Background: In 2010, the American Heart Association developed a new definition of ideal cardiovascular health (CVH) based on seven cardiovascular health metrics. This study aimed to investigate the relationship between modified ideal CVH metrics and the risk of stroke in the rural population of Northeast China. Methods: We included 11,417 adults from the rural population in Northeast China and collected all the information, including the baseline characteristics, history of stroke, and the seven ideal CVH metrics. Results: Our results showed that the presence of stroke was associated with high body mass index (BMI), poor diet score , high total cholesterol (TC), high blood pressure (BP), and high fasting plasma glucose (FPG). The prevalence of stroke increased as the number of ideal CVH metrics decreased, and peaked to 13.1% among those with only one ideal CVH metric. Participants with only one ideal CVH had a 4.40-fold increased susceptibility of stroke than those with all seven ideal health metrics. Conclusion: This study revealed that people with a better CVH status had a lower prevalence of stroke and the susceptibility of stroke increased with the decreasing of the number of ideal CVH metrics. Therefoper year .i.e., people with all seven health metrics at ideal levels), intermediate , and poor . In subsequent years, many studies worldwide have shown surprisingly low prevalence of ideal CVH among populations [et al., in the Northern Manhattan Study demonstrated a strong inverse relationship between the number of ideal CVH metrics and the total incidence of stroke across whites, blacks, and Hispanics [et al., also demonstrated that positive changes in ideal CVH metrics reduce the incidence of stroke in a city population in China [In 2010, American Heart Association (AHA) proposed the concept of “ideal cardiovascular health” (CVH), and set national goal for CVH promotion and disease reduction through 2020 and beyond . Accordiulations ,8,9,10. ispanics . Recentlin China . HoweverTherefore, we performed a cross-sectional study to examine whether ideal CVH metrics were associated with a lower risk of stroke among the rural population of Northeast China. From January 2012 to August 2013, a representative sample of people aged ≥35 years was selected in rural areas of Liaoning Province, which is located in Northeast China. The study adopted a multi-stage, stratified random cluster-sampling scheme. In the first stage of the study, three counties  were selected randomly from rural areas of Liaoning province. In the second stage, one town was randomly selected from each of these three counties. In the third stage, 26 rural villages from the three towns were randomly selected. Individuals who were pregnant, or diagnosed with malignant tumor or mental disorder were excluded from the study. All eligible permanent residents aged ≥35 years from each village were invited to attend the study. The study was approved by the Ethics Committee of China Medical University . All procedures were performed in accordance with the University’s ethical standards. Written consent was obtained from all participants after they had been informed of the objectives and benefits of the study, any medical issues and the confidentiality agreement regarding personal information. If the participants were illiterate, we obtained the necessary written informed consent from their proxies. Only those who had a complete set of data were included in the analysis.A standard questionnaire was obtained by face-to-face interview during a single clinic visit with each participant. The questionnaire collected data including the demographic characteristics, lifestyle risk factors, dietary habits, family income, and education levels. Before the survey was performed, volunteers were recruited as investigators from medical graduates of China Medical University. All eligible investigators received organized training that covered the purposes of this study, the administering of the questionnaire, the standard method of measurement, the importance of standardization, and the study procedures. Trainees were then given a thorough test and evaluation and only those who passed the test were allowed to become investigators. Additionally, further instructions and support were available during the process of data collection.The marital status of the participants was categorized into one of two groups: married or living with a partner; or unmarried, divorced, or widowed. Family income was classified as ≤5000, 5000–20,000, and >20,000 CNY/year. Educational level was categorized as low , middle (three or four years of secondary education), and high (college and university education). The subjects were asked whether or not they were currently smoking or drinking alcohol.i.e., in most weeks) intake of soybean products and/or unprocessed fish; and 5 = preference for non-salty food, in accordance with the current “Dietary Guidelines for Chinese Residents” developed by the Chinese Nutrition Society and proclaimed by the Ministry of Health [The questionnaire also included questions on their average consumption of several food items  per week. In defining a healthy diet, we originally used the following five components: (1) with legumes and cereals as the basic food; (2) ≥500 g fruits and vegetables/day; (3) <100 g red meat/day; 4 = regular , overweight  and obese (BMI ≥ 30 kg/m2) [Weight and height were measured to the nearest 0.1 kg and 0.1 cm, respectively, with the participants wearing lightweight clothing and without shoes. Waist circumference (WC) was measured at the umbilicus using a non-elastic tape (to the nearest 0.1 cm), with the participants standing, and at the end of normal expiration. Body mass index (BMI) was calculated as weight in kilograms divided by the square of the height in meters. BMIs were categorized into three groups according to the World Health Organization (WHO) criteria; as normal (BMI < 25 kg/m0 kg/m2) .Blood pressure was measured three times at 2 min intervals after at least 5 min of rest using a standardized automatic electronic sphygmomanometer . The participants were advised to avoid consuming caffeinated beverages and avoid exercise for at least 30 min before the measurement. During the measurement, the participants were seated with the arm supported at the level of the heart. The mean of three blood pressure (BP) measurements was calculated and used in all analyses. In line with the Seventh Report of the Joint National Committee on Prevention, Detection, and Evaluation of High Blood Pressure (the JNC-7 report) , hyperteFasting blood samples were collected in the morning after at least 12 h of fasting for all participants. Blood samples were collected from an antecubital vein into vacutainer tubes containing EDTA. Fasting plasma glucose (FPG), total cholesterol (TC), and other routine blood biochemical indexes were analyzed enzymatically on an autoanalyzer. All laboratory equipment was calibrated and blinded duplicate samples were used.Dyslipidemia was defined according to the National Cholesterol Education Program-Third Adult Treatment Panel (ATP III) criteria . High TCDiabetes mellitus was diagnosed according to the WHO criteria  of FPG ≥2), intermediate (25–29.9 kg/m2), or poor (≥30 kg/m2). Healthy diet was classified according to salt intake and classified as ideal (<6 g/day), intermediate (6–10 g/day), or poor (≥10 g/day). Physical activity was classified as ideal for all participants, for reasons previously given. Health factors included smoking, TC, BP, and FBG. TC was classified as ideal , intermediate , or poor (≥240 mg/dL). BP was classified as ideal , intermediate , and poor（SBP ≥ 140 mmHg or DBP ≥ 90 mmHg). FPG was classified as ideal , intermediate , or poor (≥126 mg/dL). In accordance with the definition published previously , ideal hIncidents of self-reported or family-reported stroke were obtained from a questionnaire and all participants who reported an incident of stroke were asked to review their medical records, including reports of brain imaging, such as CT or MRI scanning.2-test as appropriate. Multivariable logistic regression analyses were used to identify stroke in relation to cardiovascular health (CVH) metrics with odds ratios (ORs) and corresponding 95% confidence intervals (CIs) calculated. All the statistical analyses were performed using SPSS version 17.0 software, and p values less than 0.05 were considered to be statistically significant.Descriptive statistics were reported as mean values and standard deviations and categorical variables were reported as numbers and percentages. Differences among categories were evaluated using the non-parametric test or the χvs. 53 (10), p < 0.001). Overall, the education level and family income were lower in stroke group than that in the non-stroke group. Participants with stroke had lower smoking and drinking rates and took more salt in their daily diet. In addition, BMI and WC were greater in the stroke group than that in the non-stroke group. Furthermore, SBP, DBP, TC, TG, LDL-C, as well as FPG, were significantly higher in the stroke group compared with the non-stroke group, while the HDL-C values showed the opposite trend.A total of 11,417 subjects  aged ≥35 years participated in the study. Overall, there were 1011 participants with a history of stroke, accounting for 8.9% of our study population. 2, 56.4% took less than 6g salt in their daily diet, 52.2% had untreated total cholesterol <200 mg/dL , 15.5% had untreated blood pressure <120/<80 mm Hg , and 50.5% had untreated fasting serum glucose <100 mg/dL . Overall, compared to the stroke group, a much higher proportion of participants in the non-stroke group met ideal levels for each CVH metric, except for smoking status.The distribution of CVH metrics in our study population is shown in After adjustment for age, sex, spouse, education, family income, and drinking, the presence of stroke was associated with poor BMI ; poor diet score  ; poor TC ; poor BP ; and poor FPG , as shown in Prevalence of stroke showed a graded correlation to the number of ideal CVH metrics after adjustment for age, spouse, education, family income, and drinking status. As shown in According to the categories of ideal CVH defined by the AHA, the prevalence of stroke was 1.3% among participants with ideal CVH, 4.2% among those with intermediate CVH and 10.2% among those with poor CVH. Individuals with poor CVH thus had a 4.40-fold (95% CI: 1.62–11.91) higher odds of stroke, compared with those with ideal CVH, see This cross-sectional study found that people in the rural population of Northeast China with a better status of CVH had a lower prevalence of stroke. The prevalence of stroke correspondingly increased with the decreasing of the numbers of ideal CVH metrics. Individuals with poor CVH had a 4.40-fold (95% CI: 1.62–11.91) higher odds of stroke compared with those with ideal CVH.2, ≥30 min/d of moderate activity, a favorable overall diet quality, and moderate alcohol consumption. More health behaviors were substantially associated with lower risks for stroke in both sexes [et al., reported a similar result in a city population in China indicating that positive changes in ideal CVH metrics could reduce the incidence of stroke during a 4.89-year follow-up period [The results were consistent with the previous studies concerning the association between CVH metrics and stroke ,12,18,19th sexes ,18,19. SIn the processing of statistical data, we found that the vast majority of the participants could meet the AHA’s recommended standard healthy diet score, except for salt intake. High salt intake was an important risk factor for hypertension ,21, whicHowever, inconsistent with other studies in which smoking was a doubtless risk factor for stroke ,18,19, sFurthermore, the percentage of current smokers was 35.4% in our study, similar to two other studies in China  ,27, and et al., in another cross-sectional study indicated that 43.8% of the rural population had hypertension in Shandong Province, China [Health factors consisted of BP, TC, and FGP, which were further classified into three levels as ideal, intermediate and poor. Previous studies have indicated that hypertension ,20,21 (pe, China . The pree, China ,36,37.et al., found that participants who met more than six ideal CVH metrics were 76% less likely to develop stroke compared with those who had poor CVH [et al., in the Northern Manhattan Study demonstrated a strong inverse relationship between the number of ideal CVH metrics and the total incidence of stroke across whites, blacks, and Hispanics [et al., [We also found that these risk factors had a dose-response relationship for the presence of stroke and the odds ratio of stroke correspondingly increased with decreasing numbers of ideal CVH metrics. In a four-year-follow-up study from China, Zhang poor CVH . Dong etispanics . Consist[et al.,  estimateOverall, health promotion measures, including a low salt diet, weight control, smoking cessation, antihypertensive, antidiabetic and lipid-lowering therapy, would increase the prevalence of ideal CVH and therefore lead to a lower risk for stroke .Our study has some important limitations. First, as a cross-sectional study, it was difficult to establish a causal relationship between the ideal CVH metrics and stroke. Second, although the present study achieved a high respond rate and could be representative of the local population, the selection of each individual was not completely randomized. The selection bias could compromise the results to some extent. Third, measurement of CVH behaviors—physical activity and diet score—were modified slightly in our study and might not be as valid and reproducible as in others.This study revealed that people with a better CVH status had a lower prevalence of stroke and the prevalence of stroke increased with the decreasing of the number of ideal CVH metrics.


