Background: Inadequate hydration is a public health issue that imposes a significant economic burden. In Spain, data of total water intake (TWI) are scarce. There is a clear need for a national study that quantifies water and beverage intakes and explores associations between the types of beverages and energy intakes. Methods: The Anthropometry, Intake and Energy Balance Study ANIBES is a national survey of diet and nutrition conducted among a representative sample of 2285 healthy participants aged 9–75 years in Spain. Food and beverage intakes were assessed in a food diary over three days. Day and time of beverage consumption were also recorded. Results: On average, TWI was 1.7 L (SE 21.2) for men and 1.6 L (SE 18.9) for women. More than 75% of participants had inadequate TWI, according to European Food Safety Authority (EFSA) recommendations. Mean total energy intake (EI) was 1810 kcal/day (SE 11.1), of which 12% was provided by beverages. Water was the most consumed beverage, followed by milk. The contribution of alcoholic drinks to the EI was near 3%. For caloric soft drinks, a relatively low contribution to the EI was obtained, only 2%. Of eight different types of beverages, the variety score was positively correlated with TWI (r = 0.39) and EI (r = 0.23), suggesting that beverage variety is an indicator of higher consumption of food and drinks. Conclusions: The present study demonstrates that well-conducted surveys such as the ANIBES study have the potential to yield rich contextual value data that can emphasize the need to undertake appropriate health and nutrition policies to increase the total water intake at the population level promoting a healthy Mediterranean hydration pattern. Dehydration occurs when the body loses more water than is taken in. It is often accompanied by disturbances in the body’s mineral salt or electrolyte balance, especially in concentrations of sodium and potassium. Populations at particular risk of hypohydration are children, those engaged in professions where fluid homeostasis is regularly challenged, and older adults . LimitedOn the other hand, scientific literature recognizes that the “adequate intake” value of beverages (AI) is a variable event, in which differences are in part due to the inter-individual variation for water needs in response to different health status, metabolism, and environmental factors such as ambient temperature and humidity, as well as individual factors such as age, body size, and level of physical activity. Furthermore, the water needs also depend partially on overall diet and the water contained in food. About 80% of the required daily intake is provided by drinks, including water; the rest is acquired through solid food. Identifying the variety of drinks consumed and establishing the percentage of energy provided by each beverage to the diet allows us to set the pattern of individual or population-level beverage consumption. Understanding the contribution of each fluid type to the total fluid intake will allow us to draw conclusions about the adequacy of drinking habits.etc.). However, in the last decades [In Spain, the influence of the Mediterranean Diet is widespread. This pattern of consumption also includes the hydration pattern of the population. Traditionally, this pattern included water as a main drink, along with daily but moderate consumption of wine or beer with the principal meal, and the intake of a group of beverages elaborated with fresh vegetables  of each item consumed per participant and a record of the time of consumption. These study attributes provide a rich resource for exploring patterns of consumption according to age and gender, thereby permitting us to reach conclusions about whether or not drinking a variety of beverages helps to increase fluid intake to a level that meets current guidelines.The design, protocol, and methodology of the ANIBES study have been described in detail elsewhere ,9,10.n = 200 per age group (error ± 6.9%). The augment sample is the process of increasing the amount of interviews for a particular subgroup within the population in order to achieve an adequate number of interviews to allow analysis of population subgroups or segments that wouldn't normally yield a sufficient number of interviews in a main random survey, without the expense of increasing the sample size for the whole survey. Therefore, the random sample plus augment sample comprised 2285 participants.The ANIBES study is a cross-sectional study conducted using stratified multistage sampling. To guarantee better coverage and representativeness, the fieldwork was performed at 128 sampling points across Spain. The design of the ANIBES study aims to define a sample size that is representative of all individuals living in Spain, aged 9–75 years, and residing in municipalities of at least 2000 inhabitants. The initial potential sample consisted of 2634 individuals. For all analyses, we eliminated participants with anomalous values of energy intake (EI)   to avoid′ weight, height, and waist circumference were measured and body mass index was also calculated.The sample quotas according to the following variables were: age groups , gender (men/women), and geographical distribution . Additionally, other factors for sample adjustment were considered: unemployment rate, percentage of foreigners (immigrant population), physical activity level assessed by The International Physical Activity questionnaire (IPAQ) [The fieldwork for the ANIBES study was conducted from mid-September 2013 to mid-November 2013, and two previous pilot studies were also performed. To equally represent all days of the week, study subjects participated during two weekdays and one weekend day. The final protocol was approved by the Ethical Committee for Clinical Research of the Region of Madrid, Spain .′ customary eating habits  to facilitate further coding. Food records were returned from the field in real time, to be coded by trained coders who were supervised by dieticians. An ad hoc central server software/database was developed for this purpose, to work in parallel with the codification and verification processes. Food, beverage, and energy and nutrient intakes were calculated from food consumption records using VD-FEN 2.1 software, a Dietary Evaluation Program from the Spanish Nutrition Foundation (FEN), Spain, which was newly developed for the ANIBES study by the FEN and is based mainly on Spanish food composition tables [Study participants were provided with a tablet device  and trained in recording information by taking photos of all food and drinks consumed during the 3 days of the study, both at home and outside the home. Photos were to be taken before beginning to eat and drink, and again after finishing, so as to record the actual intake. Additionally, a brief description of meals, recipes, brands, and other information was recorded using the tablet. Participants who declared or demonstrated that they were unable to use the tablet device were offered other options, such as using a digital camera and paper record and/or telephone interviews. A total 79% of the sample used a tablet, 12% a digital camera, and 9% opted for a telephone interview. As no differences in the percentage of misreporting were found according to the type of device used to assess dietary intake, we used the measurements of the three assessment methods in the analysis. In addition to details of what and how much was eaten, for each eating/drinking event, participants recorded where they were, who they were eating with, and whether they were watching television and/or sitting at a table. After each survey day, participants recorded if their intake was representative for that day (or the reason why if it was not), and details of any dietary supplements taken. The survey also contained a series of questions about participantsn tables , with sen tables .The present analysis focused on the TWI of all food and drink, determined from food composition tables with several adaptations and updates . Metaboletc.); (7) water (including tap water and bottled water); and (8) other beverages .Beverages were combined into eight categories for further analysis: (1) hot beverages, including hot tea and coffee ; (2) milk ; (3) fruit and vegetable juices ; (4) caloric soft drinks ; (5) diet soft drinks ; (6) alcoholic drinks, including two groups: (a) low-alcohol grade ; and (b) high-alcohol grade , mid-morning (10:00 a.m.–1:00 p.m.), lunch (1:00 p.m.–4:00 p.m.), mid-afternoon (4:00 p.m.–7:00 p.m.), dinner (7:00 p.m.–10:00 p.m.), and other times.TWI was compared with the European Food Safety Authority (EFSA) Dietary Reference Values (DRV) for the Adequate Intake (AI) of water for men and women from 14 years of age onward , and for boys and girls from 9 to 13 years of age  . Furthert-tests with Bonferroni correction for multiple comparisons. Chi-squared tests were used for categorical variables. All analyses were two-tailed, with statistical significance set at p < 0.05.Owing to reported differences in water consumption and recommended intakes between male and female individuals, all analyses were carried out separately by gender. Crude differences in TWI and beverage consumption between groups were assessed through an analysis of variance test or Partial Correlations between water intake, energy intake, and beverage consumption adjusted for age, gender, body weight, and physical activity were calculated by the use of a variety score.vs. non-caloric) on EI while controlling for the effect of confounders . The effect of replacing 100 g of caloric beverages with 100 g of non-caloric beverages was estimated by including caloric beverages  as the main independent variable, with total beverage weight (g) held constant. This necessarily implies an equal and opposite change in other beverages. A further model included energy from food, thus disallowing compensation . Finally, we used within-person daily consumption data to explore the effect of changes in daily beverage consumption, with each person acting as their own control. The independent variables represent the standard deviation of the mean of the three different measurements (3-day records) for each type of beverage collected for each participant. The outcome (change in EI) was derived using the same methodology (deviation from participants′ 3-day mean in energy intake) [Multivariable linear regression models included adjustment for gender, age, weight, and physical activity level. Multiple linear regression models were fitted to assess the effect of varying the type of beverages consumed  .The ANIBES sample was of 2285 healthy subjects aged 9 to 75 years, of which 50% of the population was men and the other 50% were women. The study sample reflects the distribution of male and female individuals in the general population of Spain  , daily EI , and water intake (g/day) are presented in On average, the percentage of total beverage consumption from water over the three-day study period was 46% for women and 41% for men . Water wIn general , the conFor adolescents, the mean consumption of caloric soft drinks was 167 g/day (SE 19.1) for men, and 139 g/day (SE 15.9) for women . However, consumption was lower among adults, with 114 g/day (SE 6.3) for men and 82.1 g/day (SE 4.6) for women. Consumption of alcoholic drinks for adult men and women averaged 160 g/day (SE 9.0) and 71 g/day (SE 4.8), respectively. The intake of alcoholic drinks among the oldest participants (65–75 years) averaged 143 g/day (SE 19.0) for men and 53 g/day (SE 9.8) for women.The principal sources of total dietary water, by gender and age group, are shown in r = 0.95), and was more weakly correlated with food intake , whereas coefficients were lowest for hot beverages and diet soft drinks.TWI was highly correlated with beverage weight and water from beverages  and with EI , suggesting that beverage variety is an indicator of a higher consumption of food and drinks.Regarding beverage variety of eight types of beverages in our classification, the variety score was positively correlated with TWI , the net impact of 100 g of caloric beverages was estimated at 40 kcal (Model 2). Further adjustment for level of education, economic level, employment, etc. did not change the reported results.