinical trials in adolescents and young adults; similar studies are not known in our context. The results of this study may facilitate the recommendation of oral vitamin D supplementation in the population of interest. In addition, it is a low-cost and easy-to-apply intervention that could contribute to the formulation and implementation of health policies. TRIAL REGISTRATION: NCT04377386.

Association between body fat mass and cardiometabolic risk in children and adolescents in Bucaramanga, Colombia.

BACKGROUND: Obesity is common among children and teenagers and is associated with cardiometabolic risk factors in the adult age. The objective of this paper was to evaluate the association between the percentage of body fat and cardiometabolic risk factors in children and adolescents in the city of Bucaramanga, Colombia. MATERIAL AND METHODS: About 494 children and adolescents aged 10-20 years were studied. Laboratory tests were made for analyzing cardiovascular risk factors and anthropometric measurements. Percentage body fat was determined with Slaughter equation. Lineal regression analyses were conducted to evaluate the association between cardiometabolic risk factors and the percentage body fat. RESULTS: Prevalence of percentage body fat (>26%) was 46.1%. Variables associated with percentage body fat were HOMA-IR - insulin resistance, HDL, LDL, triglycerides, and total cholesterol levels, and high blood pressure. CONCLUSIONS: Increase in percentage body fat is significantly associated with cardiometabolic risk factors in children and adolescents in Bucaramanga. Early identification and intervention of this population at risk is fundamental.

Measuring mitochondrial respiration in adherent cells infected with Trypanosoma cruzi Chagas, 1909 using Seahorse extracellular flux analyser.

Infection with Trypanosoma cruzi Chagas, 1909 is reported to increase the production of reactive oxygen species in patients with Chagas disease. Mitochondria dysfunction, host inflammatory response and inadequate antioxidant response are described as the main factors leading to oxidative stress during acute and chronic stages of the disease. The Seahorse XFe24 extracellular flux platform allows energy metabolism determination through mitochondrial respiration and glycolysis measurements. XFe24 platform can be used in in vitro models of T. cruzi-infected cells, which allow the assessment and even modulation of endogenous conditions of infected cells, generating readouts of real-time cellular bioenergetics changes. In this protocol, we standardised the use of XFe24 technology in T. cruzi infected AC16 cardiomyocytes and SGHPL-5 trophoblasts. In addition, we provide a list of optimised assay specifications, advantages and critical steps to be considered during the process. Cardiomyocytes and trophoblasts are attractive target cells to evaluate the metabolic environment in acute, chronic and congenital Chagas transmission scenarios.

Lipid profile, plasma apolipoproteins, and pre-eclampsia risk in the GenPE case-control study.

BACKGROUND AND AIMS: Pre-eclampsia constitutes a leading cause of maternal and perinatal morbidity and mortality. Pre-eclampsia susceptibility is believed to be associated with altered lipid profiles and abnormal lipid metabolism via lipid peroxidation that leads to endothelial dysfunction. The goal of this study was to evaluate the association of maternal blood lipid and apolipoprotein levels with pre-eclampsia in a large-scale study. METHODS: Using data from a large case-control study (1366 cases of pre-eclampsia and 1741 normotensive controls), the association between the distributions of eight lipid fractions and pre-eclampsia risk was evaluated using adjusted logistic regression models. Pre-eclampsia was defined as blood pressure ≥140/90 mmHg and proteinuria ≥300 mg/24 h (>1 + dipstick). Sub-group analyses were conducted for early (<34 weeks) and late (≥37 weeks) pre-eclampsia, estimating the effect of 1 standard deviation increase in log-transformed lipid fraction levels in adjusted multinomial regression models. RESULTS: After adjustment for potential confounders, concentrations of triglycerides, apolipoprotein E (ApoE) and the relationship between apolipoprotein B and A1 (ApoB/ApoA1) showed the strongest associations with pre-eclampsia, particularly for those cases with an early onset. CONCLUSIONS: Higher levels of triglycerides, ApoE and the ApoB/ApoA1 ratio are associated with an increased risk of pre-eclampsia. Further studies that allow for a causal inference are needed to confirm or refute the aetiological role of blood lipids in pre-eclampsia.