Heart failure is sometimes incorrectly listed as the underlying cause of death (UCD) on death certificates, thus compromising the accuracy and comparability of mortality statistics. Statistical redistribution of the UCD has been used to examine the effect of misclassification of the UCD attributed to heart failure, but sex- and race-specific redistribution of deaths on coronary heart disease (CHD) mortality in the United States has not been examined.We used coarsened exact matching to infer the UCD of vital records with heart failure as the UCD from 1999 to 2010 for decedents 55 years old and older from states encompassing regions under surveillance by the Atherosclerosis Risk in Communities (ARIC) Study . Records with heart failure as the UCD were matched on decedent characteristics  to records with heart failure listed among the multiple causes of death. Each heart failure death was then redistributed to plausible UCDs proportional to the frequency among matched records.P < 0.001. The percent increase in CHD mortality after redistribution was the highest in Mississippi (12%) and lowest in Maryland (1.6%), with variations by year, race, and sex. Redistribution proportions for CHD were similar to CHD death classification by a panel of expert reviewers in the ARIC study.After redistribution the proportion of deaths increased for CHD, chronic obstructive pulmonary disease, diabetes, hypertensive heart disease, and cardiomyopathy, Redistribution of ill-defined UCD would improve the accuracy and comparability of mortality statistics used to allocate public health resources and monitor mortality trends. Accurate mortality statistics are critical for determining the burden of disease and evaluating mortality trends, but ill-defined causes of death such as heart failure are sometimes listed as the underlying cause of death (UCD) ,2. HeartEfforts to improve the comparability and accuracy of cause of death statistics call for redistributing UCDs attributed to ill-defined codes ,2,5,6. MCoarsened exact matching is a novel, validated approach to redistribute heart failure deaths . In coarDeaths attributed to heart failure are predominantly redistributed to CHD in the United States and most industrialized countries ,5,6,12. We examined vital records from decedents ≥55 years old for years 1999–2010 from states encompassing regions under epidemiologic surveillance by the ARIC study . We excluded decedents <55 years old (n = 8) because heart failure before age 55 typically reflects etiologies and coding practices that differ from those among older adults in industrialized countries. Multiple cause of death coding was provided by the 57 vital statistics jurisdictions through the National Center for Health Statistics Vital Statistics Cooperative Program. We obtained mid-year populations for 1999–2009 from the Center for Disease Control’s CDC Wonder and obtained the 2010 mid-year population from the United States 2010 Census. Heart failure was defined by ICD-10 codes for congestive heart failure (I50.0), left ventricular failure (I50.1), and heart failure, unspecified (I50.9).Before matching we eliminated deaths due to external causes, ICD-10 codes V00-Y98, and deaths due to ill-defined UCD on the basis that they were not plausible as the UCD of a heart failure death , chronic obstructive pulmonary disease , diabetes (E10-E14), hypertensive heart and kidney disease (I11-I13), cardiomyopathy (I42-I43), cerebrovascular disease (I60-I69), other cardiovascular diseases , lower respiratory infections , cancers (C00-C97), digestive diseases (K20-K92), dementia , Alzheimer's disease (G30), and other diseases (remaining UCD).The National Heart, Lung, and Blood Institute-supported ARIC Community Surveillance Study includes annual sampling and validation of hospital discharge codes for myocardial infarction, heart failure, and in-hospital and out-of-hospital CHD mortality among residents 35 to 74 years old since 1987 from Forsyth County, North Carolina; the city of Jackson, Mississippi; suburbs of Minneapolis, Minnesota; and Washington County, Maryland. We included records with the UCD of heart failure for years 1999 to 2010 for decedents ≥55 years old from the four ARIC study areas. Detailed methods have been published ,14 but bFor the purpose of this analysis, deaths were classified as a CHD death , a non-CHD death, and an unclassifiable death in which the panel reviewers could not confirm or rule out a CHD death. We also considered a reviewer’s preferred classification in which the clinical judgment of the reviewer was used to complement the standardized ARIC classification. The preferred classification allowed the physician reviewer to disagree with the ARIC algorithm for a CHD death based on information in the medical record and his/her expert opinion.We applied coarsened exact matching as proposed by Stevens et al.  implemenpost-redistribution morality rate − pre-distribution morality rate)/pre-distribution mortality rate] × 100. We graphed CHD mortality and percent increase in CHD mortality by region, sex, and race to evaluate trends over time. We suppressed data for “other” race and African Americans in Minnesota when calculating CHD mortality rates due to the small number of records.We calculated CHD mortality per 100,000 population using the direct method of standardization to the 2000 United States standard population. The percent increase in CHD mortality after redistributing heart failure deaths was calculated as [ was used for all analyses except for coarsened exact matching that was conducted with Stata, version 12.1 . All Heart failure was listed as the UCD in 3.2% n = 52,211) of all vital records, with 2.0% in Maryland, 3.7% in Minnesota, 6.4% in Mississippi, and 2.6% in North Carolina  and North Carolina (34.5%; Additional file Misclassification of deaths due to ill-defined UCD remains a problem in national vital statistics. Prominent among the ill-defined UCD is heart failure, which was listed as the UCD in over 3% of all vital records from 1999 to 2010. On a national scale, this represents approximately 63,273 deaths in 2010 among United States decedents ≥55 years old. Deaths attributed to heart failure redistributed by coarsened exact matching were predominantly assigned to CHD, with variations in redistribution proportions by state, sex, and race. Similar redistribution patterns were seen for heart failure deaths classified by a physician reviewer panel following ARIC’s Community Surveillance protocol. These approaches reclassified 22% to 37% of deaths coded as heart failure to CHD deaths and classified more heart failure deaths as CHD in Mississippi and among males. CHD mortality increased by 0.7% to 13.7% among the four states after redistributing heart failure deaths, suggesting that without redistributing heart failure deaths, CHD mortality based on vital statistics is underestimated by 0.7% to 13.7% in the four states included.a priori assumptions about the UCD target groups are necessary, and a heart failure death may be redistributed to several underlying causes of death. Stevens et al. reported that the overall percent increase in mortality for CHD after coarsened exact matching did not vary over time between 1999 to 2004 in the United States [As shown in our analysis and those of others ,6,12, heMisclassification of the UCD due to ill-defined codes has been reported to vary by location ,17, the There is plausibility for heart failure deaths to be redistributed to CHD where the predominant underlying mechanism of heart failure is ischemic cardiomyopathy ,20, and Our study is limited by the lack of autopsy data to determine the true UCD, given that very few autopsies are conducted in the United States. Also to be considered, the method we used assigns deaths to plausible UCD and records could therefore be redistributed to different UCD to account for the uncertainty of the true UCD. Our analysis is based on vital records that may have inaccurate demographic information and cause of death coding; however, redistribution of heart failure offers a way to improve the misclassification of the UCD and comparability of mortality statistics. Lastly, this analysis only included four states in the United States to allow for comparison with an established community surveillance program. Even within this constrained framework, we were able to detect geographic variations in the redistribution of heart failure deaths both from vital records and the ARIC study. We also were able to compare temporal trends in CHD mortality by race and sex to