At present, there is no evidence on whether using condition-specific Oral Health-Related Quality of Life (OHRQoL) measures provides more reliable information than generic measures for needs assessment. Therefore, the objective was to assess the discriminative ability of one generic and one condition-specific OHRQoL measure, namely, respectively, the short form of the Oral Health Impact Profile (OHIP-14) and the Condition-Specific form of the Oral Impacts on Daily Performances (CS-OIDP) attributed to malocclusion, between adolescents with and without normative need for orthodontic treatment.200 16–17-year-old adolescents were randomly selected from 957 schoolchildren attending a Sixth Form College in London, United Kingdom. The impact of their oral conditions on quality of life during the last 6 months was assessed using two OHRQoL measures; OHIP-14 and OIDP. Adolescents were also examined for normative orthodontic treatment need using the Index of Orthodontic Treatment Need (IOTN) and the Dental Aesthetic Index (DAI). Discriminative ability was assessed comparing the overall scores and prevalence of oral impacts, calculated using each OHRQoL measure, between adolescents with and without normative need. Using the prevalence of oral impacts allowed adjusting for covariates.There were significant differences in overall scores for CS-OIDP attributed to malocclusion between adolescents with and without normative need for orthodontic treatment when IOTN or DAI were used to define need (p = 0.029 or 0.011 respectively), and in overall scores for OHIP-14 when DAI, but not IOTN was used to define need (p = 0.029 and 0.080 respectively). For the prevalence of impacts, only the prevalence of CS-OIDP attributed to malocclusion differed significantly between adolescents with and without normative need, even after adjusting for covariates (p = 0.017 and 0.049 using IOTN and DAI to define need).CS-OIDP attributed to malocclusion was better able than OHIP-14 to discriminate between adolescents with and without normative needs for orthodontic treatment. Oral Health-Related Quality of Life (OHRQoL) can be assessed using either generic or specific measures ,2. GenerIt has been claimed that condition-specific OHRQoL measures may increase acceptability to subjects by including only relevant dimensions ,3,6. In Although using condition-specific OHRQoL measures for needs assessment seems theoretically sound, some recent studies have also assessed oral health needs using generic OHRQoL measures ,16. EmpiTwo hundred 16–17-year-old adolescents were randomly selected from a list containing the names of all the 957 schoolchildren attending the Havering Sixth Form College in London, United Kingdom during 2006. All the students selected agreed to take part in the study. Sample size was calculated to estimate a prevalence of 25% for the condition-specific oral impacts on daily performances attributed to malocclusion, with a maximum tolerable error of 5% [The Local Ethics Committee and the Research and Development Directorate of the University College London Hospitals National Health Service Trust approved this study. Participants signed a consent letter agreeing for their participation in the study.First, information about demographic characteristics , orthodontic treatment status and the impact of oral conditions on quality of life during the last 6 months was self-reported by the participants. Information about oral impacts was collected using OHIP-14 and OIDP. Adolescents self-completed OHIP-14 in their classrooms and were later interviewed individually with OIDP in a private room. The OHIP-14, which has been previously validated on British populations ,22, asseAdolescents were then examined for normative orthodontic treatment need using both components of the Index of Orthodontic Treatment Need (IOTN) as well as the Dental Aesthetic Index (DAI). Both indexes have gained international acceptance because they are valid, reliable and easy to use -28. For Discriminative ability was examined in terms of construct validity whereby the distributions of scores for both OHRQoL measures are compared between groups with different levels of oral health . Since oAs the aforementioned method did not allow adjusting for covariates , the prevalence of oral impacts was also compared between adolescents with and without normative need for orthodontic treatment. For that, the prevalence of oral impacts was calculated as the percentage of adolescents reporting one or more items 'fairly often' or 'very often' for OHIP-14  and as tThis study included 134 (67.0%) females and 66 (33.0%) males, 116 (58.0%) were aged 16 years and 84 (42.0%) aged 17 years; 170 were Caucasian (85%) and 30 (15.0%) were of other ethnic origins. One third (32.5%) had completed orthodontic treatment, 12.5% were currently undergoing orthodontic treatment and the remaining 55.0% were untreated. Based on the two measures of orthodontic need, 42 (21.0%) had a normative need for orthodontic treatment according to IOTN whereas 25 (12.5%) had a normative need using DAI.There were significant differences in the overall scores for CS-OIDP attributed to malocclusion between adolescents with and without normative need for orthodontic treatment when IOTN or DAI were used to define need (p = 0.029 or 0.011 respectively), and in the overall scores for OHIP-14 when DAI, but not IOTN was used to define need (p = 0.029 and 0.080 respectively). Using DAI, the mean difference in overall scores for OHIP-14 and CS-OIDP attributed to malocclusion between adolescents with and without normative need was 1.64 points  and 2.13%  respectively. The corresponding size effects for such mean differences in overall scores were 0.28  and 0.53  respectively , but not for OHIP-14 (p = 0.799 and 0.211 respectively). This finding was independent of the index used to define normative need for orthodontic treatment . The comparison of prevalences between groups with different oral health statuses has been reported for other OHRQoL measures -43. UnquOverall, different findings were found when comparing the discriminative ability of OHIP-14 and CS-OIDP attributed to malocclusion between groups with and without normative need for orthodontic treatment. These findings differed according to the indicator used to assess the impacts of oral conditions on participants' quality of life  or the index used to define normative need for orthodontic treatment (IOTN or DAI). However, based on the present findings it appears that CS-OIDP attributed to malocclusion was better able than OHIP-14 to differentiate between the two groups of adolescents based on needs. Therefore, the present findings confirmed our earlier assumption that the condition-specific OHRQoL measures were better able to discriminate between sub-groups with different levels of oral health than their generic counterparts. This also provides empirical support for using condition-specific OHRQoL measures for oral health needs assessment.Our findings agree with the few previous studies comparing generic and condition-specific OHRQoL measures -44. TheyAmong a population of 16–17-year-old British adolescents, the CS-OIDP attributed to malocclusion was better able than the more generic OHIP-14 to discriminate between different levels of normative need for orthodontic treatment. Findings differed according to the indicator used to assess the impacts of oral conditions on participants' quality of life  or the index used to define normative need for orthodontic treatment (IOTN or DAI).The authors declare that they have no competing interests.EB conceived of the study, performed statistical analysis and drafted the first version of the manuscript. CMdO organized and conducted the study, and has critically revised the manuscript. AS supervised the entire study and critically revised the manuscript. All authors read and approved the final version of the manuscript.


