Frank's Sign and Cardiovascular Risk: An Observational Descriptive Study.

PURPOSE: This study was undertaken to analyze the relationship between the diagonal earlobe crease and the main indices of cardiovascular risk, considering the crease's anatomical variations. METHODS: The study group consisted of 1050 adults residing in Spain. Participants underwent the following determinations: age, sex, body mass index, smoking habit, blood pressure, glycemia, glycated hemoglobin, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and cardiovascular events. Cardiovascular risk was calculated applying the Framingham-Anderson equation, the Systematic Coronary Risk Evaluation equation, and the Atherosclerotic Cardiovascular Disease Risk Score calculator. Both earlobes were examined, recording diagonal earlobe crease presence, length and depth, and presence of accessory creases. Results were analyzed by using chi-square test, Student's t test, analysis of variance, and Mann-Whitney or Kruskal-Wallis tests. To extract the functions of cardiovascular risk, a script in R was created (https://cran.r-project.org/). RESULTS: The estimated cardiovascular mortality risk was significantly higher in individuals who presented diagonal earlobe crease (P < .001). The number of individuals with moderate, high, or very high cardiovascular risk increased significantly as the presence of the crease increased (23.8% had no crease, 35.6% had unilateral creases, and 58% had bilateral creases; P < .001). The mean cardiovascular risk estimated was significantly higher for individuals with longest and deepest diagonal earlobe crease (P < .001 and P < .001, respectively), and with accessory creases (P < .001). CONCLUSIONS: The diagonal earlobe crease is independently associated with higher cardiovascular risk scores, especially when the crease is complete, bilateral, deep, and has accessory creases.

Structural Similarities, in Relation with the Cross-Reactivity, of Hymenoptera Allergenic Dipeptidyl Peptidases IV-An Overall Comparison Including a New Dipeptidyl Peptidase IV Sequence from Vespa velutina.

(1) Background: Dipeptidyl Peptidases IV (DPPIVs), present in many organisms, are minor components in the venoms of Hymenoptera, where they have been identified as cross-reactive allergenic molecules. Considering that the structure of homologous DPPIVs is well characterized, we aimed to explain which regions have higher similarity among these proteins and present a comparison among them, including a new Vespa velutina DPPIV sequence. Moreover, two cases of sensitization to DPPIVs in wasp- and honeybee-sensitized patients are presented. (2) Methods: Proteomic analyses have been performed on the venom of the Asian hornet Vespa velutina to demonstrate the sequence of its DPPIV (allergen named Vesp v 3, with sequence accession number P0DRB8, and with the proteomic data available via ProteomeXchange with the identifier PXD046030). A comparison performed through their alignments and analysis of the three-dimensional structure showed a region with higher similarity among Hymenoptera DPPIVs. Additionally, ImmunoCAP™ determinations (including specific inhibition experiments), as well as IgE immunoblotting, are performed to demonstrate the allergenicity of Api m 5 and Ves v 3. (3) Results and Conclusions: The data presented demonstrate that the similarities among Hymenoptera DPPIVs are most likely localized at the C-terminal region of these enzymes. In addition, a higher similarity of the Vespa/Vespula DPPIVs is shown. The clinical cases analyzed demonstrated the allergenicity of Api m 5 and Ves v 3 in the sera of the allergic patients, as well as the presence of this minor component in the preparations used in venom immunotherapy.

C-Reactive Protein versus Erythrocyte Sedimentation Rate: Implications Among Patients with No Known Inflammatory Conditions.