previous studies that used redistribution of deaths due to ill-defined causes based on vital records prior to 2008 ,6,12.Efforts to improve vital statistics are not new. Other studies have shown feasible ways to calibrate mortality to account for ill-defined UCD ,6,12,21,In summary, coarsened exact matching offers a practical way to redistribute ill-defined UCD. Further research is needed to validate this method, but our results indicate that redistribution of deaths attributed to heart failure modifies cause-specific mortality estimates and may significantly impact mortality patterns for subgroups or regions prone to suboptimal certification of the UCD. Government agencies and researchers should calibrate vital statistics through reclassification of ill-defined UCD in order to improve the accuracy and comparability of mortality statistics, to the benefit of monitoring mortality trends, public health policies, and the allocation of public health resources.ARIC: Atherosclerosis risk in communities study; CHD: Coronary heart disease; COPD: Chronic obstructive pulmonary disease; ICD-10: The international classification of disease tenth revision; UCD: Underlying causes of death.The authors declare that they have no competing interests.All authors read and approved the final version of the manuscript and its submission to the journal. Specifically, MLS, SL, PDS, WDR, CA, PAM, SH, CMS, ES, and GH contributed to the concept and design of the study. MLS, SL, WDR, and GH acquired the data. MLS, SL, PAM, CMS, and GH contributed to the analysis and interpretation of the data, and PDS, WDR, CA, SH, and ES contributed to the interpretation of the data. MLS and GH led the drafting of the manuscript and SL, PDS, WDR, CA, PAM, SH, CMS, and ES reviewed and revised the manuscript.Table S2. Characteristics of decedents with heart failure listed as the UCD, Figure S1. Age-adjusted mortality rate of CHD pre- and postredistribution of heart failure deaths by state, Figure S2. Age-adjusted mortality rate of CHD pre- and postredistribution of heart failure deaths by sex and state, Figure S3. Age-adjusted mortality rate of CHD pre- and postredistribution of heart failure deaths by race and state, Table S3. ARIC community coronary heart disease surveillance decedent characteristics of records listing heart failure as the UCD, Table S4. ARIC community surveillance CHD classification of records listing heart failure as the UCD, Table S5. ARIC community surveillance CHD classification of records listing heart failure as the UCD by field center.Characteristics of decedents, Click here for file


Was to describe 14 cases of a proliferative verrucous leukoplakia as a clinical evolution of oral lichen planus.The clinical and histopathological characteristics of 14 cases of OLP that progress towards a plaque-like and verrucous form were indicated, with monitoring over a period of six to 24.3 years.The female/male ratio was 11/3, (78.6 and 21.4%). The mean age when the first biopsy was undertaken was 56.4 years old. None of the patients smoked during the study. As bilateral reticular was clinically diagnostic criterion, the second most frequent clinical form was the plaque form , followed by the atrophic , and erosive forms . Clinically it spread towards attached gingival mucosa and the hard palate. In the histopathologic study, there were a predominance of hyperkeratosis and verrucous epithelial hyperplasia. Three of the cases progressed to a squamous cell carcinoma, and one patient developed two verrucous carcinoma.Further research is needed to demonstrate if proliferative multifocal oral lichen planus and proliferative multifocal oral leukoplakia are the same disorder but have different behaviour of malignancy for reasons of origin.Key words:Oral lichen planus, proliferative verrucous oral leukoplakia, malignant oral lichen planus, multifocal verrucous oral lichen planus, proliferative verrucous oral lichen planus. Oral lichen planus and oral leukoplakia are the most common potentially malignant disorders. Oral lichen planus (OLP) is a chronic, autoimmune mucocutaneous disease, characterised by exacerbation and remission periods. OLP can present as white papules that gradually expand in a symmetrical manner to form a reticular pattern (Wickham’s striae), or as plaques, which may or may not come with atrophic, erosive, and bullous forms . AlthougThe risk of development oral cancer in OLP patients has been the issue of much debate. The rate of transformation in individual studies ranged from 0 to 3.5% -8, non-eet al. introduced a new subtype of OL designed as “proliferative verrucous leukoplakia” (PVL) (In 1985 Hansen a” (PVL) . PVL is a” (PVL) .et al.  criteria in 1978  and on tFrom OLP patients we included in the present study, those patients with the following progression behaviour: 1) predominating plaque-like form in almost a topographical area, with roughness and thickening, white-greyish in colour or verrucous form, 2) spreading multifocal growth affecting more than two oral locations and including the attached mucosa  or the hard palate, buccal or lingual mucosa, 3) histological criterion, through a second biopsy on the plaque-like or verrucous areas, with the presence of hyperkeratosis, acanthosis, papillomatous, or hyperplasia, without band-like inflammatory infiltrate (or without dominance), 4) treatment resistant, 5) monitoring for at least 5 years by the same doctor.The studied variable were: gender, age, toxic habits , location of the OLP, clinical form of OLP, affectation of other mucosa, appendages and skin, length of the monitoring, OLP treatment, microscopic changes in the second biopsy, and type of malignancy, number of carcinomas developed and their respective treatments.The medical treatment options for OLP were: 1) Topical corticosteroids (TC) with 0.05% Clobetasol Propionate in Orabase and in aqueous solution; 2) daily oral administration of prednisone (0.5 mg/kg weight/day) followed by every other day; 3) acitretin 25-50 mg/day orally; 4) topical retinoids 0.1% 13-cis-retinoic acid in orabase. The excision treatment involved an intervention using a scalpel and CO2 laser surgery. The laser wavelength was 10.600nm and the vaporisation occurred between 4.5-7W. Treatments for the carcinomas included scalpel surgery, radiotherapy and laser CO2. Nystatin and fluconazole were used as an adjuvant treatment for complicated cases with secondary oral candidosis.This project was approved by the Ethics in Research Committee from the University Central Hospital of Asturias.Between years mentioned we recruitment a total of 515 oral lichen planus, from those, we collected a total of 14 patients (2.7%) that development proliferative verrucous leukoplakia.The details of the demographic study for each of the 14 patients are summarised in The female/male ratio was 11/3, (78.6 and 21.4%). The mean age when the first biopsy was undertaken was 56.4 years old, 58.5 years old and 48.6 years old for women and men respectively.None of the patients smoked or took narcotics during the study. Three were ex-cigarette smokers of more than 15 years. Three male patients drank one or two glasses of wine at the weekend. The women did not drink.The predominant initial clinical together bilateral reticular form was the plaque form , followed by the atrophic , and erosive forms .The most common location at baseline was the bilateral buccal mucosa n=11; 78.5%), followed by the gingiva and palate mucosa , and the lingual mucosa . They all had three or more affected areas  was present in part of all specimens, acanthosis and papillomatous squamous proliferation partly in ten cases, and verrucous hyperplasia in nine cases. Four patients (28.5%) went on to become malignant, three cases of squamous cell carcinoma (SCC) were well-differentiated, and one verrucous carcinoma. The mean time to malignant transformation from the first diagnosis was 9 years. Three cases were female and one male. The most common location of carcinoma was attachment mucosa Fig. , gingivaIn the present study we describe the characteristics of PVL in patients previously diagnosed of oral lichen planus, contributing to corroborate what in recent reports have suggested, the clinical relationship between OLP and PVL  and the et al.  and the present in the literature review, from 40% to 74% of PVL, additional long-term research is necessary to clear if proliferative multifocal lichen planus and proliferative multifocal oral leukoplakia are the same disorder but have different behaviour of malignancy for reasons of origin.