We have recently noted that ingestion of dietary lipid (in the form of heavy whipping cream) leads to greater oxidative stress than dietary carbohydrate (in the form of dextrose), when consumed in isocaloric amounts.In the present investigation we attempted to replicate our work and also to determine the oxidative stress response to dextrose and lipid meals of two different kilocalorie  amounts.2O2). Area under the curve (AUC) was calculated for each variable, and a 4 × 5 ANOVA was utilized to further analyze data.Nine young (22 ± 2 years), healthy men consumed in a random order, cross-over design one of four meals/drinks: dextrose at 75 g , dextrose at 150 g , lipid at 33 g , lipid at 66 g . Blood samples were collected Pre meal, and at 30 min, 60 min, 120 min, and 180 min post meal. Samples were assayed for glucose, triglycerides (TAG), malondialdehyde (MDA), and hydrogen peroxide . A meal × time effect (p = 0.0002), a meal effect , and a time effect was noted for H2O2 . The time effect for H2O2 was primarily influenced by the 66 g lipid meal.A meal × time effect (p = 0.0002) and a time effect was noted for glucose . The dextrose meals primarily contributed to this time effect. No other effects were noted for glucose (p > 0.05). A meal effect was noted for TAG . No other effects were noted for TAG (p > 0.05). An AUC effect was noted for MDA . A meal × time effect (p = 0.02) and a meal effect was noted for MDA . No time effect was noted for MDA (p = 0.72). An AUC effect was noted for H2O2.These data indicate that 1) minimal oxidative stress is observed following ingestion of dextrose loads of either 75 g or 150 g, or a lipid load of 33 g and 2) lipid ingestion at 66 g leads to greater oxidative stress than lipid at 33 g or dextrose at either 75 g or 150 g. Hence, in a sample of young and healthy men, only 66 g of lipid (taken in the form of heavy whipping cream) leads to a significant increase in blood oxidative stress, as measured by MDA and H The process of normal cellular metabolism leads to the production of reactive oxygen species (ROS), the majority of which are inactivated by endogenous and exogenous antioxidants . The balIn general, a low-grade production of ROS  is associated with enhanced health; whereas, excessive ROS production and a chronic oxidative shift in the redox environment has been implicated in a wide variety of pathological conditions . This laIn relation to the ingestion of food, oxidative stress has been reported to occur during the minutes to hours following intake. This "postprandial oxidative stress" is likely a result of both a dramatic increase in ROS production, coupled with a decrease in antioxidant defense (commonly measured in blood samples of human participants) . FollowiThe postprandial production of ROS appears highly correlated to both the glucose  and the In terms of comparisons between carbohydrate and lipid meals, we have recently noted that ingestion of dietary lipid (in the form of heavy whipping cream) leads to significantly greater oxidative stress than dietary carbohydrate (in the form of dextrose), when these are consumed in isocaloric amounts . Our sub-1), non-diabetic (fasting glucose < 126 mg·dL-1), not regularly using antioxidant supplements or drugs, and did not have diagnosed cardiovascular or metabolic disorders. It should be noted that only nine subjects successfully completed all meal testing. Subject descriptive characteristics are presented in Table Ten young, healthy men were recruited from the University of Memphis and surrounding community and completed all aspects of this study. Sample size was chosen based on our prior work and the work of others focused on postprandial oxidative stress using similar outcome variables. All subjects were non-smokers, of normal weight, normolipidemic  prior to be being admitted as a subject.During the initial visit to the laboratory, subjects completed the informed consent form, health form, and physical activity questionnaire. The height, weight, and body composition (via 7 site skinfold assessment) of each subject was measured using a stadiometer, digital scale, and Lange skin fold calipers, respectively. Heart rate  and blood pressure (via auscultation) were recorded following a 10 minute period of quiet rest. An explanation of dietary data recording was provided, along with data collection forms.All subjects who met study criteria reported to the laboratory in the morning following a 10-hour overnight fast. Subjects rested for 10 minutes and then a pre-meal blood sample was collected. On four different days, in random order cross-over design, and separated by 3-7 days, subjects consumed one of four meals: dextrose at 75 grams , dextrose at 150 grams , lipid at 33 grams , lipid at 66 grams . The dextrose was in powder form  and the lipid consisted of heavy whipping cream . The 300 kcal drinks contained a total of 350 mL of fluid and the 600 kcal drinks contained a total of 700 mL of fluid. The amount of dextrose powder and whipping cream was weighed  and measured prior to the mixing of each drink. The volume of water added to each drink  was measured in a graduated cylinder. All portions were mixed in a blender. Subjects were given 10 minutes to consume the assigned drink.ad libitum during the first test day and matched for all subsequent test days. These procedures are similar to those we have used in several recent investigations [The postprandial observation period lasted three hours, during which time four additional blood samples were collected . We have noted in our previous work that in healthy men, the peak oxidative stress response occurs between 2-4 hours following ingestion of a lipid meal ,18,36. Tigations -18,36-39® by a trained phlebotomist. Following collection, blood samples were processed accordingly, and the plasma/serum was immediately stored at -70°C until analyzed. All blood samples were assayed for the following variables: glucose, triglycerides (TAG), malondialdehyde (MDA), and hydrogen peroxide (H2O2). We have recently studied these same variables in response to isocaloric dextrose and lipid meals . Therefore, we wanted to have similarity in our measures for the current study.Venous blood samples (~15 mL) were taken from subjects' forearm via needle and Vacutainer2O2 was analyzed in plasma using the Amplex Red reagent method as described by the manufacturer . In the reaction mixture, hydrogen peroxide, in the presence of horseradish peroxidase, reacts with Amplex Red reagent to generate the red-fluorescence oxidation product, resorufin. All assays were performed in duplicate on first thaw. These are commonly performed within our laboratory and the coefficient of variation for all measures is ≤7%.Assays for serum glucose and TAG were performed following standard enzymatic procedures as described by the reagent manufacturer . Standard curves for all assays were developed for determination of unknown samples. MDA was analyzed in plasma using a commercially available colorimetric assay , using previously described methods . H2O2 waSubjects were instructed to maintain their normal diet, and to record their food and beverage intake during the 24 hour period prior to each test day. Subjects were asked to consume similar food choices and quantities during the 24 hours prior to each test day. Nutritional records were analyzed for total kcals, protein, carbohydrate, fat, vitamin C, vitamin E, and vitamin A . Subjects were asked to maintain their normal physical activity habits during the study period but to avoid strenuous exercise during the 24 hours immediately preceding the test days, since such activity may have impacted the chosen biomarkers, as reported previously ,42.For each biomarker, the area under the curve (AUC) was calculated using the trapezoidal method as described in detail by Pruessner et al. . In addiAs indicated earlier, although 10 subjects were enrolled in the study, only nine subjects successfully completed all meal testing. One subject decided not to complete the testing protocol due to loss of interest. Therefore, data are only presented for nine subjects. No statistically significant differences were noted for kilocalories (p = 0.34), protein grams (p = 0.87), carbohydrate grams (p = 0.50), fat grams (p = 0.53), vitamin C (p = 0.76), vitamin E (p = 0.85), or vitamin A (p = 0.73). Data are presented in Table For blood glucose, no AUC effect was noted (p = 0.44). No meal effect was noted p = 0.13), although both a meal × time effect (p = 0.0002) and a time effect was noted (p < 0.0001), with 30 min greater than Pre, 1 hr, 2 hr, and 3 hr (p < 0.05). As expected, the glucose meals contributed most to this time effect. Data are presented in Figure 3, althouFor blood TAG, no AUC effect was noted p = 0.26). No meal × time effect (p = 0.27) or time effect was noted (p = 0.63). However, a meal effect was noted (p = 0.01), with the 66 g lipid meal greater than the 75 g and 150 g dextrose meals (p < 0.05). Data are presented in Figure 6. No meaFor blood MDA, an AUC effect was noted (p = 0.04), with the 66 g lipid meal greater than the 75 g and 150 g dextrose meals (p < 0.05). A meal × time effect (p = 0.02) and a meal effect was noted (p = 0.004), with the 66 g lipid meal greater than the 75 g and 150 g dextrose meals (p < 0.05). However, no time effect was noted (p = 0.72). Data are presented in Figure 2O2, an AUC effect was noted (p = 0.0001), with the 66 g lipid meal greater than the 33 g lipid meal and the 75 g and 150 g dextrose meals (p < 0.05). A meal × time effect (p = 0.0002), a meal effect (p < 0.0001), and a time effect was noted (p < 0.0001). Regarding the meal effect, the 66 g lipid meal was greater than the 33 g lipid meal and the 75 g and 150 g dextrose meals (p < 0.05). With regards to the time effect, 2 hr was greater than Pre, 30 min, and 1 hr; 3 hr was greater than Pre (p < 0.05). Data are presented in Figure For blood HWhen considering all four meals combined and using values generated using the AUC analysis, significant positive correlations were noted between many biochemical variables (p < 0.05). A correlation matrix is provided in Table 2O2). This is true despite the transient increase in blood glucose following ingestion of both the 75 g and 150 g dextrose meals  may have responded differently to the meals. Further work should consider the above prior to attempting to generalize results to populations other than young and healthy men, as doing so may be problematic.In addition to the above, other limitations of this work should be noted. First, it is important to mention that as with most studies in this area of investigation, we only measured olecules , as oppoSecond with regards to our main findings, lipid ingestion at 66 g leads to greater oxidative stress than lipid at 33 g or dextrose at either 75 g or 150 g. These data 1) confirm the results from our prior work in which we noted that ingestion of dietary lipid (heavy whipping cream) leads to greater oxidative stress than ingestion of dietary carbohydrate (dextrose), when consumed in isocaloric amounts  and 2) c2O2 production, and subsequent formation of MDA, a greater postprandial increase following the lipid meal would be expected based on the commonly accepted mechanisms underlying the regulation of postprandial superoxide production [2 donation to electron transferring flavoprotein-coenzyme Q oxidoreductase [2 than do carbohydrate) would promote greater H2O2 production compared to the dextrose meals. These findings are in agreement with our work [In relation to Hoduction . Consideeductase ), it folour work  and the our work ,32,48, nour work .Our results for the dextrose meals parallel some previous findings of minimal increase in oxidative stress when assessed using young, healthy subjects ,29,35,442O2 . Second, it should be understood that the magnitude and time course of response for TAG, MDA, and H2O2 does not exactly parallel one another, as can be observed in Figures 2O2. Following this rise in H2O2, lipids undergo oxidation which then leads to the delayed appearance of MDA which can be detected in the circulation. In the present study, MDA was still increasing at the end of the collection period, highlighting the delayed response for this marker of lipid peroxidation, which often occurs between 4-6 hours post feeding. Our failure to extend the collection time beyond three hours may be considered an additional limitation of this work.Related to the lipid meals, in particular the 66 g lipid meal, the TAG response to feeding was greater than that of the dextrose meals Figure . Based oO2 Table , it follThe present study is the fourth in which we have shown strong, positive correlations between the TAG response to feeding and the oxidative stress response to feeding -18. BecaIn relation to meal size, we did not observe any further increase in either blood glucose or oxidative stress with the 150 g vs. the 75 g dextrose meal. Therefore, we feel confident that simple sugar in the form of dextrose is rapidly and efficiently processed by young, healthy men. However, based on the present design, we cannot rule out that a ceiling effect occurs with lipid in relation to either blood TAG or oxidative stress. There is clearly a greater response with the higher lipid load, and further study is needed with ingestion of even higher amounts of lipid in order to adequately address the question of whether or not a ceiling effect occurs for oxidative stress in response to lipid feedings.From an applied point of view, we are uncertain that such work will provide practical data. That is, while subjects generally did not have a problem consuming either dextrose meal or the 33 g lipid meal, the 66 g lipid meal was challenging for some subjects--in particular for those who do not routinely ingest high fat meals--and would generally not be consumed in isolation without the inclusion of other macronutrients. However, while this amount of dietary lipid (66 g) can easily be consumed in a mixed meal (whole food or milkshake), it is likely that a similar oxidative stress response may be observed in a non-laboratory based setting where individuals consume high fat, high calorie meals. In a recent study we have compared a pure lipid meal (heavy whipping cream) to an isocaloric mixed meal of lipid, carbohydrate, and protein, noting a much greater oxidative stress response for the pure lipid meal . HoweverThe present findings indicate that minimal oxidative stress is observed following ingestion of dextrose at either 75 g or 150 g, or lipid at 33 g. Moreover, lipid ingestion at 66 g leads to greater oxidative stress than lipid at 33 g or dextrose at either 75 g or 150 g. Based on these data we conclude that in a sample of young and healthy men, only 66 g of lipid (consumed in the form of heavy whipping cream) leads to a significant increase in blood oxidative stress. Future research should consider the inclusion of older and metabolically compromised individuals, in an effort to determine their response to such feedings. These studies should consider the incorporation of a more realistic "mixed meal" in terms of macronutrient composition. This should provide for practical applications that may have clinical relevance pertaining to oxidative stress specific ill-health and disease.Financial support for this work was provided by the University of Memphis. The authors declare no competing interests.RJB was responsible for the study design, biochemical work, statistical analyses, and manuscript preparation; REC, MMK, KEM, and TMF were responsible for data collection, blood collection and processing, and assistance with manuscript preparation. All authors read and approved of the final manuscript.