′ beverage consumption habits on any day could be associated with a change in their total EI (compared with their three-day mean). Modeling each beverage separately, with total beverage weight held constant, each of the above two non-caloric beverages (diet soft drink and water) was negatively associated with energy (as were hot beverages), whereas the five caloric beverages mentioned above were positively associated with energy (Model 3). When combining caloric beverages, the final models (Models 4 and 5) gave an estimated effect of 43 kcal per 100 g of caloric drinks substituted, or 34 kcal if EI from food was held constant.The second regression model analysis Table A2Participants who fulfilled the EFSA AI recommendations of TWI for men and women  were classified as Criterion 1. Participants with ratios of water/energy intake >1.0 were included as Criterion 2 . Finally, participants who met both definitions (Criteria 1 and 2) were classified as Criterion 3. For children 9–13 years old, the EFSA AI is 2.1 L for boys and 1.9 L for girls. Following this analysis, This study provides analyses of total water intakes from all sources among a nationally representative sample of the Spanish population aged 9–75 years, included in the 2013 ANIBES study database. To our knowledge, the present analyses represent one of the few explorations of the consumption of water and beverages in Spain, as well as the association with energy intake, consumption according to time of day and day of the week, the association between beverage variety and increased fluid intake, and compliance with current AI recommendations, by gender and age.The main findings of this study indicate that for the entire sample, TWI was 1625 g/day (SE 14.2). In general, and as expected, male individuals had statistically higher intakes than female individuals for both food and beverages. However, neither men nor women consumed sufficient amounts of water , according to EFSA AI reference values [Most of the data analysis in this work was based on an earlier survey by Gibson and Shirreffs , who anaThe comparison is difficult to do when we want to compare American and Spanish populations. The NHANES study, developed in the US between 2005 and 2010, used the proposal by the Institute of Medicine of the United States of America (IOM) as reference value, set as 3.7 L/day for men and 2.7 L/day for women . This leMean daily EI was 1809 kcal/day (SE 11.1), of which 12% was provided by the beverages, close to the 10% proposed by some international authorities  ,20 who rOn the other hand, beverage consumption is uneven throughout the day; in this study, it tended to be concentrated at lunchtime and was slightly higher on Fridays in men and on Saturdays in women. Although we did not find large variation, these findings reflect certain cultural trends of consumption that appear to be attributable to a higher intake of alcoholic beverages on weekends among both genders. The contribution of alcoholic drinks to the diet in the ANIBES study  was slightly higher than that in the ENIDE dietary survey of Spanish adults in 2011 (117 g/day) ,27. In fThe strengths of this study include the careful design, protocol, and methodology used in the ANIBES study. The present analysis can be used to inform approaches to improving the overall quality of diet and hydration status of the Spanish population.Two important limitations of this study must be noted. This study is a cross-sectional design, which provides evidence for association but not causal relationships. The second limitation is that, for logistical reasons, there was no inclusion of a hydration biomarker, which would allow assessment of dietary beverage intake and hydration status without the bias of self-reported dietary intake and also intra-individual variability. This biomarker should be included in further studies.The present study shows clearly that neither men nor women consumed adequate TWI when compared with EFSA reference values. The ANIBES study demonstrated that well-conducted national surveys have the potential to yield rich contextual value data that can emphasize the need to undertake appropriate health and nutrition policies to increase the total water intake at the population level, promoting a healthy Mediterranean hydration pattern.


Purpose. To evaluate the pooled prevalence rate and risk factors of dry eye symptoms (DES) in mainland China. Methods. All the published population-based studies investigating the prevalence of DES in China were searched and evaluated against inclusion criteria. A systematic review and meta-analysis were performed. Results. Twelve out of the 119 identified studies were included in the meta-analysis. The pooled prevalence of DES in China was 17.0%. Female individuals, subjects living in the Northern and Western China, and over 60 years of age had significantly higher prevalent rates  compared with their counterparts. Patients with diabetes were also found to be more vulnerable to DES. Conclusions. The pooled prevalence rate of DES in mainland China was lower than that in other Asian regions and countries. A remarkable discrepancy in the prevalence in different geographic regions was noted. Aging, female gender, and diabetes were found to be risk factors for DES in China. Dry eye disease (DES) is a major tear deficiency disorder which causes discomfort, visual disturbances, and tear film instability with potential damage to the ocular surface . The teaSome population-based studies investigating the prevalence and risk factors of DES in China have been published –18. ThesTo obtain regional epidemiologic data, we searched Medline , Embase , the Cochrane Central Register of Controlled Trials , Chinese Biological Medicine , China National Knowledge Infrastructure , Wan Fang Data , and Chongqing VIP database  using the free combinations of the terms “Dry Eye,” “prevalence,” and “China” in both English and Chinese languages. Reference lists were checked. The corresponding authors or first authors of the publications were contacted if additional information was needed, results were unclear, or relevant data were not reported.The review and analysis were guided to be conducted by the PRISMA statement for preferred reporting of systematic reviews and meta-analysis . ReportsThe literatures were searched independently by two researchers (Lei Liu and Yi-zhou Sun). Data were extracted from each article using a standardized form which included the first author, publication year, region or province, age range, sample size, diagnostic criteria, prevalence definition, response rage, and quality of the studies (in a score of 1–5) .I2 test and Q test [I2 estimated the percentage of the total variance in all of the data under consideration that was related to heterogeneity. If a moderate or high level heterogeneity was observed, random-effects meta-analysis was performed by the DerSimonian and Laird method, except when using fixed-effects models. Assessment of publication bias was done by inspecting a funnel plot and using Egger's and Begg's test. P < 0.05 was considered statistically significant [Odds ratio (OR) was analyzed using RevMan version 5.0  statistical software package. Multivariate analyses to test the individual association of each variable with the overall pooled prevalence estimate using meta-regression analyses were performed by Comprehensive Meta-Analysis software version 2.0 . All meta-analyses were evaluated for heterogeneity using the Chi-square based nificant , 22.The flow chart showing how the identified published studies were included in the meta-analysis was demonstrated in I2 = 49.9%,  Q = 0.99,  P < 0.001) in overall population       for elder age (≥60 years). Seven studies explored the relationship between the prevalence of DES and genders. The pooled OR was 1.15   for female gender. In addition, diabetes also showed a significant risk factor for DES and the pooled OR was 3.82  . The results are presented in Five studies investigated the association between age and DES. The pooled OR was 3.34  (P < 0.05 for both Egger's test and Begg's test).All comparisons passed the test of heterogeneity, as previously defined. Random-effects models were used for meta-analysis. There was no significant publication bias in this meta-analysis . Comparisons between the studies are hence difficult . Not surReport suggested that the prevalence of DES increased with age , which iA larger number of DES cases were identified in individuals with diabetes, particularly those with type 2 diabetes . Our metOther risk factors for DES  were initially included in the present study but were excluded because the pooled OR was not able to be calculated as a result of insufficient information provided.Our findings revealed remarkable difference in DES prevalence in different geographic regions in China. Western China and Northern China had significantly higher prevalence when compared with Central, Eastern, and Southern China, possibly because of the difference in the climate conditions and geographic characteristics in these regions. Previous study suggested there was a significant relationship between ultraviolet radiation and dry eye . QinghaiI2, we did meta-regression to analyze and verify the results to avoid substantial heterogeneity. Although pooled prevalence of DES in mainland China was derived in the present study, there are some limitations. Firstly, the pooled prevalence data was estimated using meta-analysis, rather than prevalence in a single national population-based study. Secondly, China is a vast country geographically with 34 provincial-level administrative units . Our study only included data from 12 units, which may be inaccurate to represent the pooled prevalence of the whole country. More regional epidemiologic studies are warranted, particularly those units with no published data, so that a more accurate picture of prevalence in China can be drawn. Lastly, our data should be updated as a result of the emerging new data.Because the findings in pooled prevalence of DES had moderate Compared with some of the other Asian regions and countries, the pooled prevalence of DES in mainland China was lower. There is remarkable discrepancy in the prevalence in different geographic regions in China, with Western and Northern China presenting higher prevalence, possibly because of the difference in the climate conditions and geographic characteristics. Female, elder individuals, and patients with diabetes seemed to be more vulnerable to DES. More studies focusing on Chinese populations in regions without epidemiologic data are of great value.


