Objective. To investigate the effects and to analyze the mechanism of the combination of Astragalus polysaccharide (APS) and Rhein on apoptosis in rats with chronic renal failure (CRF). Methods. Thirty-seven male Wistar rats were randomly divided into a control group, a model group, a low-dose APS and Rhein combination group, and a high-dose APS and Rhein combination group. CRF was induced by orogastric gavage with adenine. Rats were observed for renal function, electrolyte, and pathological changes for 7 weeks after administration. Renal tubular cell apoptosis was assessed by TUNEL and protein expressions of IRE1 and CHOP were detected by Western-blotting. Results. The combination of APS and Rhein decreased the kidney weight and index, improved renal pathological injury, maintained the stability of serum electrolytes, and reduced SCr and BUN levels in rat models. Moreover, APS and Rhein combination could effectively inhibit the apoptosis and reduce the protein expressions of IRE1and CHOP of renal tubular cells. Conclusions. The combination of APS and Rhein could improve renal function and reduce renal cell apoptosis to protect against further progression of CRF, whose mechanism may be related to alleviate endoplasmic reticulum stress (ERS) in the renal cells. Radix Astragali seu Hedysari) and Da huang (Radix et Rhizoma Rhei), with tonifying and purging effects, respectively, appeared in a lot of TCM formulas and was reported to be effective for the diseases coexisting deiciency and excess syndromes such as CRF, which is consistent with TCM's basic treatment principles [As the number of patients worldwide with chronic renal failure (CRF) increases at an alarming rate, CRF has become a major public health problem. Compared to patients with other diseases, patients with CRF require more frequent and longer hospitalizations and have a poorer quality of life and a higher morbidity and mortality. Therefore, it is imperative to develop new medicines and alternative therapies for CRF . In Chininciples –4.Radix Astragali seu Hedysari), and Rhein, an anthraquinone from Da huang (Radix et Rhizoma Rhei), which has been patented for CRF treatment. The effects of APS and Rhein combination on renal function, renal pathology, and tubular cell apoptosis in model rats were assessed to investigate the protective mechanism of APS and Rhein on the kidney.In this study, CRF model rats were produced by adenine. Drugs chosen for intervention were Astragalus polysaccharide (APS), the most intensively observed and effective monomer from Huang qi . The rats were reared in natural light conditions at a humidity of 50–60% and a constant temperature of 20 ± 3°C. Before the experiment, all rats were housed with food and water, freely available for 1 week, so they could adapt to the environment. Adenine  was purchased from Amresco Inc . APS  and Rhein  were purchased from Nanjing Zelang Medical Technology Co., Ltd. . A hematoxylin and eosin (HE) staining kit was purchased from Solarbio . A terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) apoptosis kit was purchased from Dingguo Changsheng Biotechnology Co., Ltd. .n = 7), a model group (n = 10), a low-dose APS (200 mg/kg/d) and Rhein (25 mg/kg/d) combination group (n = 10), and a high-dose APS (400 mg/kg/d) and Rhein (100 mg/kg/d) combination group (n = 10). The control group received normal food and water during the experiment. In the other 3 groups, a 2% adenine suspension was given at 200 mg/kg/d by gavage every morning to induce CRF. Every afternoon, the low- and high-dose APS plus Rhein groups were administered APS and Rhein by gavage at their respective doses. The rats in the model group were given an equal volume of distilled water by gavage. On the 28th day of the experiment, 6 rats were randomly selected from each group and underwent tail cutting, and a blood sample was collected from each rat. Serum creatinine (SCr) and blood urea nitrogen (BUN) levels were measured to determine whether the animal model was successfully established. During the subsequent 3 weeks, the model group and the low- and high-dose APS plus Rhein groups were given adenine by gavage every other day, and the other procedures remained the same. In total, the treatment period was 7 weeks.The 37 male Wistar rats were randomly divided into a control group , we collected a 5 mL blood sample from the abdominal aorta of each rat without anticoagulant. After standing for 20 min, the blood samples were centrifuged for 20 min at 2000 rpm. Then, the separated serum was stored in Eppendorf tubes for later measurement of kidney function and electrolytes. Meanwhile, the kidneys were quickly removed, decapsulated, washed with saline at 4°C, and weighed. One-fourth of the left kidney was fixed with 4% paraformaldehyde and stained with HE. The right kidney and three-fourths of the left kidney were stored at −80°C for later use.μm slices, dewaxed with water, stained with hematoxylin for 10 min, differentiated with 0.5% hydrochloric acid alcohol for 20 s, and stained with eosin for 5–10 min, after which they were then dehydrated, cleared, mounted, and photographed by a high-power microscope.The rat kidneys' color and morphology were assessed by visual inspection with the unassisted eye. Rat kidney injury was evaluated using HE staining, and pathological scoring was performed as follows: tissues were embedded in paraffin, cut into 2 μm) were dewaxed, digested with proteinase K, washed with PBS, incubated with blockers in the dark at room temperature, and then incubated with the TUNEL reaction mixture in the dark at 37°C. Blocking buffer was added after the reaction was terminated, followed by incubation with Streptavidin-HRP at 37°C. Diaminobenzidine was then added for color development, and hematoxylin was added for counterstaining. Finally, the sections were dehydrated, cleared, and mounted. TUNEL-positive nuclei that stained brown were observed under an optical microscope at a 200-fold magnification. Six slices were randomly selected from each group. Apoptotic cells were counted within 3 fields of view. The total number of apoptotic cells was then calculated for each group.Paraffin sections of kidney tissue . Measurement data were presented as mean ± standard deviation (mean ± SD). Comparison among groups was conducted using a one-way analysis of variance (ANOVA). If homogeneity of variance was present, a Student-Newman-Keuls (SNK) test was used; otherwise, a Tamhane's test was performed.In the control group, the rats had thick and shiny hair, active behavior, a normal food and water intake, blue-black and well-formed stools, and normal urination during the experiment.The rats in the model group began to take less food and water and had formed slightly loose, stools the day after modeling. As of day 8 after modeling, the rats had darkened, thinning hair and a loss of hair; had a worse mental state; exhibited the phenomenon of clustering, arching of the back, curling, and slow response; had less food and water intake; and had loose and less stools. From day 30 after modeling, 4 rats died intermittently. The deaths might have been caused by the modeling, adverse reactions to the monomer, individual differences, or experimental operations.In the low-dose APS plus Rhein group, since the day after modeling, the rats ingested less food and water and had slightly increased stools; stools were formed but loose, smelly, and reddish, which was probably the color of the APS metabolites. From day 9, rats began to participate in slightly fewer activities and had a slightly worse mental state; however, their stools were the same as before. From day 15, the rats had dull, pale yellow, thin hair and a loss of hair; had a poor mental state; and exhibited the phenomenon of clustering, curling, and arching of the back; and had similar food and water intake and stools as before the experiment. Two rats died during the experiment that might have been caused by the experimental operation, modeling, or adverse reactions to the monomer.In the high-dose APS plus Rhein group, since the day after modeling, the rats had less food and water intake; their stools had increased in amount and became loose, smelly, and a brownish-reddish color; their stools sometimes were in the shape of a string of beads; and the anus of the rats was often dirty. Compared with the control group, the hair color and mental state were slightly worse, but no other differences existed. Two rats died during the experiment that was probably caused by mistakes in the experiment operation.In summary, the high-dose treatment group was better than the model group with respect to general condition, and great differences were observed in stool volume and shape between the 2 groups.P < 0.01). The kidney weight of the model group was significantly higher than that of the treatment group (P < 0.01). No significant differences were observed between the 2 treatment groups (P > 0.05).The kidney weights of the treatment groups and model group were significantly higher than that of the control group (3) of the model group was significantly increased, as compared with that of the control group (P < 0.05). Furthermore, the kidney indexes of the treatment groups were significantly increased, as compared with that of the model group (P < 0.05)  .P < 0.01). In addition, the BUN levels were significantly decreased in the treatment groups, as compared with that of the model group (P < 0.01).The BUN levels were in the normal range in the control group, while they were increased in model group; moreover, significant differences were observed between the 2 groups (P < 0.01). The SCr levels were significantly decreased in the treatment groups, as compared with that of the model group (P < 0.01).As for the SCr levels, they were in the normal range in the control group, but they were increased in the model group; significant differences were observed between the 2 groups (P < 0.01). Furthermore, the serum calcium concentration in the high-dose group was significantly higher than that of model group (P < 0.01), while there was no significant difference demonstrated in the control group (P > 0.05). The serum phosphorus concentration in the treatment groups was significantly decreased, as compared with that of the model group (P < 0.01)  .We visually inspected the rats' kidneys. In the control group, the rats' kidneys were reddish-brown and difficult to decapsulate; the kidneys had a smooth surface without spots, were of relatively small size, and had a clear boundary between the cortex and medulla on the frontal section. As for the model and low-dose groups, the rats' kidneys were pale and easy to decapsulate and had dark spots on the surface, were of the largest size, and had an unclear boundary between the cortex and medulla on the frontal section. Meanwhile, in the high-dose group, the rats' kidneys were between a reddish-brown and white color, and the kidneys were easy to decapsulate, had dark spots on the surface, and had a relatively clear boundary between the cortex and medulla on the frontal section. Moreover, the kidney size of the rats in the high-dose group was larger than that of control group but smaller than that of model and low-dose groups.The control group had no significant hypertrophy, contracted or distended glomerular capsule, basement membrane hyperplasia, or inflammatory cell infiltration within the glomeruli. Juxtaglomerular tubules and medullary tubules were tightly packed and in a regular shape. There was only a small amount of interstitium. Hypertrophy of the juxtaglomerular apparatus was observed, but it was not common and had no pathological significance.The model group was observed to have contracted