Acceptability of a Dapivirine/Placebo Gel Administered Rectally to HIV-1 Seronegative Adults (MTN-026).

This study describes the acceptability of a rectal microbicide gel formulation using dapivirine (DPV) among men and women from two countries (United States and Thailand) participating in the Microbicide Trials Network-026 trial. We evaluated participants' acceptability of a rectal DPV/placebo gel as part of a Phase I trial (N = 26; 18 male, 8 female). Participants reported favorable acceptability of the study gel, with most participants reporting that they liked the gel the same (n = 14; 53.8%) or more (n = 11; 42.4%) than when they started the trial. Over half of participants noted that they would prefer the gel over condoms (n = 13; 50%) or that they liked condoms and the gel equally (n = 8; 30.8%). Side effects across products included leakage (n = 8; 30.8%), diarrhea (n = 4; 15.4%), or soiling (n = 1; 3.8%). The high acceptability of a rectal gel underscores its promise as a short-acting biomedical prevention, warranting future research for HIV prevention.Trial Registration: NCT03239483.

RESUMEN: Este estudio describe la aceptabilidad de un microbicida rectal (RM) con dapivirina (DPV) formulado como un gel por hombres y mujeres de dos países (Estados Unidos y Tailandia) que participaron como parte del Microbicide Trials Network (MTN)-026. Evaluamos la aceptabilidad de un gel rectal de DPV y un placebo como parte de un estudio de Fase I (N = 26; 18 hombres, 8 mujeres). Los participants informaron una aceptabilidad favorable sobre el gel del estudio; la mayoría de los participantes informaron que les gustó el gel igual (n = 14; 53.8%) o más (n = 11; 42.4%) que cuando comenzaron el estudio. Más de la mitad de los participantes señalaron que preferirían el gel sobre los condones (n = 13; 50%) o que les gustaban los condones y el gel por igual (n = 8; 30,8%). Los efectos de los productos incluyeron fugas (n = 8; 30,8%), diarrea (n = 4; 15,4%) o ensuciamiento (n = 1; 3,8%). La alta aceptabilidad de un gel rectal enfatiza su promesa para la prevención biomédica de acción corta y justifica futuras investigaciones para la prevención del VIH.

Predicting Future Renal Function Decline in Patients with Autosomal Dominant Polycystic Kidney Disease Using Mayo Clinic Classification.

INTRODUCTION: Mayo clinic classification (MCC) has been proposed in patients with autosomal dominant polycystic kidney disease (ADPKD) to identify who may experience a rapid decline of renal function. Our aim was to validate this predictive model in a population from southern Spain. METHODS: ADPKD patients with measurements of height-adjusted total kidney volume (HtTKV) and baseline estimated glomerular filtration rate (eGFR) >30 mL/min/1.73 m2 were selected. Last eGFR was estimated with Mayo Clinic (MC) equation and bias and accuracy were studied. We also analyzed predictive capacity of MCC classes using survival analysis and Cox regression models. RESULTS: We included 134 patients with a mean follow-up of 82 months. While baseline eGFR was not different between classes, last eGFR decreased significantly with them. eGFR variation rate was different according to the MCC class with a more rapid decline in 1C, 1D, and 1E classes. Final eGFR predicted was not significantly different from the real one, with an absolute bias of 0.6 ± 17.0 mL/min/1.73 m2. P10 accuracy was low ranging from 37.5 to 59.5% in classes 1C, 1D, and 1E. Using MC equation, the rate of eGFR decline was underestimated in 1C, 1D, and 1E classes. Cox regression analysis showed that MCC class is a predictor of renal survival after adjusting with baseline eGFR, age, sex, and HtTKV, with 1D and 1E classes having the worst prognosis. CONCLUSION: MCC classification is able to identify patients who will undergo a more rapid decline of renal function in a Spanish population. Prediction of future eGFR with MC equation is acceptable as a group, although it shows a loss of accuracy considering individual values. The rate of eGFR decline calculated using MC equation can underestimate the real rate presented by patients of 1C, 1D, and 1E classes.