BACKGROUND: Measurements of C-reactive protein (CRP) concentration and erythrocyte sedimentation rate (ESR) are frequently ordered jointly in clinical practice. AIM: To investigate the factors associated with discordances between CRP concentration and ESR in adults. METHODS: We conducted a cross-sectional study of 1472 adults with no known inflammatory disorders (44.5% male; median age, 52 years; range, 18-91 years), randomly selected from a municipality in Spain. The participants underwent simultaneous measurements of ESR, serum CRP, and interleukin-6 concentrations. Alcohol consumption, smoking, and physical activity were evaluated by questionnaire. Body mass index (BMI) measurement and metabolic syndrome criteria were available for all participants. RESULTS: Most (n = 1123, 74.9%) of the participants showed normal CRP and ESR values. Sixty-nine (4.6%) participants showed high CRP and ESR values. Seventy-two (4.8%) participants showed a discordant pattern of high ESR and normal CRP values, which was associated with age after adjusting for sex, alcohol consumption, physical activity, BMI, and the presence of metabolic syndrome (odds ratio [OR], 1.052; 95% CI, 1.034-1.071; P < .001). A total of 208 (13.8%) participants showed a discordant pattern of high CRP and normal ESR values, which was associated with BMI after adjusting for covariates (OR, 1.099; 95% CI, 1.064-1.136; P < .001). BMI appeared to be the main determinant of serum CRP concentrations in this population. Serum interleukin-6 concentrations were positively associated with the discordant pattern of high CRP and normal ESR values. CONCLUSION: In this general adult population with no overt inflammatory disease, the discordant pattern of high ESR and normal CRP was associated with greater age, whereas the pattern of high CRP and normal ESR was associated with higher BMI.

Factors associated with serum IgM concentrations: a general adult population study.

BACKGROUND AND AIM: To investigate the influence of common factors on serum immunoglobulin M (IgM) concentrations in adults, and clinical associations with high and low values. METHODS: We measured serum IgM levels using immunonephelometry in a random sample of 1510 individuals (aged 18-91 years, 44.7% male). We obtained data defining metabolic syndrome from all participants, defined atopy by skin prick tests to aeroallergens, and assessed lifestyle factors by questionnaire. RESULTS: Women showed higher IgM concentrations than men; 95 (6.3%, mostly male) individuals showed low (<0.40 g/L) IgM values, and 64 (4.2%, mostly female) showed high (>2.30 g/L) IgM values. Individuals with abnormal IgM concentrations had no history of opportunistic infections nor a different atopy prevalence. Serum IgM concentrations decreased with age, and obesity was negatively associated with IgM concentrations. Alcohol consumption, smoking, physical activity, and metabolic syndrome had no significant influence in the multivariate analyses. CONCLUSIONS: Many adults in the general population show abnormally high or low IgM concentrations with no evidence of immunodeficiency-associated diseases. Sex and age should be considered when defining reference IgM concentrations.

Factors Influencing Total Serum IgE in Adults: The Role of Obesity and Related Metabolic Disorders.

BACKGROUND AND AIM: Few reports have investigated the association between metabolic abnormalities (obesity and related metabolic syndrome) and total serum IgE concentrations. METHODS: This cross-sectional study included a random sample of 1,516 adult individuals (44.7% men, aged 18-91 years, median 52 years) from a single municipality in Spain. Serum IgE was measured in the ADVIA Centaur system. Atopy was defined by the presence of positive skin prick tests to a panel of common aeroallergens in the area. Body mass index and data related to the definition of metabolic syndrome were obtained from all participants. Alcohol consumption, smoking, and regular physical exercise were assessed by a questionnaire. RESULTS: Atopy (present in 21.9% of 1,514 evaluable individuals) was the strongest factor determining serum IgE concentrations. Male sex and heavy alcohol drinking were independently associated with higher IgE concentrations, particularly in the non-atopic individuals. Body mass index was positively associated with IgE concentrations, independent of potential confounders, although the effect was only evident among non-atopic individuals. In that group, median IgE concentrations in normal-weight and obese individuals were 15 and 24 kU/L, respectively (p < 0.001); likewise, obesity was associated with high (>100 kU/L) IgE concentrations after adjusting for potential confounders (odds ratio: 1.79, 95% confidence interval: 1.26-2.56, p = 0.001). The presence of metabolic syndrome and its components, particularly abdominal obesity and hyperglycaemia, was also positively and independently associated with higher IgE concentrations in non-atopic individuals. CONCLUSIONS: Obesity and metabolic syndrome components are associated with high total serum IgE concentrations, particularly in non-atopic individuals.

Diagnostic accuracy of IL1ß in saliva: The development of predictive models for estimating the probability of the occurrence of periodontitis in non-smokers and smokers.