glomeruli and distended glomerular capsules without deposition of adenine metabolites along with atrophy of the proximal tubule, distal tubule, medullary loop, and collecting duct; and stenosis or dilatation of the lumen or even disappearance of the tubules. The epithelial cells had a reduced size and a heavily stained nucleus. A heavy deposition of adenine metabolites was found in the lumen. Interstitial inflammatory cells and fibroblast infiltration, as well as interstitial deposition of adenine metabolites, were also observed.The low-dose group demonstrated the same pathological changes as the model group but had a reduced deposition of adenine in the interstitium and lumen.In the high-dose group, the glomeruli were slightly contracted, and the glomerular capsules were relatively distended and had no adenine deposition. The tubules were of a regular shape, with a small amount of adenine deposition. Interstitial inflammatory cells and fibroblast infiltration were at a level lower than that of the model and low-dose groups . The HE We also assessed the HE staining results as follows.P < 0.01)  .P < 0.05). Compared with the model group, the protein expressions of IRE1 in the treatment groups were decreased, while there were no significant differences between the treatment groups and the normal group. As for CHOP, the protein expression in the high-dose treatment group increased compared with the normal group (P < 0.05), while there were no significant differences between the low-dose treatment group and the normal group  and Da huang (Radix et Rhizoma Rhei) is common for treating CRF in Chinese traditional medicinal formulas, such as the Qize Decoction [TCM pathogenesis of CRF is deficiency in origin and excess in superficiality. Deficiency in origin refers to spleen and kidney deficiency, while excess in superficiality refers to stasis of toxic dampness. Therefore, the principle of treating CRF is reinforcement and elimination in combination. The combination of Huang qi (ecoction , Shenqi ecoction , and UreModern medicine thinks that the pathogenesis of CRF includes intact nephron hypothesis, trade-off hypothesis, glomerular hyperfiltration hypothesis, inflammatory mediators, and cytokines hypothesis. The main pathologic changes of CRF are glomerular sclerosis, tubular atrophy, and interstitial fibrosis. APS and Rhein are the main active ingredients of Huang qi and Da huang, respectively. It has been reported that APS can significantly reduce kidney weight/body weight of the diabetic nephropathy rats, improve renal function, and retard the development of glomerular sclerosis  and reliIn the research, CRF model rats induced by adenine showed obvious impairment of glomerular filtration function and disturbance of calcium and phosphorus metabolism, and renal pathology was also consistent with clinical pathology of CRF patients. The APS and Rhein combination could alleviate the functional damage of glomeruli, relieve pathologic changes of tubules, and decrease proliferation and invasion of the interstitial inflammatory cells.Clinical researches showed that cell apoptosis widely appeared in CRF patients and inhibition of apoptosis could delay the progress of CRF disease and reduce or prevent occurrence of the related complications . ApoptosThis research proved that the expression level of apoptosis in the CRF model rats was significantly higher than that of the other groups, and APS and Rhein combination could effectively inhibit the apoptosis of renal tubular cells in the rats. Our previous researches showed that excessive ERS occurred in the renal tissues of the CRF model rats induce by adenine on the basis of significantly increased the expression of Caspase-12 in the rats . This re


Objective: We aimed to study the associations between peripheral artery disease (PAD) and ankle-brachial index (ABI) and performance in a range of cognitive domains in nondemented elderly persons. Methods: Data were collected within the Lothian Birth Cohort 1921 and 1936 studies. These are two narrow-age cohorts at age 87 (n = 170) and 73 (n = 748) years. ABI was analyzed as a dichotomous (PAD vs. no PAD) and a continuous measure. PAD was defined as having an ABI less than 0.90. Measures of nonverbal reasoning, verbal declarative memory, verbal fluency, working memory, and processing speed were administered. Both samples were screened for dementia. Results: We observed no significant differences in cognitive performance between persons with or without PAD. However, higher ABI was associated with better general cognition  and processing speed  in the older cohort and better processing speed  in the younger cohort. This was after controlling for age, sex, and childhood mental ability and excluding persons with abnormally high ABI (>1.40) and a history of cardiovascular or cerebrovascular disease. Conclusion: Lower ABI is associated with worse cognitive performance in old age, especially in the oldest old (>85 years), possibly because of long-term exposure to atherosclerotic disease. Interventions targeting PAD in persons free of manifest cardiovascular and cerebrovascular disease may reduce the incidence of cognitive impairment and dementia. Old age is associated with high prevalence of vascular disease. In addition to being associated with adverse health outcomes and mortality, vascular disease is also associated with an increased risk of cognitive impairment. At one end of the spectrum, vascular disease and vascular risk factors are related to increased incidence of vascular dementia  and AlzhA highly prevalent vascular condition in the older population is lower-extremity peripheral artery disease (PAD), causing narrowing of the peripheral arteries. The prevalence of PAD is strongly related to age, and PAD affects approximately 10% of the population by the age of 65 and over 20% after the age of 80 . PAD is A recent systematic review targeted the ABI as a marker of cognitive impairment in the general population . The autAnother major limitation of previous studies is the lack of any premorbid measures of cognitive ability. This is important because lower cognitive ability in childhood is associated with a range of adverse vascular outcomes, such as hypertension , cardiovThe aim of the present study was to examine the associations between PAD and ABI and cognitive performance in a range of cognitive domains. On the basis of previous research, we hypothesized that higher ABI would be related to better cognitive performance. This was tested in two age-homogenous population-based samples of different ages, 87 and 73 years old, in which premorbid mental ability scores were available.Data were collected within the Lothian Birth Cohort (LBC) 1921 and 1936 studies. Recruitment and data collection in these studies have been described in detail elsewhere . In brieOf the 550 participants tested at wave 1 of the LBC1921, 321 persons (mean age = 83 years) came back for a second and 237 persons (mean age = 87 years) came back for a third wave of testing at approximately 4-year intervals. At wave 1 of the LBC1936, 1,091 participants were assessed, 866 (mean age = 73 years) of who came back for a second wave approximately 3 years later. Reasons for attrition were death, severe acute illness, refusal, and loss of contact. Each assessment involved an interview, cognitive testing, physical examination, and self-report questionnaires. Ethics permissions were obtained from the Multi-Centre Research and the Lothian Research Ethics Committees for Scotland, and the ethical guidelines from the World Medical Association Declaration of Helsinki were followed throughout all parts of the studies. Informed consent was collected from all participants.For the present study, we used data from those data collection waves when a measurement of ABI was introduced. At wave 3 of the LBC1921, 207 persons participated in the cognitive testing. ABI was not assessed for 28 of these because the person was tested at home or because the measurement was disrupted because of discomfort for the participant. For the purpose of the present study, nine additional persons were excluded because of a low MMSE score (<24) or other indication of dementia in the medical history, resulting in a sample of 170 persons for the LBC1921.At wave 2 of the LBC1936, 756 persons had data on ABI and cognition. Of these, eight persons were excluded because of low MMSE score or other indication of dementia, resulting in a sample of 748 persons for the LBC1936.For both cohorts, childhood mental ability was assessed with the Moray House Test No. 12. This is a general mental ability test that was validated against the Terman–Merill revision of the Binet scales ; 1949; tU.K.  or the Wechsler Matrix Reasoning subtest (LBC1936). Raven’s Matrices  is a 60-In the Logical Memory subtest of the Wechsler Memory Scale WMS; , 1998b, In letter fluency , the parIn Letter-Number Sequencing from the WAIS-III, the interviewer reads increasingly long strings of alternating numbers and letters. The participants are instructed to repeat first the numbers, in numerical order, and then the letters in alphabetical order. The score used was the number of correctly reproduced sequences.In Digit Symbol (WAIS-III), the participants are instructed to enter symbols according to a given number-symbol code. The score recorded is the number of completed symbols within 2 min. Two reaction time (RT) tasks were administered, both with an interstimulus interval that varied between 1 and 3 s . In simpM = 100, SD = 15). A g factor score, representing general cognitive ability, was derived from three of the tests described above: Raven’s Matrices, Logical Memory-total, and letter fluency. For the LBC1936, a more comprehensive g factor score was derived from scores on six WAIS-III subtests: Letter-Number Sequencing, Matrix Reasoning, Block Design, Digit Symbol, Digit Span Backwards, and Symbol Search. Further, a g speed factor score was derived from scores on a set of processing speed measures: Symbol Search, Digit Symbol, simple and choice RT, and inspection time  genotyping was performed with TaqMan technology for single-nucleotide polymorphisms rs7412 and rs429358. In this study, APOE status was coded as ε4 or non-ε4 carrier. The participants also completed self-report questionnaires, including the Hospital Anxiety and Depression Scale  and t tests (continuous variables). The associations between ABI and cognitive performance were first analyzed according to diagnostic category (PAD vs. no PAD). Group differences in cognitive performance were analyzed with t tests. Thereafter, the ABI was treated as a continuous variable. Four regression models were fitted to the data. The most basic model included age and sex as covariates. The second model included age, sex, and age-11 IQ. In the third model, we excluded persons with ABI greater than 1.40 because these values fall outside of the normal range. Abnormally high values may be a sign of severe PAD because calcification of the artery walls may cause incompressible vessels  were examined by χ vessels . In the 4 allele .APOE ε4 carriers. However, there were no significant group differences for the demographic variables or childhood mental ability. Also, the correlation between childhood mental ability and ABI was not significant . As for the health-related variables, persons with PAD tended to be more affected by cardiovascular disease (p = .06). Differences in cognitive performance on the basis of the dichotomized variable (PAD vs. no PAD) are also reported in p = .05).The characteristics of the LBC1921 sample are shown in g), better working memory performance (Letter-Number Sequencing), and better performance in two of three