This study examines changes in socio-demographic, environmental and intrapersonal factors associated with dog acquisition in non-dog owners at baseline to 12-months follow-up and the effect of dog acquisition on minutes per week of recreational walking.RESIDE study participants completed self-administered questionnaires (baseline and 12-months follow-up) measuring physical activity, dog ownership, dog walking behavior as well as environmental, intrapersonal and socio-demographic factors. Analysis was restricted to 'Continuing non-owners'  and 'New dog owners' .p < 0.05). After adjusting for baseline variables the effect of dog acquisition on the increase in minutes of recreational walking within the neighborhood was 31 minutes . However, this reduced to 22 minutes  after further adjustment for change in baseline to follow-up variables. Increase in intention to walk was the main factor contributing to attenuation of the effect of dog acquisition on recreational walking.Overall, 12% of baseline non-owners had acquired a dog at follow-up. Dog acquisition was associated with working and having children at home. Those who changed from single to couple marital status were also more likely to acquire a dog. The increase in minutes of walking for recreation within the neighborhood from baseline to follow-up was 48 minutes/week for new dog owners compared with 12 minutes/week for continuing non-owners (leads to an increase in walking. The most likely mechanism through which dog acquisition facilitates increased physical activity is through behavioral intention via the dog's positive effect on owner's cognitive beliefs about walking, and through the provision of motivation and social support for walking. The results suggest that behavioral intention mediates the relationship between dog acquisition and walking and that dogs may have a significant role in the maintenance of owner walking behavior.This study used a large representative sample of non-owners to examine the relationship between dog acquisition and recreational walking and provides evidence to suggest that dog acquisition  Over half of all adults in the United States and Australia do not meet the recommended level of physical activity necessary for health benefit ,2. GrowiCross-sectional studies suggest that dog owners are more physically active than non-owners ,7 and arEvidence of the potential for dog ownership to facilitate higher levels of physical activity has been limited to date because it is mainly cross-sectional. One small study of adults who acquired a pet (dog or cat) from an animal shelter (n = 71) examined whether pet acquisition changed owner's health status, including their physical activity. Compared with cat owners and the control group, dog owners increased and maintained their walking from one hour/week at baseline to five hours/week at 10 months follow-up ,15. WhilOnly two prospective studies have examined the association between dog ownership and physical activity over time and both of these studies were conducted in an elderly population ,16. ThorThe sample included all baseline non-dog owners taking part in the RESIDential Environments (RESIDE) project, a 5-year longitudinal study evaluating the impact of a state-government sub-division code in Perth, Western Australia . DescribAt both time points participants were asked about the type of pet(s) owned. The responses included dog, cat, bird and other pet. Only baseline non-dog owners who at 12 months follow-up either remained non-owners or had acquired a dog were included in the study (n = 773). Participants' who did not own a dog at baseline but who had acquired a dog at follow-up were classified as 'New dog owners' while participants who were non-dog owners at baseline and follow-up were classified as 'Continuing non-owners'.Self-reported physical activity over a usual week was collected using the Neighborhood Physical Activity Questionnaire (NPAQ), which differentiates between walking within and outside of the neighborhood and has acceptable reliability . NPAQ meBaseline socio-demographic variables included: gender, age, country of origin, marital status, presence of children <18 years at home, mean age of children <18 years at home, education level attained, work status, number of hours worked/week, occupational status, household income and type of residence. New categorical socio-demographic variables were created to reflect changes in these variables between baseline and follow-up.A modified version of the Neighborhood Environment Walkability Scale (NEWS)  was usedMost change variables were coded as no change, increase or decrease from baseline to follow-up. Four socio-demographic change variables were coded differently: marital status ; work status ; children under 18 years at home ; and type of residence . For example, no change in marital status included participants who were the same marital status [either single  or couple (married or defacto)] at both time points.p ≤ 0.05 were entered (forced entry) into a linear regression model to investigate the association between dog acquisition and change in minutes of recreational walking in the neighborhood. Three models were constructed. The first model was unadjusted; the second model adjusted for baseline recreational walking in the neighborhood and significant baseline socio-demographic variables from Table p ≤ 0.05.Chi square and independent sample t-tests were used to examine the association between dog acquisition and, baseline socio-demographic and change from baseline to follow-up variables. Those variables found to be significant at p < 0.05). No significant differences between new dog owners and continuing non-owners baseline physical or social environments were observed (results not shown).Twelve percent (n = 92) of baseline non-dog owners (n = 773) acquired a dog by follow-up. A number of baseline socio-demographic characteristics were significantly associated with dog acquisition Table . At basep < 0.05). Furthermore, more new dog owners than continuing non-owners reported an increase in their intention, self-efficacy and use of behavioral skills for walking in the next month (p < 0.05). There were no other significant changes in physical and social environments or individual factors by dog acquisition at follow-up.Changes in marital status Table , intentip < 0.05)  Table . Mean wep < 0.05). Moreover, new dog owners increased their total walking by 38 minutes/week between baseline and follow-up. In the same period, continuing non-owners decreased their walking by 5 minutes/week (p < 0.05). While new dog owners reported an increase in their overall physical activity of 32 minutes/week, this was not significantly different to that of continuing non-owners (3 minutes/week).At follow-up, new dog owners walked with their dog in their neighborhood an average of 130 minutes/week Table . Increasp < 0.01) greater in those who acquired a dog compared with continuing non-owners. After adjusting for baseline walking for recreation within the neighborhood and significant baseline socio-demographic variables (model 2), the effect of dog acquisition on the increase in minutes of recreational walking within the neighborhood attenuated to 30.8 minutes but remained statistically significant . Baseline walking for recreation in the neighborhood accounted for almost all of the attenuation. Nevertheless, when the model was further adjusted for significant change in baseline to follow-up variables (model 3), the effect of dog acquisition on the increase in minutes of recreational walking within the neighborhood was reduced to 21.9 minutes and was no longer statistically significant . Further modeling revealed that when the variable for change in intention to walk was dropped from model 3, the effect of dog acquisition on the increase in the minutes of recreational walking within the neighborhood increased to 27.3 minutes and was once again statistically significant  thus indicating that adjustment for change in intention to walk was the principal reason for the reduced effect of dog acquisition. The other three change variables  collectively were responsible for the remaining difference of 3.5 minutes.Linear regression models were used to examine the unadjusted and adjusted effects of dog acquisition on change in minutes of recreational walking within the neighborhood. In the unadjusted model (model 1), the increase in minutes/week of recreational walking within the neighborhood was 35.9 minutes , the increase in minutes of recreational walking reduced from 36 to 22 minutes/week and was no longer statistically significant. Thus, increase in intention to walk was associated with both dog acquisition and increased recreational walking and explains a large part of the effect of dog acquisition on increased recreational walking. While it appears that change in intention to walk is a significant mediator of this relationship, the temporal order of dog acquisition and increased intention to walk is unconfirmed. For instance, does interest, capacity or intention to walk in the next month increase and as a result a dog is acquired to assist in shifting intention to action, or is a dog acquired and through a sense of obligation to care for the dog, intention to walk increases ?Acquiring a dog is coupled with a responsibility to care for the health and well-being of that dog . Basic cIn this study, the increase in overall walking was greater than the increase in recreational walking in the neighborhood (43 vs. 36 minutes). Although the increase in minutes of recreational walking associated with dog acquisition represented a significant increase, walking for recreation makes up only one component of all walking. Thus, it is possible that new dog owners also increased their time spent walking for recreation outside their neighborhood  as well as transport-related walking . Moreover, at baseline new dog owners did significantly less weekly minutes of overall walking than continuing non-owners. This suggests that new dog owners had greater potential than continuing non-owners to increase their weekly minutes of overall walking and may in part explain why the increase in minutes of overall walking was more than the increase in minutes of recreational walking in the neighborhood.Furthermore, the increase in minutes of recreational walking and overall walking associated with dog acquisition was not reflected in the increase in total physical activity (36 vs. 30 and 43 vs. 30 minutes respectively), suggesting that recreational walking was substituted in place of other types of physical activity. It could be that confounding factors