Vitamin D deficiency and pre-eclampsia in Colombia: PREVitD study.

PURPOSE: Pre-eclampsia is a multisystem disorder characterized by new-onset hypertension and proteinuria during pregnancy. Pre-eclampsia remains a major cause of maternal death in low-income countries. Vitamin D has a very diverse biological role in cardiovascular diseases. This study will evaluate the association of vitamin D levels and relevance to pre-eclampsia. METHODS: We conducted a case-control study of women recruited from the GenPE (Genetics and Pre-eclampsia) Colombian registry. This is a multicenter case-control study conducted in eight Colombian cities. 25-Hydroxyvitamin D (25(OH)D) concentration was measured using liquid-chromatography-tandem mass spectrometry from 1013 women with pre-eclampsia and 1015 mothers without pre-eclampsia (controls). RESULTS: Fifty-two percent of women with pre-eclampsia were vitamin D deficient. The 25(OH)D concentrations were significantly lower in the pre-eclampsia (mean 29.99 ng/mL; 95% CI: 29.40-30.58 ng/mL) group compared to controls (mean 33.7 ng/mL; 95% CI: 33.20-34.30 ng/mL). In the unadjusted model, maternal vitamin D deficiency, defined by maternal 25(OH)D concentration <30 ng/mL, was associated with an increased probability of suffering from pre-eclampsia (OR 2.10; 95% CI, 1.75-2.51). After adjusting for covariates, a similarly increased probability of having pre-eclampsia was observed (OR 2.18; 95% CI, 1.80-2.64) among women with vitamin D deficiency, relative to controls. CONCLUSION: Although the results suggest that low maternal concentrations of 25(OH)D increase pre-eclampsia risk, this evidence may not be indicative of a causal association. Future studies are needed to confirm a definite causal relationship between concentrations of vitamin D and the risk of pre-eclampsia, by means of powered clinical trials.

Association of pre-eclampsia risk with maternal levels of folate, homocysteine and vitamin B12 in Colombia: A case-control study.

BACKGROUND: Maternal serum concentrations of folate, homocysteine, and vitamin B12 have been associated with pre-eclampsia. Nevertheless, reported studies involve limited number of cases to reliably assess the nature of these associations. Our aim was to examine the relation of these three biomarkers with pre-eclampsia risk in a large Colombian population. MATERIALS AND METHODS: Design: A case-control study. Setting: Cases of pre-eclampsia and healthy pregnant controls were recruited at the time of delivery from eight different Colombian cities between 2000 and 2012. Population or Sample: 2978 cases and 4096 controls were studied. Maternal serum concentrations of folate, homocysteine, and vitamin B12 were determined in 1148 (43.6%) cases and 1300 (31.7%) controls. Also, self-reported folic acid supplementation was recorded for 2563 (84%) cases and 3155 (84%) controls. Analysis: Adjusted odds ratios (OR) for pre-eclampsia were estimated for one standard deviation (1SD) increase in log-transformed biomarkers. Furthermore, we conducted analyses to compare women that reported taking folic acid supplementation for different periods during pregnancy. Main Outcomes Measures: Odds ratio for pre-eclampsia. RESULTS: After adjusting for potential confounders in logistic regression models, the OR for pre-eclampsia was 0.80 (95% CI: 0.72, 0.90) for 1SD increase in log-folate, 1.16 (95%CI: 1.05, 1.27) for 1SD increase in log-homocysteine, and 1.10 (95%CI: 0.99, 1.22) for 1SD increase in log-vitamin B12. No interactions among the biomarkers were identified. Women who self-reported consumption of folic acid (1 mg/day) throughout their pregnancy had an adjusted OR for pre-eclampsia of 0.86 (95%CI: 0.67, 1.09) compared to women that reported no consumption of folic acid at any point during pregnancy. CONCLUSIONS: Maternal serum concentrations of folate were associated as a protective factor for pre-eclampsia while concentrations of homocysteine were associated as a risk factor. No association between maternal vitamin B12 concentrations and preeclampsia was found.