processing speed tasks (Digit Symbol and mean simple RT). Controlling for childhood mental ability (Model 2) rendered the association between ABI and g nonsignificant and slightly weakened the associations with working memory and processing speed. After removing persons with abnormally high ABI (Model 3), general cognitive ability and Digit Symbol performance were significantly associated with ABI. Model 4 resulted in a similar pattern of results as Model 1, suggesting that in a sample free of severe vascular disease, higher ABI is associated with better general cognitive ability  and processing speed . Effect sizes expressed in R2 change, indicating the additional amount of variance explained by the ABI after having entered the covariates, ranged between .05 and .08 for the significant associations, with a larger effect observed for processing speed. Further adjustment for smoking status (never smoked vs. ex- or current smoker), alcohol consumption (no vs. yes), history of hypertension, or history of diabetes did not affect the pattern of results (data not shown). Controlling for the number of depressive symptoms did not attenuate the association between ABI and cognition. Rather, it resulted in slightly larger βs for ABI and rendered the associations with age-87 IQ  and Raven’s Matrices  significant. Finally, we checked for potential interaction effects between APOE and ABI. However, no such interaction effect was observed (data not shown).r = −.03, p = .45). As for the vascular risk factors, there was a higher prevalence of current smokers in the PAD group. Persons in this group also had higher systolic blood pressure and were more likely to have a history of diabetes and cardiovascular disease. Regarding the cognitive measures, there was a significant group difference in memory performance, with the PAD group showing better performance compared with the no PAD group.The characteristics of the LBC1936 sample are shown in g speed . Effect sizes, expressed in R2 change, were .01, indicating that ABI explained 1% of the variance in processing speed in the younger cohort. Further adjustment for smoking status, alcohol consumption, history of hypertension, history of diabetes, or number of depressive symptoms did not affect the pattern of results. Also, no significant interaction effect between APOE and ABI was observed (data not shown).In this study, we observed no significant group differences in cognitive performance between persons with or without PAD (ABI < 0.90). However, we did observe an association between a continuous measure of ABI and cognitive functioning. This association was most consistently found for processing speed.ps > .40). Second, the association between ABI and cognitive performance was significant also after controlling for childhood mental ability . This was not due to more severe PAD in the older cohort—mean ABI was very similar for the two groups with PAD. Furthermore, the prevalence of vascular disease was not higher in the old PAD group  and 3.Why was the effect most evident in the older cohort? One explanation could be that the older persons with PAD had suffered from this condition for a longer time. The prevalence of PAD is strongly related to age , which mAn additional explanation for why the older cohort was more affected is that older age may be associated with increased vulnerability for different vascular conditions. Gray and white matter volumes are known to show age-related shrinkage, which is in turn related to poorer cognitive performance . Normal g speed in the younger cohort. This is consistent with previous studies observing associations between cerebral blood flow, white matter hyperintensities, and silent infarcts with processing speed , only the associations with processing speed would have remained significant. Another limitation is that although the samples were population based, they are still likely to be of superior health compared with the general population. Persons with severe health problems would have been more likely to decline participation in these quite extensive examinations. Moreover, because PAD is related to increased mortality  was measured by self-report, which is always associated with some uncertainty. It should also be mentioned that analyses were performed for a relatively large number of cognitive tests, thus increasing the risk of committing a Type I error. If we had applied a more stringent α level . These findings are highly relevant given that vascular cognitive impairment is a common and possibly preventable condition that is associated with a high risk of progressing to dementia or dying . The ABI


Bomarea (2340 records), and 1031 genera of both plants and animals (100118 records) distributed across the Northern Andes, demonstrated that a geometrical approach to panbiogeography is a feasible quantitative method to determine general distribution patterns for taxa, reducing complexity, and the time needed for managing large data sets.Panbiogeography represents an evolutionary approach to biogeography, using rational cost-efficient methods to reduce initial complexity to locality data, and depict general distribution patterns. However, few quantitative, and automated panbiogeographic methods exist. In this study, we propose a new algorithm, within a quantitative, geometrical framework, to perform panbiogeographical analyses as an alternative to more traditional methods. The algorithm first calculates a minimum spanning tree, an individual track for each species in a panbiogeographic context. Then the spatial congruence among segments of the minimum spanning trees is calculated using five congruence parameters, producing a general distribution pattern. In addition, the algorithm removes the ambiguity, and subjectivity often present in a manual panbiogeographic analysis. Results from two empirical examples using 61 species of the genus  The geographic distribution of species has been considered an important source for documenting and conserving biodiversity In this context, different biogeographic approaches make use of tools, to manage and analyze these kind of data. Within these approaches panbiogeography is considered an important tool for the primary management of distributional data Panbiogeography delimits distributional patterns for multiple species and is known as track analysis. This method is based on three graphic elements: individual tracks, generalized tracks, and nodes Different approaches exist within panbiogeographic methods. For example, Croizat's manual reconstruction Considering that individual and generalized tracks are lines in a geometrical context, and congruence of individual tracks is a geometric property, in this study, we describe new software, named MartiTracks, based on a new algorithm to perform a panbiogeographic track analysis using a geometrical approach. The algorithm includes geometric functions and processes, which makes this approach a feasible quantitative alternative to the traditional track analysis. Finally, this approach is a unique and useful technique to capture distributional patterns or structures in studies employing spatial data.For a new MartiTracks project, distribution point records (latitude and longitude data) of a particular set of taxa must be compiled. A typical MartiTracks input file consists of a text file, which has the following structure: taxon-name, latitude, and longitude data. These data points are utilized to build an individual track for each species. The spatial congruence of the individual tracks is then evaluated through the congruence algorithm in order to determine whether there are generalized tracks representing the general patterns of distribution. Finally, the individual tracks of each species and the generalized patterns of distribution are represented in a KML (Keyhole Markup Language) file that can be visualized using any Geographic Information System (GIS) program such as GoogleEarth, or Qgis .In the same way as most of panbiogeographic software, for example, Croizat Once the individual tracks are defined, the panbiogeographic method determines the spatial congruence of the individual tracks in order to delimit generalized tracks representing general patterns of distribution. The geometrical approach of MartiTracks considers each MST' segment or edge as the basic unit of congruence between two species. Thus, given an individual track or MST as ertices  .http://local.wasp.uwa.edu.au/pbourke/geometry/pointline/. Given segment (P1–P2) and point P3 . This index (SI) measures the similarity between tracks , and depending on a pre-established threshold, determines whether two tracks can be considered as the same element or not. Given two MSTs  and  , the simIt is important to emphasize that this is an asymmetrical index, due to its dependence on the length of the MSTs. Thus, er than  . Given  Finally, the parameters cut value, lmin, lmax, lmax.line, and min-SI can be predefined according to the user's required level of congruence. It is important to consider that the value of each parameter of congruence depends on the value of the other parameters. Similarly, there is a constraining rule for these values, hence the cut valueBomarea, obtained from the Global Biodiversity Information Facility GBIF ( http://www.gbif.org/datasets/resources/ 24/07/2010). We used three different sets of parameters values in order to calculate the general distributional patterns of Bomarea with different levels of congruence. The generalized tracks obtained by one of the sets are shown in An empirical analysis was conducted with 2340 records belonging to 61 species of the genus To run the program, we used a PC-compatible computer with an Intel Core 2 Quad Q6600 at 2.40 GHz and 4 GB of RAM, running Ubuntu 9.04 64 bits. The panbiogeographical analyses of the genus required 30 to 60 seconds.Bomarea, using a traditional panbiogeographic analysis by Alzate et al.et al. used 2205 records belonging to 101 species of the genus Bomarea. Although there is a difference between the number of species evaluated in both analyses, similar patterns of distribution were found (These results were compared to the results of a previous panbiogeographic work on re found .http://www.gbif.org/datasets/resources/26/06/2009), and was not filtered for errors in distributions or taxonomy; therefore, mimicking an exploratory analysis to evaluate a very large data set. Four parameter sets were employed to visualize general patterns of distribution with different levels of congruence.We analyzed 100118 georeferenced records belonging to 1031 genera of plants and animals, distributed across the Northern Andes, in order to evaluate MartiTracks efficiency with large data sets. This data set was obtained from the Global Biodiversity Information Facility GBIF . Consequently, the ambiguity and the subjective factor, produced when overcrowded geographical points are evaluated http://tux.uis.edu.co/labsist/martitracks and http://code.google.com/p/martitracksMartiTracks was written in Freepascal language under the Unix Operative System, Linux - Ubuntu 10.04 64 bits. Compiled versions of the program for Windows and Linux platforms, along with the source code are freely available under a GNU General Public license GPL 2.1 at Availability and RequirementsProject name: MartiTracksProject home page:http://tux.uis.edu.co/labsist/martitrackshttp://code.google.com/p/martitrackshttp://code.google.com/p/martitracksBug tracking Operating system(s): Platform independent(but 64 bits OS is recommended for medium/large data sets)Programming language: FreepascalLicense: GNU GPL 2.1Any restrictions to non-academics: none