influence the relationship between dog acquisition and change in minutes of total physical activity as was shown for recreational walking. However, it is more likely that new dog owners increased their minutes of recreational walking at the expense of other types of physical activity. In this study, baseline levels of total physical activity were well above the recommended level of 150 minutes/week and there was no significant difference in baseline minutes of total physical activity for new dog owners and continuing non-owners. These results suggest that there was little potential for minutes of total physical activity to increase post dog acquisition and it is likely that new dog owners substituted other types of physical activity for more dog walking.The Marchetti principle  applied While dog acquisition appears to positively influence the initiation of walking behavior, dog ownership may be more important for the maintenance of such behavior over time. For example, a study in the elderly found that after three years, dog walkers maintained their mobility advantage over owners who did not walk their dog and non-owners . A dog mIn addition, dog ownership may help with the maintenance of physical activity behavior during periods of transition. For example, in this study, dog acquisition was associated with people moving from a single to couple relationship. Previous research has shown that changing from a single lifestyle to cohabitation is associated with changes in health-related behaviors such as decreased physical activity, poorer dietary habits and weight gain -52. PeopThis study's large sample size with sufficient power to examine the association between dog acquisition and increased recreational walking is a strength. However, generalizability of the findings may be compromised because RESIDE study participants are moving into new housing developments and may not be representative of all new dog owners and continuing non-owners. Moreover, this study relied on self-reported physical activity and it is possible that new dog owners may have over-estimated the minutes spent walking with their dog. Future studies would be strengthened by objectively measuring dog walking behavior. Finally, this study was not able to ascertain the causal pathway between dog acquisition and increase in intention to walk. Reasons for acquiring a dog, type of dog acquired and age of dog at follow-up are relevant factors to consider when investigating whether dog acquisition increases walking and should be considered in future prospective studies. Furthermore, it may be useful to examine the effect of long term intention  on the relationship between dog acquisition and walking.Our study provides longitudinal evidence to suggest that dog acquisition leads to an increase in walking. Dog acquisition increased recreational walking by 31 minutes/week and this relationship persisted after adjusting for baseline recreational walking and baseline factors associated with dog acquisition. Moreover, increased intention to walk mediated the relationship between dog acquisition and increased recreational walking. It is likely that the mechanisms through which dog acquisition facilitates increased physical activity is through behavioral intention via the dog's positive effect on owner's cognitive beliefs about walking and from motivation and social support for walking. Furthermore, while it appears dog owners may substitute dog walking for other types of physical activity; it is likely that the long-term commitment of dog ownership plays a significant role in assisting owners to maintain their walking behavior. Considering that 40% of households in the United States and Australia own a dog, examination of the effect of dog ownership on physical activity adoption and adherence warrants further investigation.The first author (Hayley Cutt) is supported by an Australian Research Council, Australian Postgraduate Award – Industry which has Petcare Information and Advisory Service as the Industry Partner. The Petcare Information and Advisory Service placed no restrictions on the design, analysis, interpretation or publication of study findings. All other authors declare that they have no competing interests.HC conceived and designed the study and, analyzed and interpreted all data. HC drafted the manuscript revising it critically at each stage. MK advised on the design and analysis of the study, the interpretation of results and provided input at each stage of the manuscript draft. BG-C advised on interpretation and implications of results also providing input at each stage of the manuscript draft. All authors read and approved the final manuscript.


The early flowering of siz1 was suppressed by expressing nahG, indicating that SIZ1 represses the transition to flowering mainly through suppressing SA-dependent floral promotion signaling under short days. Previous results have shown that exogenous SA treatment does not suppress late flowering of autonomous pathway mutants. However, the siz1 mutation accelerated flowering time of an autonomous pathway mutant, luminidependens, by reducing the expression of FLOWERING LOCUS C (FLC), a floral repressor. This result suggests that SIZ1 promotes FLC expression, possibly through an SA-independent pathway. Evidence indicates that SIZ1 is required for the full activation of FLC expression in the late-flowering FRIGIDA background. Interestingly, increased FLC expression and late flowering of an autonomous pathway mutant, flowering locus d (fld), was not suppressed by siz1, suggesting that SIZ1 promotes FLC expression by repressing FLD. Consistent with this, SIZ1 facilitates sumoylation of FLD that can be suppressed by mutations in three predicted sumoylation motifs in FLD (i.e. FLDK3R). Furthermore, expression of FLDK3R in fld protoplasts strongly reduced FLC transcription compared with expression of FLD, and this affect was linked to reduced acetylation of histone 4 in FLC chromatin. Taken together, the results suggest that SIZ1 is a floral repressor that not only represses the SA-dependent pathway, but also promotes FLC expression by repressing FLD activity through sumoylation, which is required for full FLC expression in a FRIGIDA background.Loss-of-function  AtSIZ1, facilitates SUMO modification of transcription factors, PHR1 and ICE1, which regulate phosphate-starvation signaling and low-temperature response, respectively  to protein substrates . SUMO E3ectively . A SUMO Flowering is the result of a plant developmental process that controls the transition from vegetative maturity to the reproductive stage . Floral GIGANTEA (GI), CONSTANS (CO) and FLOWERING LOCUS T (FT), cause significantly delayed flowering under long days (CO transcript is regulated by circadian clock oscillators [e.g. CIRCADIAN CLOCK-ASSOCIATED PROTEIN 1 (CCA1)] (GI) (FLOWERING LOCUS T (FT) expression. FT in turn activates expression of SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (SOC1) and floral identity genes such as APETALA1 (AP1) (Photoperiodic-pathway genes promote transition to flowering in response to a long-day photoperiod ( (CCA1)]  and clocFLOWERING LOCUS C (FLC)  in winter-annual ecotypes causes increased expression of FLC and delayed flowering, which is reversed by lesions in FLC or by vernalization treatment (FLOWERING LOCUS D (FLD), a plant ortholog of the human protein KIAA0601/LYSINE-SPECIFIC HISTONE DEMETHYLASE1 (LSD1), represses FLC expression by facilitating deacetylation of histone H4 in FLC chromatin, but how this process is regulated remains to be elucidated  . FLC encreatment . Among tSOC1 and LEAFY expression, and is considered to be involved in the main floral-inducing cascade under short days (SD)  are implicated in the regulation of floral transition  loss-of-function mutant plants  in siz1-2 plants suppressed the dwarf and early flowering phenotypes of plants from multiple, independent transformed lines (ProSIZ1:GUS:GFP (SGG) in siz1-2 failed to complement these siz1-2 phenotypes in the same experiments  were determined (CCA1 and CCR2::LUCIFERASE (CCR2::LUC) was not altered by siz1 mutations, suggesting that SIZ1 does not regulate the circadian clock .Mutations in circadian oscillator genes cause a short-period phenotype, which results in early flowering under SD . To determine whether siz1 mutations affect the GA-dependent floral promotion pathway, exogenous GA was applied to wild-type, siz1-2 and siz1-3 plants, and flowering times were determined under LD and SD . Exogenous GA treatment accelerated the flowering time of both wild-type and siz1 plants to an equivalent extent , indicating that the GA floral promotion pathway is not impaired in siz1 plants.To determine if there is an interaction between  pathway . Consistsiz1 plants accumulate higher levels of SA, which causes increased plant innate immunity /MADS AFFECTING FLOWERING1 (MAF1), MAF2, MAF3, MAF4 and MAF5, and SHORT VEGETATIVE PHASE (SVP) were analyzed  .To test whether reduced  (flc-3) . Under Le plants . The flo2 plants . Consist2 plants , the flounder SD . Double-under SD . These rSOC1 transcript levels were greater in siz1 compared with wild-type plants under both LD and SD , SIZ1 appears to be required for full FLC expression in late-flowering autonomous pathway mutants and a FRI background. Double mutants were made between siz1-2 and dysfunctional alleles of late-flowering autonomous pathway mutants, such as luminidependens (ld-1) and fld-6 , indicating that SIZ1 does not regulate expression of FLD.Although reduction of nd fld-6 . Also, a FRI-Col , ld-1 ane plants . The sizl plants ,c. Consiectively ,d. Note under SD . Moreovemutation . These rhttp://www.abgent.com/tool/sumoplot) analyses. Thus, FLD could be a potential SUMO target protein  in FLD were identified by SUMOplot  reduced FLC expression to a greater extent than expression of HA:FLD (sumoylated) relative to vector control (Effects of FLD and FLDK3R (constitutively unsumoylated) on activity . HA:FLD,time PCR . Transie control ,c.FLD mutations, which disturb protein function, cause FLC transcript accumulation and late flowering that is linked to hyperacetylation of histone 4 (H4) in chromatin associated with the first intron of FLC . Under SD, SIZ1 function on flowering time also showed little dependence on FLC (i.e. the flowering time of flc-3 siz1-2 was similar to that of siz1-2 plants), indicating that under SD, SA promotes transition to flowering mainly through FLC-independent pathway(s). These results further indicate that SA accelerates flowering through pathways that are independent of the vernalization and the autonomous pathways, as these two