AIM: To obtain salivary interleukin (IL) 1ß-based models to predict the probability of the occurrence of periodontitis, differentiating by smoking habit. MATERIALS/METHODS: A total of 141 participants were recruited, 62 periodontally healthy controls and 79 subjects affected by periodontitis. Fifty of the diseased patients were given non-surgical periodontal treatment and showed significant clinical improvement in 2 months. IL1ß was measured in the salivary samples using the Luminex instrument. Binary logistic regression models were obtained to differentiate untreated periodontitis from periodontal health (first modelling) and untreated periodontitis from treated periodontitis (second modelling), distinguishing between non-smokers and smokers. The area under the curve (AUC) and classification measures were calculated. RESULTS: In the first modelling, IL1ß presented AUC values of 0.830 for non-smokers and 0.689 for smokers (accuracy = 77.6% and 70.7%, respectively). In the second, the predictive models revealed AUC values of 0.671 for non-smokers and 0.708 for smokers (accuracy = 70.0% and 75.0%, respectively). CONCLUSION: Salivary IL1ß has an excellent diagnostic capability when it comes to distinguishing systemically healthy patients with untreated periodontitis from those who are periodontally healthy, although this discriminatory potential is reduced in smokers. The diagnostic capacity of salivary IL1ß remains acceptable for differentiating between untreated and treated periodontitis.

Factors influencing erythrocyte sedimentation rate in adults: New evidence for an old test.

The erythrocyte sedimentation rate (ESR) is a routine test for inflammation. Few studies have investigated the potential influence of lifestyle factors and common metabolic abnormalities on the ESR. This study investigates the influence of demographic factors, alcohol consumption, smoking, physical activity, obesity, and metabolic syndrome on the ESR in adults.This cross-sectional study covered 1472 individuals (44.5% males; age range, 18-91 years) randomly selected from the population of a Spanish municipality. The ESR was measured using a standardized method. We assessed habitual alcohol consumption in standard drinking units, along with tobacco smoking, regular physical exercise (by questionnaire), body mass index, and variables defining metabolic syndrome. Multivariate analyses were performed, including mean corpuscular volume and hemoglobin concentration in the models.The ESR was higher in females than in males, and increased steadily with age. Median ESR of females was 2-fold higher than that of males, and median ESR of individuals aged >65 years was 2-fold higher than that of individuals in the youngest category (ages 18-35 years). Body mass index, presence of metabolic syndrome, and smoking were independently and positively associated with higher ESR values. Light alcohol drinkers and individuals with high regular physical activity displayed lower ESR values than did alcohol abstainers and individuals with low physical activity, respectively.ESR varies greatly with age and sex, and corresponding reference values are proposed. Lifestyle factors (physical activity, smoking, and alcohol consumption) and common metabolic abnormalities (obesity and related metabolic syndrome) may also influence ESR values.

Prediabetes defined by HbA1c and by fasting glucose: differences in risk factors and prevalence.

AIMS: To investigate, in a sample of nondiabetic adults from a Spanish community, the differences between prediabetes as defined by HbA1c ("H-prediabetes") and by fasting plasma glucose (FPG) ("F-prediabetes") in regard to prevalence and the influence of potential risk factors, adjusting the latter for confounders. METHODS: A total of 1328 nondiabetic participants aged ≥ 18 years were classified as normoglycemic, H-prediabetic [HbA1c 5.7-6.4% (39-47 mmol/mol)] or F-prediabetic (FPG 5.6-6.9 mmol/L). Multivariable analyses were used to compare the impacts of risk factors on the prevalence of H-prediabetes, F-prediabetes and their conjunctive and disjunctive combinations ("HaF-prediabetes" and "HoF-prediabetes," respectively). RESULTS: Some 29.9% of participants were HoF-prediabetic, 21.7% H-prediabetic, 16.3% F-prediabetic and only 8.1% HaF-prediabetic. Whatever the definition of prediabetes, increasing age, fasting insulin and LDL cholesterol were each a risk factor after adjustment for all other variables. Increasing BMI and decreasing mean corpuscular hemoglobin (MCH) were additional risk factors for H-prediabetes; male sex and increasing uric acid for F-prediabetes and increasing BMI for HaF-prediabetes. The participants satisfying the compound condition "hypertension or hyperlipidemia or obesity or hyperuricemia" (59.9% of the whole study group) included 83.1% of all subjects with HoF-prediabetes. CONCLUSIONS: In this population, the most sensitive risk factor for detection of prediabetes was age, followed by fasting insulin, LDL cholesterol, BMI, MCH, male sex and uric acid, with differences depending on the definition of prediabetes. MCH, an indirect measure of erythrocyte survival, significantly influences the prevalence of HbA1c-defined prediabetes. This study suggests that screening of individuals with selected risk factors may identify a high proportion of prediabetic persons.