KIF1Bβ, EGLN1, TMEM127, and MAX, added to the well-known PCC familial syndrome  presents new challenges for diagnosis. In this review, we discuss the diversity of clinical and genetic approaches to this syndrome as well the diverse criteria that should guide genetic investigation.Pheochromocytomas (PCCs) and paragangliomas (PGLs) are neuroendocrine tumors derived from the chromaffin tissue. Diagnosis of these tumors is extremely important as they are linked to the hypertension syndrome with great cardiovascular morbidity and mortality. A great majority of PCCs and PGLs are sporadic and benign tumors; however, the classic idea of 10% exception of these features is changing. The description of new genes linked to familial forms of PCC/PGLs, such as succinate dehydrogenase (SDH) complex subunits,  Pheochromocytomas (PCCs) and paragangliomas (PGLs) are neuroendocrine tumors derived from the chromaffin tissue of the adrenal medulla or from extra-adrenal sympathetic and parasympathetic paraganglia. Parasympathetic PGLs are mostly non-secreting, whereas sympathetic PGLs generally produce catecholamine , 2.The diagnosis of these neoplasias is extremely important, as they are associated with hypertension syndrome and great cardiovascular morbidity and mortality. The prevalence of PCC/PGLs in general hypertensive population is on average 0.1–0.6% and even higher in children (1.7%), with 5% of incidentally discovered adrenal mass , 4. HoweThe American Endocrine Society guidelines advocate that it is important to be aware of the main clinical features for proper diagnosis of PCC/PGLs . The cliSDHA, SDHB, SDHC, SDHD, and SDHFA2, related to familial PCC–PGL and novel susceptibility genes, such as KIF1Bβ, EGLN1, TMEM127, and MAX, have led to the diagnosis of new phenotypes . This 21-exon proto-oncogene is located on chromosome 10 and encodes a receptor tyrosine kinase that works in conjunction with glial-derived neurotrophic factor family ligands. The interaction of these ligands results in the dimerization of the RET receptor, auto-phosphorylation of tyrosine residues, and finally cell growth and survival mediated by the mitogen-activated protein kinase intracellular signaling cascade. One germ-line activating mutation of this gene, generally missense and located in exons 10, 11, 13, 14, 15, 16, has been implicated in this syndrome (Multiple endocrine neoplasia type 2 is described by medullary thyroid carcinomas (MTC) in association with PCC. This syndrome has three clinical variants: MEN2A (55% of cases), familial medullary thyroid carcinoma (FMTC – 35–40%), and MEN2B (5–10%) . The disRET mutation can influence the management of an apparently sporadic MTC.MEN2 types carry approximately 100% risk for MTC and at 50% risk for PCC. FMTC tumors are less aggressive and, by definition, without incidence of other endocrine neoplasia. There is a strong correlation between the phenotype and genotype in the clinical subtypes of MEN2 with respect to age of onset and aggressiveness of MTC. These aspects are used to determine the time of prophylactic thyroidectomy and whether patients should be screened for PCC and hyperparathyroidism. In this way, positive results for a specific RET is representative of MEN2A in approximately 80% of patients. A single missense mutation in codon 918 is found in nearly 90% of MEN2B cases. Based on this genotype and phenotype correlation, the American Thyroid association has proposed the classification of four risk-categorized mutations and recommends the screening for PCC by the age of 20 years for MEN2A and by 8 years for MEN2B  hemangioblastomas, pancreatic islet cell tumors and pancreatic cysts, epididymal cystadenomas, endolymphatic sac tumors, clear-cell renal carcinomas and PCCs, and PGLs , rhabdomyosarcomas, breast cancer, and chronic myeloid leukemia, have also been described. Some patients can also present cognitive impairment (Neurofibromatosis type 1 (NF1) or Von Recklinghausens’s disease is an autosomal dominant syndrome characterized by pairment , 30.Pheochromocytomas are a rare finding in NF1, being identified in <6% of cases; however, they have a higher prevalence (13%) in autopsy series. The preferential mean age of presentation is in the fourth decade. A majority of these PCCs are unilateral and benign, while approximately 10% can be bilateral or malignant. The presence of PGLs is not common in NF1 , 32. ConNF1 is a tumor suppressor large gene with 60 exons located on chromosome 17 with described missense, nonsense, and splice-site mutations, indels, and chromosomal rearrangements  genes related to this syndrome. The SDH complex is described as a heterotetrameric protein involved in the electron transport in the Kreb’s cycle and mitochondrial respiratory chain. This enzyme is composed of four subunits  that catalyze the oxidation of succinate to fumarate. The catalytic subunits, SDHA and SHDB, are inserted in mitochondrial matrix, and they are affixed to the inner membrane by subunits SDHC and SDHD. The SDHx genes are supposed to work as classical tumors suppressors, as tumors frequently show loss of heterozygosity (LOH) of the non-mutated allele.SDHD mutations were associated to the occurrence of PCC/PGLs , although they have been reported in apparently sporadic tumors; they are often associated with the risk of multiple tumors, especially head and neck PGLs . Average 20% of patients with SDHB mutation will present malignant PGLs, and more than 50% of the individuals with malignant PGLs will have a SDHB mutation , and the esophagus. The stomach features GIST, the lung chondroma, the paraganglionic system paraganglioma, the adrenal adenoma and pheochromocytoma, and the esophagus leiomyoma .SDHA, SDHB, SDHC, and SDHD mutations has been always negative. The mutated genes, often associated to GIST (KIT and PDGFRA), are also not affected.The etiology of the Carney triad syndrome is unknown; no candidate gene has been discovered until now and the disease does not appear in a family pattern. The younger age and female predilection of affected individuals do implicate in a link with an inherited genetic defect; however, the screening of SDHB, SDHC, or SDHD supporting another molecular mechanism linked to GIST besides KIT and PDGFRA mutations usually described  role, and overexpression of HIF1α and 2α were found in this cluster.Despite identification of multiple genetic causes of PGLs and PCCs in the last decade, around two-thirds of these tumors remain without molecular diagnosis, suggesting that other susceptibility genes could be implicated. Using a wide-genomic approach, PCC/PGLs were clustered in two major groups depending on their global transcription profiles. Cluster 1 includes RET, NF1, KIF1Bβ, and undefined tumors enriched for kinase receptor signaling pathways, translation initiation, protein synthesis, and genes involved in neural/neuroendocrine identity  covered PCCs with identity –52. Nove cluster . Also, d cluster .KIF1β is a tumor suppressor gene necessary for neuronal apoptosis. It is located on chromosome 1  is a transcription factor that was recently linked to PCC/PGL susceptibility. ppressor , 60. Whotary PCC . The absVHL, 6.38% for PGL4, 3.72% for PGL1 e 1.55% for RET)  .VHL, RET, SDHD, and SDHB genes; these patients presented at a younger age (average of 24 years), and they had multiple tumors and 28% extra-adrenal tumors  of them had tumors with younger onset, not more than 45 years old . The authors did not find any difference between hereditary and sporadic disease concerning age, sex, and tumor size; bilateral and recurrent diseases were most common in hereditary cases .Currently, the overall hereditary predisposition of PCCs is estimated to be approximately 20–35%. The high prevalence of unsuspected mutations indicates a demand for more extensive genetic tests for patients with these tumors . HoweverVHL, RET, SDHB, and SDHD but their frequency was reported to be low. The COMETE cohort has demonstrated the occurrence of somatic mutations in VHL and RET genes in 14% of sporadic pheochromocytoma/paraganglioma, one germ-line, and three somatic mutations in the MAX were described by the same cohort  were diagnosed 11 years later than those with tumors lacking appreciable epinephrine production (mean age 42 years). This finding reinforces that the cut-off age for genetic screening could consider tumor catecholamine phenotypes . HoweverNF1 is a large gene, costly, and difficult to screen.For family diseases, such as MEN2A/B, NF1, and VHL, a phenotype suspicion, because they are commonly associated to other tumors, helps to direct to genetic studies. The presence of hemangioblastomas calls attention for VHL disease, as the association of medullary thyroid carcinoma for MEN2. MEN2-associated tumors always produce epinephrine and can be uni- or bilateral, but malignant disease and extra-adrenal tumors are rare in this syndrome. PCCs in VHL always secrete NE and can be extra-adrenal. The biochemical profile, as shown in Figure SDHB, SDHD, and VHL mutations  PCCs are frequently associated with VHL and RET, while extra-adrenal sympathetic PGLs  are usually caused by utations –77. Headand SDHC , 40. SDHPCC/PGLs . Tests fTMEM127 is customarily associated with benign PCC but not with PGL. Ordinarily, these tumors occur in old age, mimicking a truly sporadic PCC (adic PCC , 64.SDHB and VHL should be considered. The most important clinical aspects related to different genes are provided in Table SDHD and SDHC mutations.Routine screening for germ-line mutations in patients with PCC/PGLs is costly and time consuming. Although some algorithms have been proposed, no routine guideline is available . For theRET screening and genotype and phenotype correlation permits prophylactic surgery for an aggressive tumor. Nevertheless, further clinical studies are indispensable to better correlate genotype and phenotype features with the new genes.Currently, it is recommended that if a mutation is found, it is not necessary to search for additional genomic alterations; however, with the description of new genes, we have to be aware of new possibilities. Identification of a gene mutation in patients with PCC/PGLs results in precocious diagnosis and better surveillance, resulting in better prognosis. In specific cases, To guide better screening strategy and optimize therapeutic options, the knowledge of PCC/PGL-implicated syndromes and genes is incredibly important. This review summarizes the main syndromes and the gene associated with these diseases. Further studies are needed for wider genotype to phenotype correlations, especially for new genes and pathways recently described for these tumors.MC, TO-C, AV, and MV contributed to the conception and design of the collection of the data for the revision, drafted the work, and critically revised the intellectual content. All the authors approved the last version of the manuscript and agreed to be accountable for all aspects of the work.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