pathways promote transition to flowering through repression of FLC expression. SA could facilitate transition to flowering by shortening the circadian period , suggesting that SA does not regulate the circadian clock. Moreover, GA-dependent floral promotion is operative in siz1 plants that contain a high level of SA . Thus, it is likely that SA accelerates flowering through pathways that are independent of photoperiodic- and vernalization-dependent pathways, and the autonomous and GA-dependent pathways. Despite the major role of SA in the early flowering of siz1 under SD, the flowering time of nahGsiz1-2 was slightly earlier than that of nahG plants under SD  by which SUMO modification of FLD affects HDAC activity remains unelucidated. The FLD homolog, KIAA0601/LSD1, has lysine-specific demethylase activity that is associated with numerous co-repressor complexes, such as CoREST, BHC80 and HDAC in humans . LSD1 ansiz1-2 (SALK_065397) and siz1-3 (SALK_034008) lines were obtained from ABRC at Ohio State University  were described previously (fld-6 (SAIL_642 C05) was isolated from T-DNA mutant SAIL lines, which were kindly provided by Dr R.M. Amasino . Homozygous double mutants were obtained by crossing various flowering-time mutants with siz1-2. The presence of siz1-2 and fld-6 mutations were analyzed by diagnostic PCR analysis according to the SALK T-DNA verification protocol , and the presence of the FRI-SF2, ld-1, flc-3, gi-2, co-1, ft-1 and soc1-2 mutations was analyzed according to a previous report  in growth chambers, which were equipped with seven ALTO PLUS T8 fluorescent lamps  and one PLANT & AQUARIUM 40W lamp . For exogenous GA treatment, 100 μM GA3 was sprayed twice onto 7- or 14-day-old seedlings grown under either LD or SD. The flowering time is estimated based on the number of rosette leaves formed by the primary shoot apical meristem prior to flowering under LD and SD, as described above. At least 15–20 plants were used to determine the flowering time of each genotype.To break seed dormancy, seeds were stratified on soil for 4 days at 4°C before transfer to normal growth conditions. Plants were grown at 23°C in a greenhouse under LD (16-h light/8-h dark), whereas for SD (8-h light/16-h dark), plants were grown at 22°C under fluorescent lights  according to the manufacturer’s protocol. A 200-ng sample of RNA was used as the template for first-strand cDNA synthesis with the ThermoScript RT-PCR System  and an oligo (dT21) primer. Specific gene expression levels were analyzed by semiquantitative RT-PCR or real-time PCR  with protein-A-sepharose CL-4B . Immunoprecipitated proteins were released in 2× SDS sample buffer, separated by SDS- PAGE, and detected by western blotting using anti-HA monoclonal antibodies   (siz1-2 and fld-6 plants and anti-acetylated H4 antibody were used for ChIP analyses. To check the activity of the sumoylation-deficient mutant, FLDK3R, HA:FLD or HA:FLDK3R were transiently expressed in SD-grown 20-day-old fld-6 protoplasts. After 40 h of incubation, ChIP analysis was performed to determine the acetylation status of H4 in FLC chromatin as described above. The fold enrichment in H4 acetylation was calculated as follows: FLC was first normalized to ACTIN in each sample, and these values were normalized against their respective wild type or vector controls.The chromatin immunoprecipitation experiments were performed as described previously (Rhythm analysis was performed as described by


It is shown that at least three intracellular pathways are implicated in the Ia induction, p21ras is the first protein activated by the two agents while further signalling requires Ca2+ mobilization and PKC activations. When the in vitro results are transferred to live animals using the same inducing agents and pathway inhibitors, it is found that theophylline (Ca2+/CaM inhibitor) and anti-p21ras are the most potent suppressors of the IFN-γ- and 5-azaC-induced side effects during pregnancy. The data presented here point to novel directions not only as to the intracellular signalling, but also to the use of pathway inhibitors in vivo to treat aberrant antigen expression associated with fetal loss.The placenta, one of the most important fetal tissues during gestation, ensures nutrition, development and protection of the fetus. Although placenta lacks expression of class II MHC antigens, they can be induced either by interferon-gamma (IFN-γ) on the spongiotrophoblast zone, or by 5-azacytidine (5-azaC) on the labyrinthine trophoblast zone, two agents actively participating in a plethora of immunological and inflammatory reactions. This induction is correlated with fetal abortion and fetal developmental abnormalities. In this work the


To ensure carers of people with dementia receive support, community services increasingly use measures of caregiver (carer) burden to assess for unmet need. This study used Bradshaw's taxonomy of need to explore the link between measures of carer burden (normative need), service use (expressed need), and carer's stated need (felt need).This mixed method exploratory study compared measures of carer burden with community services received and unmet needs, for 20 community-dwelling carer/care-recipient pairs.A simple one-item measure of carers' felt need for more services was significantly related to carer stress as measured on the GHQ-30. Qualitative data showed that there are many potential stressors for carers, other than those related to the care-giving role. We found a statistically significant rank correlation (p = 0.01) between carer's use of in-home respite and the care-recipient's cognitive and functional status which is likely to have been related to increased requirement for carer vigilance, effort and the isolation of spouse carers. Otherwise, there were no statistically significant relationships between carer burden or stress and level of service provision.felt need may be a better indicator of service need, and a red flag for recognising growing stress in carers of people with dementia. Assessment of service needs should recognise the fallibility of carer burden measures, given that carer stress may not only come from caring for someone with dementia, but can be significantly compounded by other life situations.When carers are stressed or depressed, they can recognise that they would like more help from services, even if measures of carer burden and care recipient status do not clearly indicate unmet service needs. A question designed to elicit carer'  Assessment and monitoring of caregiver (carer) burden are increasingly seen as essential factors in ensuring that carers receive community support , but theThe focus of this study is carers of persons with dementia, who provide critical support for care recipients by improving their quality of life and delaying entry to care homes . With esIn comparison with the general carer population, carers of people with dementia exhibit higher levels of unmet need and lower levels of service use ,15,16. TBrodaty et al.  developeService organisations typically use a range of assessment tools at admission to assess carers' service needs, which generally act as a 'gateway' to services. In this approach, a care professional "begins with the identification of specific difficulties, accounts for the presence and efficacy of current help, recognises perceived need and finally specifie[s] the type of intervention required to meet those needs" : 323]. W23. W3]. normative need, felt need, expressed need, and comparative need. The carer burden assessment approach described by Meaney et al.  and she just won't have a bar of it" [(2) Int 2].Carers felt 'caught' and 'trapped' when care recipients were reluctant to leave the home, as most care recipients could not be left alone. As a consequence, our sample of carers needed in-home respite as dementia severity increased, in order to address the basic requirements of their lives and households. One interviewee caring for a person with a DRS-2 score of 35 (i.e severe dementia) reported that:"With [IHR] I can leave the house to go out and do the things that I am interested in" [(13) Int 2].Another carer felt that in-home respite was necessary because:"You just go out, pay your bills, (then) you've got to get back again because you can't leave them on their own, they're not safe to be on their own" [(8) Int 3].In instances of in-home respite, carers also felt reassured that their 'time-out' had not been obtained at the cost of distressing the care recipient by exposure to new environments and unfamiliar circumstances.The interviews also suggested reasons why practical help was the least used service in this sample. Most of the carers were female spouses, and for many  of this group, caring fell within their normative expectations of the spousal role. The increased 'work' within the home  was accepted as an extension of the regular duties that this role implied. For carers such as this one, offers of practical help were deemed unnecessary and inappropriate:"All I ever wanted was someone to be here in the house so he was safe, to feed him. I never expected or wanted anyone to come in and do my housework or any of those types of thing." [(13) Int 1].This quote illustrates the difference between the carer's felt need and a normative assessment of need, demonstrating that the carer is quite clear about the type of service she would like to receive and would accept.normative measures of need may fail to identify carers experiencing significant stress.The interviews supported documented evidence that care-giving is stressful, but also showed that carers' stress may originate from events that are unrelated to the cognitive or functional status of care recipients. The carer sample proffered examples of other events that had generated stress in their lives, such as a carer diagnosed with a life-threatening illness or with a medical history of mental illness, the death of a pet, and grief for the loss of the partnership that the care recipient had once provided. These diverse life situations and expectations highlight problems inherent in basing carers service needs on measures of carer burden or care recipient disease status, and explain why The interviews also indicated that the process of finding out about existing services and about their own eligibility for those services could be onerous for carers. Some carers felt that assessments were time consuming and achieved no satisfying result, either because particular services were not what the carer wanted or because the care recipient was not deemed eligible. The following quote is from a carer whose care-recipient had only