Protein-Based Salivary Profiles as Novel Biomarkers for Oral Diseases.

The Global Burden of Oral Diseases affects 3.5 billion people worldwide, representing the number of people affected by the burden of untreated dental caries, severe periodontal disease, and edentulism. Thus, much more efforts in terms of diagnostics and treatments must be provided in the fight of these outcomes. In this sense, recently, the study of saliva as biological matrix has been identified as a new landmark initiative in the search of novel and useful biomarkers to prevent and diagnose these conditions. Specifically, saliva is a rich reservoir of different proteins and peptides and accessible due to recent advances in molecular biology and specially in targeted and unbiased proteomics technologies. Nonetheless, emerging barriers are an obstacle to the study of the salivary proteome in an effective way. This review aims at giving an overall perspective of salivary biomarkers identified in several oral diseases by means of molecular biology approaches.

Fetal Exposure to High Maternal Thyroid Hormone Levels Causes Central Resistance to Thyroid Hormone in Adult Humans and Mice.

Context: Fetuses exposed to the high thyroid hormone (TH) levels of mothers with resistance to thyroid hormone beta (RTH-ß), due to mutations in the THRB gene, have low birth weight and suppressed TSH. Objective: Determine if such exposure to high TH levels in embryonic life has a long-term effect into adulthood. Design: Observations in humans with a parallel design on animals to obtain a preliminary information regarding mechanism. Setting: University research centers. Patients or other participants: Humans and mice with no RTH-ß exposed during intrauterine life to high TH levels from mothers who were euthyroid due to RTH-ß. Controls were humans and mice of the same genotype but born to fathers with RTH-ß and mothers without RTH-ß and thus, with normal serum TH levels. Interventions: TSH responses to stimulation with thyrotropin-releasing hormone (TRH) during adult life in humans and male mice before and after treatment with triiodothyronine (T3). We also measured gene expression in anterior pituitaries, hypothalami, and cerebral cortices of mice. Results: Adult humans and mice without RTH-ß, exposed to high maternal TH in utero, showed persistent central resistance to TH, as evidenced by reduced responses of serum TSH to TRH when treated with T3. In mice, anterior pituitary TSH-ß and deiodinase 3 (D3) mRNAs, but not hypothalamic and cerebral cortex D3, were increased. Conclusions: Adult humans and mice without RTH-ß exposed in utero to high maternal TH levels have persistent central resistance to TH. This is likely mediated by the increased expression of D3 in the anterior pituitary, enhancing local T3 degradation.

Glycemic Variability and Its Association With Demographics and Lifestyles in a General Adult Population.

OBJECTIVE: The objective was to investigate glycemic variability indices in relation to demographic factors and common environmental lifestyles in a general adult population. METHODS: The A Estrada Glycation and Inflammation Study is a cross-sectional study covering 1516 participants selected by sampling of the population aged 18 years and over. A subsample of 622 individuals participated in the Glycation project, which included continuous glucose monitoring procedures. Five glycemic variability indices were analyzed, that is, SD, MAGE, MAG, CONGA1, and MODD. RESULTS: Participants had a mean age of 48 years, 62% were females, and 12% had been previously diagnosed with diabetes. In the population without diabetes, index distributions were not normal but skewed to the right. Distributional regression models that adjusted for age, gender, BMI, alcohol intake, smoking status, and physical activity confirmed that all indices were positively and independently associated with fasting glucose levels and negatively with heavy drinking. SD, MAGE, and CONGA1 were positively associated with aging, and MAG was negatively associated with BMI. None of the GVI studied were influenced by physical activity. Age-group-specific reference values are given for the indices. CONCLUSIONS: This study yielded age-specific reference values for glucose variability indices in a general adult population. Significant increases were observed with aging. Heavy drinking of more than 140 g/week was associated with significant decreases in variability indices. No differences were found between males and females. These normative ranges provide a guide for clinical care, and may offer an alternative treatment target among persons with diabetes.