Studies on the effect of organizational factors on the involuntary admission of psychiatric patients have been few and yielded inconclusive results. The objective was to examine the importance of type of service-system, level of care, length of inpatient stay, gender, age, and diagnosis on rates of involuntary admission, by comparing one deinstitutionalized and one locally institutionalized service-system, in a naturalistic experiment.5538 admissions to two specialist psychiatric service-areas in North Norway were studied, covering a four-year period (2003-2006). The importance of various predictors on involuntary admission were analyzed in a logistic regression model.Involuntary admission to the services was associated with the diagnosis of psychosis, male sex, being referred to inpatient treatment, as well as type of service-system. Patients from the deinstitutionalized system were more likely to be involuntarily admitted.Several factors predicted involuntary status, including male sex, the diagnosis of psychosis, and type of service-system. The results suggests that having psychiatric beds available locally may be more favourable than a traditional deinstitutionalized service system with local outpatient clinics and central mental hospitals, with respect to the use of involuntary admission. The use of involuntary admission and other types of coercion in psychiatric care involves ethical dilemmas and may result in uncertain clinical outcomes-4. PriorHowever, little is known about the how the organization of services may affect the use of involuntary admission, although a general increase has been seen in many countries following the area of deinstitutionalization of psychiatric care-15. SomeThe rate of involuntary admission in Norway is among the highest in Europe. Recent In the present study, we compared two demographically similar areas with differently organized services in a naturalistic experiment. The aim was to examine how a range of factors, including the organization of mental health services, affected rates of involuntary admission.According to Norwegian legislation, the invIn Norway, the organization of psychiatric services differs somewhat between geographical areas. The DPCs, which provide the major part of all psychiatric services locally often differ in their organization of services. While some rely on several types of outpatient services locally in combination with inpatient services at larger centralized regional hospitals, other have beds available at small local psychiatric institutions,28. The The present study compares the neighbouring DPCs of Vesterålen and Lofoten, located in the County of Nordland, North Norway. The catchment areas’ characteristics strongly resemble each other structurally and demographically. The areas are characterised by small towns and communities along the coast. The majority of people work in fisheries, agriculture, tourism, small-scale industry, and public service. Communications to the county capital of Bodø are good, and local administrative institutions and educational facilities are in line with modern Norwegian standards. The population is very similar in the two areas in terms of the distribution of gender, age groups, and educational levels.We also examined the epidemiological characteristics of the two areas by the use of publicly available statistics on living-conditions and demography. A ‘Care Need Index’ (CNI) was calculated, and weighted for size of the populations of the two catchment areas,31. The The psychiatric services on the other hand, are very differently organized,32. In VIn a previous study, we found that the rates of hospitalization were remarkably alike between the systems, with a population rate of 7.7 inpatients per 1000 (Vesterålen) vs. 8.4 per 1000 (Lofoten), and a bed-utilization rate of about 1 per 1000 inhabitants in both areas. This suDrawing on the routine case-registries of the services, 5538 individual treatment-episodes in the four-year period 2003-2006 were identified. These represent all admissions to the psychiatric specialist services in the two areas, both at the local level of the DPCs and at the CMH. The registry contains demographic variables, service-variables, and clinical variables. All clinical variables in the registries were registered by clinical staff during individual treatment courses. The use of diagnostic tools and procedures in the services was not systematic. Diagnoses of inpatients were often discussed and set in joint meetings with psychiatrists, clinical psychologists, and specialist nurses. Only 9 patients were treated in both areas, and less than .5% were outside residents. These were omitted from further analyses. Missing data were collected from medical records when possible.Involuntary admissions were analysed by studying the following variables: A) gender, age and home-address; B) the level of care (outpatient/inpatient) and the volume of treatment ; and C) diagnoses (according to the ICD-system).In order to obtain adequate sizes for analysis, we collapsed less frequent diagnoses into eight broader categories: 1) Psychiatric observation , 2) Substance abuse (F10-19), 3) Psychotic disorders, including affective psychoses, excluding substance related psychoses and organic psychotic disorders , 4) Affective disorders, excluding affective psychoses , 5), Anxiety disorders (F40-48), 6) Anorexia and other eating disorders (F50), 7) Personality disorders (F60-62), and 8) ‘Other’ (including dementia (F00-04), organic psychoses and deliria (F05-09), hyperkinetic disorders (F90) and ‘social problems’ (Z64-65).Uni-variate analyses of differences were performed with Chi-square tests, t-tests, and Mann-Witney U-tests. A multivariable logistic regression analysis was performed with all variables as predictors to control for possible interactions, and with legal status at admission as the dependent variable (involuntary/voluntary). The predictors were entered in a stepwise manner, following the Forward LR method in SPSS (‘Observation’ was used as contrast for diagnoses). To increase readability, variables that did not reach the level of significance were omitted from the resulting table, with the exception of age.The present study was approved by the Regional Medical Ethics Committee, the Norwegian Data Protection Agency, and the Norwegian Directorate for Health.Table Most relevant for the present study are the differences in the variables regarding involuntary admission. The deinstitutionalized system had a significantly higher rate of involuntary admission than the other system (5.6% vs. 4.0%), see Table In order to control for possible interactions or differences in populations, a multivariable analysis was performed. The model was statistically significant , indicating that it could distinguish between legal status at admission (i.e. voluntary or involuntary). Log-likelihood was 1483.825, and the model explained between 9.0% (Cox & Snell R Square) and 28.7% (Nagelkerke R Square) of the variance in legal status at admission. The results are displayed in Table Psychosis emerged as the strongest predictor of involuntary admission, giving a confidence interval for EXP(B) of 1.372 – 4.930 (p = .003), controlling for all other factors in the model. This indicated that patients with psychosis-related disorders were more likely to be involuntarily admitted than patients with other diagnoses. Also, male patients were more likely to be involuntarily admitted than female patients. Notably, besides these known and individual predictors for involuntary admission, the most important predictor was Service-system, which had a confidence interval of 1.133 – 2.026 (p = .005). This indicated a higher risk for patients from the deinstitutionalized system of being involuntarily admitted.The diagnostic category of The most important finding of this study was that the deinstitutionalized system without available local beds had the highest rate of involuntary admission. In addition, the present study also supported prior findings suggesting that male patients, patients suffering from psychotic disorders, and patients that are referred to inpatient stays, are more likely to be involuntarily admitted,34,35.This study is one of very few in recent years that have studied whether the organisation of services is of importance to the use of involuntary admission. Some earlier studies have suggested that organisational and structural differences in psychiatric care may be of importance to rates of involuntary admission,37. In oContinuity of care for severely ill patients has been an important topic in mental health services research,39. SeveAnother possible explanation may be that the fact that many of the inpatients in the deinstitutionalized system are treated in a Central Mental Hospital may increase the risk of being subjected to different types of coercion, including involuntary admission,21. The The present results may also be in accordance with the longstanding notion of supply–induced demand,46. The Another possible explanation may be that, in the service area without available local psychiatric beds, the GPs and local psychiatric specialists more often prefer to refer patients involuntarily strategically , as there could be a perception that involuntary patients are more likely to be accepted for admission.One weakness of this study is that the data concerns admissions to psychiatric specialist services rather than individual patients. This may introduce a bias as some patients may have been admitted to the services several times, and some might have been referred both to inpatient services and outpatient services. On the other hand, the data concern more than 5000 admissions, which is a relatively high number and a strength in case-register studies. Most prThe diagnoses used in this study are based on routinely collected data. There might be limitations in accuracy and standardization of information collection that may impact the quality of the data. The observed differences in diagnoses Table  could inOne of the major advantages of the study is the control over the patient-population. There are no private local providers, and availability of services outside the catchment areas is limited due to considerable geographical distance,55. ThusHowever, as the two service areas compared in this study are very similar demographically and in other respects – we believe that it is unlikely that the population in the two areas differ substantially. Hence, we believe that this natural experiment lends support to the idea that organizational factors may affect the use of involuntary admission, either through the selection of persons into treatment or through clinical decisions made during treatment.Factors such as diagnosis, gender, type of service system, and level of care are predictors of importance to patients’ legal status. Having psychiatric beds available locally may be a more favourable type of psychiatric service organization with respect to minimizing the use of involuntary admission.The authors declare that they have no competing interests.LHM designed the study, collected the data, analysed the data, drafted the manuscript, revised the manuscript and approved the final manuscript. KS designed the study, analysed the data, revised the manuscript and approved the final manuscript. RW analysed the data, drafted the manuscript, revised the manuscript and approved the final manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6963/14/64/prepub


