Asparagus acutifolius L. is a dioecious and native plant species, widely distributed in the Mediterranean Basin. It is known for its fine flavour and could represent an important resource for cultivation programs in desert areas. Few molecular studies have been performed on this species. In the present paper, the ISSR technique was employed to study genetic diversity in Italian A. acutifolius.ST (0.4561) and Theta B (0.4776) values indicate a wide genetic variation among the samples examined. The distance UPGMA tree grouped together the genotypes strictly according to their geographical origin, showing that each sample is genetically structured and can be considered a distinct population. AMOVA analysis further confirmed genetic structuring of the populations. Population-specific fragments were also detected.Twenty-three primers produced a total of 228 polymorphic fragments used to evaluate genetic variation. FA. acutifolius according to geographical origin, and confirm the importance of genetic studies for designing germplasm conservation strategies.The results suggest that ISSR markers are useful in distinguishing the populations of  The availability of a variety of DNA markers, such as restriction fragment length polymorphism (RFLP), amplified fragment length polymorphism (AFLP), random amplified polymorphic DNA (RAPD), simple sequence repeat (SSR) and intersimple sequence repeat (ISSR) has enabled researchers to investigate genetic diversity among various plant species across natural populations -5. Amongin situ and ex situ of genetic diversity in natural populations is imperative to guarantee sustainable development [Local populations of traditional cultivars provide a valuable resource for plant breeding as well as for the preservation of genetic diversity . The expelopment .Asparagus acutifolius L. (Liliaceae) is a native, perennial plant species widely distributed throughout the Mediterranean areas, whose flowers are classified as dioecious and are mainly bee-pollinated; it generally does not reproduce by self-pollination. It grows in bushy and semi-dry places, sunny or semi-shade, mainly on limestone.A. officinalis and does not require rich soils for cultivation; for these reasons, it could be an economically important resource for the recovery of arid rural areas where controlled introduced programs could be achieved.This species is known for its strong taste compared to the cultivated A. officinalis, for which many molecular markers have been characterized (RAPD, RFLP, AFLP) [A. acutifolius are drawn from RAPD analyses [Viola pubescens [Oryza [To date, there is little information available on the genetic variability of this species. At present, the most widely studied species is P, AFLP) . The fewanalyses  and the analyses . The ISSanalyses . They haanalyses , Viola pubescens , potato ubescens , and Orys [Oryza .A. acutifolius collecting samples in eight different scattered rural areas: six continental and one each from the Italian islands of Sardinia and Sicily.In this study we used ISSR markers to analyse the genetic diversity of Italian A. acutifolius was collected and their characteristics.Figure A. acutifolius is summarized in Table Among the 42 primers tested, 23 proved useful to characterize the samples (Table A high level of genetic variation was observed using ISSR markers, with 100% polymorphic loci at the species level. The highest number of polymorphic loci (51.75%) was exhibited in the Sassari and the lowest (35.09%) in the Recco samples.Genetic structuring was evident due to the detection of specific bands in each sample examined. Spoleto and Caserta samples showed one and three fixed specific fragments, respectively, found to be statistically significant (P < 0.0001). For the other samples, 27 ISSR specific polymorphic fragments were detected, with a varying degree of statistical significance ranging from P < 0.0400 to P < 0.0001.Genetic distances  were exaSamples collected at different geographic site grouped together, as shown in the UPGMA tree Fig. , and theThe values of gene diversity are summarized in Table T) was 0.2618 ± 0.0240 and the average variation within samples (average HS) was 0.1424 ± 0.0084. The mean diversity among the samples (DST) was 0.1194. The fixation index FST = (HT-HS)/HT