This study was performed to assess the relationship between the consumption of coffee and periodontitis using nationally representative data.The data from the Korea National Health and Nutrition Examination Survey were used; the analysis in this study was confined to a total of 16,730 respondents over 19 years old who had no missing values for the consumption of coffee or outcome variables. A community periodontal index greater than or equal to code 3 was defined as periodontal disease.Consumption of coffee was significantly higher in the individuals with periodontitis in males. The odds ratios of the percentage of individuals with periodontitis tended to increase with the consumption of coffee. Adjusted odds ratios and their 95% confidence intervals of the male participants were 1, 1.131(0.792–1.617), 1.161(0.857–1.573), 1.053(0.805–1.379), 1.299(1.007–1.676), and 1.458(1.141–1.862) for once per month or less, once per month<x≤3 times per week, three times per week<x≤6 times per week, once per day, twice per day, and three or more per day, respectively.Consumption of coffee may be considered an independent risk indicator of periodontal disease in Korean male adults, and we suggest that the periodontal health of male may benefit from reduction of coffee consumption. Coffee is one of the most frequently consumed caffeine-containing beverages,2. CoffeOne report showed a negative influence on bone metabolism, but another report demonstrated that coffee consumption showed no significant association with bone mineral density,13. PeriThe data used in this study were derived from the Korea National Health and Nutrition Examination Survey (KNHANES), conducted between 2008 and 2010 by the Division of Chronic Disease Surveillance under the Korea Centers for Disease Control and Prevention and the Korean Ministry of Health and Welfare. The KNHANES is a nationwide survey of noninstitutionalized civilians who uses a stratified and multistage probability sampling design with a rolling survey sampling model. The samInitially, a total of 29,235 individuals participated in the KNHANES survey. The 7,424 subjects aged < 30 were excluded, and the 3,681 participants without nutritional information were excluded. Among the remaining 17,058 patients, 1,072 subjects who had periodontitis with a community periodontal index (CPI) of 3 were selected. After removing 328 subjects who had missing parameters, 16,730 total subjects were included in this study. All of the participants received written informed consent. This study was approved by the Institutional Review Board of the Korean Center for Disease Control and Prevention and conducted according to the Helsinki Declaration-based Ethical Principles for Medical Research Involving Human Subjects. The Institutional Review Board at the Catholic University of Korea approved this study.All participants were asked about sociodemographic and lifestyle variables by trained interviewers. Consumption of coffee and carbonated beverages was calculated based on the survey. Education level was categorized into two groups according to whether or not the participant had graduated from high school. Monthly household income was divided into quartiles after adjusting for the number of family members. The lowest quartile included households with a monthly income < $1092.40 USD. The amount of pure alcohol consumed (in grams per day) was calculated using the average number of alcoholic beverages consumed and the frequency of alcohol consumption. The participants were divided into three groups depending on the amount of alcohol consumed per day: nondrinker, light-to-moderate drinker (1–30 g/day), and heavy drinker (> 30 g/day). Smoking2), and waist circumference was measured at the narrowest point between the lower border of the ribcage and the iliac crest in a standing position.Anthropometric measurements were performed by trained staff members. Body weight and height were measured to the nearest 0.1 kg and 0.1 cm, respectively, with participants in light indoor clothing without shoes. Body mass index was calculated as body weight (kg) divided by the squared height  was used for blood pressure measurement. Systolic blood pressure and diastolic blood pressure were measured twice at five-minute intervals, and the average values were used for the analysis.To measure concentrations of serum-fasting plasma glucose and high-density lipoprotein cholesterol and white blood cell count, a blood sample was collected from the antecubital vein of each participant after fasting for more than eight hours. Blood samples were analyzed within 24 hours of transportation. Levels of serum-fasting plasma glucose, total cholesterol, triglycerides, and high-density lipoprotein cholesterol were measured with a Hitachi Automatic Analyzer 7600  by enzymatic methods using commercially available kits .Metabolic syndrome was defined according to the American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement criteria for Asians. AccordiTooth brushing frequency and the use of secondary oral products were used as indicators of oral health behavior. The frequency of daily tooth brushing was calculated as the total number of times the teeth were brushed per day. Secondary oral products included dental floss, mouthwash, interdental brush, and electric toothbrush.The World Health Organization community periodontal index (CPI) was used to assess periodontal treatment needs and defined periodontal disease as a CPI greater than or equal to code 3. A CPI score of code 3 indicates that at least one site had a > 3.5 mm pocket in the index teeth, which are 11, 16, 17, 26, 27, 31, 36, 37, 46, and 47 according to the Federation DentaireInternationale system. The mouth was divided into sextants. A CPI probe  with a 0.5 mm ball tip was used. A sextant was examined only if there were two or more teeth present that were not scheduled for extraction. If no index teeth were present in a sextant qualifying for examination, all remaining teeth were examined and the highest score was recorded as the score for that sextant. An approximate 20-gram probing force was used. Trained and calibrated dentists examined the periodontal status of the participants. Chewing ability, speech, dental checkup within a year, and self-reported oral status were evaluated. The CPI score represented periodontitis status as follows: 0: normal, 1: gingival bleeding, 2: calculus, 3: a shallow pocket with depth of 3.5–5.5 mm or moderate periodontitis, and 4: a deep pocket depth ≥ 5.5 mm or severe periodontitis. Dental P values of < 0.05 were considered statistically significant.All data are presented as mean ± standard error or as a percentage (standard error). Logarithmic transformation was performed to achieve normal distribution when necessary. A student’s t-test or chi-square test was used to investigate the differences in the presence of periodontal treatment needs according to the variables. Multiple logistic regression analyses were used to assess the associations of periodontal treatment needs and consumption of carbonated beverages. The model was adjusted for age, sex, body mass index, smoking, drinking, exercise, metabolic syndrome, frequency of tooth brushing per day, use of secondary oral products, dental examination within a year, and consumption of beer and coffee. A survey procedure of a statistical software package  was used for statistical analysis to account for the complex sampling design. Two-sided P for trend < 0.05). Adjusted odds ratios and their 95% confidence intervals of the female participants were 1, 1.154(0.862–1.545), 0.951(0.750–1.205), 0.941(0.771–1.148), 1.034(0.825–1.296), and 1.265(0.969–1.65) for once per month or less, once per month<x≤3 times per week, three times per week<x≤6 times per week, once per day, twice per day, and three or more per day, respectively (P for trend > 0.05). The results show that consumption of coffee was positively associated with the risk of periodontal disease in Korean male adults.In the present study, the risk of periodontal disease was positively associated with consumption of coffee among Korean male adults. This association between consumption of carbonated beverages and periodontal disease was independent of various potential confounding factors such as age, body mass index, smoking, drinking, exercise, metabolic syndrome, frequency of tooth brushing per day, use of secondary oral products, consumption of carbonated beverage, and dental checkup within a year.Limited numbers of studies have been performed regarding the effect of coffee consumption on periodontal disease,30,31,32The different results for the association between the consumption of coffee and periodontitis may be partially explained by the following. Coffee contains complex chemicals, including carbohydrates, nitrogenous compounds, vitamins, minerals, and phenolic compounds,2. CoffeA previous report showed that 76% of the Korean subjects were habitual coffee drinkers, most of whom consumed instant coffee mix containing sugar and powder creamer. DrinkinThe major strength of our study is the large, nationally representative sample of adult Koreans. Second,The results showed that consumption of coffee was positively associated with the risk of periodontal disease in Korean male adults. In conclusion, consumption of coffee may be considered an independent risk indicator of periodontal disease in Korean male adults, and we suggest that the periodontal health of male individuals may benefit from the reduction of coffee consumption.S1 Table(DOC)Click here for additional data file.


Our aim was to examine the associations between childhood or adult height and adult mortality.In the prospective British 1946 Birth Cohort Study, childhood height was measured at 2, 4, 6, 7, 11, and 15 years, and adult height was measured at 36 years. Deaths were reported from the national health service register.P < .001; and hazard ratio, 1.42; 95% confidence interval, 1.08–1.88; P = .01, respectively). Several determinants of childhood stunting (height at 6 years less than the second percentile) were directly associated with adult mortality; these included shorter parental heights and adverse early life nutrition and housing.A total of 3877 study members  contributed 106,333 person-years of follow-up; 391 deaths  were reported between the ages of 36 and 64 years. The strongest sex-adjusted association between height and mortality between ages 36 and 64 years was seen for height at age 6 years. The association was nonlinear; only study members in the shortest quintile at 6 years had a higher relative risk of adult mortality compared with those in the tallest quintile. By contemporary growth standards, 5.7% (n = 188) had heights at 6 years less than the second percentile, and a further 15.0% (n = 490) had heights between the second to ninth percentiles; these groups had higher adult mortality than all other study members (hazard ratio, 2.18; 95% confidence interval, 1.52–3.13; British men and women born in 1946 were relatively stunted as children by contemporary standards. Those who were short at age 6 years had substantially higher mortality 30 to 60 years later. Furthermore, they accounted for the well-recognized inverse association between adult height and mortality. Linear growth retardation (“stunting”) during early childhood is a marker of chronic undernutrition caused by poor nutrition and compounded by infectious disease . In depr3–We hypothesized that short height in early childhood would be adversely associated with adult survival even in a high-income setting, that it would explain the association between shorter adult height and mortality, and that it would be independent of the association of weight status with mortality. We compared the associations between childhood or adult height and adult mortality in the British 1946 Birth Cohort Study. We also investigated whether adverse early childhood environments, poor nutrition, and physical illness, which are risk factors for poor childhood growth , might bThe Medical Research Council's National Survey of Health and Development (NSHD) is a socially stratified birth cohort of 2547 men and 2815 women of white European descent born during 1 week in 1946 who have been followed with repeated data collections since then . The stuStudy members were flagged for death on the National Health Service Central Register from 1972. At that time, 2325 men and 2136 women were alive and residing in Britain; of the remaining cohort, 288 had already died, 586 had emigrated, and 27 were not flagged on the register. The underlying cause of death was coded according to the International Classification of Diseases (ICD)-9 or ICD-10 and were categorized as follows: cardiovascular diseases (ICD-9 codes 401–454 and ICD-10 codes I10–I89); cancers (ICD-9 codes 140–239 and ICD-10 codes C00–C97); externalizing disorders  and other causes. Cause of death was missing in 10 cases.Birth weight to the nearest quarter pound 113 g) was extracted from medical records within a few weeks of birth and was converted to kilograms. Heights and weights were measured by trained personnel using standard protocols at ages 2, 4, 6, 7, 11, 15, 36, 43, 53, and 60 to 64 years and were self-reported at ages 20 and 26 years. Adult height was taken as the measured height at age 36 years; for 604 study members with missing data, we used self-reported height at age 26 years. Body mass index (BMI) was calculated as weight in kilograms divided by height in meters squared. Measures of BMI, weight, and height were converted into Z-scores using internally generated growth charts, constructed using the LMS method  g was ex.Mothers were, when possible, measured at the examination of their cohort child at age 6 years, and they reported their husband's height. Midparental height was calculated as an indicator of genetic height potential.Various early life factors, namely, female sex, shorter midparental height, lower birth weight, higher birth order, higher number of young siblings, lower childhood (father's) social class, lower father's education, lower mother's education, and higher household crowding, have been examined previously as being potential determinants