Social capital refers to the resources linked to having a strong social network. This concept plays into health outcomes among People Living with HIV/AIDS because, globally, this is a highly marginalized population. Case studies show that modifying social capital can lead to improvements in HIV transmission and management; however, there remains a lack of description or definition of social capital in international settings. The purpose of our paper was to describe the degree of social capital in an international sample of adults living with HIV/AIDS.n = 1,963) completed a cross-sectional survey and data were collected between August, 2009 and December, 2010. Data analyses included descriptive statistics, factor analysis, and correlational analysis.We recruited PLWH at 16 sites from five countries including Canada, China, Namibia, Thailand, and the United States. Participants (r = 0.25) and psychological condition (r = 0.36), social support (r = 0.31), and total social capital. No relationships between mental health factors, including substance use, and social capital were detected.Participant's mean age was 45.2 years, most (69%) identified as male, African American/Black (39.9%), and unemployed (69.5%). Total mean social capital was 2.68 points, a higher than average total social capital score. Moderate correlations were observed between self-reported physical (This is the first report to describe levels of total social capital in an international sample of PLWH and to describe its relationship to self-reported health in this population. Social capital is a concept that has been widely studied and discussed in public health over the past decade -4. It haThe relationship between social capital and health may be different among PLWH in comparison to a more general population. Globally, PLWH are highly marginalized -13 oftenResearch on social capital and HIV has predominantly focused on preventing HIV transmission . AuthorsBuilding upon qualitative research, investigators reporting on population-based surveys of social capital and HIV prevention illustrated complex relationships between social capital and HIV transmission. Social capital has significantly predicted AIDS and other sexually transmitted diseases case rates throughout the United States . IncreasDespite the substantial evidence exploring the multiple aspects of social capital and prevention of HIV transmission, many questions remain unanswered about social capital among PLWH. These gaps in the literature include both the lack of a basic description of social capital, and a description of its health correlates, in a diverse sample of PLWH. The purpose of this paper is to close these gaps and describe social capital in an international sample of men and women living with HIV/AIDS. Therefore, in this report we aim to: Describe levels of social capital in an international sample of adults living with HIV/AIDS, provide evidence for the validity of the individual-level, Social Capital Scale in this population, and determine the nature of associations between social capital, physical and psychological health, social support, and HIV status among PLWH.Exploring the Role of Self-compassion, Self-efficacy and Self-esteem for HIV-positive Individuals Managing Their Disease. In this study, there were 16 sites from five countries and Puerto Rico. Data were collected between August, 2009 and December, 2010. Each site recruited approximately 100 participants. Participants included adults (> 18 years of age), living with HIV/AIDS, and recruited from Infectious Disease clinics and AIDS Service Organizations. Each site adhered to the common protocol and all participants gave informed consent before completing a pen and paper, cross-sectional survey [Data for this cross-sectional study come from the International Nursing Network for HIV/AIDS Research, Study V: l survey .After completing the survey, all data were entered into an electronic database and were de-identified. The de-identified data were sent to the coordinating center, cleaned, entered into the master database, and stored until all sites completed data collection and entry. Original data were stored at each individual site. Prior to recruitment at study sites, the Committee on the Protection of Human Subjects at the University of California, San Francisco, reviewed and approved the overall protocol and each site also received approval from their local human subjects review committees.The instruments used to measure the variables of interest are listed below. Social Action Theory -39 guideMeasurement of social capital in the academic literature is varied and often critiqued ,42. The Demographic, HIV disease status, and criminalization of HIV was assessed with a 20-item demographic and illness characteristics instrument. This included age, gender, race, ethnicity, education, adequacy of income, health insurance, date first learned of HIV diagnosis, current CD4 count, viral load, HIV transmission route, and general health. In addition to demographic and biomedical disease status indicators, we also assessed whether or not HIV transmission was formally criminalized. Criminalization of HIV transmission was assessed by reviewing the relevant laws and policies in the jurisdiction of residence  that pertained to each individual site.Mental Health was measured with several instruments including SF-12 Mental Health Quality of Life subscale, CES-D Depression Scale [on Scale ,50. Anxion Scale , the CAGon Scale , and thrPhysical and Psychological Health and Social Support were measured with three self-report questions asking participants about their current physical and psychological health condition, and their current perceived level of social support. These questions were measured on a 10-point scale .All data were entered into a data management program and the data integrity and assumptions were checked. Analyses were conducted in Stata (version 11.2) and included descriptive statistics, exploratory factor analyses using a principle components factor analysis with oblique rotation, bivariate correlational analyses including the Pearson product-moment correlation and Spearman's rank order correlation, and multiple regression analysis. These analyses allowed us to (1) describe the average individual-level total social capital score for PLWH, (2) provide evidence for validity and reliability of the Social Capital Scale in an international sample of adults living with HIV/AIDS, and (3) examine the relationship between social capital and psychological health, psychological support, social support, and HIV disease status.A total of N = 1963) HIV + adults from 16 sites in 5 countries and Puerto Rico completed the cross-sectional survey. Participants' average age was 45.2 years (SD ± 9.4) and most were male (69%), African American/Black (39.9%), and had a high school diploma (38.3%). The mean year of HIV diagnosis was 1998 (SD ± 7.4 years) indicating that our sample was fairly experienced with their HIV disease. Accordingly, most were currently prescribed anti-retroviral therapy (80.4%) and reported undetectable HIV viral loads (87.4%). Additional demographic and HIV disease information are reported in Table 963 HIV +The mean total social capital score for all participants was 2.68 (SD ± 0.55), which indicates higher than average social capital. For individual sites the mean total social capital scores ranged from 2.56 (SD ± 0.49) in Shanghai, China to 2.95 (SD ± 0.66) in Namibia Figure . The ovedata not shown), but observed no gender differences.We observed weak correlations between mental health variables and total social capital across all study sites. The correlation coefficient for social capital and mental health quality of life was 0.02; for depression it was -0.01; for anxiety it was -0.05; for intravenous drug use it was 0.02, and for alcohol it was 0.03. We observed stronger, yet still small, effect sizes between social capital and mental health variables in Thailand and Puerto Rico. The overall correlation coefficients appear to be heavily weighted toward the U.S., perhaps due to the disproportionate number of U.S. study sites. Additional details on the relationship between mental health variables and total social capital are reported in Additional file Moderate correlations were observed between self-reported physical and psychological condition, social support, and total social capital. The overall correlation between self-reported physical condition and total social capital was 0.25. For self-reported psychological condition, the correlation coefficient was 0.31. For self-reported social support, the correlation coefficient was 0.36. There was variability among the different countries, with Thailand and Puerto Rico respondents reporting weaker relationships and those in Namibia being stronger. Again, overall correlation coefficients appear heavily weighted toward U.S. results. Additional information on relationships observed between self-reported physical and psychological condition, social support, and total social capital are reported in Table data not shown).We examined the relationship between total social capital and select HIV health status variables including CD4 count, HIV viral load, AIDS diagnosis and HIV medication adherence. No significant relationships were observed between these variables  do not give guidance on how to interpret the mean score, previous investigations of individual-level social capital using the Social Capital Scale have classified a mean social capital score greater than 2.5 as high social capital and anything less than 2.5 as low social capital . In our The measurement of social capital is challenging ,55. ConsIn summary, among our sample of PLWH, we observed that more of the items on the Social Capital Scale appeared to represent a subscale of friends and family connections, followed by participation in the local community, which suggests a modification to the factor structure for anyone wishing to explore the individual factors or subscales in this population in the future. However, in our analyses, we only examined relationships between social capital and health-related outcomes using the total Social Capital Scale. This alternative strategy is advantageous because it can identify factors that contribute to health outcomes among PLWH. For example, those who perceive themselves to be healthy and in possession of social capital may be empowered to collaborate with public health researchers, clinicians, and policy-makers to participate in HIV prevention, HIV treatment, and health promotion strategies ,62. ChalThe moderate relationships we observed between total social capital score and self-reported physical and psychological health condition underscore the importance of perceived social resources and trust in organizations when assessing personal health. Previous investigators examining the relationship between perceived health and social capital observed similar findings in large, national samples . It is pWhile this study has several advantages, including filling a significant gap in the literature, there are limitations that must be considered by the reader. The first limitation is that we used a convenience sampling method, not random sampling. Therefore, our data are only representative of the samples surveyed and the information cannot be extrapolated to the entire population in any country where the samples were obtained. With the exception of the United States, every country only had one site where data were collected. Therefore, it would be inappropriate to base conclusions about an entire country on a single site, especially when considering the geographic size and demographic diversity of the countries studied . However, even though country-level extrapolation is not appropriate, our study is among the first to describe individual-level social capital in some of these sites, which allows for tempered cross-national comparison. An additional limitation may be the modification of the Social Capital Scale by the removal of the 5 work-related items. While this strategy was similar to the one adopted by Onyx and Bullen, it is possible that this strategy could have led to an upward bias in our overall summary statistics. Finally, most of our data collection sites were in the United States and in our summary statistics, the U.S. estimates exerted more weight, leading to an overall U.S. bias in these statistics. These analyses also assume that there is a level of homogeneity among the participants simply because they are all PLWH, which may be an unjustified assumption. We tried to address these concerns by providing the data at both individual site level and at the country level. Additionally, to better determine the influence that country may have had on our results, we explored this issue with multiple regression analyses 1.Click here for file