Severe periodontitis is linked with increased peripheral levels of sTWEAK and PTX3 in chronic migraineurs.

OBJECTIVES: Periodontitis (PD) and chronic migraine (CM) have been recently linked, and inflammatory processes and vascular endothelial changes are hypothesized as potential mediators of this relationship. The aim of this cross-sectional analysis was to investigate the potential association of PD with vascular systemic inflammation and complement activation in patients with CM. MATERIALS AND METHODS: Ninety-four chronic migraineurs underwent a full-mouth periodontal evaluation and a measure of PD activity and severity, namely the periodontal inflamed surface area (PISA) was calculated for each patient. We divided CM patients according to their periodontal status: mild PD (N = 14), moderate PD (N = 22), severe PD (N = 19), and non-PD (N = 39). Serum levels of C-reactive protein (CRP), pentraxin 3 (PTX3), soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK), and complements C3 and C4 were measured outside of migraine attacks. RESULTS: We found that severe periodontal patients had significantly higher circulating levels of PTX3 and sTWEAK compared with those without PD (2475.3 ± 1646.8 pg/mL vs. 516.6 ± 1193.8 pg/mL, P < 0.0001 and 672.4 ± 118.2 pg/mL vs. 485.7 ± 112.2 pg/mL, P < 0.0001; respectively). For the remaining biomarkers, no significant differences were found between groups. Severe PD was independently associated with higher levels of PTX3 (ß = 1997.6, P < 0.0001) and sTWEAK (ß = 187.1, P < 0.0001) but not with CRP, C3, and C4. PISA positively correlated to PTX3 (r = 0.475, P < 0.0001) and sTWEAK (r = 0.386, P < 0.0001). CONCLUSIONS: Based on these preliminary results, severe PD was linked with vascular systemic inflammation in patients with CM. However, further longitudinal studies should be performed to confirm these findings. CLINICAL RELEVANCE: sTWEAK and PTX3 measured in serum could be used as biomarkers in the PD-CM link.

Association between periodontitis and chronic migraine: a case-control study.

The aim of this investigation was to examine whether chronic periodontitis (CP) is a risk indicator of chronic migraine (CM). We performed a case-control study consisted of 102 cases (patients diagnosed with CM) and 91 controls (non-CM individuals) matched by age and gender. Full-mouth periodontal charts, demographic, medical, clinical, as well as neurological data were obtained. In addition, high sensitive C-reactive protein serum levels were determined from blood samples of both cases (taken during migraine interictal period) and controls. The prevalence of CP was significantly higher in patients with CM compared to those without CM (58.8 vs. 30.8%, p < 0.0001). Logistic regression analysis showed that CP was significantly associated with the presence of CM, independently of well-known chronifying factors of migraine (OR 2.4; 95% CI 1.2-4.7; p = 0.012). Based on our results, CP could be considered as a risk indicator of CM. However, more evidence is necessary to investigate if this relationship is causal or not.

Comorbidity between idiopathic overactive bladder and chronic migraine.

Objective We tested whether overactive bladder (OAB) and chronic migraine (CM) could be comorbid. Patients and methods CM women, aged 40-69 years, answered a validated OAB questionnaire. Prevalence data were compared with those reported in our country in the general population (GP) using the same questionnaire. Results We interviewed 231 CM women. Eighty-four met OAB criteria. OAB prevalence in CM patients was significantly higher than that found in the GP (36.4% vs. 21.8% in the GP; p = 0.0001). There were 34 CM women aged 40-49 years (34.3% vs. 15.2%; p = 0.001), 35 aged 50-59 years (38.9% vs. 21.7%; p = 0.004) and 15 aged 60-69 years (35.7% vs. 24.5%; p = 0.15) meeting OAB criteria. Seventy-seven (33% vs. 9.9%; p = 0.002) needed more than eight micturitions/24 h, 61 (26.4% vs. 8.1%, p = 0.002) experienced nocturia and 43 (18.6% vs. 8.1%; p = 0.001) urinary incontinence. Conclusion In this exploratory study, at least in women, OAB and CM are comorbid, which suggests shared mechanisms.