Recent studies demonstrated pigmented cells both in the murine heart, in pulmonary veins, and in brain arteries. Moreover, a role for melanocytes in the downregulation of inflammatory processes was suggested. As there is increasing evidence that inflammation is contributing significantly to the pathogenesis of intracranial aneurysms, melanocyte-like cells may be relevant in preventing age-related impairment of vessels. As pigmentation of the heart reflects that of coat color, aspects of body pigmentation might be associated with the incidence of intracranial aneurysms. We performed a case-control study to evaluate associations between the pigmentation of hair and eyes and the formation of aneurysms. In addition to hair and eye color, constitutive and facultative skin pigmentation were assessed in a replication study as well as individual handedness which can be seen as a neurophysiological correlate of developmental pigmentation processes. Hair pigmentation was highly associated with intracranial aneurysms in both samples, whereas eye pigmentation was not. In the replication cohort, facultative but not constitutive skin pigmentation proved significant. The strongest association was observed for individual handedness. Results indicate a significant association of intracranial aneurysms with particular aspects of body pigmentation as well as handedness, and imply clinical usefulness for screening of aneurysms and possible interventions. The pathogenesis of intracranial aneurysm formation and rupture remains mostly unknown. Current evidence favors an interaction of multiple environmental , 2 and gNevertheless, the various results on the involvement of inflammation in aneurysm formation raise another still unresolved issue, in particular why only in some individuals several unfavorable conditions  result in serious inflammatory responses and, consequently, in aneurysm formation, but in the vast majority of individuals they do not. Therefore, any new perspective in aneurysm research may help to increase the understanding of etiological processes and, consequently, may improve screening methods and therapeutic interventions. One such new and possibly fruitful approach relates to recent studies investigating the distribution and function of “non-classical” melanocytes, that is, pigmented cells which are not located in the skin and are not involved in skin pigmentation. Such nonclassical melanocytes are located in sites as different as the eye, inner ear, bones, and meninges. Additionally, recent evidence exists that there is also a consistent distribution of pigmented cells in several structures of the mouse heart , 9. Moreα-MSH) mediated by melanocortin receptors of different subtypes (MC1R to MC5R). Although α-MSH/MC1R interactions primarily contribute to the regulation of skin physiology, MC1 receptor functions extend well beyond the regulation of melanogenesis as it is expressed in a variety of cells, especially in cells of the immune system, that is, macrophage/monocytic cells, lymphocytes with antigen-presenting and cytotoxic functions, neutrophils, and also peripheral blood-derived dendritic cells, downregulating the production of specific proinflammatory cytokines  was calculated as a measure of degree of handedness, with positive values indicating left-handedness. Statistical analysis was based on terciles of laterality coefficients, defining subgroups of pronounced right-handed, moderate right-handed, and bimanual or left-handed subjects.Handedness was assessed by an objective and standardized paper and pencil test  consistiz > 3.5  was excluded from the respective analysis, reducing the number of cases to 57. Multivariate logistic regression was done on the three global groups of hair and eye color, as well as on the three subgroups of photosensitivity. Results of case-control comparisons are shown in P for trend = 0.001). Compared to dark pigmented hair, light pigmentation was highly associated with intracranial aneurysm . While positive findings for hair color were fully replicated, associations between eye pigmentation and aneurysms were again nonsignificant.The same statistical methods were applied as in Study I. One aneurysm patient with a handedness score of P for trend of 0.04. The strongest association was observed for individual handedness. Compared to subjects with pronounced right-handedness, the odds of an intracranial aneurysm were 22.36 (95% CI: 2.64 to 189.32) for subjects with moderate right-handedness and increased to 64.09 (95% CI: 5.40 to 760.69) for bimanual or left-handed subjects. The degree of association increased with an increasing shift from right- to left-handedness (P for trend = 0.001).Skin phototype as an explanatory variable proved significant, while skin color did not. The odds ratio for subjects reporting easy burning and minimal/no tanning was 6.08 (95% CI: 1.11 to 33.45) in comparison to rarely/never burning and profusely tanning participants, with a P < 0.000), with the following classification parameters: sensitivity = 94.7% and specificity = 86.8%; that is, 94.7% and 86.8% of patients and controls, respectively, were classified correctly. Accordingly, the false positive/negative rates were 13.2 and 5.3 percent.To give a rough estimate of their predictive power as a screening tool, a logistic regression was additionally calculated with a combination of those independent variables in the data set of Study II which had revealed significant associations with case-control status, that is, hair color, skin photosensitivity, and handedness. For this purpose, the respective global group values for each variable were averaged for each individual and modeled as single, continuous, and independent variable and case-control status was modeled as the dependent variable. Logistic regression showed a highly significant result . Secondly, the odds ratio for the particular state “blond to strawberry blonde/red hair” and the respective confidence limits are substantially reduced indicating a lower error of measurement. Moreover, the lower confidence limit still amounts to about 4, that is, a remarkable value which is based on both data sets and therefore a more valid parameter.Finally, we combined the data from both samples and calculated two logistic regressions to get a more reliable estimation of odds ratios and, especially, their confidence limits. A combination was possible for the variables of hair and eye color determined in both samples, resulting in a data set of 111 patients and 174 controls. Results of these regression analyses are given in β and interleukin 6) in left versus right cortices and motor lateralization has also been demonstrated [Intracranial aneurysms were clearly associated with particular aspects of body pigmentation, and the strongest association with aneurysm formation was observed for individual handedness. As for handedness, it is an essential indicator of direction and degree of individual brain lateralization, which in turn is correlated with several aspects of body pigmentation: aberrant and limited migration of cephalic neural crest cells, defective/reduced melanin production, and/or dysfunctional melanocortin receptors, for instance, may be considered as a common basis of two different but related manifestations, that is, reduced pigmentation/albinism and various anomalies in brain lateralization, such as in the motor system manifested as ambidexterity or left-handedness –31. Brainstrated , 42. ConOne possible explanation relates to an important functional characteristic of melanocytes: recent evidence indicated distinct differences in the antioxidative efficiency of the melanocyte system between individuals. These differences are caused by the melanocortin 1 receptor which is highly polymorphic and a major contributor to the diversity of human pigmentation. Some variants of the MC1R gene are strongly associated with light pigmentation and especially with red hair color in humans , and melanocytes with such MC1R mutations were recently shown to have diminished ability to cope with oxidative stress . Therefoα-MSH and other receptor ligands was demonstrated, for instance, in proteinuria [α-melanocyte-stimulating hormone was shown to regulate vascular NO availability and to protect against endothelial dysfunction [Beyond that, the importance of inflammatory processes in intracranial aneurysm formation is further substantiated by the results of recent studies showing that frequent use of acetylsalicylic acid both attenuates inflammation in the walls of human cerebral aneurysms  and, theteinuria , uveitisteinuria , and skiteinuria . Treatmeteinuria , and thefunction .Agonists of the melanocortin system, therefore, may prospectively be seen as efficient therapeutic strategies to fight against developing inflammation in brain arteries and, most importantly, to prevent aneurysm rupture. The logic behind such a strategy, however, requires empirical evidence that particular aspects of body pigmentation, that is, specific processes and functions of the melanocortin system, are significantly associated with the incidence of intracranial aneurysms. Such associations were documented for the first time by the present study which, therefore, adds some new aspects to etiological models of intracranial aneurysm formation.α-MSH hormone which is mediated by the MC1R receptor. The MC1R receptor and its genetic mutations, again, are the main source of individual variation in hair and skin pigmentation, a fact well documented in the literature . Ho. Hoα-MSHe  . DespiteThere are several limitations of the present study. The main sources of imprecision result from the relatively small sample size, especially in Study II. First, this fact specifically concerns facultative and constitutive skin pigmentation. Whereas one of the estimated odds ratios for skin phototype reached significance, logistic regression failed to show an effect for skin color, although a (nonsignificant) trend in the frequency distributions for the three categories of skin color can be observed in the expected direction (distribution in patients opposed to that in controls). However, confidence limits for both skin pigmentation variables are unrealistically high indicating a large portion of error variance caused by the small sample size. This is especially true for the effect of handedness: the highly significant odds ratios for both handedness categories as well as the significant overall trend indicate fundamental importance of this variable. The actual figures, however, appear highly implausible. Future studies determined on a much larger data base will provide more realistic estimates for the common variance between brain lateralization, body pigmentation , and the formation of intracranial aneurysms. Secondly, a further source of imprecision relates to the quantification of pigmentary traits. With the exception of skin color, pigmentation variables have been based on subjective phenotypes using categorical scales in estimating the level of pigmentation. In future studies, objective and quantitative measures of skin, hair, and eye color should be collected by using, for instance, reflectance or digital spectroscopy and, thereby, excluding a further source of error variance. Finally, our study provides only indirect evidence of an association between the melanocyte system and the formation of aneurysms. As already mentioned above, effects of the melanocyte system on aneurysm formation should be demonstrated directly by analyzing specific genetic variations in patients and controls.A significant association between particular aspects of body pigmentation and the incidence of intracranial aneurysms was demonstrated in the present study. Odds ratios increased with a decreased pigmentation of hair and a reduced ability to adjust melanization of epidermal cells after sunlight exposure (“skin photo-type”). Results for hair color were validated in a second independent sample of cases and controls, and the replication study yielded virtually identical results. In addition, individual handedness as a neurophysiological correlate of developmental pigmentation processes was also strongly associated with aneurysm formation; that is, the degree of association increased with an increasing shift from right- to left-handedness.