Hepatitis B virus (HBV) infection is a significant global health problem, especially in China. Chronic liver disease affects health related quality of life (HRQOL). The intervention method to improve HRQOL in patients with hepatitis B has been one-dimensional with inconsistent results. The purpose of this study was to evaluate the effect of comprehensive intervention on health-related quality of life and provide guidance on improving HRQOL for patients with chronic hepatitis B.Patients with chronic hepatitis B eligible for our study were randomly selected in three model regions of Jiangsu Province in June 2010. 272 patients were invited and 254 took part, with a refusal rate of 6.62%. Comprehensive intervention included government support, technical guidance from the Chinese Centre for Disease Control and Prevention, standardised medical care, and community involvement. HRQOL before and 1 year after intervention was measured with the Short Form 36 and HBV-specific health surveys. Chi-square test, t-test and multiple linear regressive analyses were used.After comprehensive intervention, the HRQOL in patients with chronic hepatitis B showed significantly improvements in bodily pain, vitality, social functioning, and mental, as well as physical and mental component score (p < 0.05). Family and social support increased, and financial concerns decreased (p < 0.05). Marital status, duration of illness-related absence from work, education level, family financial status, and health insurance type were important factors affecting HRQOL change between the baseline and final assessment in patients with chronic hepatitis B.The comprehensive intervention was effective in improving the HRQOL of patients with chronic hepatitis B.CTR-OCH-12001882Chi Hepatitis B virus (HBV) infection is a significant global health problem. An estimated two billion people worldwide have been infected with the hepatitis B virus and more than 240 million have chronic liver infections. About 600000 people die every year due to the acute or chronic consequences of hepatitis B . The preRecently, increased attention has been given to the patients’ opinions regarding their health status in measures such as health-related quality of life (HRQOL), which is a subjective indicator for evaluation of physiological, psychological and social dimensions. HRQOL has been measured widely in clinical and health service management ,8. CertaThe aim of the present study was to evaluate the effects of comprehensive intervention through comparing the changes in patients with chronic hepatitis B patients before and 1 year after comprehensive intervention. We also analyzed the main factors that affect HRQOL. These results would provide guidance on improving HRQOL and comprehensive management of chronic hepatitis B patient.This study was conducted in major model regions for infectious disease prevention and control in Jiangsu Province, China from June 2010 to May 2011. The Jiangsu Provincial Centre for Disease Control and Prevention (CDC) initiated and assigned this programme. Patients with chronic hepatitis B eligible for our study were randomly selected in June 2010. The patients were recruited by doctors under the instruction of research assistants. Comprehensive intervention was performed for 1 year. The study had obtained study the approval of the Ethics Committee of the Jiangsu Provincial Centre for Disease Control and Prevention.Two hundred seventy-two patients were invited and two hundred fifty-four took apart in the end, the refused rate 6.62%. Two hundred fifty-four patients with hepatitis B were involved before intervention, and two hundred twenty-eight patients remained 1 year after intervention began, while twenty-six patients dropped out during intervention with at a rate of 11.4%. The primary reasons for leaving the programme included relocation and patient drop-out during intervention. The study objectives and design were explained to all patients. Afterwards they signed the informed consent.Criteria for the inclusion of participants were: According to the 2010 Manual of Prevention and Management of Viral Hepatitis in China , we inclKendall suggested that the sample size of Health-related quality of life was 10 times of the variable number. Our sample size was calculated by it. The variable number is about twenty, so the sample size is about two hundred.Two surveys were conducted in June 2010 (pre-intervention) and in May 2011 (post-intervention) by the trained investigators using the questionnaires. Flow diagram of participants’ progress in the trial is showed in Figure Comprehensive intervention was used in our study, and pre- and post-intervention surveys were performed Figure . AccordiHRQOL was measured at months 0 and 12 using two questionnaires: the Medical Outcomes Study 36-item Short-Form Survey (SF-36) Chinese Mainland version 1  and a HBSF-36 consisted of eight dimensions: physical functioning (PF), physical role functioning (RP), bodily pain (BP), general health (GH), vitality (VT), social functioning (SF), emotional role functioning (RE), and mental health (MH). Each scale contained 2–10 items, totalling 36 items, which could be reduced to two summary scores: a physical component score (PCS) and a mental component score (MCS). The PCS included the PF, RP, BP and GH scales, and the MCS included the VT, SF, RE and MH scales. For each question, the raw score was transformed into a scale from 0  to 100 . Each scale and total score were calculated in accordance with the corresponding formula .In addition, we designed a HBV-specific health survey to assess HRQOL according to the characteristics of patients with hepatitis B and other related studies. The survey consisted of six scales, including concerns for health and responsibility, family and social support, a psychological tendency toward hostility, concerns over economic status, doctor support, and the sense of being discriminated against. The choices for each item ranged from “all the time” to “none of the time”. For the first four scales, 1, 2, 3, 4, and 5 indicated all of the time, most of the time, some of the time, a little of the time, and none of the time, respectively. For the latter two scales, 1, 2, 3, 4, and 5 indicated none of the time, a little of the time, some of the time, most of the time, and all of the time, respectively. The score from each scale was transformed into a 0–100 score, and higher scores indicated better HRQOL.2 = 1142.6, p < 0.001. Factor cumulative contribution of variance was 72.29%. Furthermore, intercommunity of all indexes was >0.5, which indicated good structural validity of the questionnaire. For the surface validity and content validity, relevant experts were invited to discuss the designed questionnaire. They modified the items of inappropriate expression for ensuring its surface and content validity.The patients completed the questionnaires in outpatient clinics by face-to-face interviewer. Before the investigation, a pilot study was conducted in some patients and the questionnaire was modified according to the results of the pilot study. The reliability and validity of SF-36 are well documented in a range of language versions, including Chinese. Cronbach’s α coefficient of internal consistency for each scale was 0.70–0.90. They all reached the standard of 0.70, which demonstrated the good reliability of the questionnaire. Structural validity of the questionnaire was reflected by factor analysis of principal component analysis and varimax orthogonal rotation, and KMO index was 0.855. Bartlett statistic was χhttp://www.epidata.dk/). Epidata software was used to check for consistency between the two sets of data entries for quality assurance. Any discrepancies between two people were resolved such that the data entered were a true reflection of that recorded. The quality of data was ensured by setting up logic constraining conditions and valid value ranges of relevant variables. Categorical variables were analysed using χ2 test, the measurement data were analysed using t test, and a paired t test was used to compare the related scales for HRQOL in patients with chronic hepatitis B at baseline and after the final intervention. Multiple linear regression analyses were used to analyse the factors that affected HRQOL. All analyses were performed in SPSS17.0 , with 0.05 set as the required level of significance.The survey data were double-entered by two different people with Epidata 3.1 software (The socio-demographic characteristics of the patients were shown in Table t test (Table Using the differences in the scores before and after intervention (score after intervention subtracted from the score before) as an index, we compared the changes in HRQOL for each scale in patients with chronic hepatitis B by the paired st Table . After 1The scores of HBV-specific health survey were showed in Table Multiple linear regression analysis was performed to identify the effect of age, sex, marital status, education level, family economic status, type of medical insurance, chronic disease, years of infection, free treatment status, duration of illness-related absence from work, educational material and activities . This may be that the family and social support of widowed/divorced and unmarried patients were less than the married patients and comprehensive intervention could improve the support. For the patients who could not work for illness-related reasons over a longer duration, they had lower changes in the scores for the PCS and MCS; concerns over health and responsibility; and psychological trends toward hostility. When the duration of the illness-related absence from work was ≤3 days, the intervention-mediated positive changes in concerns over economic status, doctor support, and the sense of being discriminated against were larger compared with patients who were absent from work for ≥11 days . A duration of 4–10 days resulted in minimal changes. The patients who believed that educational material was helpful had larger changes in their family, social and doctor support. Patients with higher education levels had greater changes in the scores for the PCS. Higher family economic status resulted in a smaller change for concerns over health and responsibility. Patients with urban employee/resident basic medical insurance had the largest changes in psychological trends toward hostility, which was followed by those with new rural cooperative medical care. Those who pay their own expenses had the smallest changes. Patients without chronic diseases had larger changes in psychological trends toward hostility than those with chronic diseases. To the best of our knowledge, there was little evidence in analyzing the factors influencing the intervention on the change of HRQOL. Based on our analysis, the comprehensive intervention