was 0.4561, indicating a reduction of genetic diversity of about 45%. The Theta-B value obtained by Hickory analysis is an estimate of FST under a random-effects model of population sampling. Its mean value is 0.4766 ± 0.0173; the HT and HS values are, respectively, 0.2859 ± 0.0115 and 0.1619 ± 0.0026 showing that there is a general agreement between the results obtained using the two different approaches.As summarized in Table A. acutifolius in an Italian population. ISSRs also revealed diversity within each sub-population. The results obtained are in accordance with the principle that the number of individuals used to estimate average heterozygosity can be very small if a large number of loci is studied [ISSR markers can be used in population genetic studies of plant species as they effectively detect very low levels of genetic variation . They al studied .The gene diversity values Table  ranged fST and the Theta-B value (0.4766) demonstrated a very great genetic differentiation among samples, possibly caused by random genetic drift. Further statistical support to the genetic structuring of the samples examined comes from the AMOVA analysis. Despite the continuous distribution of A. acutifolius, the eight samples represent genetically differentiated populations.The fixation index is 0.4561, which indicates a substantial reduction of genetic diversity (about 45%), probably due to the high genetic isolation of samples analysed. The FA. acutifolius populations.In each population it was possible to identify ISSR specific fragments. As shown in Table A. acutifolius throughout the Italian peninsula, there is poor gene flow through the isolates. The high genetic differentiation of the A. acutifolius populations examined might be attributed to the kind of pollinators (mainly bees) that can act at short distances, preventing the gene flow, and to the effects of anthropogenic habitat fragmentation.The high degree of genetic differentiation is confirmed by the UPGMA tree topology, in which all accessions from the same population grouped together Fig. . The popA. acutifolius populations [The results obtained using ISSR markers are in agreement with the RAPD analysis that also identified population-specific fragments in different Italian ulations .A. acutifolius has well-differentiated populations, despite their morphological low variability. These results show that to maintain genetic diversity within A. acutifolius it is necessary to conserve many populations.Information about the spatial organization of genetic variability is essential for the conservation of genetic resources . Our resA. acutifolius collected in the eight different locations in Italy  and 1X Taq DNA polymerase buffer, in a total volume of 25 μL. The amplification programme was 1.5 min at 94°C; 35 × 40 s at 94°C, 45 s at the primer annealing optimal temperature  and negative and positive controls were loaded and run at constant voltage (150 V) for 2 hours. After running, the gels were UV visualised and recorded using a Kodak Digital Science dS1D DC40/DC120 Camera. To verify the repeatability of the results, each DNA extraction, PCR amplification, and gel running was repeated twice.Unequivocally scorable and consistently reproducible amplified DNA fragments were transformed into binary character matrix (1 = presence, 0 = absence).T), heterozygosity within population (HS), diversity among populations (DST), fixation index (FST), and genetic distance [Genetic variation within and among sub-populations was analysed on the basis of the banding profile using various parameters such as percentage polymorphism (P), total heterozygosity (Hdistance ,22-24, udistance . Since Idistance  based onAMOVA analysis, implemented in Arlequin , was conThe Mantel test of genetic and geographic distances was carried out to evaluate the correlation between the two data matrices.The UPGMA tree was generated using the PAUP*4.0 software , and BooMS carried out part of the sample collection, designed ISSR primers and carried out ISSR work; GG did part of DNA extraction; SM carried out part of the sample collection and DNA extraction; LG participated in the manuscript preparation and revision; SA conceived the study, carried out data analysis, co-ordination and interpretation of the results.