of adult height in this study . We examHeight in childhood and adulthood is strongly related to adult SEP, smoking status, and lung function, which are themselves strong risk factors for mortality . Adult SCox regression models were used to investigate the relationships between childhood or adult height Z-score and adult mortality, adjusted for sex. Follow-up time was from the cohort members' 36th birthday in 1982 until the first of death, emigration, or the end of February 2011 (just before the cohort's 65 birthday). If death had not occurred, follow-up was treated as censored. The proportional hazards assumption was checked graphically.To explore the shape of the association with mortality, height Z-score was also entered as a quadratic term, and, if this term was significant, mortality rates were calculated by quintiles of height Z-score. We explored the interactions between childhood height and adult body size (height and BMI) by adding these additional interaction terms to the Cox regression models. Additional analyses of the association between childhood stunting and mortality during specific age periods from childhood were performed by logistic regression, with adjustment for sex, SEP, and smoking.We tested which indicators of the early environment, childhood nutrition, and physical illness were independently associated with childhood stunting and whether these factors were also associated with adult mortality. Finally, further models for adult height Z-score and adult mortality were adjusted separately for potential adult confounders or mediators, including adult SEP, smoking status, weight, arterial BP, resting pulse rate, and PEFR. All analyses were performed using SPSS (version 15.0).P = .001).Details of the 3877 study members  with data on adult height (at age 36 or 26 years) who were flagged on the national death register are summarized in P < .001) and adult height . In a combined multivariable regression model, height at 6 years  but not adult height  was associated with all-cause mortality between ages 36 and 64 years.Heights at all ages from 4 years onward were inversely associated with all-cause mortality between ages 36 and 64 years, after adjustment for sex . In lineP < .001). Adult height showed a reverse J-shape association with the lowest mortality rate being in the second tallest quintile (P < .001) (P = .4).The shape of the associations between height at age 6 years or adult height and all-cause mortality were nonlinear, as indicated by the highly significant height-squared terms in the regression models (quintile A. At age < .001) B and 2. P = .01); taller adult height was protective against mortality only among those in the shortest height quintile at 6 years , but not among those in any of the taller childhood quintiles  . There was weak evidence of interaction between short height at 6 years and adult BMI status  and mortality (P for interaction = .08); the highest mortality rates were seen in those in the shortest height quintile at 6 years and subsequently either underweight  or obese as adults  .There was a significant interaction between height at 6 years and adult height with mortality  or nonlinear models (not shown) but was inversely associated with deaths from CVD , externalizing disorders , and all other causes . Similarly, being in the shortest vs all other quintiles at 6 years was not associated with a higher risk of death from cancer , but showed similar sizes of associations with deaths from CVD , externalizing disorders , and all other causes .Adult height was not associated with death from cancer, either in linear models , and also in those between the second and ninth percentiles  compared with those with heights at 6 years that were taller than the ninth percentile (3.2 deaths per 1000 person-years) . The association of stunting at age 6 years with earlier mortality (between ages 6 and 43 years: odds ratio (OR), 2.45; 95% CI, 0.92–6.55; P = .07; 105 deaths) was broadly similar to that with later mortality .When height at 6 years was assessed against the contemporary WHO 2007 growth reference , all-cauSeveral indicators of the early environment, childhood nutrition, and physical illness were associated with risk of childhood stunting at age 6 years . Because these indicators were interrelated, we performed a forward stepwise regression model and identified 6 factors that were independently associated with being in the shortest height quintile at age 6 years. These factors were shorter midparental height, never breastfed, the presence of 3 or more young children (age <5 years) in the house, lower birth weight, a chronic illness requiring prolonged hospital admission before age 4 years, and intermediate or poor care of the house and child as assessed by the health visitor at age 4 years .P = .04), never breastfed , and 3 or more young children in the house  were also associated with all-cause mortality at age 36 to 64 years after adjustment for adult SEP and smoking  and women separately  and was only modestly attenuated when adjusted for potential confounders, adult SEP and smoking . Of the In keeping with several previous studies , 18–21, 18–The birth cohort study design allowed us to identify early life factors that were related to both childhood short height and adult mortality. Midparental height is commonly interpreted as a marker of the child's genetic height potential. Most of the variation in growth after age 2 years is estimated to be genetically determined , 25. AltIn the British 1946 Birth Cohort Study, 38% of children grew up in poor environmental circumstances, defined as a combination of overcrowding, mothers who had only primary school education, and fathers in manual occupations, and many such adverse early life factors were associated with shorter adult height . EnvironOur study has a number of limitations. Adult and childhood height, their determinants, such as breastfeeding, and mortality are strongly socially patterned. Although we performed statistical adjustments for SEP, it is possible that residual effects remained. SEP in childhood has a strong influence on adult mortality , throughRather than adult height per se, it is likely that some other physiological mechanism related to childhood or adult height explains the link to later mortality. Similar to some previous studies , we founIn conclusion, in a long-running British birth cohort study, the well-recognized association between shorter adult height and higher all-cause mortality was explained by short height during early childhood, which in turn appeared to reflect both genetic factors and early life adversity.


Background. The present retrospective study was intended to investigate whether working out and other low-speed sports can provoke cardiovascular, neurological, or traumatic damage. Material and Methods. Patient data from 2007 to 2013 was collected and saved at the university department of emergency medicine in an electronic patient record database. Results. Of the 138 patients included in this study, 83.3% (n = 115) were male and 16.7% female (n = 23). Most admissions were due to musculoskeletal accidents , followed by neurological incidents , cardiovascular incidents , soft tissue injuries , and others . The mean age of the allover injured people was 36.7 years. The majority of the patients  were treated as outpatients; 24 (17.4%) were inpatients. Discussion. In Switzerland, this is the first study that describes emergency department admissions after workout and examines trauma and neurological and cardiovascular incidents. As specific injuries, such as brain haemorrhages, STEMIs, and epileptic seizures, were relatively frequent, it was hypothesised that workout with its physiological changes may be an actual trigger for these injuries, at least for a specific population.  Conclusion. Strenuous physical activity may trigger the risk of cardiovascular, neurological, or trauma events. Working out and other sports, such as cycling, jogging, or swimming, are becoming more and more popular, not only among the young but also among the older generation . RegularThe Swiss Survey for Health (SGB) of the Federal Statistical Office for 2002, 2007, and 2012 shows that, in 1978, approximately 20% of the population exercised regularly, meaning more often than twice a week, whereas in 2007 as many as 56% of the population performed exercises or workout, including 51% several times a week and 30% only once per week [It is well known that gentle and regular physical activity promotes good health. It is less clear whether a strenuous workout can also be the trigger for cardiovascular or neurological incidents. Working out is very popular, but there is little published data on the types of injuries or incidents among the participants.We studied a sample of 138 adults admitted to the emergency department after workout and describe their injuries, as well as neurological and cardiovascular incidents. We wanted to see whether there is a specific population at risk or a pattern of specific injuries or incidents after workout.Our university department of emergency medicine, the only Level I trauma centre in the Canton of Bern, serves about 1.8 million people and treats more than 35,000 cases per year, caring for patients older than 16 years. From 2007 to 2013, patient data was collected and saved at the university department of emergency medicine in an electronic patient record database . The database was browsed for the key words “Training,” “Hantel,” and “Fitness”  and manually analysed for its accuracy. Search terms also included workout, indoor cycling, treadmill, and swimming. In the database, we identified 138 patients who were admitted to the emergency department after workout, either immediately or, at the latest, one day after workout. Since this medical database allows instantaneous recall of past diagnostic reports, consultations, X-rays, and other relevant medical documents, the authors were able to analyse retrospectively the identified patients. We included all patients presenting to our emergency department (ED) during the study period and after performing the following sporting activities: workout, indoor cycling, treadmill, or swimming. We excluded any contact sports , as well as high-speed sports . The data were classified by gender, age, outcome , type of sport, and cardiovascular, neurological, and musculoskeletal events, soft tissue injuries, and “others,” such as hyperventilation and rhabdomyolysis.n = 19; 13.8%), neurological incidents , musculoskeletal accidents , soft tissue injuries , and others   and 23 women (16.7%). We subdivided the 138 emergency department admissions into 5 subgroups: cardiovascular incidents  .n = 62) of all patients belong to the age group of the young generation from 17 to 30 years; 46% (n = 64) belong to the generation aged between 31 and 65 years; and only 9% (n = 12) are older than 66 years.The mean age of the injured people was 36.7 years. The mean age of the patients was different for each category: for cardiovascular incidents, the mean age is 47.2 years, for neurological incidents 44.2 years, for musculoskeletal trauma 33.2 years, for soft tissue injuries 20.0 years, and for the “others” 33.1 years.n = 77), followed by neurological events (n = 23) and cardiovascular events (n = 19). Soft tissue injuries (n = 3) and others causes such as infection, hyperventilation, and rhabdomyolysis (n = 16) were less significant.The main causes for emergency department admissions were musculoskeletal accidents  and that most patients were between 31 and 65 years of age  (n = 7), followed by syncope and presyncope (n = 4), STEMIs (n = 3), and hypertensive crisis (n = 3); two of the latter patients had already been treated with antihypertensive medication. Carotid dissection, aortic dissection, and symptomatic varicosis of the limb were exceptional (http://dx.doi.org/10.1155/2015/610137); the other medication in the cardiovascular group was heterogenous (Supplement 2).Division of the subcategories by gender and age groups  showed that, for cardiovascular events, males are predominant  . The leaeptional . As predn = 19, females 17.4%; n = 4) and most of the patients were aged between 31 and 65 years , followed by 17–30 years  and 66–100 years . Most neurological events after workout were epileptic seizures (n = 5) (including two patients with prior epileptic episodes) and cerebral haemorrhage (n = 5), followed by ischaemic stroke (n = 3), transient global amnesia (n = 3), and other neurological events (n = 7), such as dizziness, migraine, craniocerebral injury, and