A gradual increase in the longevity due to advancement of treatment modalities and a subsequent surge in elderly population in India have led to a growing curiosity in the geriatric age group with Alzheimer’s disease (AD). Behavioral and psychological symptoms of dementia (BPSD) represent epiphenomena of AD. However, no comprehensive study has been carried out in South East Asia , to assess the behavioral and psychological symptoms in subtypes of AD.The purpose of this study was to assess BPSD in early-onset Alzheimer’s disease (EOAD) and late-onset Alzheimer’s disease (LOAD).The study was conducted in the Memory clinic of the postgraduate department of psychiatry, Government Medical College, Kashmir, India from January 2012 to March 2014. The diagnosis of AD patients was done according to NINCDS-ADRDA criteria. A total of 80 patients of AD were screened . Neuropsychiatric inventory (NPI) was the instrument used for evaluating symptoms of BPSD. The data was analyzed using paired t-test.The mean age of presentation of EOAD and LOAD was 63.10 years and 84.28 years, respectively, and the difference between the two was found to be statistically significant. The LOAD group had significantly higher symptom severity for delusions, agitation, anxiety, disinhibition, and nighttime behavioral disturbances (NBD) than the EOAD group (p ≤.0001).The behavioral and psychological symptoms are significantly severe in late onset subtype compared to the early onset subtype of Alzheimer’s disease in the Kashmiri (Indian) population.  Alzheimer’s disease (AD) is the most common type of dementia and is a worldwide health problem, especially in a developing country like India -3. AD isAD is characterized by loss of cognitive and noncognitive functions in various domains. The loss of these functions causes significant disability in activities of daily life. The appearance of noncognitive symptoms occasionally occurs before the onset of cognitive symptoms. Noncognitive symptoms include behavioral and psychological symptoms of dementia (BPSD) and neurological symptoms. The mechanism by which BPSD occurs in some patients with AD is not completely understood . VariousVarious standardized instruments like Neuropsychiatric Inventory (NPI), behavior pathology in Alzheimer's disease (BEHAVE-AD) scale and Alzheimer's disease assessment scale (ADAS) are used to assess BPSD in AD . Early dThe study was conducted in the Memory Clinic of the Postgraduate Department of Psychiatry, Government Medical College, Srinagar, Kashmir, India from January 2012 to March 2014. The Government Medical College and its associate hospitals provide care to the whole of the Kashmir region, along with the adjoining areas of the Jammu and Ladakh regions (population of over 6 million).A total of 80 patients with AD were screened . The two groups were divided by the conventional division line of the 65 years. Each patient had a structured clinical interview, laboratory routine exams, physical and neurological examination, and imaging (CT or MRI).The diagnoses of AD were done according to NINCDS-ADRDA criteria  by two e1. Patients with a one-year history of unchanged symptoms after the onset of BPSD. This was done as BPSD fluctuates over time and can subside for long periods .2. Diagnosis of probable AD according to the NINCDS-ADRDA criteria .3. Availability of a reliable caregiver. A reliable caregiver was defined as someone who was able to ensure the patient’s compliance with assessment procedures and who contacted the patient at least twice weekly, with one contact being a personal visit.4. Classification in mild to moderate severity using the mini-mental state examination (MMSE).1. Patients with a MMSE score below 10.2. Patients with a past history of psychiatric illness and/or any neurological illness that could interfere with neuropsychological tests.The instruments used for BPSD evaluation were applied at the time of the diagnosis by two trained psychiatrists. The instruments used in assessing behavioral and psychological symptoms in subtypes of AD included:1. Mini-Mental State Examination (MMSE)It is a brief 30-point questionnaire test that is used to estimate the severity of cognitive impairment .The inst2. The Clinical Dementia Rating (CDR)It is a scale with good reliability and validity used to assess and quantify the severity of symptoms of dementia  .3. The Neuropsychiatric Inventory (NPI)It is an informant rating scale used to measures various behavioral symptoms in AD like delusions, hallucinations, agitation/aggression, dysphoria/depression, anxiety, euphoria/elation, apathy/indifference, disinhibition, irritability/lability, aberrant motor behaviors (AMB), nighttime behavioral disturbances, and appetite/eating disturbances. An informant rates the frequency and severity of each of these dimensions; the final score is obtained by multiplying the first two scores. In NPI, every domain has a screening question. If it is not answered positively, the interviewer moves to the next domain. If it is answered positively, then specific behavioral symptoms are assessed within that domain. If any of these symptoms are presented, they are rated on a 4-point frequency scale and a separate 3-point severity scale. The score for each dimension ranges from 0 to 12. The maximum total score in the 12-item version of NPI is 144 .The study was done after obtaining clearance from the ethical committee of the Government Medical College, Srinagar, India, and no grant was funded by the committee. The patients gave their consent before being subjected to various tests.The study sample consisted of 80 patients: 40 with EOAD, and 40 with LOAD. Both groups were matched for education, gender, MMSE, disease duration, and severity. The mean age of presentation of EOAD and LOAD was 63.10 years and 84.28 years, respectively, and the difference between the two was found to be statistically significant. The significant mean differences were found for age of onset and MMSE (p <0.05). Table With regard to the NPI scores, the LOAD group had significantly higher symptom severity for delusions, agitation, anxiety, disinhibition, and nighttime behavioral disturbances than the EOAD group, and the differences were found to be statistically significant (p <0.05). Table The data was analyzed using paired t-test, and the mean difference between the two groups was considered to be statistically significant (p ≤0.05). Demographic quantitative characteristics were presented as mean and standard deviation (SD).The burden of dementia in India, particularly of AD, is increasing due to increase in life expectancy. There has been growing importance of BPSD in AD over the last few years, particularly with regard to the quality of life of patients. BPSD is a term used to delineate diverse range of psychological responses, psychiatric symptoms, and behaviors occurring in any type of dementia including AD . The aveTwo arbitrary types of AD have been described, i.e., EOAD and LOAD . EarlierThe study also showed that the LOAD group had significantly higher symptom severity for delusions, agitation, anxiety, disinhibition, and nighttimes behavioral disturbances compared to EOAD group. This finding of the study is consistent with other studies . In a stBoth types of AD (EOAD and LOAD) in the study were associated with psychotic features including delusions and hallucinations. This is in accordance with the other studies. However, delusions are known to occur more frequently compared to hallucinations in LOAD , 20-21. It is a quite well known fact that AD patients have increased verbal and physical aggression, and thus, the handling of the patients by their caretakers is quite difficult. NPI scale underlines resistance to somatic and verbal concern , 24. TheIndian culture and societal attitudes necessitate caring for the elderly in the home environment rather than nursing homes. The majority of the Indian population lives below the poverty line, and the management of BPSD with compromised cerebral functions is rather difficult . Low-cos1. The sample size was small; therefore the generalization of the results may be questioned.2. Another limitation included the possibility of selection bias as the sample was drawn from one hospital only.Although research on the subtypes of AD appears to be understudied and least explored in India, our study was a maiden attempt to understand the epiphenomenology of cognitive symptoms in subtypes of AD. Wider dysfunctions in BPSD, especially higher symptom severity for delusions, agitation, anxiety, disinhibition, and nighttime behavioral disturbances, were observed in LOAD compared to EOAD in the Kashmiri (Indian) population.