Role of adipocytokines in the pathophysiology of migraine: A cross-sectional study.

Background Obesity is a risk factor for migraine and headache chronification. Adipocytokines may be involved in this correlation. Objective To relate serum adipocytokine levels to clinical and biochemical parameters associated with migraine. Methods We measured levels of leptin, adiponectin and other inflammatory (interleukin 6, interleukin 10, tumor necrosis factor α, high sensitivity C-reactive protein) and endothelial (pentraxin 3, soluble TNF-like weak inducer of apoptosis) molecules potentially related to migraine pathophysiology in a group of migraine patients (IHS 2013) and healthy controls. Results One hundred and eleven patients (mean age 39.7 years, 93% female) and 24 healthy controls (mean age 35.9 years, 90% female) were included. Fifty-six patients were diagnosed with episodic migraine (mean age 35.1 years, 98.2% female) and 55 patients with chronic migraine (mean age 44.4 years, 89.5% female). Leptin serum levels (15.2 ng/mL, SD = 10.5 vs . 3.1 ng/mL, SD = 0.9; p < 0.001) and adiponectin serum levels (72.3 µg/mL, SD = 38.5 vs . 37.7 µg/mL, SD = 16.9; p < 0.001) were significantly increased in migraine patients. Leptin serum levels (15.5 ng/mL, SD = 9.7 vs . 10.8 ng/mL, SD = 6.0; p < 0.001) and adiponectin serum levels (65.8 µg/mL, SD = 42.9 vs . 33.2 µg/mL, SD = 31.0; p < 0.001) were significantly higher in chronic compared to episodic migraine patients. We found a positive correlation between leptin levels and inflammatory biomarkers: IL6 (r = 0.498; p < 0.001), TNF-α (r = 0.389; p < 0.001), and hs-CRP (r = 0.422; p < 0.001). Conclusions Leptin and adiponectin are increased in migraineurs. There is a correlation between adipocytokine levels and other inflammation-related molecules. This suggests a potential role of adipocytokines in migraine pathophysiology and chronification.

CGRP and PTX3 as Predictors of Efficacy of Onabotulinumtoxin Type A in Chronic Migraine: An Observational Study.

OBJECTIVE: The aim of this study is to find a relation between several biomarkers in peripheral blood and outcome after treatment with onabotulinumtoxin A (OnabotA). BACKGROUND: OnabotA is an effective treatment in chronic migraine (CM). Different studies have tried to find predictors of response to treatment, either with clinical characteristics, neuroimaging features, or molecular biomarkers; however, it is still not possible to predict the individual outcome. METHODS: We measured serum levels of biomarkers of inflammation (IL-6, IL-10, TNF-α, and hs-CRP), endothelial dysfunction (PTX3 and sTWEAK), blood-brain barrier disruption (cFN), brain damage (S100b, NSE), and trigemino-vascular activation (CGRP) by ELISA in a group of CM patients treated with OnabotA and healthy controls. After 24 weeks, patients were classified in two groups according to their outcome considering variations in headache frequency: nonresponders (nonimprovement or improvement <50%) and responders (improvement >50%). We compared baseline levels of biomarkers between these groups. RESULTS: Sixty-two patients diagnosed with CM (IHS 2013 criteria) who fulfilled criteria for treatment with OnabotA and 24 healthy controls were included. Fifteen patients did not respond to treatment (24.2%) and 47 were responders (75.8%). Pentraxin 3 (PTX3) serum levels (1455.4 ± 487.5 pg/mL versus 720.3 ± 334.1 pg/mL, P < .0001) and calcitonin gene-related peptide (CGRP) serum levels (133.1 ± 86.6 ng/mL versus 58.2 ± 91.7 ng/mL, P = .004) were significantly higher in responders than nonresponders. Serum basal levels of PTX3 >1000 pg/mL (AUC 0.908; 95% CI: 0.827-0.990) and CGRP >50 ng/mL (AUC 0.800; 95% CI: 0.652-0.947) were associated with good response to OnabotA treatment. CONCLUSIONS: These results show that molecular markers of trigeminovascular activation (CGRP) and endothelial dysfunction (PTX3) are associated with response to OnabotA and may act as new biomarkers for the selection of treatment in chronic migraineurs.