unclear neurological symptoms  but were clearly younger than the other two groups, most being between 17 and 30 years old  (n = 43) is the leading cause for emergency department admissions. This was followed by distortion, dislocation, torn ligament, tendinitis (n = 13), fractures (n = 6), contusion and open wound (n = 3), and others (n = 12)  . In this(n = 12) .n = 120; 87%), followed by treadmill , indoor cycling , and swimming .Most of the incidents of all types were due to workout  and cardiovascular  incidents. Workout was the main source of emergency department admissions in all 5 subgroups. Treadmill just figured in the subgroup of musculoskeletal accidents (10.4%). Events related to swimming were found in the cardiovascular (10.5%) and the “other” (6.3%) subgroups.The largest class of events after indoor cycling were neurological  was treated as outpatients; 24 patients were treated as inpatients (17.4%); and there was one death (0.7%) from a pericardial tamponade after a type A aortic dissection.The largest section of patients  linked to heavy exercise is controversial. Subarachnoid haemorrhage (SAH) and ischaemic stroke (IS) must be distinguished in this context.Anderson et al. studied a group of patients with the first event of SAH, of which 76% presented an aneurysm as origin of the bleeding. By analysing the activities at the very moment of the SAH or the activities preceding the haemorrhage, they could show that, in people who engaged in moderate to heavy physical activity, there is a threefold risk for SAH in a time window of the following 2 hours, when compared to periods of low physical activity . Fann etAs with the increased risk of MI in the morning hours , 13, theAs an epileptic seizure seems to be one of the leading neurological problems resulting in emergency department admission after workout see ; Table 2n = 77; 55.8%) of emergency department admissions after workout , followed by distortion, dislocation, torn ligament, tendinitis (n = 13), fractures , contusions and open wounds (n = 3), and others (n = 12)  . SchneidFurthermore it would be interesting to know about the frequency of workouts, as some studies show an association between sports injuries and training sessions per week , 31.Our findings have to be considered with some caution, as the study was conducted retrospectively. As the information in our medical history database is presented in a narrative comment, there is no guarantee that the number of patients was fully reported. Furthermore, our study was limited to adults (≥16 years old), as children are treated at a separate emergency department in our hospital. We think, however, that the retrospective time window from 2007 to 2013 balances the seasonal variations for injury likelihoods and environmental changes.Furthermore our study population is not balanced with respect to age or gender distribution, so that there might be a bias regarding the younger and male patients. Generally it is difficult to compare groups of different ages, as they differ greatly in terms of underlying diseases or general body condition. In a follow-up study, it would be interesting to describe the exact time (morning versus evening) of the exercise, the general condition of the participants , the intensity level of the exercise, the regularity and duration of physical activity or practice, the type of exercise, and documentation of any warming up period.Workout and other low-speed sports seem to be protective for human health, when performed regularly and cautiously. Strenuous physical activity however may exacerbate the risks of cardiac death and myocardial infarction, mainly for the untrained people and people at some cardiovascular risk (due to degeneration and/or lifestyle) or people with occult heart disease , 32, 33.For the neurological events, the younger (17–30 years and 31–65 years) groups are more at risk than the oldest group (66–100 years). One reason is that the older generation in general works out less often than the younger generation . Even thOur study shows that the younger male generation (with 52% in the group of 17–30 years) has a pronounced risk of traumatic injury during workout. One reason could be that ligaments and bones are less stable in adolescents, who are then more susceptible to trauma . FurtherSupplement 1: Detailed information about all patients regarding sex, age, region of injury, direct trauma and outcome classified as cardiovascular or neurological incident, musculoskeletal injury, soft tissue injury and others. Supplement 2: Detailed information about risk factors, prior events and medical treatment of patients in the cardiovascualr group aged > 30 years and the neurological patients presenting with IS or epileptic seizures.


Each experimental period lasted 14 days with the first 12 days used for diet adaptation and two days of data collection with a 3-days wash-out period between treatments. The results revealed a beneficial increasing effect of garlic (at the level of 70 g kg-1 of DM) on serum glucose concentration (p < 0.05). No effects of garlic supplementation on blood non-esterified fatty acids (NEFA), β-hydroxybutyrate (BHB), total triglycerides, total protein, and albumin concentration were observed, except for serum cholesterol concentration, which was reduced (p < 0.05) with 70 g kg-1 of DM of garlic supplementation. Dry matter intake was the same between the different treatment groups and throughout the trial period. Concerning the blood indicators of negative energy balance, no significant effects were found for NEFA and BHB in pre-partum goats however, serum glucose was improved significantly, which showed that garlic supplementation may improve the efficiency of feed utilization. In conclusion, garlic, as feed additives in ruminant nutrition, holds promise for improving feed efficiency and controlling the negative energy balance.To evaluate the effects of garlic on some blood metabolites in pre-partum dairy goats, the ration was supplemented with raw garlic at the doses of 0, 30, 50 and 70 g kg Feed intake can be low at the end of gestation due to compression of the rumen by the fetuses which reduces the rate at which the products of fermentation-synthesis are absorbed.3 An extreme negative energy balance can result in fatal consequences, such as pregnancy toxemia, in pre-parturient ewes and goats.4 The precipitating cause for these consequences is the increased energy demand of the conceptus in the latter part of pregnancy. The most important etiological factor in pregnancy toxemia is a decline in the plane of nutrition during the last 4 to 6 weeks of pregnancy. This is the period when fetal growth is rapid and the demands for energy is markedly increased.5Nutritional requirements during the last third of gestation are very high in small ruminants due to the high prolificacy of these animals. In goats, the conceptus acquires 80.00% of its birth weight in the last two months of gestation.Allium sativum) has been used as spice and folk medicine since antiquity.6 Bioactive components of garlic, including several sulfur-containing compounds such as alliin, diallylsulfides and allicin, may partly account for some effects of garlic.7 Effects of some these secondary compounds have already been demonstrated on rumen manipulation .8-9 The hypothesis addressed in this paper was that dietary addition of raw garlic would lead to improvements in feed utilization and in energy related blood metabolites.Any attempt to diminish the negative effect of feed intake depression and negative energy balance during the transition period should improve the nutritional and metabolic status and also well-being of dairy goats. In recent years, aromatic plants and their extracts have received increased attention as potential alternatives to growth promoters. Garlic . The animals were randomly assigned to a replicated 4×4 Latin square design with 12 days of adaptation and two days of sampling periods with a 3-days wash-out period between treatments. The study was started and completed in the last two months of pregnancy. At day 80 ± 1 of pregnancy, the goats were divided into four groups, housed indoor in individual pen (5 m2) and were fed daily a diet designed to cover 16.10 MJ of metabolizable energy and 11.50 % of crude protein per kg of DM.10 All animals were fed with alfalfa hay and corn silage (control) without or with raw garlic  on top of concentrate, . Feed consumption was recorded daily by weighing feeds offered to and refused by the goats. Samples of feed and orts were collected daily and kept frozen. On day 10 of each experimental period, goats were transferred to metabolic cages allowing the collection of feces for digestibility studies. For four consecutive days, feces were weighed and mixed daily, and a representative sample was taken and stored at −20 ˚C for later chemical analysis. Body weight was determined at the beginning and the end of each experimental period on two consecutive sampling days. Sample Collection and Analytical Procedures. Analytical dry matter (DM) contents of basal diet, garlic, orts, and feces were determined by oven-drying at 105 ˚C for 48 hr.11 Ash contents of basal diet, garlic, orts, and feces were determined by incineration at 550 ˚C overnight, and the organic matter (OM) content was calculated as the difference between 100 and the percentage of ash.11 Crude protein (CP) was calculated as nitrogen (N) × 6.25. The concentrations of neutral detergent fiber (NDF) in basal diet, garlic, orts, and feces were determined as described by Van Soest et al.12 without the use of sodium sulfite. The acid detergent fiber (ADF) content of diet, garlic, orts, and feces were determined according to AOAC .11g. Serum for determination of glucose, NEFA, BHBA, total triglyceride, cholesterol, total protein, albumin, sodium, potassium, calcium and phosphorus were stored at −20 ˚C until analyses.Blood samples were collected from the jugular vein on day 13 and 14 of each experimental period at three hours after morning feedings. Blood samples were left at room temperature until clotting. Tubes were then centrifuged for 20 min at 2500 Serum concentration of β-Hydroxybutyrate (BHB) and non-esterified fatty acids (NEFA) were determined by D-3-hydroxybutyrate kit and NEFA Kit , respectively. The concentration of plasma glucose, cholesterol, triglyceride, total protein, albumin, calcium and inorganic phosphorus were determined by auto-analyzer spectrophotometer  using commercial kits . Serum concentrations of sodium and potassium were measured with flame photometery .Statistical analysis. All data were analyzed as 4×4 Latin square using the PROC of GLM of SAS . Source of variation in the model were goat, period, and treatment. Tukey’s multiple comparisons tests were used to determine differences between treatments. Differences were considered significant at p ≤ 0.05. The following model was used for statistical analysis:Yijk = m + Gi + Pj + Tk + EijkYijk is the observed response, m is the overall mean, Gi is the effect of goat i, Pj is the effect of period j, Tk is the effect of treatment k, and Eijk is the residual error.where, Feed intake, total tract digestibility and body weight changes. Blood metabolites. Blood metabolites concentrations are shown in -1 DM of garlic was lower (p < 0.05) than that of control group. There were no differences between treatments in serum BHB and NEFA concentrations (-1). No significant effects were found in triglycerides, total protein, albumin, calcium, inorganic phosphorus, sodium and potassium between groups,  of garlic has been proved in previous studies in humanset al. reported marked breed differences in mineral metabolism in goats.29 To the best knowledge of the authors, there is no published report on the influence of garlic on metabolism of minerals and electrolytes in pre parturient goats. In the current study, garlic did not affect calcium, inorganic phosphorus, sodium and potassium content of blood.Mahusoon In conclusion, feeding pre-partum goats with raw garlic increased serum glucose concentration compared to the un-supplemented control group, in this trial. The results of this study showed that garlic is a promising additive to influence positively the energy status of pre-partum goats. Increased serum glucose concentration could support the hypothesis that garlic supplementation can improve efficacy of feeding which in turn may improve production performance of the pregnant goats. Further researches are needed to determine the mechanism of garlic constituent action on feed efficiency and performance of ruminants.