The least potent antioxidants were ginger and cilantro with LC50 of 7604 mg/L of phenol and 7876 mg of phenol/L, respectively.Thirty eight bottles of red wine (Carbanet Sauvignon) were randomly selected based on vintage, region, price, and age (number of months in a barrel). The total phenolic content of each wine was determined using Folin-Ciocalteau assay. The radical scavenging activity was evaluated using 2,2-diphenyl-1-picryhydrazyl (DPPH) assay. Apart from a few bottles that exhibited above average radical scavenging activity and phenolic content, there was no good correlation of those two quantities with region, price or vintage. The average phenolic amount was 2874 mg/L. The lowest phenolic content was found to be 1648 mg/L for an eight dollar wine. Wine with the highest amount of phenol of 4495 mg/L was a 2007, nine dollar bottle from South America. High amount of phenols did not translate into high radical scavenging activity. Barrel-aging did not increase the amount of phenols or the radical scavenging activity of wine. In order to discover new and potent sources of antioxidants from plants, the following spices were studied: ginger, cilantro, cumin, anise, linden, eucalyptus, marjoram, oregano, sage, thyme and rosemary. Whole spices were crushed and extracted for 96 h at room temperature using a combination of ethyl acetate, ethyl alcohol and water in the ratio of 4.5:4.5:1 (v/v/v). The radical scavenging activity of extracts was evaluated using 2,2-diphenyl-1-picryhydrazyl (DPPH) assay. The total phenolic content of each spice was also determined using the Folin-Ciocalteau assay. Eucalyptus was found to be the most potent antioxidant with an LC The frexidation ,14,15,16Antioxidants are also used to preserve food quality mainly because they slow oxidative deterioration of lipids. Much research is focused on finding ways to prevent or to delay the oxidation of fats and oils, which leads to deterioration of foods containing those components. Even small amounts of oxidizing free radicals can cause reactions that produce undesirable flavor, rancid odor, discoloration and other spoilage. Lipids that contain large amounts of unsaturated fatty acids can be easily oxidized to lipid peroxide or hydroperoxide, which then rapidly decomposes by radical chain reaction to give lower molecular weight compounds such as aldehydes, ketones, carboxylic acid and others. These compounds contribute to food rancidity. Various efforts have been made to minimize the oxidation reactions in foods such as reducing the amount of oxygen in the head space of containers, filling with inert gas, or addition of antioxidants. The addition of antioxidants to food is an effective way to prevent the development of various off-flavors and undesirable compounds that result from lipid oxidation. There has been a decreased use of the stable and effective synthetic antioxidants such as butylated hydoxytoluene (BHT) and butylated hydroxyanisole (BHA) because of the possibility of toxicity as well as rejection by the general consumer. As a result, there is worldwide interest in finding new and safe antioxidants from natural sources. The development of safe and effective antioxidants is focused on edible plants, especially spices, because man has used them not only as flavoring agents but also for antiseptic or medicinal purposes since prehistoric era. Natural antioxidants have the potential to prevent not only lipid peroxidation in food but also oxidative damage to living cells. Many spices have been examined for their antioxidative activity. Rosemary, sage, oregano, thyme, and turmeric were found to be effective antioxidants and some retarded the oxidation of lard ,18. The Both wine and spices are consumed in large amounts daily worldwide and are of interest as potent sources of antioxidants. A bottle of wine, bought from a liquor store, is usually consumed on the same day, and the number of people drinking wine is on the rise because wine is thought to have health benefits. In this report, our interest was to discover the type of Carbanet Sauvignon wine with the highest free radical scavenging activity. Cabernet Sauvignon is one of the world's most widely recognized red wine grape varieties. It is also grown in nearly every major wine producing country among a diverse spectrum of climates. In addition, in an attempt to come up with safe and effective antioxidants that could be used in the food industry, to delay and prolong the shelf-life of various products that contain lipid, spices that not only flavor food but also are consumed for their medicinal purposes were evaluated.Cabernet Sauvignon from Argentina, Australia, California, Chile, France, and South Africa was purchased from liquor stores in central Pennsylvania. McCormick, Clover Valley, Badia, and Price Rite spices were purchased from grocery stores in the same area. Spice Latin names were not listed on spice containers. Optical densities were read using Cole Parmer Instrument  2800 UV/Vis spectrometer. 2,2-Diphenyl-1-picrylhydrazyl (DPPH), sodium carbonate, potassium acetate were purchased from Sigma-Aldrich, St Louis, MO, USA.Determination of total phenolics as gallic acid equivalent was carried out using Folin-Ciocalteau method with minor modifications . Wine ; and ODs was the absorbance of the samples. The percent inhibition was plotted against volumes of wine using Microsoft Excel and the volume needed to decrease DPPH concentration by 50% was calculated from the graph (R2 ≥ 0.95). The experiment was carried out in triplicate and the results are mean values.The free radical scavenging activity was measured by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method described by Blois, with some modification . Stock sSpices were dried at 75 °C in oven to constant weight. Whole dried spice (1 g) was crushed and extracted for 96 h at room temperature using a combination of ethyl acetate, ethyl alcohol and water (20 mL) in the ratio of 4.5:4.5:1 (v/v/v). This extraction process, developed in our laboratory , was exhversus optical density calibration curve.To each spice extract (20 μL) was added 1.58 mL water and 0.1 mL Folin-Ciocalteau reagent. After nine minutes, 0.3 mL of saturated solution of sodium carbonate was added and the mixture kept in a water bath at 40 °C. After 30 min, optical density was read at 765 nm and the amount of phenol calculated using amount of gallic acid per liter 50, aliquots of original or diluted extract ranging from 10 μL to 80 μL were mixed with enough methanol and DPPH (2900 mL of 0.03 mg/mL solution) to give a total volume of 3 mL. The volume of extract needed to decrease the initial DPPH concentration by 50%, together with amount of phenol as measured by the Folin-Ciocalteau method were used to determine LC50 values.Extracts of rosemary, eucalyptus leaves, and marjoram were diluted five times before carrying out the DPPH assay. In order to find the LC50 of 1.60 mg of phenol/L. Wine from California, entry 1–10, generally exhibited good total phenol numbers ranging from 1648 mg/L to 3475 mg/L. Their overall RSA was slightly higher than the average for all wines. An eight dollar bottle, entry 5, with the lowest amount of phenols of 1648 mg of phenol/L had the highest RSA with an LC50 of 1.0 mg phenol/L. Wine from Argentina had consistently higher levels of phenols and lower RSA than wine from California. One bottle of wine from Argentina had the highest amount of phenols, entry 23. However, the radical scavenging activity was found to be one of the lowest with an LC50 of 1.9 mg phenol/L. Each region had wine with high phenol numbers and high RSA activity. At the same time, wine with low phenol numbers and low RSA relative to the phenols was also found in every region. Overall, high amounts of phenol did not produce high radical scavenging activity. This is not surprising because Folin-Ciocalteau reagent reacts with vitamins, thiols, dihydroxyacetone, inorganic salts, and nitrogen-containing compounds [Cabernet Sauvignon from the Australia, Chile, Argentina, Pennsylvania, California, South Africa, and France were used in two assays to determine the radical scavenging activity and total phenols. ompounds . Moreoveompounds ,37, but ompounds .The effect of barrel-aging on the total phenols and radical scavenging activity is shown in 50 for each spice given in the table are averages from twelve different determinations. Total phenolic content was expressed as mg gallic acid equivalents (GAE)/g. Linear regressions were performed to obtain LC50 values using Word Excel. The data in Each spice was obtained from four different suppliers, namely, McCormick, Price Rite, Badia, and Clover Valley. Leaves of spices were used for all plants except for cumin and ginger; seeds and roots were used for cumin and ginger, respectively. The total phenols and LCWhat distinguishes a great wine from a good wine is usually balance, which takes into account aroma, bouquet, fruit flavors, body, structure and mouth-feel. In this study, cheap wine was found to have more or less the same radical scavenging activity as the more pricey wine. The amount of total phenols as measured by GAE was also comparable. Our study indicates that there isn’t a major difference between wine from different regions based on total phenolic content and radical scavenging activity. Barrel aging that softens tannins and contributes to the overall roundedness did not seem to affect the total phenols or the radical scavenging activity of wine. Without blind tasting, coupled with the measurement of total phenolics, it was not possible to correlate taste to amount of phenols. It is possible that wine producers make the right adjustments to wine before selling it to the public. Adjustments may include blending and addition of enological tannins from different sources. Future studies will take into account blind wine tasting and the measurement of phenols and radical scavenging activity to evaluate the gradual evolution of phenolics.Rosemary, eucalyptus, marjoram, and thyme, all had good radical scavenging activity compared to other spices. Rosemary has a unique aroma and has been used in food preservation. Our study indicates that eucalyptus leaves, marjoram and thyme could be good substitutes for rosemary, expanding the aroma choice, as each spice has its own characteristic smell. The total phenolics in wine and in the spices we examined in this study are in the same range, however, the radical scavenging activity of wine is about two hundred times that of eucalyptus, the spice with the highest radical scavenging activity. Taking two glasses of wine would provide more antioxidants that eating a whole rosemary-flavored chicken.