moderate cognitive impairment, but whose GHQ-30 score was 13:"Well there's been five actual assessments and three interviews... over the last four months...then there was the day care lady came and assessed her and that was fruitless" [(3) int 3].normative need assessments (five home visits), without necessarily benefiting stressed carers. Overall, the interview data highlighted the complexity of interactions between the care-giving situation and service use, and the limitations of relying on professional assessments.This quote also demonstrates how many resources can be applied to felt needs expressed by carers of people with dementia are an important indicator of service need. The extensive list of possible causes of burden in carers' lives extends beyond the fact of caring for someone with dementia. Within the context of particularly challenging life circumstances, even modest care recipient demands may 'tip the scales' for carers and cause excessive stress. This means that relying on assessments of the status of care recipients with dementia, and on carer burden, may inadvertently exclude those for whom the basis of their need for services falls outside existing measures. While large data sets indicate that key factors such as cognition and ADL functions increase the probability of carers needing services [felt need should be given greater priority over normative need in assessing service needs for carers of people with dementia.A key implication arising from our data is that services , unknownnormative measures of need and the expressed need of service use in the case of dementia carers. Insufficiently acknowledged interactions between carer life circumstances and identity issues, and the disease status of care recipients may mean that measures of normative need capture only a limited range of causes of carer stress and service needs. Measuring stress clinically with a more direct tool such as the GHQ-30 objectively measures carer stress, since professionals are not trying to 'work backwards' by assessing possible causes of stress, in the manner of many burden measures. Given the complexity of carers' life situations, and the benefits that carers provide to the health care system in supporting people with dementia, it may be that offers of services should be based primarily on carers felt needs. This suggestion is supported by previous studies finding that unmet service needs have complex causes [Our interview data shed light on the limited relationship between x causes , and thax causes .The correlation between DSR-2 and BADLS and in-home respite suggests that the cognitive and functional aspects of care recipient deterioration are linked to in-home respite need. The reported social isolation of spouse carers  is an exfelt) service needs should be considered a 'red flag' by service providers.Assisted by the provision of only modest service hours, carers who participated in this study were able to support care recipients to remain at home until they reached moderate to severe stages of dementia. Carers such as these make an important contribution to the health care system and save health and social services significant costs thereby benefiting the public purse. In line with previous research ,10 howevWhat of those who refuse services? These findings suggest carers could be refusing services because particular services are not suitable, or because the carer does not identify his or her stress as directly linked to the care recipient. In these cases, services may need to offer more flexible options, a conclusion also reached by other researchers . These cThe small convenience sample used in this study is a limitation that raises the risk of Type II errors and prevents generalisability. The participants comprising our sample were already linked into and using some services, as could be expected by the dementia severity of their care recipients, and did not include isolated carers, or carers of persons with early stage dementia. Our sample also consisted mostly of female spouses, and this clearly influenced their belief systems about the appropriateness of using services. However the mixed method design we utilised provides a different strength through triangulation of quantitative with qualitative data, in which interlinked contextual information informed the interpretation of measurement results.normative need is not as useful as felt need when considering the health service needs of carers of people with dementia. A focus on measuring the care recipient's disease status and carer's burden overlooks the influences that broad life circumstances have on carer's service needs. Attempts to index the carer's service needs via objective cataloguing of functional and cognitive impairments may therefore be inadequate Our data suggest that felt need is a suitable indicator of carer unmet needs, because it is significantly related to carers' mental health status. Felt need may therefore be an appropriate 'red flag' of carer burnout, even in the absence of obvious "flags" raised by behavioural, functional and cognitive decline. In view of the current client-centred focus of health services, and the acknowledged burgeoning of numbers of people with dementia, our study contributes to the growing knowledge of how services can better support carers. Health services and professionals may need to reorient their approach away from traditional normative need assessments toward more participatory felt need. The small sample of carers and care recipients used in this mixed-methods study means that a larger investigation is required to assess the relevance of our findings to the general population of carers of people with dementia. However the similarity of our findings to larger data sets suggests that such a wider investigation needs to focus on felt carer need and service access, rather than on assessment.Overall, this exploratory study suggests that None declared. This study was funded by the JO and JR Wicking Trust (ANZ Charitable Services). The funders played no role in the study, data analysis or writing of the article. All researchers had complete independence from the funders in undertaking the study.CS and SA analysed the data and wrote the paper. TC, AR, JV and PT designed and supervised the study. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6963/10/122/prepub


ANOVA analyses detected significant differences in dN/dS ratios among races (P < 0.02). gp120 sequences from the black individuals showed higher mean dN/dS ratios for all estimators (1.24–1.45) than in other races (0.66–1.35), and several pairwise comparisons involving blacks remained significant (P < 0.05) after correction for multiple tests. In addition, black-placebo individuals showed significantly (P < 0.02) higher mean dN/dS ratios (1.3–1.66) than placebo individuals from the other races (0.65–1.56). These results suggest intrinsic differences among races in immune response and highlight the need for including multiple ethnicities in the design of future HIV-1 vaccine studies and trials.Differences in HIV-1 gp120 sequence variation were examined in North American volunteers who became infected during a phase III vaccine trial using the rgp120 vaccine. Molecular adaptation of the virus in vaccine and placebo recipients from different ethnic subgroups was compared by estimating the  P = 0.012). After adjustment for multiple tests, this difference was not significant (P = 0.13) [More than 33 million people are currently infected with HIV-1, resulting in 2–3 million deaths every year. Natural immunity to the virus is virtually nonexistent; hence, the creation of a vaccine to combat this global pandemic is an international public-health priority . OveralldN/dS) [HIV-1 evolution is driven, to a significant extent, by the immune response. If viruses isolated from non-white patients are in fact under a stronger selection pressure either because of genetic differences in the magnitude, specificity, or potency of the natural immune response, or because of differences in factors affecting virus replication, we should expect higher ratios of nonsynonymous (amino acid changing) to synonymous nucleotide substitutions (dN/dS) -8 than i). Full-length HIV-1 subtype B gp120 sequences were amplified as described in Gilbert et al. [dN/dS ratios were estimated using Nei and Gojobori's method [dN/dS ratios independently for each fragment.To test whether levels of selection were significantly different between vaccinated and placebo individuals in different races, we analyzed 3 clones per individual from 345 infected North Americans from the VAX004 study  and pairwise t-tests. Because treating all non-whites as a single unit is unrealistic considering their own genetic differences [Mean ferences , we testferences .dN/dS obtained with SNAP, PAML and HYPHY were all significantly correlated among the different estimators used . Importantly, the mean dN/dS ratios varied across races (Table P < 0.02) for SNAP and PAML estimates. Blacks (vaccinees and placebo combined) showed higher dN/dS ratios for all the estimators than individuals from other ethnicities (Table P < 0.05) between black and white, Hispanic and "others" viral samples were observed for all the estimators before corrections, but only the comparisons involving SNAP and PAML estimates remained significant after the Benjamini and Hochberg's adjustment  in SNAP dN/dS ratios were detected among placebo individuals. Moreover, black-placebo patients showed significantly  higher mean dN/dS ratios  than the other races . These results might indicate that natural differences in the immune response may have increased viral rgp120 adaptation in blacks.Does the greater virus adaptive variation presumed in black participants reflect genetic differences in the intrinsic (no-preconditioned) immune response to HIV-1, or is it a consequence of the conditioned immune response induced by vaccination with rgp120? Comparison of vaccine and placebo recipients showed different results based on the In North America, blacks correspond to 42% of all newly diagnosed HIV/AIDS cases, while white (non-Hispanic) and Hispanic individuals represent approximately 40% and 17%, respectively . If moreThe authors declare that they have no competing interests.MPL, DP, and KC developed the genetic and statistical strategies implemented in this work. MPL, DP, and MA performed the genetic and statistical analyses. DVJ, FS, and PWB carried out the molecular genetic studies and immunoassays. All authors participated in the design of the study and helped to draft the manuscript. All authors read and approved the final manuscript.