In a previous study, when adult subjects were exposed to a level of 400 lux light for more than 30 min or a level of 300 lux light for more than 2 hours, salivary melatonin concentration during the night dropped lower than when the subjects were exposed to dim illumination. It was suggested that such light exposure in adolescents or children during the first half of subjective night in normal life might decrease the melatonin level and prevent the falling into sleep. However, there has been no actual study on the effects of light exposure in adolescents.Effects of exposure to the bright light (2000 lux) from fluorescent light bulbs during a period of three hours from 19:30 to 22:30 in one evening were examined on evening salivary melatonin concentrations from 19:45 to 23:40. The control group was exposed to dim light (60 lux) during these three hours. Both the dim light control group [DLCG] and the bright light experimental group [BLEG] consisted of two female and three male adolescent participants aged 14–15 y.The salivary melatonin level increased rapidly from 3.00 pg/ml at 21:45 to 9.18 pg/ml at 23:40 in DLCG, whereas it remained at less than 1.3 pg/ml for the three hours in BLEG. Melatonin concentration by BLEG at 22:30 of the experimental day was lower than that at the same time on the day before the experimental day, whereas it was significantly higher in the experimental day than on the day before the experimental day in DLCG.Bright lights of 2000 lux and even moderate lights of 200–300 lux from fluorescent light bulbs can inhibit nocturnal melatonin concentration in adolescents. Ancient Japanese lighting from a traditional Japanese hearth, oil lamp or candle (20–30 lux) could be healthier for children and adolescents because rapid and clear increase in melatonin concentration in blood seems to occur at night under such dim light, thus facilitating a smooth falling into night sleep. Night sleep duration of Japanese children aged 10–18 y has become shorter by one hour during the last 30 years in Japan . Student"Convenience stores" are open for 24 hours and provide several kinds of food and other goods for general civilian life. Convenience stores are now common all over Japan even in suburban areas. Illumination inside the convenience stores is very bright (2000 lux or more at the level of the eyes). Bright lighting in retail stores seems to be a merchandising technique which has been in use worldwide for at least 60 years. Unconscious use of bright light in the evening or at night inside the convenience store may promote a circadian phase delay in students exposed to the bright light during the first half of subjective night. This hypothesis is based on a "light-pulse" experiment in the laboratory  as folloMelatonin, which is synthesized in the pineal organ and secreted to the blood, is well known as a key substance which may be effective in promoting the falling into night sleep by humans . Blood mCurrently, more than 80% of junior high school students of the third grade aged 14–15 y in Kochi go to private school in the evening. If they take a short stop at the convenience store to get some fast food and enjoy talking with their colleagues in front of the store before or after going to the private school in the evening, they suffer the double exposure to bright lights at the school and at the convenience store. Such bright lights are from fluorescent light bulbs and include blue or blue-green lights with 470–500 nm wave lengths which were reported to be powerful to suppress melatonin concentration . Based oIn this study, two light conditions were investigated. One was bright and high color-temperature light of more than 2000 lux, which is used in the evening and at night inside the convenience stores, at preliminary and private school for entrance examination, and at rental video shops in Japan. The other condition was a dark and low color-temperature light with less than 60 lux which is usual in the evening for traditional Japanese settings (a fireplace, candle, or a naked light bulb).Experimental participants were ten Japanese junior high school adolescent students  aged 14–15 y who were attending Motoyama junior high school located in the mountain area of Reihoku district (33.5°N) in Kochi Prefecture. They had enjoyed New Year holidays for 7 days before the experiment. They were instructed to keep usual diurnal rhythm (for example bed time and wake-up time) during the holidays. Before the experiment, participants were divided into the two groups of "bright light experimental group (BLEG)" and "dim light control group (DLCG)". Participants in BLEG were selected to show similar circadian typology to those in DLCG based on the scores in the morningness-eveningness (M-E) questionnaire of Torsvall and Åkerstedt   under fluorescent light bulbs based on our unpublished questionnaire study on 950 families having small children aged 0–6 yrs in Kochi. More than 85% of the 950 families enjoyed evening life under fluorescent light bulbs. We measured the illumination at the level of 1 m above floor just under a usual type of round-shaped fluorescent light bulb in a typical one-room apartment for students and it was 340 lux.th January 2003, all the ten participants got together in front of Motoyama junior high school at 8:00 in the morning. A wagon car took them to the experimental place which was a Japanese style hotel located at a mountain area, Yusuhara town in Kochi Prefecture, 126 km west from Motoyama town. During the driving, illumination inside the car was 350–500 lux. The car arrived at the hotel around noon. It was snowing through the day. Behavior of all the participants was controlled during the stay in the hotel till the next morning of the experimental day. All