Familial hypercholesterolemia (FH) is a common and serious dominant genetic disease, and its main pathogenic gene is the low-density lipoprotein receptor (LDLR) gene. This study aimed to perform a systematic review of LDLR mutations in China. Using PubMed, Embase, Wanfang (Chinese), the Chinese National Knowledge Infrastructure (Chinese), and the Chinese Biological and Medical database (Chinese), public data were limited to December 2014. The Medical Subject Headings terms and the following key words were used: “familial hypercholesterolemia”, “Chinese”, “China”, “Hong Kong”, and “Taiwan”. A total of 74 studies including 295 probands with 131 LDLR mutations were identified. Most of the mutations were located in exon 4 of LDLR and approximately 60% of the mutations were missense mutations. Thirty new mutations that were not recorded in the LDLR databases were found. In silico analysis revealed that most of the mutations were pathogenic. The primary LDLR mutations were C308Y, H562Y, and A606T, and all of the mutations had functional significance. Prevalence data suggest that there are nearly 3.8 million FH patients in China, although reported numbers are much smaller, suggesting that FH is widely misunderstood. This systematic review provides information that is specific to China for inclusion in the international FH database. Familial hypercholesterolemia , which is characterized by tendon xanthoma, severely elevated LDL cholesterol (LDL-C) and premature coronary heart disease (pCHD), is a common and serious dominant genetic disease and has recently become a topic of extensive concern worldwidewww.ucl.ac.uk/ldlr/LOVDv.1.1.0/ and https://grenada.lumc.nl/LOVD2/UCLHeart/home.php?select_db=LDLR), there are more than 1700 mutations in the LDLR gene worldwide, reflecting the extensive genetic heterogeneity of FH patients, especially among different races. Researchers have speculated that the reason for this heterogeneity may be related to genetic drift, the founder effect, or intermarriage between FH patients. Large-scale clinical studies of FH have been conducted in many countries, but fewer data have been reported from China. Our group began to focus on FH in 2003 and has contributed to research on FH in China6789FH is a monogenic autosomal dominant disease in which a single causative mutation in the pathogenic gene affects cholesterol metabolism. The major pathogenic genes for FH are low-density lipoprotein receptor , apolipoprotein B APOB, MIM107730), and proprotein convertase subtilisin/kexin type 9 07730, anResearchers reported the first Chinese case of FH in 1971et al. identified the first five Chinese HoFH patients using a radio-labeled ligand assay, although the technology at that time could not be used to define the site of the mutationet al. identified LDLR mutation sites and their functions using PCR and cDNA cloning technology, respectively, in patients with FH from Jiangsu Province13In 1985, Cai Among all of the 131 mutations, three mutations were reported more frequently: C308Y , H562Y  and A606T  , which ain silico analysis for these mutations. A total of 13 mutations were analyzed, and most of the mutations were pathogenic, excluding two variants that were identified as non-pathogenic: N494S  and S533L .In addition, we identified 30 mutations that were not recorded in the above two LDLR databases . The mosChiou and Charng’s group has been devoted to studying FH in Taiwan Province and has contributed greatly to the study of FH in the Chinese population. Since 2003, Charng has screened 170 unrelated hyperlipidemic Chinese patients using DNA screening and identified 10 mutations and two polymorphisms22in silico analysis revealed that this mutation is likely to be pathogenic , W462X  and D601Y , which account for 29.3% of probands in mainland China. (1) The first mutation, A606T, is located in the thirteenth exon encoding the EGF precursor homology domain. This mutation can lead to reductions in the mobility of the mature LDLR protein, precursor protein synthesis, LDL binding, and the rate of recirculationet al. in 1998In addition to the LDLR mutations, other mutations can also cause FH, such as mutations in the apoB and PCSK9 genes. However, only 12 studies have reported apoB and PCSK9 mutations in China. The most common apoB mutation is R3500W , which is located in exon 26 and was first reported by Huang The first study to discuss phenotypic variations in HeFH patients in China was published in 1998, in which Chinese patients with FH were compared with patients with the same or similar mutations in Canada31The data obtained for clinical features and lipid values in the included studies were also collected. A total of 524 patients were diagnosed with FH by gene screening, but clinical features or (and) lipid values were reported for only 355 patients. There are three internationally recognized clinical diagnostic criteria for FH worldwide: the DLCN criteria, the “Simon Broome” UK-FH register criteria, and the MEDPED Systemet al. published an SSCP and DNA sequencing analysis to screen all 18 exons and exon-intron boundaries in the LDLR gene. The authors identified one mutation in exon 6 6810The gene diagnoses are also important. The Chinese researcher Sun first used SSCP and Southern blotting to detect LDLR mutations in Chinese patients in 1994, but all of the experiments were completed in the UKIn this systematic review, we analyzed the characteristics, distribution, gene frequency, and relationship between the genotype and phenotype of LDLR gene mutations in the Chinese population. A total of 74 studies, involving 586 patients (including 357 probands) with 141 related mutations in FH, were included in this review. In summary, the findings from these studies indicate that although FH is widely distributed in most regions of China, the diagnostic and therapeutic rates of FH were less than 1%. This finding suggests that most doctors and people lack an understanding of FH and also pay insufficient attention to the occurrence of FH in China.et al. identified only 5 mutations in 100 hyperlipidemia patients and did not detect any LDLR or apoB mutationsTo date, only one study has estimated the prevalence and treatment of FH, which included 9,324 Chinese subjects from the Jiangsu Nutrition Study. The researchers reported that the prevalence of probable/definite FH was 0.28% (1.4/500) based on the modified DLCN definition, only 15.9% of the patients were receiving drug treatment, and none of the patients achieved the LDL target value (<2.5 mmol/L)It is well known that high-frequency LDLR gene mutations can aid in the screening for FH. For example, the S472RfsX44 mutation (in exon 10) is responsible for approximately 42% of the patients with FH in TunisiaIn the analysis of clinical phenotypes, we discovered that levels of TC and LDL-C in patients from Hong Kong and Taiwan Province were similar to the levels measured in patients in Western countries and higher than those in patients in Asia and parts of Europe. One possible explanation for this finding is that the diets and lifestyles of these patients are similar to those of patients in Western countries. In analyses of the relationship between mutations and clinical phenotypes, we discovered two interesting phenomena: (1) the mutation-negative group had lipid values that were comparable to the HeFH group and (2) there were 6 probands that were diagnosed as having a HeFH genotype but actually had a clinical homozygous phenotype. These data suggest that there may be other pathogenic genes or many minor genes that participate in the development of disease, as suggested in a previous studyThere are several limitations to this review. First, different nomenclatures were utilized for the LDLR mutation in the included studies. Hence, we unified the nomenclature of the mutations in this review. Second, some of the studies did not mention the origin of the probands. Consequently, we used the location of the first author affiliation. Thus, there are some deviations in the regional distribution of the mutations. Third, we reviewed and analyzed the clinical data obtained for the FH patients. However, the conclusions from these data analyses should be treated with caution because this was a systematic review, and all the data were analyzed in a secondary manner. Finally, we included only LDLR mutations identified in China, which may result in regional limitations.In recent years, interest in FH has grown among the international community, and many countries have published FH guidelines to facilitate improved management and treatment of patients with FH1Using the computerized literature databases of PubMed, Embase, Wanfang (Chinese), the Chinese National Knowledge Infrastructure , and the Chinese Biological and Medical database , and public data were limited to December 2014. The Medical Subject Heading terms and the following key words were used: “familial hypercholesterolemia”, “Chinese”, “China”, “Hong Kong”, and “Taiwan”. Only English and Chinese language articles were included in the analysis.www.hgvs.org/mutnomen, starting with nucleotide + 1 as the A in the ATG translation initiation codonThe inclusion criteria for the included studies were as follows: any reports of pathogenic mutations in FH, such as LDLR, APOB, and PCSK9 gene mutations. Two nomenclatures were used to describe LDLR gene mutations in the LOVD databases. The first nomenclature was based on the guidelines from Two independent researchers (L.Y.S. and Y.F.D.) reviewed the relative articles based on the abstracts and full texts to assess their eligibility. One researcher (F.Z.) collected information concerning the LDLR mutations, including the exons, cDNA, proteins, distribution, and function of the LDLR gene mutations. If the articles reported sequencing information, then the information for mutations was assessed between the images and original nucleotide sequence. If the information differed between the images and text describing the mutations, we collected information regarding mutations from the sequencing results. The clinical characteristics included age, sex, and lipid values, among others. All authors of this review were consulted if additional data were collected or the data were unclear.silico mutation prediction tools, including PolyPhen2Novel LDLR variants were assessed by in All of the statistical analyses were performed using SPSS version 18.0 . Measurement data are presented as the mean ± SD, and count data are presented as rates.How to cite this article: Jiang, L. et al. The distribution and characteristics of LDL receptor mutations in China: A systematic review. Sci. Rep.5, 17272; doi: 10.1038/srep17272 (2015).


The purpose of this study was to explore the relationship between job burnout and neuroendocrine indicators in soldiers living in a harsh environment. Three hundred soldiers stationed in the arid desert and 600 in an urban area were recruited. They filled in the Chinese Maslach Burnout Inventory questionnaire. One hundred soldiers were randomly selected from each group to measure their levels of noradrenaline, serotonin, heat shock protein (HSP)-70, adrenocorticotropic hormone, and serum cortisol. Job burnout was more common in soldiers from urban areas than those from rural areas. Job burnout was significantly higher among soldiers stationed in the arid desert than those in urban areas. For soldiers in the arid desert, the levels of HSP-70, serum cortisol, and adrenocorticotropic hormone were significantly higher than in soldiers in urban areas. Correlation analyses showed that the degree of job burnout was weakly negatively correlated with the level of HSP-70. Being an only child, HSP-70 levels, cortisol levels, and ACTH levels were independently associated with job burnout in soldiers stationed in the arid desert. A higher level of job burnout in soldiers stationed in arid desert and a corresponding change in neuroendocrine indicators indicated a correlation between occupational stress and neurotransmitters. Job burnout is a state of stress that is an important issue worldwide since it has a direct impact on the efficiency and quality of work ,2. Job bConsensus has been reached that job burnout mainly results from changes in the neuroendocrine system, in which excessive activation of the hypothalamus-pituitary-adrenal (HPA) axis leads to neuroendocrine and homeostasis disorders, with alteration of various hormones, neurotransmitters, and cytokines associated with the HPA axis ,10. Prevet al. [In arid deserts and other harsh environments, people’s physical and mental health is affected by the natural conditions and monotonous lifestyle ,18,19. Ket al.  found thet al. .Therefore, the aim of the present study was to obtain preliminarily data about the prevalence of job burnout in soldiers stationed in the arid desert of Xinjiang, and to investigate the relationship between military