Is Periodontal Disease Associated with Alzheimer's Disease? A Systematic Review with Meta-Analysis.

BACKGROUND: In the last decade, several observational studies have suggested that there exists an association between periodontal disease (PD) and Alzheimer's disease (AD). The aim of this systematic review was to investigate whether or not this link exists. SUMMARY: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis guideline for systematic review was used and registered at PROSPERO (CRD42016035377). The search strategy included using electronic databases and by hand searching articles published up to January 2016. MEDLINE via PubMed, EMBASE and Web of Science were searched by 2 independent reviewers. Observational studies including patients meeting criteria for both AD and PD were eligible to be included in the analysis. Quality assessment of selected studies was performed by the Newcastle-Ottawa Scale. From a total of 550 titles and abstracts, 5 studies were included (2 cross-sectional, 2 case-control and one cohort study) in the review. A fixed effects meta-analysis showed that the presence of PD is associated with the presence of AD (OR 1.69, 95% CI 1.21-2.35). When only severe forms of PD were evaluated, a significant association was also observed (OR 2.98, 95% CI 1.58-5.62). Key Messages: In the present review, a significant association was observed between PD and AD. Further studies should be carried out in order to investigate the direction of the association and factors that may confound it.

The role of leptin as a biomarker in the relationship between periodontitis and chronic migraine.

AIM: To evaluate the prevalence of periodontitis (CP) and its contribution to serum leptin levels in chronic migraine (CM). MATERIAL AND METHODS: In this case-control study, we included 150 subjects divided into healthy controls (n = 58) and CM patients (n = 92). Demographic, neurological, clinical data as well as full-mouth periodontal records were obtained. Serum leptin levels were measured by ELISA technique. RESULTS: Both the prevalence of CP and mean serum leptin levels were significantly higher in patients with CM in comparison with controls (57.6% versus 36.2%, p = .01 and 16.4 versus 7.2 ng/ml, p < .0001, respectively). Patients from the CM group who had CP showed significantly higher leptin concentrations than CM patients without CP (19.8 versus 11.8 ng/ml, p < .0001). Multivariable linear regression analysis showed that CP was an independent contributor to raised leptin levels in CM patients (R2  = 0.270, p = 0.013). CONCLUSIONS: CP is prevalent in CM patients and when present it contributes to elevated serum leptin levels, independently of other confounding factors. Therefore, it seems that CP via leptin could be involved in the process of migraine chronification.

Association between periodontitis and peripheral markers of innate immunity activation and inflammation.