Chronic suppurative otitis media (CSOM) is considered one of the most common causes of acquired hearing impairment in developing countries. CSOM is a multifactorial persistent inflammatory disease of the middle ear. A distinct pathophysiologic mechanism linking allergic rhinitis (AR) and CSOM remains to evolve. The purpose of this study was to investigate the association between AR and CSOM in adults.This was a case-control study.The subjects were 62 adults  with established CSOM and 61 healthy controls. CSOM was diagnosed when there was a history of chronic (persisting for at least 3 months) otorrhea, accumulation of mucopurulent exudates in the external auditory canal or middle ear and/or perforated tympanic membrane on otoscopy. All participants were evaluated for the presence of AR by clinical evaluation of allergic symptoms, and underwent a skin-prick test for 23 common regional allergens. Statistical analysis was performed using SPSS version 16.The prevalence of clinical rhinitis  was significantly higher among the cases compared with controls . The prevalence of AR (proven by positive skin-prick test) was also significantly higher among affected adults than controls . Adjusting for age, a logistic regression model showed that there was a significant difference between the two groups. Patients with AR and non-AR were at 3.27-  and 2.57- fold increased risk of developing CSOM, respectively, compared with healthy individuals.The study showed a higher prevalence of AR in CSOM patients than in controls. It may be valuable to evaluate and control this factor in these patients. Chronic supportive otitis media (CSOM) is a major problem facing health systems around the world. The condition is characterized by persistent inflammation of the middle ear and mastoid cavity associated with otorrhea through a perforated tympanic membrane, persisting for more than 6 weeks . The worThe pathogenesis of CSOM is considered multifactorial, and most patients with CSOM have a history of recent acute onset of otitis media, risk factors associated with acute otitis media, or otitis media with effusion. The pathogenesis is thought to include Eustachian tube (ET) dysfunction, immature or impaired immunologic status, upper respiratory allergy, familial predisposition, presence of other siblings, male sex, passive smoking and other factors ,5. HowevWith the prevalence of 10–30%, allergic rhinitis (AR) is the most common allergic disorder. AR occurs in association with a number of other disorders, principally sinusitis, asthma, allergic conjunctivitis , and atopic dermatitis -10. StudDespite the existence of a few studies, there remains controversy about the relationship of AR and CSOM, and more studies are needed relating to the prevalence and role of allergy in the pathogenesis of CSOM ,15,17,18In a case-control study, 62 patients who were candidates for tympanoplasty and mastoidectomy due to established CSOM were chosen, as well as 61 controls. The controls were selected from patients who were referred to the same hospital for minor head and neck trauma, with no history of CSOM or ear symptoms.One of the cases and three of the controls were excluded from the study due to an inability to discontinue current medication or the presence of dermographism.All subjects were examined by ear, nose and throat (ENT) specialists, and a thorough medical history and physical examination including anterior rhinoscopy and otoscopy, were performed.The study was performed in Amiralmo- menin Educational Hospital and ENT Research Center of Guilan University of Medical Sciences (GUMS) in Rasht, Iran. Written informed consent was obtained from all the participants. The study protocol was approved by the ethics committee of GUMS.CSOM was diagnosed when there was a history of chronic (persisting at least 3 months) otorrhea, accumulation of mucopurulent exudates in the external auditory canal or middle ear and/or perforated tympanic membrane on otoscopy.AR was defined as the presence of signs and symptoms of clinical rhinitis, including watery anterior rhinorrhea, nasal obstruction or congestion, nasal pruritus, and sneezing, especially paroxysmal (according to standard questionnaire ). Post-nAll subjects underwent a SPT for 23 common allergens  relevant in the north of Iran by a single immunologist, who was blind to both the otologic and rhinologic situation of participants. Allergens included six types of grass, four weeds, nine trees, two mites, cat allergen and Cladosporium.The positive control was histamine hydrochloride (10 mg/mL) and the negative control was diluent (AllergoPharma). The mean wheal size was evaluated after 15 minutes, and SPT was determined as positive when observing a wheal with a mean diameter at least 3 mm larger than wheals at the site of the negative control. All subjects who were pregnant or had a history of recent consumption of antihistamines, immunotherapy with a specific allergen, or dermographism were excluded from the study. A positive SPT result could confirm the robust clinical diagnosis of AR, and negative results were considered as non-AR.All data were analyzed using SPSS version 16. The χ2 and Fisher exact tests were used to test the significance of the differences between the two groups. A p-value lessthan 0.05 was defined as significant. Odds ratio and 95% confidence intervals were also calculated.A total of 61 cases  with a mean age of 37.1±14.3 years (range 15–70 years) and 58 controls  with mean age of 28.3±11.7 years (range 15–70 years) completed the study. There was a statistically significant difference between the groups in terms of age (P=0.047). Among the 61 cases with CSOM, 26 (42.6%) patients had right ear, 25 (41%) had left ear, and 10 (16.4%) had bilateral involvement. The female–to-male ratio was 1.7:1, but the difference was not statistically significant. Thirty-seven (60.7%) patients had a history of CSOM from childhood (<18 years); others developed the disease in adulthood. The exact time of presenting CSOM symptoms for those who developed CSOM from childhood was unavailable.The proportion of patients with clinical rhinitis  was significantly higher in the cases compared with the control group . The prevalence of AR  was 24.6% (n=15) and 13.8% (n=8) among cases and controls, respectively. However AR was more prevalent among patients with CSOM compared with controls, although the difference was not statistically significant (P=0.065) .Using a logistic regression model, after correcting for the age factor, the difference between the two groups became significant. Patients with AR and non-AR had a 3.27-  and 2.57-  fold increased risk of developing CSOM, respectively, compared with healthy individuals.Patients with a history of childhood CSOM were more likely to have AR than the control group .Among all participants with AR, 52.2% (n=12) had a posterior nasal drip, 34.8% (n=8) had lower turbinate hypertrophy, and 60.7% (n=14) had pallor and swelling of the turbinate mucosa. Indoor allergens, especially mites (dermatophagoides farina and dermatophagoides pteronyssinus) were the most prevalent allergens in both groups, while outdoor allergens such as grass pollen and weeds were less prevalent .As CSOM is associated with recurrent attack of otitis media and allergy and contributes to chronic otitis media with effusion, it is plausible that allergy also contributes to CSOM. Previous studies have reported wide prevalence of AR in otitis media with effusion, ranging from 24–89% ,20,21. TFliss and colleagues collected data during the children’s visit to the clinic by means of a structured interview with the parents using an appropriate questionnaire and by extracting from the records if necessary . GorguluCSOM could be a complication of acute otitis media or otitis media with effusion, both of which are more prevalent in the early childhood . Also, AAR is more frequent in CSOM patients, and may be a risk factor for CSOM. Avoidance of recognized allergens may reduce this risk and improve the outcome of surgical therapy. Further studies in this regard are warranted.