The burden of psychiatric morbidity is ever increasing, cutting across regional, socio-economic and cultural barriers.The global burden of disease due to neuropsychiatric disorders was measured to be 6.8% world wide in 1990. This is projected to increase to 15% by the year 2020. Psychiatric disorders account for 5 of the 10 leading causes of disability across the world.[Population - 1081.2 millionPopulation per sq km - 328.9Population under 15-32.1%Population over 60-7.1%Urban population -28.7%Men per 100 women - 105Mental-health disorders account for nearly a sixth of all related disorders. Yet we have just 0.4 psychiatrists and 0.02 psychologists per 100,000 people and 0.25 mental health beds per 10,000 population.Depression, child abuse, domestic violence, adjustment disorders are on the rise; so is the rate of suicide. The suicide rate in India in the early eighties used to be 6 per 1,00,000 per year. More than a decade later, the rate is 11 per 1,00,000 per year. The highest rate of suicide is prevalent among the younger age groups - between 18 and 29 years.[Despite such high rates of mortality and morbidity associated with psychiatric disorders, the psychiatrist to population ratio in India is very low.Besides, not all patients with psychiatric disorders or symptoms consult the psychiatrist. The findings of the ICMR-collaborated effort in Bangalore. Hyderabad and Vellore showed that an overwhelming majority of patients with neurosis, depression, alcohol-related problems, sexual problems and psychosomatic disorders seek advice from general physicians and not from the psychiatrists .Studies have also revealed that nearly two-thirds of all persons who commit suicide contact their family physicians in the month preceding the event. Physicians being aware about psychiatric symptomatalogy therefore, can prevent many untimely deaths.Patients from all disciplines of Medicine or Surgery may develop psychiatric complications at any point of time.Delirum, one of the commonest psychiatric diagnoses, is present in nearly 10% of emergency department patients and 40% of all terminally ill patients. Nearly 53% of all patients of chronic renal failure have been shown to have definite psychiatric disturbances. Deafness lasting more than six years is associated with a higher incidence of paranoid schizophrenia.Depression is an independent risk factor for coronary heart diseases and an indicator of poor prognosis in post myocardial infraction patients.Psychooncology is one of the expanding facets of oncology research in India and abroad.Apart from postpartum psychosis, which is a psychiatric emergency, maternal anxiety and depression are definitely known to influence developmental quotient (DQ) of infants, their weight gain and over all morbidity.Therefore there is an urgent need to sensitize and teach psychiatry in detail to all undergraduate medical students so that they do not falter with or miss psychiatric symptoms in their patients and establish an appropriate liaison with the specialist at the right time.Unless this is done, important advances made in the different fields of Medicine are likely to go in vain.In this era of increasing complications of treatment regimens and public awareness, doctor-patient relationships are often at stake. Driven by fear of litigations, doctors too often practice “defensive medicine”, an approach that adds unnecessarily to the public exchequer. Some basic knowledge of into the patients psychology and own reactions may help reduce unnecessary litigations.The need to train medical students and nonpsychiatrists has been emphasized by various policy making bodies, starting from the Mudaliar Committee (1962) to the National Health Policy (NHP) 1983.Thorough training of undergraduate students in Psychiatry andTraining nonpsychiatrists in the basic principles of psychiatric diagnosis and treatment.This object can be fulfilled by:The training of a specialists from other streams can pose problems of time, attitude and other constraints. However, a general practitioners (GPs) training carried out by the ICMR revealed the following difficulties.GPs tend to zealously protect their unique professional freedom and dread to function as an extension of specialistsGPs expect their patients to be referred back when they refer them for specialist consultation.Besides, training of nonpsychiatrists across the country would pose operational difficulties, like bringing all non psychiatrists in government, private, rural, urban sectors under one umbrella. A single short-term training session would hardly be comparable to a rigorous subject training in the M.B.B.S course.All these factors emphasize the need to train medical students, first and foremost, in the basic principles of Psychiatry. This should include an adequate period of compulsory clinical exposure.Present status of psychiatry training in the M.B.B.S. course.Twelve hours lecture classTwo weeks clinicsTheory paper: 1-2 short notes These evidences urge the need to include psychiatry as an examination subject in under graduate curriculum.In fact, psychiatry is being taught with due importance globally. Even in our neighbouring countries, psychiatry is an examination subject in the undergraduate curriculum.If we scrutinize the course and curriculum of Nursing training, we find that they also have given immense importance of psychiatry.


Prader-Willi (PWS) and Down Syndrome (DS) are two genetic disorders characterised by some common clinical and functional features. A quantitative description and comparison of their patterns would contribute to a deeper understanding of the determinants of motor disability in these two syndromes. The aim of this study was to measure gait pattern in PWS and DS in order to provide data for developing evidence-based deficit-specific or common rehabilitation strategies.19 PWS patients (17.7-40 yr) and 21 DS patients (18-39 yr) were evaluated with an optoelectronic system and force platforms for measuring kinematic and kinetic parameters during walking. The results were compared with those obtained in a group of normal-weight controls .The results show that PWS and DS are characterised by different gait strategies. Spatio-temporal parameters indicated a cautious, abnormal gait in both groups, but DS walked with a less stable strategy than PWS. As for kinematics, DS showed a significantly reduced hip and knee flexion, especially at initial contact and ankle range of motion than PWS. DS were characterised by lower ranges of motion (p < 0.05) in all joints than CG and PWS. As for ankle kinetics, both PWS and DS showed a significantly lower push-off during terminal stance than CG, with DS yielding the lowest values. Stiffness at hip and ankle level was increased in DS. PWS showed hip stiffness values close to normal. At ankle level, stiffness was significantly decreased in both groups.Our data show that DS walk with a less physiological gait pattern than PWS. Based on our results, PWS and DS patients need targeted rehabilitation and exercise prescription. Common to both groups is the aim to improve hypotonia, muscle strength and motor control during gait. In DS, improving pelvis and hip range of motion should represent a major specific goal to optimize gait pattern. Prader-Willi (PWS) and Down Syndrome (DS) are two different chromosomal disorders characterised by some common clinical features, such as obesity, muscular hypotonia, ligament laxity and mental retardation.PWS is a complex multisystemic disorder equally affecting males and females. The genetic basis is the absent expression of the paternally active genes in the PWS critical region on chromosome 15 ,3.DS is caused by trisomy of chromosome 21 (Hsa21) and is associated with a number of signs and symptoms including learning disabilities, heart defects, craniofacial dysmorphia and childhood leukaemia . PhysicaAmong the latter, gait disorders are common in both syndromes. They tend to progressively worsen as the clinical picture advances, severely limiting the patients' quality of life.In previous studies, gait analysis has mainly focused on DS with special reference to their specific associated orthopaedic conditions and biomechanical limitations.Caselli et al.  reportedTo our knowledge, only one quantitative study has investigated the biomechanical strategy during gait in PWS . These aDespite a different aetiology, the two genetic conditions do share several clinical and functional features. Whether the biomechanical determinants of such motor limitations are the same is still unknown and needs further investigations at various levels. Rehabilitation specialists are challenged by motor disability in PWS and DS patients, but they fail to provide evidence-based treatment modalities. A deeper understanding of the causes of their gait abnormalities, and ultimately of their motor disability, may well generate novel spin-offs for rehabilitation planning and treatment. 3-D gait analysis (GA) is nowadays the most accurate tool to investigate the gait pattern. From a clinical perspective, measuring the joint angular displacement, reactions, moments and powers provides insight into the 'how' (kinematics) and the 'why' (kinetics) of the movement observed. No studies up to now have addressed this issue of defining quantitative differences in gait strategy between DS and PWS. We could hypothesise that due to their common clinical and functional features rehabilitation strategies aimed at reducing motor disability in these two genetic conditions may share some common bases. In this wake of evidence, appropriate and effective rehabilitation and exercise prescription could be tailored to the unveiled specific or common deficits.The aim of our study was therefore to identify, quantify and compare the spatiotemporal, kinematic and kinetic parameters of gait in PWS and DS adult patient using 3D-Gait analysis (GA) and compare their results with those obtained in a group of normal-weight control subjects.Nineteen PWS and twenty-one DS patients matched for age, height, weight and body mass index (kg/m2: BMI), were enrolled in this study Table .The PWS patients had been periodically hospitalised at the Ospedale San Giuseppe, Istituto Auxologico Italiano, Piancavallo (VB), Italy. At admission, they underwent a clinical assessment and attended a 4-week comprehensive rehabilitation program. All patients showed the typical PWS clinical phenotype . CytogenThe DS patients were all referred to the IRCCS "San Raffaele Pisana", Tosinvest Sanità, Roma, Italy. The distribution of chromosomal anomalies is pure trysomy 21 in all of the DS patients.All PWS and DS patients were able to understand and complete the test and walk independently without aids.Twenty age-matched individuals were included as controls (Control Group: CG). Exclusion criteria for the control group included prior history of cardiovascular, neurological or musculoskeletal disorders. They showed normal flexibility and muscle strength and no obvious gait abnormalities.The study was approved by the Ethics Committees of the two Institutes for PSW and DS patients. Written informed consent was obtained by the parents or, when applicable, by the patients.The complete evaluation consisted of: clinical examination, video recording and 3 D Gait Analysis (GA).The PWS patients were evaluated at the Movement Analysis Lab of the San Giuseppe Hospital, Istituto Auxologico Italiano, Piancavallo (VB), Italy, using an optoelectronic system with 6 cameras  with a sampling rate of 100 Hz, and two force platforms .DS patients were assessed at the Movement Analysis Lab of the IRCCS "San Raffaele Pisana", Tosinvest Sanità, Roma, Italy, using a 12-camera optoelectronic system  with a sampling rate of 100 Hz, two force platforms  and 2 TV camera Video system  synchronized with the system and the platforms for videorecording.To evaluate the kinematics of each body segment, passive markers