Physiological and pathological implications of laminins: from the gene to the protein.

The extracellular matrix plays an important role in modulating the behavior of cells with which it interacts. There are a number of families of extracellular matrix (ECM) proteins including collagens, proteoglycans and laminins (LM). LM are the major component of the basal lamina (BL). Here, we review the current knowledge on their structure, self-assembly, binding mechanisms, diverse tissue-expression patterns and its impact on pathology. Studies and hypothesis exploring the role of LM and their polymorphic genes on autoimmune diseases (AIDs) such as systemic lupus erythematosus and Sjögren's syndrome (SS) are also discussed.

Angiotensin-converting enzyme I/D polymorphism and preeclampsia risk: evidence of small-study bias.

BACKGROUND: Inappropriate activation of the renin-angiotensin system may play a part in the development of preeclampsia. An insertion/deletion polymorphism within the angiotensin-I converting enzyme gene (ACE-I/D) has shown to be reliably associated with differences in angiotensin-converting enzyme (ACE) activity. However, previous studies of the ACE-I/D variant and preeclampsia have been individually underpowered to detect plausible genotypic risks. METHODS AND FINDINGS: A prospective case-control study was conducted in 1,711 unrelated young pregnant women (665 preeclamptic and 1,046 healthy pregnant controls) recruited from five Colombian cities. Maternal blood was obtained to genotype for the ACE-I/D polymorphism. Crude and adjusted odds ratio (OR) and 95% confidence interval (CI) using logistic regression models were obtained to evaluate the strength of the association between ACE-I/D variant and preeclampsia risk. A meta-analysis was then undertaken of all published studies to February 2006 evaluating the ACE-I/D variant in preeclampsia. An additive model (per-D-allele) revealed a null association between the ACE-I/D variant and preeclampsia risk (crude OR = 0.95 [95% CI, 0.81-1.10]) in the new case-control study. Similar results were obtained after adjusting for confounders (adjusted per-allele OR = 0.90 [95% CI, 0.77-1.06]) and using other genetic models of inheritance. A meta-analysis (2,596 cases and 3,828 controls from 22 studies) showed a per-allele OR of 1.26 (95% CI, 1.07-1.49). An analysis stratified by study size showed an attenuated OR toward the null as study size increased. CONCLUSIONS: It is highly likely that the observed small nominal increase in risk of preeclampsia associated with the ACE D-allele is due to small-study bias, similar to that observed in cardiovascular disease. Reliable assessment of the origins of preeclampsia using a genetic approach may require the establishment of a collaborating consortium to generate a dataset of adequate size.

Non-HLA associations with autoimmune diseases.

Susceptibility to autoimmune diseases (AID) has been associated with multiple combinations of genes and environmental or stochastic factors. The strongest influence on susceptibility to autoimmunity is the major histocompatibility complex (MHC), in particular HLA; however, linkage analyses among multiple affected family members have established that non-MHC chromosomal susceptibility regions also influence the susceptibility towards AID. Besides HLA, three non-HLA genes have been convincingly associated with different AID: Citotoxic T lymphocyte-associated antigen 4 (CTLA4), Protein Tyrosine Phosphatase (PTPN22) and Tumor Necrosis Factor-alpha (TNF), indicating that autoimmune phenotypes could represent pleiotropic outcomes of non-specific diseases' genes that underline similar immunogenetic mechanisms. Identification of genes that generate susceptibility will enhance our understanding of the mechanisms that mediate these complex diseases and will allow us to predict and/or prevent them as well as to discover new therapeutic interventions.