BACKGROUND: Immune response leading to increased systemic inflammation is one of the mechanisms linking periodontitis to chronic inflammatory diseases. The aim of this study was to compare the expression of toll-like receptors 2 and 4 in monocytes and neutrophils (TLR2M, TLR2N, TLR4M, and TLR4N) and its endogenous ligands (cellular fibronectin [cFN] and heat shock protein 60 [HSP60]) in patients with and without periodontitis. Additionally, the relationship between cFN and HSP60 expression with innate immunity activation and systemic inflammatory response (interleukin 6 [IL-6]) was also evaluated. METHODS: A case-controlled study was designed in which 30 patients with periodontitis (cases) and 30 age- and sex-matched participants without periodontitis (controls) were included. Fasting blood samples were collected to determine: (1) expression of TLR2N, TLR2M, TLR4N, and TLR4M by flow cytometry; and (2) serum concentrations of cFN, HSP60, and IL-6 by ELISA technique. RESULTS: Expression of TLR2M (411.5 [314.2, 460.0] vs. 236.5 [204.0, 333.0] AFU), TLR2N (387.0 [332.0, 545.5] vs 230.0 [166.2, 277.7] AFU), TLR4M (2478.5 [1762.2, 2828.0] vs 1705.0 [1274.5, 1951.2] AFU), and TLR4N (2791.0 [2306.7, 3226.2] vs. 1866.0 [1547.5, 2687.2] AFU) as well as serum levels of cFN (301.1 [222.2, 410.9] vs. 156.4 [115.3, 194.0] ng/ml) and IL-6 (10.4 [6.5, 11.5] vs. 3.5 [2.6, 4.9] pg/ml) were significantly higher in periodontitis patients than those without periodontitis. A positive association was found between periodontitis and cFN (odds ratio [OR] = 1.028, p < 0.001), TLR2N (OR = 1.026, p < 0.001), TLR4M (OR = 1.001, p = 0.002), and IL-6 (OR = 1.774, p < 0.001). CONCLUSIONS: Periodontitis patients exhibited high expression of TLRs, cFN, and IL-6.

Challenges in the design and analysis of sequentially monitored postmarket safety surveillance evaluations using electronic observational health care data.

PURPOSE: Many challenges arise when conducting a sequentially monitored medical product safety surveillance evaluation using observational electronic data captured during routine care. We review existing sequential approaches for potential use in this setting, including a continuous sequential testing method that has been utilized within the Vaccine Safety Datalink (VSD) and group sequential methods, which are used widely in randomized clinical trials. METHODS: Using both simulated data and preliminary data from an ongoing VSD evaluation, we discuss key sequential design considerations, including sample size and duration of surveillance, shape of the signaling threshold, and frequency of interim testing. RESULTS AND CONCLUSIONS: All designs control the overall Type 1 error rate across all tests performed, but each yields different tradeoffs between the probability and timing of true and false positive signals. Designs tailored to monitor efficacy outcomes in clinical trials have been well studied, but less consideration has been given to optimizing design choices for observational safety settings, where the hypotheses, population, prevalence and severity of the outcomes, implications of signaling, and costs of false positive and negative findings are very different. Analytic challenges include confounding, missing and partially accrued data, high misclassification rates for outcomes presumptively defined using diagnostic codes, and unpredictable changes in dynamically accessed data over time (e.g., differential product uptake). Many of these factors influence the variability of the adverse events under evaluation and, in turn, the probability of committing a Type 1 error. Thus, to ensure proper Type 1 error control, planned sequential thresholds should be adjusted over time to account for these issues.

Hypocitraturia is present when renal function is impaired in diverse nephropathies and is not related with serum bicarbonate levels.

BACKGROUND: In autosomal dominant polycystic kidney disease (ADPKD) it is frequently found a reduction in urinary citrate of unknown origin. It has been suggested that it could be a marker of acid retention in chronic kidney disease. Our aim was to compare urinary citrate in ADPKD with other nephropathies and to show its relation with serum bicarbonate. METHODS: We determined urinary citrate in patients with several nephropathies and varied renal function. We included 291 patients, 119 with glomerular diseases, 116 with ADPKD, 21 with other nephropathies, and 35 patients with normal renal function. RESULTS: Urinary citrate was higher in women and in patients with normal renal function. ADPKD patients showed similar values of urinary citrate to patients with glomerular diseases and with other nephropathies. We observed a progressive reduction in urinary citrate with renal impairment, in a comparable way among patients with ADPKD and glomerular diseases. We did not observe a relationship with serum bicarbonate. Serum uric acid levels were significantly higher in patients with glomerular diseases than in ADPKD patients, even after correction with the degree of renal function. CONCLUSIONS: Hypocitraturia is not specific of ADPKD but it is also present in all tested nephropathies and is related with renal impairment and not with serum bicarbonate. It could be interesting to study urinary citrate as a marker of renal function and as a prognostic factor.