were positioned on the participants' body, as described by Davis After placement of the markers, subjects were asked to walk barefoot at their own natural pace (self-selected speed) along a walkway containing the force platforms at the mid-point. Kinematic and kinetic data were collected for each patient from five trials in order to guarantee reproducibility of the results.A potential bias of this study is the variability of data originating from the two different laboratory settings. Variability can indeed be present if different systems for kinematic acquisition are used and differences in marker positioning are evident. Therefore, two control subjects were tested in both laboratories in order to assess the consistency of the data measured with the two systems, the markers' placement and the data collection procedures.All graphs obtained from GA were normalized as % of gait cycle and kinetic data were normalized for individual body weight.For each participant (both patients and controls), three out of five trials, consistent in terms of gait pattern  using the STATISTICA computer package . This procedure was performed by the same operator to ensure data reproducibility. The following parameters were evaluated:Spatio-temporal parameters:- % stance (as % of the gait cycle);- mean velocity, normalised to the individual's height (1/s);- anterior step length, normalised to individual's height;- cadence: number of steps in a time unit (steps/min).Kinematics:- the mean value (Mean PT index) of pelvis on sagittal plane during the gait cycle;- the values of angle of ankle (AIC index), knee (KIC index) and hip joint (HIC index) at the Initial Contact (IC);- the values of maximal ankle dorsiflexion during stance phase (AMSt index) and the maximal flexion of the knee (KMSw index) during swing phase;- the values of minimal ankle dorsiflexion in stance phase (AmSt index), knee (KmSt index), and hip flexion (HmSt index) during the gait cycle;- the range of motion of the pelvis on the coronal (PO-ROM index) and transversal (PR-ROM index) plane; the range of motion of hip on coronal (HAA-ROM index) and sagittal (HFE-ROM) plane; the range of motion of knee (KFE-ROM index) on sagittal plane; the range of motion of ankle on sagittal plane during stance phase (ADP-ROM index).Kinetics:2). This parameter represents the push-off capacity during walking and is related to the forward propulsive power during gait.- the maximum ankle power during terminal stance  and the same index normalized to the velocity of progression  were expressed by plotting the values of the flexion-extension moment versus the flexion-extension angle over the gait cycle interval between 10% and 30%. The 10% to 30% interval (corresponding to the second rocker) of the gait cycle was selected and the linear regression was fitted. The angular coefficient of the linear regression corresponded to the joint stiffness index, as described in previous studies ,17. KneeThese parameters were chosen in line with the studies on gait strategy in PWS  and DS ,12.All the previously defined parameters were computed for each participant and then the mean values and standard deviations of all indexes were calculated for each group.Data of the two individuals acquired in the two different laboratories were compared with the Wilcoxon's test, in order to detect significant differences due to marker placement and data collection procedures in the two laboratories. Data of the PWS and DS were compared using Mann-Whitney U tests, in order to detect significant differences between PWS and DS. The patients' and the controls' data were compared with Mann-Whitney U tests. Null hypotheses were rejected when probabilities were below 0.05.We verified that marker placement and data collection procedures in the two laboratories were compared and the differences of all the computed kinematic and kinetic data of the two healthy subjects were not statistically different (p > 0.05). On this basis data from other 18 control subjects who served as the CG were acquired at the Movement Analysis Lab of the San Giuseppe Hospital, Istituto Auxologico Italiano.In Table Age was not significantly different among groups. BMI, weight and height were similar in PWS and DS but significantly different from CG. In order to take in account the variability in height and weight between pathological groups and CG, stride length was normalised to the subject's height and kinetic data were normalised to the subject's weight.In Tables PWS patients were characterised by longer stance duration than DS and normal cadence when compared to DS patients. In terms of anterior step length and velocity of progression, both PWS and DS showed reduced values as compared to CG, with PSW performing better than DS.As for the pelvic joint, PWS and DS showed a forward tilted pelvis in the sagittal plane (Mean PT index) with no significant differences between groups. Their pelvic range of motion in the transversal plane (PR-ROM index) was close to normal. In the frontal plane (PO-ROM index), PWS group was characterised by a higher pelvic range of motion during walking as compared to DS and CG.The hip joint exhibited excessive flexion during the whole gait cycle (HIC and HmSt indices) in both PWS and DS patients, but PWS walked with a more flexed hip at the initial contact (HIC index). The hip range of motion (HFE-ROM index) was close to normal in PWS and reduced in DS. So despite an increased hip flexion in PWS, its range of motion was more functional as compared to DS.As for hip ab-adduction, the PWS patients were characterised by an increased hip movement in the frontal plane as compared to DS (HAA-ROM index).The knee flex-extension plot revealed that, whilst the PWS group showed an excessively flexed knee as compared to DS at the initial contact (KIC index), both PWS and DS obtained values close to normal in midstance (KmSt index). In the swing phase, the maximum value of knee flexion (KMSw index) was reduced in both PWS and DS, with generally higher mean values in PWS leading to a wider joint range of motion (KFE-ROM index) than that observed in DS.The analysis of the ankle kinematics showed a plantar flexed position with reduced range of motion (ADP-ROM index) during the whole stance phase  in DS, while PWS were limited at the initial contact (AIC index) and during midstance (AMSt index), even if their dorsiflexion capacity, and therefore their range of motion (ADP-ROM index), in stance phase was higher than that observed in DS. During the swing phase, PWS were characterised by higher values of ankle dorsiflexion when compared to DS and CG. All these differences are significant from a statistical point of view (p < 0.05).2; DS: 2.02 ± 0.86 m/s2; CG: 2.42 ± 3.06 m/s2; PWS vs. DS: p = 0.2261)As for kinetic parameters (ankle power), both PWS and DS showed lower maximum ankle power during terminal stance  than CG (3.07 ± 0.86 W/Kg), with DS significantly more limited than PWS. The APMax index normalised to the velocity of progression (APMax norm index) did not reveal significant differences among groups . This strategy allows PWS a fair hip range of motion during gait (HFE-ROM index), whereas DS showed a limited excursion. The reason for that may be linked to the anatomical configuration of their pelvic girdle: the so-called "mongol pelvis" is characterised by a deeper acetabulum and a decrease in the cephalo-caudal diameter and acetabular angle ,19.In the frontal plane, hip excursion (HAA-ROM index) was higher in PWS than DS and CG. This strategy, directly linked to the pelvis movement in the frontal plane (PO-ROM index), appears to produce together with obesity and hypotonia the typical external rotation of the hip during stance . This maAs for ankle kinematics, DS were characterised by an increased plantar flexion and reduced dorsal flexion throughout the gait cycle with a globally limited ankle range of motion. On the contrary, PWS showed an ankle strategy close to normal, apart from a slight plantar flexion at the initial contact and an increased dorsal flexion during swing. The PWS group was generally characterised by a wider, closer to normal range of motion in all of the lower limb joints in the sagittal plane.In terms of ankle kinetics, PWS and even more DS showed lower peak ankle power than CG (APMax index), meaning a lower propulsion capacity during terminal stance. This result was consistent with previous studies . Two posInterestingly, we found differences in joint stiffness in PWS and DS. At hip level, PWS showed values close to normal, while in DS increased stiffness values were measured. At ankle level, joint stiffness was significantly decreased in both groups.It is known that hypotonia and ligament laxity are common in PWS  and DS . Our resThe increased hip stiffness in DS we found is consistent with the literature and may represent, together with the anatomical configuration of the pelvic girdle , a compeA potential weakness of this study may be the variability of data, since PWS and DS patients were evaluated in two different laboratories. However, we had previously compared markers' placement, procedures and data from normal-weight subjects in the two laboratories and no inconsistencies between laboratories occurred. Another bias of the study is that participants were not compared in terms of orthopaedic characteristics. PWS patients tend to develop a range of orthopaedic problems including scoliosis, hip dysplasia, flat feet, and pain syndromes of the lower limbs which may have an impact on gait. Also, the degree of muscular hypotonia and weakness, ligament laxity and cognitive impairment had not been measured nor compared between groups, thus hindering interpretation of the findings. As overweight is a distinctive feature in both PWS and DS, their gait pattern should have been more rigorously compared with obese instead of normal-weight individuals. However, the main object of our investigation was to compare gait strategy in PWS and DS patients to identify possibly common rehabilitation strategy.From a clinical point of view, quantitative characterisation of gait patterns in PWS and DS is important to develop, differentiate and enhance the rehabilitative options. The quantification of their peculiar gait deficits strongly support the issue that PWS and DS patients need targeted rehabilitation and exercise prescription. Common to PWS and DS is the aim to improve hypotonia, muscle strength and motor control during gait. Both patient groups should be encouraged to walk for its positive impact on muscle mass and strength and energy balance. In DS, improving pelvis and hip range of motion should represent a specific major goal to optimize gait pattern and prevent the onset of compensatory strategies. Evidence-based rehabilitation programs would contribute to improve daily functioning, quality of life and weight management issues in those patients.All authors haven't any conflicts of interest and any financial interest.All authors attest and affirm that the material within has not been and will not be submitted for publication elsewhereVC made substantial contributions to analysis and interpretation of data and was involved in drafting the manuscript. MG made contribution to conception, design and interpretation of data, revising the manuscript critically and gave the final approval of the manuscript. GG made contribution to interpretation of data, revising the manuscript critically. LV made substantial contributions to data acquisition, elaboration and interpretation. GA made contribution to interpretation of data, revising the manuscript critically. CR made contribution to interpretation of data and to revision of the final version of the manuscript. PC made contribution to conception, design and interpretation of data, revising the manuscript critically and gave the final approval of the manuscript. All authors read and approved the final manuscript.