used in this study could reduce psychological trends toward hostility for patients with chronic hepatitis B, as well as improve their family, social and doctor support. In addition, we found that for patients who could not work because of illness, the intervention was more effective for those who were out of work for a shorter duration. Therefore, intervention in chronic hepatitis B patients as soon as possible is recommended and the support for the widowed/divorced and unmarried patients should pay more. Ng et al. showed that information and support they receive at the early stage of the disease determine their adherence to follow up and treatment , so it wMiri et al. showed that the primary vertical route—mothers—has shifted to horizontal routes of HBV transmission . Only thSeveral limitations of the current study should be highlighted. Firstly, the focus of this study was to evaluate the impact of comprehensive intervention on HRQOL in patients with chronic hepatitis B patients in major model regions. We did not evaluate a single intervention method, such as the impact of standardised medical care or community health education. Clearly, this feature of the study represents a possible limitation to future investigations. Secondly, the study did not select other non-model regions as a randomised control group. Thirdly, we did not compare clinical parameters with patients with or without improvement of life quality. The comparations of clinical parameters between before and after intervention were done, there were no significant changes. The reason was that the subjects we studied were chronic hepatitis B, quality of life could change in short time after intervention, but the changes of clinical parameters need a long time. In the future, we will analyze the change and effect of clinical parameters.Our study suggest that a comprehensive intervention combining government support, technical guidance from the CDC, standardised medical care and community involvement could be effective for improving the HRQOL of patients with chronic hepatitis B. The results showed that physical pain, VT, SF, MH, PCS and MCS were significantly improved after comprehensive intervention; levels of family and social support were increased; and concerns over economic status were decreased. The impact factors that affected HRQOL for chronic hepatitis B patients included marital status, duration of illness-related absence from work, education level, family economic status, and type of medical insurance. These would provide guidance on improving HRQOL of chronic hepatitis B patient. Further study may better demonstrate potential effect of the comprehensive intervention and impact factors.The authors declare that they have no competing interests.JQC conducted the data analysis, drafted the manuscript and contributed to subsequent revisions. PL conceived the idea for the study, participated in study design, contributed to the data analysis, the drafting and revising of the manuscript. LS, HZ, LGZ, LT, HJ contributed to implementing the study, analysing the data and editing of the final manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6963/13/386/prepub


Microscopic colitis (MC) induces gastrointestinal symptoms, which are partly overlapping with irritable bowel syndrome (IBS), predominately in middle-aged and elderly women. The etiology is unknown, but association with smoking has been found. The aim of this study was to examine whether the increased risk for smokers to develop MC is a true association, or rather the result of confounding factors. Therefore, patients suffering from MC and population-based controls from the same geographic area were studied regarding smoking- and alcohol habits, and other simultaneous, lifestyle factors, concerning the clinical expression of the disease.Women at the age of 73 years or younger, who had been treated for biopsy-verified MC at any of the Departments of Gastroenterology in Skåne, between 2002 and 2010, were invited to the study (240 patients). Women (737) from the population-based prospective cohort study, Malmö Diet and Cancer Study (MDCS), served as controls. A self-administered questionnaire about lifestyle factors, gastrointestinal symptoms, medical conditions and medication at the time for the study was sent by post.Altogether, 131 women with MC could be included after age-matching with controls (median age 56 years) and exclusion of secondary MC. Patients were divided into persistent MC (MC1) and transient MC (MC2). Past smoking was associated with increased risk to develop MC2 , whereas current smoking was associated with increased risk to develop MC1 . Concomitant symptoms of IBS were associated with smoking . Alcohol drinking had no association with MC or IBS.The results suggest that past smoking is associated with transient MC, whereas current smoking is associated with persistent MC. Smoking is associated with MC patients with concomitant IBS-like symptoms. Microscopic colitis (MC) is an inflammatory disorder of the colonic mucosa, which causes gastrointestinal symptoms, but has a normal or near-normal endoscopic appearance . CollagePrevious studies have shown a correlation between past and current smoking and MC, in analogy with other subgroups of inflammatory bowel disease (IBD) -10. We hThe aim of this study was to examine whether the increased risk for smokers to develop MC is a true association, or rather the result of confounding factors. Thus, smoking- and alcohol habits, and other simultaneous, lifestyle factors, were compared between patients suffering from MC and population-based controls from the same geographic area, concerning the clinical expression of the disease.The study protocol for patients was approved by the Ethics Committee of Lund University, Dnr 2009/565 and 2011/209, and all participants gave their written, informed consent to take part in the study. The study protocol for controls was approved by the Ethics Committee of Lund University, Dnr 51–90.Women who had been treated for MC at any outpatient clinic of the Departments of Gastroenterology in the district of Skåne, between 2002 and 2010, were identified by search for the ICD-10 classification of the two forms CC and LC (K52.8) in outpatient records, as well as in the local register at the Department of Pathology, Skåne University Hospital, Malmö. About one-third of the total numbers of patients identified were excluded due to age over 73 years, as they had many other concomitant diseases and drug therapies. Of the patients recognized, only the 240 patients  who had the diagnoses verified by colonic biopsy, and were under 73 years of age, were invited to participate in the present study. Altogether, 159  of the 240 patients invited accepted and were recruited to the study, but one patient was excluded due to another IBD diagnosis a few weeks after the inclusion, leaving 158 patients (66). Of these, 133 (55) also agreed to provide blood samples. These patients represent the majority of female cases of diagnosed MC in the southernmost districts of Sweden under the age of 73 years.Both MC and IBS are more frequent in women than in men, and the quality of life and the perception of symptoms differ between the genders ,14. For The MDCS, a population-based, prospective cohort study, invited all women in Malmö born between 1923 and 1950. Recruitment was carried out between 1991 and 1996, and 41 of eligible subjects participated. In all, 17,035 women completed the baseline examination . This MDBetween March and June 2011, invitations, including information about the study and the same questionnaire as sent to controls about marital status, education, employment, smoking habits, wine consumption, physical activity, medical conditions, and medication was dispatched by post to all 240 women identified as having MC. In addition, also questionnaires about gastrointestinal symptoms, psychological well-being and Rome III criteria were sent by post to the women with MC. The data collection concerned the status for the patients at the time of follow-up and inclusion in the study, and not the status at the time of diagnosis. They were invited to visit the outpatient clinics of the Departments of Gastroenterology, Skåne University Hospital, Malmö or at the Central Hospital in Kristianstad, to provide blood samples. A reminding letter was sent a month after the invitation letter to those who had not answered. Questionnaires were completed 1–3 weeks before the blood samples were collected. Medical records were scrutinized, and age, gastrointestinal symptoms, examinations, and treatments were recorded. Their diagnosis, either CC or LC, was registered. Patients were divided into two groups based on their clinical presentation of their MC. One group included patients with at least two episodes of watery diarrhea; and/or their dependence on long-term treatment of corticosteroids to maintain remission; and/or two pathological intestinal mucosa biopsies . These criteria are in line with those suggested for diagnosing IBD . The othThe patients completed a shortened version of the Rome III questionnaire, including only IBS symptoms . This quabdominal pain, diarrhea, constipation, bloating and flatulence, vomiting and nausea, perception of psychological well-being, and the intestinal symptoms’ influence on daily life are graded on a scale from 0 to100 mm, with 100 mm representing the fewest symptoms/health. The two questions urgency and feeling of incomplete evacuation of bowel passage are answered by “yes/no”.The VAS-IBS is a short, psychometrical test developed to measure the treatment response and well-being during the previous two weeks in patients suffering from IBS . The que© . The patients were significantly older, with a wider age range than the controls. Therefore, the 12 patients younger and the two patients older than the controls were excluded, as were patients with celiac disease and gastroenteritis (13 patients), leaving 131 of the original 158 patients for the statistical calculations comparing patients with controls. Thus, both controls and patients were within the same age range 45–73 years. First, the distribution of continuous variables , days of wine drinking/month, and minutes of physical activity/week) was tested using an one-sample Kolmogorov-Smirnov test. All distributions differed significantly (p < 0.05) from a normal distribution, and therefore the factors studied were categorized and the values were given as median (interquartile range). There was no difference between CC and LC in any patient characteristics (data not shown), in accordance with a previous systematic review [U -test. Correlations were performed by the Spearman rank correlation test. Fisher’s exact test was used for categorical variables. The Kruskal-Wallis test was used to calculate differences in VAS-IBS between subgroups of smoking- and alcohol habits, and was the only calculation including all 158 patients. A p-value < 0.05 was considered statistically significant.The data were analyzed using the statistical software package SPSS for Windowsc review . For thiAge was divided into 5-year intervals. The cohort was divided into quartiles of the number of days of drinking wine/month and the average number of exercising minutes per week during the year. Smoking was divided into three categories: subjects who had never smoked, subjects who had stopped smoking, and current smokers, including both regular and occasional smokers at the time of inclusion in the study. Subjects who denied intake of beer, wine, and liquor during the previous month before completion of the questionnaire were defined as having no alcohol intake. All subjects were then divided into four groups: subjects not using tobacco and alcohol, subjects only drinking alcohol, subjects only smoking, and subjects both smoking and drinking alcohol. Employment was divided into three categories: employed, retired or others, where others included housewives, students and unemployed. Education was divided into having a university education or not. There were missing values in days of drinking wine/month, smoking- and alcohol habits, physical activity, and level of education, which were labeled each as a specific category. The first category was used as reference. Factors intended for study (independent variables), namely, smoking habits and smoking- and alcohol habits, were initially examined using an unconditional logistic regression to calculate odds ratios with 95 confidence intervals (OR with 95 CI). Analyses of smoking habits were then performed adjusted for age at baseline, physical activity, days of drinking wine/month, level of education, and type of employment, as these characteristics had > 5 percentage difference between controls and patients, except in the case of MC2, where level of education did not differ between patients and controls. Smoking- and alcohol habits were adjusted for age, physical activity, level of education, and employment, except for MC2, where no adjustment for level of education was performed. Calculations were first performed on the whole patient group compared to controls, and then separately for patients with primary, persistent MC (MC1), transient MC (MC2), patients with IBS-like symptoms in addition to MC, and patients without IBS vs. controls (dependent variables).In total, 131 women (median age 63 (59–67) years) with MC were included in the statistical calculations, CC was diagnosed in 82 patients (62.6) and LC in 49 patients (37.4) (Table bloating and flatulence (p = 0.011) and the gastrointestinal symptoms’ influence on daily life (p = 0.012).Of the patients, 91.7 were born in Sweden, compared with 90.2 of the controls. More patients than controls had a university degree (p = 0.001). As the patients were older than the controls, more patients were retired (p < 0.001) . The values for the controls are shown in Table There were only few patients and controls drinking beer and stronger alcoholic beverages, albeit with many missing values. Therefore, only the parameter of “number of days of drinking wine/month” was used in the adjustments. The majority of patients drank 1–2 glasses a day when drinking. Those who drank beer and stronger alcoholic beverages were those who drank wine most days in the month (data not shown).There was no statistically significant difference between MC1- and MC2 patients regarding smoking habits (p = 0.128), days of drinking wine/month (p = 0.711) or smoking- and alcohol habits (p = 0.160) Table .There were more smokers in the IBS group than in the non-IBS group p = 0.021). The number of days drinking wine/month did not differ between groups p = 0.508), but the smoking- and alcohol habits differed, with more patients who neither smoked nor drank alcohol in the non-IBS group (p = 0.019)   and overChronic alcohol exposure is known to have a number of deleterious effects on the intestinal mucosa. Alcohol may trigger relapses and pronounced symptoms in patients with already developed IBD . In animRed wine contains phenolic compounds, which have been shown to affect the composition of human gut microbiota . There iIrritable bowel syndrome mostly affects young people, and colonoscopy is avoided in this entity. However, when older women consult a physician for the same symptoms, a colonoscopy is requested in order not to overlook a malignancy. When scrutinizing the medical records, we found that several of the patients had suffered from IBS for decades, but a colonoscopy was not ordered until the patient had reached higher age, due to the risk of malignancy. This may make the peak age for the MC incidence falsely high, and means that, on the basis of the same gastrointestinal symptoms, the younger patients are given the diagnosis IBS, while the elder patients are diagnosed as having MC. The MC patients are considered as IBS patients if not examined by a colonoscopy, which obscures the true incidence and prevalence figures ,38.Although MC is considered to be a subgroup of IBD, conventional anti-inflammatory drugs, with the exception of budesonide, are not as successful in the treatment of MC as in the treatment of classic IBD . The resOne limitation of this study is that the women are elderly, with many concomitant diseases and drug treatments, thus generating several confounding factors . The IBSIn this study, we found that in MC patients under the age of 73 years, smoking is associated with MC, independently of alcohol consumption and other lifestyle factors. Future research has to examine how smoking increases the risk to develop MC, and also whether smoking increases in particular the risk to develop IBS and IBS-like symptoms, in comparison with MC.CC: Collagenous colitis; CI: Confidence interval; FGID: Functional gastrointestinal disorders; IBD: Inflammatory bowel disease; IBS: Irritable bowel syndrome; LC: Lymphocytic colitis; MC: Microscopic colitis; OR: Odds ratio.The authors declare that they have no competing interests.BR made substantial contributions to the conception and design, acquisition of data and was involved in drafting the manuscript. RJG was involved in drafting the manuscript and made substantial contributions to the acquisition of data. BJ was involved in revising the manuscript critically for important intellectual content. JM made substantial contributions to the design of the study, participated in the interpretation of the statistical analysis and was involved in revising the manuscript critically for important intellectual content. BO conceived of the study, and participated in its design and coordination and helped to draft the manuscript. All authors have read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6874/14/16/prepub


We discuss how BHPs can be specifically designed to create bifunctional proteins, to produce and to characterize proteins that are otherwise difficult to express, to determine the epitope of specific antibodies, to generate antibodies against nonimmunogenic epitopes, and to better understand the structure/function relationship of proteins.Designing hybrid proteins is a major aspect of protein engineering and covers a very wide range of applications from basic research to medical applications. This review focuses on the use of class A  Engineering proteins with improved properties or new functions is an important goal in biotechnology. In this context, numerous bi- or multifunctional proteins have been created for applications in a broad range of fields including biochemical analysis, protein purification, immunodetection, protein therapies, vaccine development, functional genomics, analysis of protein trafficking and analysis of protein interaction network . The mosβ-lactamase (263 aa) into four different positions of phosphoglycerate kinase (415 aa). Betton et al. . Th. ThThb/CCHBD/Thb . RemarkaCHBD/Thb , and ~18β-lactamase activity as a reporter, (ii) to screen therapeutic molecules, that is, molecules neutralizing the biological properties of the polypeptide inserted, as further exemplified in the section of this review describing the use of BlaP for vaccine development, (iii) to screen molecules stabilizing and preventing protein aggregation (see section “BHPs as model proteins to investigate structure/function relationships”), and (iv) to facilitate the determination of the three-dimensional structure of polypeptides that are otherwise unnameable to X-ray crystallography due to their insolubility, since BHPs allow an increase in the solubility of the insert . A lanalysis  confirmedomain 4 .E. coli, conserves the β-lactamase activity and binds to mab 8015 with a high affinity (KD ~26.2 nM)  . To iden26.2 nM)  11]. Th. ThE. co26.2 nM) . The bin26.2 nM)  8]..E. coli,HA mab) and (ii) the characterisation of complex epitopes . Moreover, BlaP has enough conformational flexibility to allow inserted antigen fragments of various lengths to fold and interact with the antibody. BHPs allow therefore the identification of non-linear epitopes  that are directly linked to the nucleotide sequence of the antigen  . Thiin vitro neutralization of the β-lactamase activity was observed by mixing purified TEM-1 with sera. In contrast, specific anti-STa IgG and IgG1 antibodies were only detected at non-significant levels, and no IgG2 were detected in the sera of the immunized cattle. These results suggest that the response of the bovine immune system is different from that observed in mice [Following these encouraging results, Zervosen et al. immunized cattle with a TEM-1 hybrid protein containing the STa in position 197 in the presence of 3 different adjuvants   . The purh chitin . Taken all together, the results of these studies indicate that both BlaP and TEM-1 are appropriate scaffolds for producing and presenting antigens and inducing the production of antibodies neutralizing biological properties of the inserted fragment .Ten progressive neurodegenerative disorders, referred to as polyglutamine (polyQ) diseases, and, including Huntington's disease and several spinocerebellar ataxias, are associated with ten unrelated proteins containing an expanded polyglutamine (polyQ) tract . PolyQ tracts are encoded by a repetition of an unstable CAG trinucleotide repeat in the corresponding genes –77. The So far, there is no preventive or curative treatment for these pathologies and existing therapies only treat the symptoms . In order to design curative and/or preventive treatments, it is crucial to better understand how polyQ tracts trigger protein aggregation and by which mechanism some of the aggregates formed are cytotoxic. β-lactamase BlaP and polyQ tracts inserted at position 197 [Although the presence of the expanded polyQ tract is the critical trigger factor of the aggregation phenomenon, a growing number of studies suggest that the non-polyQ regions can, however, modulate both the kinetics and the aggregation pathway of polyQ proteins , 87–90. tion 197 . Signifition 197 . BlaP is−1; β-lactamase moiety on the aggregating properties of the hybrid proteins. Accordingly, the aggregating properties of BlaP and of the different hybrid proteins were investigated under both native and denaturing conditions. The aggregation behaviour of BlaP-polyQ hybrid proteins recapitulates that of disease-associated polyQ proteins. Only hybrid proteins with 55Q and 79Q readily form amyloid fibrils; therefore, analogous to the proteins associated with diseases, there is a polyglutamine threshold required for the formation of amyloid fibrils. Moreover, above this threshold, the longer the polyQ, the faster the aggregation rate , can be readily designed and used for multiple purposes, notably to produce difficult-to-express peptides/proteins/protein fragments, to map epitopes, to display antigens, and to study protein structure/function relationships. The wide ranging impact of the BHP approach essentially originates from (i) the efficient enzymatic activity that can be easily measured and that can serve as a reporter or factor for selection and (ii) the facility with which they can be recombinantly produced and purified. In addition to the numerous applications summarized in this review, many other applications can be envisaged: BHPs could be used as biosensors and in affinity chromatography, drug screening, and drug targeting. They are also of special interest to better understand more fundamental aspects of protein evolution and structure/function relationships.Class A