Urinary citrate as a marker of renal function in patients with autosomal dominant polycystic kidney disease.

INTRODUCTION: Autosomal dominant polycystic kidney disease (ADPKD) is frequent to find low urinary citrate levels. Recently, it has been suggested that urinary citrate could be a marker of covert metabolic acidosis in chronic kidney disease. OBJECTIVE: Our aim was to analyze relationship between urinary citrate levels, renal function, and serum bicarbonate in ADPKD patients. METHODS: We determined citrate in 24-h collected urine from ADPKD patients and correlated with glomerular filtration rate (CKD-EPI equation) and serum bicarbonate concentration. RESULTS: We included 120 patients, 60% men, eGFR was 71 ± 32 mL/min/1.73 m2. Urinary citrate/creatinine ratio was 195 ± 152 mg/gCr (range 1.2-689) with levels significantly higher in females. Urinary citrate lower than 300 mg/gCr was present in 75% of patients and when considering chronic kidney stages (CKD), we observed reduced levels in 48.8% in CKD1 stage, in 79.4% in CKD2 stage, in 96.2% in CKD3 stage, and in 94.7% of patients in CKD4 stage. Urinary citrate was correlated with serum creatinine (r = - 0.61, p < 0.001) and eGFR (r = 0.55, p < 0.001) in both gender. We did not find any correlation with serum bicarbonate. Using a general linear modeling analysis, we found as predictors of urinary citrate/creatinine ratio to glomerular filtration rate, gender, and age. Lower levels of urinary citrate were accompanied by a decline in urinary osmolality and in renal excretion of calcium and uric acid. In a subgroup of patients, we measured total kidney volume and we found an inverse correlation with urinary citrate levels that disappeared when it was corrected with glomerular filtration rate. CONCLUSIONS: Urinary citrate is very frequently reduced in ADPKD patients being present from very early CKD stages. Their levels in urine are inversely correlated with glomerular filtration rate and it is not related with serum bicarbonate concentration. We think that it would be interesting to study urinary citrate as a marker of chronic kidney disease in ADPKD patients.

Whole blood DNA methylation analysis reveals respiratory environmental traits involved in COVID-19 severity following SARS-CoV-2 infection.

SARS-CoV-2 infection can cause an inflammatory syndrome (COVID-19) leading, in many cases, to bilateral pneumonia, severe dyspnea, and in ~5% of these, death. DNA methylation is known to play an important role in the regulation of the immune processes behind COVID-19 progression, however it has not been studied in depth. In this study, we aim to evaluate the implication of DNA methylation in COVID-19 progression by means of a genome-wide DNA methylation analysis combined with DNA genotyping. The results reveal the existence of epigenomic regulation of functional pathways associated with COVID-19 progression and mediated by genetic loci. We find an environmental trait-related signature that discriminates mild from severe cases and regulates, among other cytokines, IL-6 expression via the transcription factor CEBP. The analyses suggest that an interaction between environmental contribution, genetics, and epigenetics might be playing a role in triggering the cytokine storm described in the most severe cases.

Mild systemic inflammation enhances response to OnabotulinumtoxinA in chronic migraineurs.