job burnout and neuroendocrine indicators. This will provide important information on the risk factors for job burnout in soldiers in a harsh environment and may help develop methods to prevent this form of stress.This was a prospective study performed from April to July 2013. One battalion stationed in the arid desert region of Xinjiang was selected as the observation group and two battalions stationed in the urban area of Xinjiang were selected as the control group. All included soldiers had to have been enlisted for at least one year. Subjects using tricyclic antidepressants, hexadecadrol, estrogens, or glucocorticoids within 1 week to enrollment were excluded. The arid group comprised field operation personnel that were stationed in the desert as their main job. This was not a tour of duty but rather a long term placement. They worked five days on and three days off. This group could expect an increase in wages and full support in terms of articles required for daily use to compensate for their heavier work load. This study was approved by the Ethics Committee of the First Teaching Hospital of Xinjiang Medical University. Written informed consent was obtained from all participants.The CMBI questionnaire includes three factors: emotional exhaustion, depersonalization, and reduced accomplishment. Emotional exhaustion mainly refers to the weary and worn-out states that results from physical and emotional depletion; it is complicated in particular with emotional symptoms like fatigue, exhaustion, and worrying that one’s work will affect their own emotional states. Depersonalization mainly reflects individual’s poor social relationship and their negative, indifferent, and evasive attitudes towards their work, which include manifestations like indifference to the feelings of their subjects, blaming their subjects, and refusing their subjects’ requirements. Reduced accomplishment mainly indicates individual’s negative self-assessment of their work achievements, such as a sense of incompetence, and a lack of efficiency, morale, and achievement in their work.Each factor consists of five items, for a total of 15 items. The questionnaire used seven magnitudes to score each item: 1 representing “completely fitting” and 7 representing “completely unfitting”. The dimension of reduced accomplishment  used reverse scoring.Four levels of job burnout were determined based on the cut-off values : no burnout , mild burnout , moderate burnout , and severe burnout . This questionnaire and the cut-off values have been shown to be valid and reliable .All questionnaires were handed out and retrieved in the activity center. The questionnaires were completed anonymously within 20 min. Prior to the survey, soldiers were mobilized by two experienced psychologists and two officers to ensure the cooperation with the research team and to ensure the authenticity and effectiveness of the questionnaire filling. Study staff explained how to fill out the questionnaires, explained the methods and significance of the study, and ensured that the soldiers cooperated positively with a scientific and down-to-earth attitude so that they could honestly complete every item of the questionnaire. During the survey and after recording the results, all contents were comprehensively checked by the researchers, making sure any doubts about the responses could be inquired into and reconfirmed, mistakes corrected, and omissions completed.One hundred soldiers who correctly filled out their questionnaire were selected from each group using simple random sampling to determine the neuroendocrine indicators -70, adrenocorticotropic hormone (ACTH), and serum cortisol). Fasting blood samples (5 mL) were obtained with the study subjects in the decubitus position. The blood samples were placed in heparin-anticoagulant tubes and centrifuged at 3000 rpm for 5 min at 4 °C. Plasma was collected and stored at −20 °C. Participants were asked to refrain from a high-fat diet and alcohol for three days before blood sampling. Levels of heat shock protein (HSP-70), noradrenaline, and serotonin were measured by ELISA , and the levels of cortisol and ACTH were measured by radioimmunoassay , using a GC-2016 16-probe γ-radioimmune counter.p-values < 0.05 were considered to be statistically significant.The survey results were independently entered into the database by two researchers and a consistency test was conducted. SPSS 17.0  was used for data processing and statistical analysis. Results are presented as mean ± standard deviation or as frequencies, as appropriate. Continuous data were compared using the Student’s t-test. Categorical data were analyzed using the chi-square test. The Pearson correlation test was used to analyze the correlations between job burnout and neuroendocrine indicators. Multivariate logistic regression was used to identify the factors independently associated with job burnout including age, length of military service, ethnic background, education level, marital status, location of household registration before recruitment, monthly family income, rank, and neuroendocrine response. p = 0.028) were retrieved and validated as being satisfactory, for a total retrieval rate of 91.1%. The age of the soldiers ranged from 16 to 44 years, with an average of 21.4 ± 3.3 years, without difference between the two groups (p = 0.096). The duration of military service ranged from 1 to 26 years, with an average of 3.1 ± 3.0 years, without difference between the two groups (p = 0.094) , and 574 (95.7%) from the urban group, = 0.094) .p < 0.001). The degree of military job burnout (p < 0.001), reduced achievement (p = 0.001), and emotional exhaustion (p < 0.001) were significantly higher in the arid desert group than in the control group (The degree of military job burnout differed significantly with primary area of residence (ol group . This sup = 0.043), serum cortisol (p = 0.012), and ACTH (p < 0.001) were significantly higher in soldiers stationed in the arid desert than those in the urban areas (The levels of HSP-70 (an areas .p = 0.025), HSP-70 levels , cortisol levels , and ACTH levels  were independently associated with job burnout  and related neuroendocrine indicators were entered as independent variables. Multiple regression analysis showed that being an only child , cortisol levels and reduced accomplishment , and ACTH levels and reduced accomplishment   .In the arid desert, soldiers find themselves in a tough natural environment, far removed from other people, traffic and communications, and they become a secluded population with uncommon characteristics. Furthermore, this particular special living environment deprives them of interpersonal interactions, and has monotonous cultural activities . In addiCompared with soldiers stationed in urban areas, the degree of job burnout of soldiers stationed in the arid desert group was higher. The results suggest that special environments affect the degree of job burnout. These results are consistent with other studies showing that people living in harsh environments have a higher risk of developing mental illnesses ,19.The results of this study showed that the level of HSP-70, serum cortisol, and ACTH in the arid desert group were higher than in the control group, which is possibly due to the influence of dry climate, strong solar radiation, and evaporation on HSP-70 ,25. IndeThese changes in neuroendocrine factors are probably a response to the harsh working environment that results in job burnout and they may also lead to changes in the incidence of job burnout. Indeed, previous studies have shown that long-term stress and job burnout are associated with changes in neurotransmitters, neuropeptides, and steroidal stress mediators ,14,20. IThe “little emperor syndrome” is an aspect of China’s one-child policy in which the only child attracts excessive amounts of attention from his parents. One-child families are more prevalent in urban areas. The child often receives too much love and has been highly mentally and physically restricted to devote himself to a heavy load of schoolwork, considering that the economic future of the family depends on his success. There is also evidence that many young Chinese feel heavily burdened and a huge sense of responsibility toward their parents, understanding that their success can have crucial consequences for their family . In the This study showed no relationship between the ethnic group of the study subjects and job burnout score (data not shown). There is a suggestion that ethnicity may be an important factor because South Asians resident in the UK showed lower self-reported work strain than Europeans . HoweverThe present study is not without limitations. Indeed, the cross-sectional design prevented us to explore other causes of burnout. The sample size was small and from a single military region in China. Only a few markers of stress were measured, and more markers could be assessed in the future to obtain a more comprehensive picture. Only weak correlations were observed, which might be due to the small sample size of the subset of patients in whom biochemical tests were performed. In future we plan to undertake a cohort study to investigate occupational stress-induced hypertensive disorders of people exposed to the arid desert environment of Xinjiang. This will provide more evidence for the importance of understanding stress and job burnout in this military population.In conclusion, these results suggest a higher level of job burnout in soldiers stationed in arid desert and a corresponding change in neuroendocrine indicators, indicating a correlation between occupational stress and neurotransmitters.


Eighty-two percent of graduates reported being “very much improved” or “much improved”. A second analyses provided evidence that treatment effects were robust across sites with no differences (<0.001) found on five of seven selected outcome measures. A third analysis found that number of days of treatment was correlated on three of seven measures at the <0.01 level. However, the amount of variance explained by days of treatment was under 5% on even the most highly correlated measure. These finding are consistent with previous research and explore short-term effectiveness of treatment across treatment sites and with variable duration of treatment.Chronic low back pain is one of the major health problems in the U.S., resulting in a large number of years of disability. To address the biopsychosocial nature of pain, interdisciplinary pain programs provide integrated interventions by an interdisciplinary team in a unified setting with unified goals. This study examined outcomes of an interdisciplinary program located at two sites with different staff, yet with a unified model of treatment and documentation. Efficacy at the combined sites was examined by comparing standard measures obtained upon admission to the program with measures at completion of a 3–4 week long program for 393 patients with chronic low back pain (CLBP). Repeated measures included pain severity, pain interference, efficacy of self-management strategies, hours of activity, depression, ability to do ADLs, and physical endurance. All repeated measures differed at the  Patient with chronic pain.This patient’s (probably accurate) perception captures the frustration of both healthcare providers and patients facing chronic low back pain (CLBP). This subjective impression of being “stuck” is reflected in the continued suffering and disability despite the high cost of ongoing healthcare. As evidenced by recent reports by the Institute of Medicine ,2, betweIn an effort to better understand the problem of CLBP, some have suggested that the problem is more accurately understood and more effectively treated by use of a biopsychosocial model . The bioThe role of psychosocial factors has been well documented in both the development of CLBP and the resulting disability. These factors have been found to increase risk for acute low back pain developing into chronic pain, and for increased risk of disability associated with low back pain ,8,9. In A variety of psychosocial factors have been found to be of relevance ,14. ClinIn light of data indicating the impact of a biopsychosocial model, interventions based on these factors are used with varying degrees of frequency and have become commonly recommended ,16. The In light of the interactive nature of many factors using the biopsychosocial model, one response has been the development of the interdisciplinary pain management program . To addrThese programs include multiple types of providers  offering coordinated services “under one roof”, with frequent communication through team meetings around a unified vision and goals. They utilize standardized measurement of functioning of physical ability, pain and suffering, emotional distress, utilization of medical resources, and functional activities