The anti-inflammatory effect of OnabotulinumtoxinA (OnabotA) has been a matter of discussion for many years. In chronic migraine, however, increased pro-inflammatory state is associated with good response to OnabotA. We aimed to investigate whether a mild systemic inflammatory state elicited by a common oral infection (periodontitis) could enhance treatment response to OnabotA. In this study, we included 61 chronic migraineurs otherwise healthy treated with OnabotA of which 7 were poor responders and 54 good responders. Before receiving OnabotA therapy, all participants underwent a full-mouth periodontal examination and blood samples were collected to determine serum levels of calcitonin gene-related peptide (CGRP), interleukin 6 (IL-6), IL-10 and high sensitivity C-reactive protein (hs-CRP). Periodontitis was present in 70.4% of responders and 28.6% of non-responders (P = 0.042). Responders showed greater levels of inflammation than non-responders (IL-6: 15.3 ± 8.7 vs. 9.2 ± 4.7 ng/mL, P = 0.016; CGRP: 18.8 ± 7.6 vs. 13.0 ± 3.1 pg/mL, P = 0.002; and hs-CRP: 3.9 ± 6.6 vs. 0.9 ± 0.8 mg/L, P = 0.003). A linear positive correlation was found between the amount of periodontal tissue inflamed in the oral cavity and markers of inflammation (IL-6: r = 0.270, P = 0.035; CGRP: r = 0.325, P = 0.011; and hs-CRP: r = 0.370, P = 0.003). This report shows that in presence of elevated systemic inflammatory markers related to periodontitis, OnabotA seems to reduce migraine attacks. The changes of scheduled inflammatory parameters after treatment and subsequent assessment during an adequate period still need to be done.

The prevalence of anemia decreased in Mexican preschool and school-age children from 1999 to 2006.

OBJECTIVE: To compare the distribution of anemia in children, based on information from Mexican National Health and Nutrition Survey 2006 (ENSANUT 2006) and Mexican National Nutrition Survey 1999 (ENN-99), and examine the association of anemia with potentially explanatory variables. MATERIAL AND METHODS: Adjusted prevalence and means as well as associations with potentially explanatory variables were assessed by multiple linear and logistic regression models for complex samples. RESULTS: From 1999 to 2006, the prevalence of anemia decreased 13.8 percentage points (pp) in toddlers and 7.8 pp in children 24-35 months of age; it also decreased 0.7 pp/year in urban and rural populations, 1.8 pp/year in indigenous and 0.61 pp/year in non-indigenous toddlers, 1.5 pp/year in children 5-8 years of age and 0.78 pp/year in children 9-11 years of age. In toddlers served by Oportunidades, Hb was inversely associated with indigenous ethnicity (p=0.1) and they had a lower risk of anemia (OR=0.002). In school-age children, age (OR=0.98), affiliation to Liconsa (OR=0.42) and living in the central region (OR=0.56) were protective factors for anemia. CONCLUSIONS: The national prevalence of anemia in Mexico has decreased in the past seven years, especially in toddlers. Being a beneficiary of Liconsa or Oportunidades was protective for anemia.

Periodontal inflammation is related to increased serum calcitonin gene-related peptide levels in patients with chronic migraine.

BACKGROUND: Recently, a relationship was found between periodontitis and chronic migraine. Calcitonin gene-related peptide (CGRP) is a key element in migraine pathophysiology. However, no information exists of the potential association between periodontal inflammation and CGRP in chronic migraine. The aim of the study was, therefore, to investigate whether there is a link between periodontitis and peripheral levels of CGRP in a cohort of patients with chronic migraine. METHODS: We included 102 chronic migraineurs and 77 age- and sex-matched individuals free of headache/migraine. Full-mouth periodontal parameters were recorded and the periodontal inflamed surface area (PISA) was calculated to quantify the periodontal inflammatory status for each participant. Sociodemographic data and comorbidities were assessed by means of a standard questionnaire. We collected blood samples and serum concentrations were done for CGRP, interleukin (IL)-6 and IL-10. RESULTS: In the chronic migraine group, patients with periodontitis had greater levels of serum CGRP (19.7 ± 6.5 versus 15.3 ± 6.2 pg/mL, P < 0.0001) and IL-6 (15.1 ± 9.2 versus 9.6 ± 6.3 pg/mL, P < 0.0001) while non-significant differences were observed with IL-10 (2.0 ± 1.0 versus 2.8 ± 1.5 pg/mL, P = 0.675) concentrations than those without periodontitis. PISA was independently associated with CGRP in patients with chronic migraine (ß = 0.003; 95% confidence interval: 0.001 to 0.006, P = 0.031). PISA correlated positively with CGRP (r = 0.236; P = 0.017) and IL-6 (r = 0.262; P = 0.008) in chronic migraine. CONCLUSIONS: Periodontal inflammation is associated with increased circulating levels of CGRP in chronic migraineurs. Elucidating the exact mechanisms through which periodontitis and CGRP are linked in these patients deserves further investigation.

Iron deposition in periaqueductal gray matter as a potential biomarker for chronic migraine.

OBJECTIVE: To study iron deposition in red nucleus (RN), globus pallidus (GP), and periaqueductal gray matter (PAG) as a potential biomarker of chronic migraine (CM) and its association with levels of biomarkers related to migraine pathophysiology. METHODS: This case-control study included 112 patients with migraine (55 CM, 57 episodic migraine [EM]) and 25 headache-free controls. We analyzed iron deposition using 3T MRI and the NIH software platform ImageJ; we analyzed serum levels of markers of inflammation, endothelial dysfunction, and blood-brain barrier (BBB) disruption by ELISA in peripheral blood during interictal periods. RESULTS: Patients with CM showed larger iron grounds volume in RN compared to patients with EM (70.2 ± 6.8 vs 25.5 ± 7.3 µL, p < 0.001) and controls (70.2 ± 6.8 vs 15.1 ± 10.8 µL, p < 0.001), as well as larger iron deposits in PAG compared to patients with EM (360.3 ± 6.5 vs 249.7 ± 6.9 µL, p < 0.001) and controls (360.3 ± 6.5 vs 168.6 ± 10.3 µL, p < 0.001). In PAG, differences were also significant between patients with EM and controls. No significant differences were obtained for GP. Receiver operating characteristic curves showed that the optimal threshold for iron volume was 15 µL in RN (80% sensitivity, 71% specificity) and 240 µL in PAG (93% sensitivity, 97% specificity). Iron grounds volume in PAG was correlated with higher plasma levels of soluble tumor necrosis factor-like WEAK (r = 0.395, p = 0.005) and cellular fibronectin (r = 0.294, p = 0.040). CONCLUSIONS: Patients with CM showed increased iron deposition in RN and PAG compared to patients with EM and controls. Iron grounds volume in PAG identified correctly patients with CM and was associated with elevated biomarkers of endothelial dysfunction and BBB disruption.

The Oportunidades program increases the linear growth of children enrolled at young ages in urban Mexico.

The goal of this study was to evaluate the impact of Mexico's conditional cash transfer program, Oportunidades, on the growth of children <24 mo of age living in urban areas. Beneficiary families received cash transfers, a fortified food (targeted to pregnant and lactating women, children 6-23 mo, and children with low weight 2-4 y), and curative health services, among other benefits. Program benefits were conditional on preventative health care utilization and attendance of health and nutrition education sessions. We estimated the impact of the program after 2 y of operation in a panel of 432 children <24 mo of age at baseline (2002). We used difference-in-difference propensity score matching, which takes into account nonrandom program participation and the effects of unobserved fixed characteristics on outcomes. All models controlled for child age, sex, baseline anthropometry, and maternal height. Anthropometric Z-scores were calculated using the new WHO growth reference standards. There was no overall association between program participation and growth in children 6 to 24 mo of age. Children in intervention families younger than 6 mo of age at baseline grew 1.5 cm (P < 0.05) more than children in comparison families, corresponding to 0.41 height-for-age Z-scores (HAZ) (P < 0.05). They also gained an additional 0.76 kg (P < 0.01) or 0.47 weight-for-height Z-scores (P < 0.05). Children living in the poorest intervention households tended (0.05 < P < 0.10) to be taller than comparison children (0.9 cm, 0.27 HAZ). Oportunidades, with its strong nutrition component, is an effective tool to improve the growth of infants in poor urban households.