of living. The model emphasizes the use of structured supervised physical activation with treatment to change behavioral and social patterns which have evolved from, and have changed, the patients’ experience of pain as well as their life functioning. Treatment is designed to address the array of factors impacting patients’ pain, distress, and subsequent disability. It is interesting that some of these factors are ones found by Pincus , which pet al. [et al. [et al. [Over the last 30 years, the effectiveness of these programs has been extensively examined for both treatment efficacy and cost-effectiveness ,24,25,26et al.  documentet al. , in the et al. . When clet al. ,30, the  [et al.  document [et al. , Smith e [et al.  repeatedet al. [i.e., greater number of hours resting a day and high levels of pain) profited more with high intensity treatment, whereas persons with lower dysfunction did not respond differentially to levels of intensity of treatment.Several issues warrant further exploration. First, few studies have examined the impact of providing similar programs at multiple sites to see if effectiveness is similar in various treatment settings. Second, the role of the duration of treatment has been explored in a limited fashion ,35,36 wiIn order to further evaluate these issues, the present study utilized a large data set collected over 14 years from two programs with similar models but different locations to address three questions. First, prior to analyzing site and duration, did the program as a whole produce clinically significant change at the completion of treatment across a broad range of outcomes in a large sample of persons with low back pain? Second, were outcomes at the two sites of the program similar or significantly different? Third, did a range of intensity (days of treatment) create differences in outcomes? Data were collected from a larger data set accumulated for quality control purposes of patients attending the comprehensive interdisciplinary program (Baylor Center for Pain Management) from 2000 to 2014. Four hundred eighty five patients (40%) had a primary diagnosis of back pain according to the Pain Region, as defined by the International Association for the Study of Pain . Of thesThe comprehensive outpatient program at the Baylor Center for Pain Management in Dallas, Texas, has provided interdisciplinary treatment since 1995. This program was carried at two sites—in Dallas and Richardson—with the same treatment protocol, staffing patterns, program direction, and standard outcomes measures and procedures. Each site utilized a psychologist, a licensed professional counselor providing biofeedback, an occupational therapist, a physical therapist, and a case manager. Both sites were under the direction of the same program director over the 15 years providing broad stability in treatment and data collection. Program size would range from 2–12 patients at a time. Patients were included if pain was chronic (over 6 months), it interfered with functional activities and/or demonstrated elevated emotional distress, and patients reported desire for improvement and functional goals. Patients were excluded if their level of psychiatric problems or cognitive functions would interfere with participation and understanding in a group-oriented program. As an outpatient program, patients were required to be safe and independent for all self-care, ambulation, and transfers. Patients were also required to set goals and to commit to regular participation in the programs.Initially, the program consisted of 20 days of treatment (approximately 100 h) but, over time, has been reduced to 12 days of treatment (approximately 60 h) to adapt to scheduling needs of patients and insurance carriers. Daily patients participated in one hour of physical therapy, one hour of aquatics therapy, one hour of counseling or biofeedback, one hour CBT group, one hour occupational therapy group, one mind/body technique for pain control, and one hour occupational therapy with focus on lifestyle management for adaptive living including return to work. Training in meditative practice, biofeedback, as well as consultation with chaplain services and nutrition services were included.Data were gathered upon admission to the program (Day 1) and at the final day of treatment. Outcomes included changes in pain, emotional distress, activity levels, medical utilization, physical abilities, instrumental activities of living, and patients’ perception of change. These data are used to measure primary outcomes indicated by the IMPACCT group ,38.Upon admission, patients completed a questionnaire which included demographic data, duration of pain (in months), and estimate of utilization of medical resources in the year prior.Abbreviations are as follows: the Multidimensional Pain Inventory (MPI) ; Beck DeIn addition, at graduation, patients completed the Patients’ Global Impression of Change (PGIC) scale  and a raInitial analysis was made by combining data from graduates from the two sites. Descriptive analysis was conducted for the program’s primary descriptors of the participants, including frequency of categorical variables and means and standard deviations for continuous variables with the exception of duration for which median and range were chosen due to the extreme variability. Shapiro-Wilk tests for normality of distribution were carried out on variables. Because distributions did not meet assumptions of normality, a series of Wilcoxon signed rank tests were used to measure the effects of treatment. Effect size was measured using the value of r, which is appropriate for Wilcoxon tests.Second, outcome variables from the two sites were carried out using repeated-measures ANOVAs, with treatment site as one variable and individual patient’s change in scores from pre to post as the second variable. It should be noted that, although some measures were not normally distributed, ANOVAs are robust to minor deviations from normality. Chi-square tests were used for categorical variables, such as the Patient’s Global Impression of Change.Third, the relationship between the numbers of days of treatment and the amount of change was calculated using a series of correlation coefficients.t(392)= −2.78, p = 0.004) younger  than those at Site 2 . The duration of pain in months was also significantly shorter (t(354)= 3.0, p = 0.002) in Site 1  than in Site 2 , although the distribution was so broad as to undermine meaningfulness of central tendency. Gender distribution was not different . Payer source was also significantly different .Analysis of descriptive statistics see  found sit-tests found that changes for all variables were significant at the 0.001 level using Wilcoxon signed rank t-tests.Seven standard measures see  were usep = 0.001.These changes were found for both self-report repeated measures—self-reported perception of clinical progress and objective measures obtained by a physical therapist . Changes were large as evidenced by effect sizes (ES’s), ranging from 0.66–0.85. All changes were at Although only 36% of patients see  achievedProminent changes in function were also found. Interference by pain was reduced by at least 30% for 47% of patients (ES = 0.77), 70% of patients increased hours of activity by 30% (ES = 0.78), and 91% of patients increased by at least 30% in their ability to carry out primary desired activities of living as measured by the COPM (ES = 0.85).These self-reported changes in activity and functional ADLs were mirrored by changes in physical functioning. Distance walked in a 5-min timed task improved by at least 30% in 61% of patients (ES = 0.85).Ratings of emotional distress markedly improved. Using standard interpretation of scores, depression decreased by at least 30% in 78% of patients (ES = 0.82) with mean scores changing from moderate (pre-treatment mean = 21.5) to minimal (post-treatment mean = 10.2) range of depression using standard interpretation of the scores.Due to the challenges in quantifying medication usage in this clinical setting, data were not collected on specific types or dosages of medication used by each patient. However, patients were asked at graduation to report any change in the use of pain medication. Of the 344 patients in this group: 13 (9%) reported taking no medications; 162 (47%) reported taking fewer; 138 (40%) were unchanged in the use of medication; and 31 (9%) reported taking more medication.a priori goal of either “much improved”  or “very much improved ”. Forty-four (15%) reported “minimal improvement”, and only 3 (1%) reported “no change”. No patients reported being “minimally worse,” “much worse”, or “very much worse”.Patients reported positive changes on global impression of change. Eighty-two percent of 281 patients reporting met the p = 0.002) and distance walked in five minutes . Second, as reviewed above in p < 0.05 level and, in fact, were at the p = 0.001 level.It should be noted that, although some measures were not normally distributed, it was decided that parametric tests would be conducted because of the clarity of presentation, as well as the fact that ANOVAs are quite robust to minor deviations from normality. Therefore, repeated-measures ANOVAs see  were conp = 0.05 level. Hours of activity and distance walked each demonstrate an interaction effect of Site × Change and an amount of change . Chi-square tests of patient ratings of five ratings of improvement by pain site revealed no significant difference between sites .Some variability was found between measures in the interaction of the site and outcome measures. For four of the seven measures , the interaction of Site × Change was not significant at the p = 0.01 level  and at the p = 0.001 level , these correlations were quite low. For example, although significant, the number of days of treatment completed only accounted for 4% of the variance (r2 = 0.41) in the change in hours active per day.Finally, the amount of change for selected variables was evaluated to determine correlation with the number of days of treatment completed. Although several change scores were correlated at the This study explored three aspects of interdisciplinary programs for treatment of chronic pain. In the first analysis, results were consistent with previous literature indicating that interdisciplinary pain management programs can provide broad-based change, even for patients with entrenched CLBP associated with high pain, emotional distress, functional disability, and excessive use of medications and medical resources. Consistent with recommendations by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) group and others for research with chronic low back pain ,44, it iAlthough this study was confirmatory of previous studies, a number of potential limitations should be noted. First, this was not a randomized controlled trial, but data were collected on a prospective basis as part of a quality assurance assessment. As such, there was no control group, so a potential placebo effect could not be measured or ruled out. Second, 20% of patients discontinued treatment for a variety of reasons, and, due to the focus of this study, no analysis was made of factors predicting non-completion or the degree of change during the program. A previous study of these programs, however, with all diagnostic groups included, found predictors for non-completion and identified factors predicting a response to treatment .p > 0.001 level, both six months and one year following treatment. However, six months later, some measures had regressed towards the pre-treatment scores, yet others had remained stable, and some had even continued to improve. All measures had regressed somewhat one year following treatment.In addition, these changes reflect immediate effects of treatment at program completion. Additional literature ,32,33 suIn the second analysis, this study also documented that interdisciplinary programs were effective across treatment sites. Patient populations were somewhat different based on descriptive data, such as age and duration of pain. Despite this, groups did not differ globally on a variety of measures selected to represent an array of domains. In addition, there were no differences in change at the two sites on six of seven measures, although difference in response was noted on one measure: change in distance walked in five minutes. This study suggests that, even with somewhat different populations, interdisciplinary programs were robust in the change they produced.In the third analysis, this study also provided evidence that change was only minimally correlated with the number of days of treatment. Despite statistically significant correlations between the numbers of days of treatment, days of treatment only accounted for 4% of variance at most. This finding is consistent with the results of a previous review .et al. [As Gatchel et al.  noted in