the participants played outside exposed to the sun light with 6000–7500 lux at the eye level during 12:30–13:30 and 14:00–14:50. They were allowed to have a rest in a living room in which the floor was filled with 12 tatami mats and the illumination at the eye level was 250 lux from fluorescent light bulbs during the rest of the time till 16:30. Participants took bath one by one between 16:30–18:00 and had supper all together between 18:15 and 19:20 in the living room. At 19:25, the participants of BLEG moved to a Japanese style room with 8 tatami mats where they were exposed to the light with 2000 lux at the eye level from fluorescent light bulbs, whereas DLCG group members moved to another Japanese style room with 8 tatami mats where they were exposed to the light of 60 lux and relatively low color-temperature from a electronic light bulb. All the participants included in both groups were home-working or making a small wooden folk craft object that is typical in the Yusuhara district, under each light condition till 22:30. Room temperature was controlled at 15 ± 2°C with an oil heater in both groups. Then they came back to the former living room (12 tatami mats) and stayed there under the light of 250 lux till 23:40. Then female and male participants moved to separate rooms and went to bed just before 24:00. Salivary samples were collected in collection tubes at 21:45, 22:30, and 23:40, and these salivary samplings were preserved in a refrigerator at less than -20°C. Melatonin concentration in the samples was analyzed by a professional analyzing company (MSL Co. Ltd.) which was a specialist for several chemical and microbiological analyses. All the participants from both groups were called out to get up at 7:00 in the next morning. All the participants got up between 7:00–7:15 responding to the calling out. After taking breakfast, they left the experimental place at 9:00 back for Motoyama junior high school. Throughout the study, light exposure was measured on the eye level with a digital illumination meter.On the experimental day of the 5Detailed explanation of the objectives and methods of the experiment was provided before the experimental performance to the participants and their parents. The research project received full and complete agreement from all of them.The results are shown in Fig. In Japan, bright and high color-temperature light of more than 2000 lux is available in the evening or night inside convenience stores which are open for 24 hours and private schools for the preparation to go through the entrance examination to upper schools. Also in usual life, such exposures to bright lights in the evening private school and convenience store can suppress the night increase in blood melatonin level as a direct effect and possibly delay the circadian system that drives the melatonin secretion rhythm and sleep-wake cycle.The results of this study suggest that ancient Japanese lighting in the evening and at night, which could be supplied by a traditional Japanese hearth fire or a oil lamp or candle (20–30 lux), might be healthy for adolescents and children, because the ancient lights could allow rapid and clear increase in melatonin level leading to a smooth falling into night sleep .Bright lights of 2000 lux and even moderate lights of 200–300 lux can inhibit, as a direct effect, nocturnal melatonin concentration in children. Ancient Japanese light conditions which could be supplied by a traditional Japanese hearth fire or a small oil lamp or candle might be healthy for children, because the ancient lights could allow rapid and clear increase in melatonin level in the evening, leading to a smooth falling into night sleep.None declared.


There is a possibility of clock genes having pleiotropic effects on clock period and pre-adult development time. In order to avoid such pleiotropic effects we have used wild type flies of same genotype under environments of different periodicities, which phenotypically either speeded up or slowed down the eclosion clock of D. melanogaster.In insects, circadian clocks have been implicated in affecting life history traits such as pre-adult development time and adult lifespan. Studies on the D. melanogaster, under five different light regimes, continuous light (LL), continuous darkness (DD), and light-dark (LD) cycles of 10:10 h (T20), 12:12 h (T24), and 14:14 h (T28). Although the development time was significantly different in most light regimes, except for females under T24 &T28, pre-adult survivorship remained largely unaffected. The development time was shortest under LL, followed by T20, DD, T24 and T28 regimes, in that order. Interestingly the development time showed a positive correlation with the period of eclosion rhythm, i.e., faster oscillations were associated with faster development, and slower oscillations with slower development.We assayed pre-adult development time and pre-adult survivorship of four laboratory populations of D. melanogaster in a manner that does not involve direct pleiotropic effects of clock genes on both clock period and development time.Based on these results we conclude that periodicity of imposed LD cycles, and/or of eclosion rhythm plays a key role in regulating the duration of pre-adult development in  The cDrosophila melanogaster has been quite elegantly addressed in an exhaustive study on the period (per) mutants, which display circadian rhythms with widely different periods [per mutants under continuous dim light (LL) and continuous darkness (DD) was positively correlated with the free-running period (τ) of their circadian clocks, i.e. perS mutants (τ = 19 h) developed faster than wild type flies (τ = 24 h), which in turn developed faster than perL mutants (τ = 28 h) [Bactrocera cucurbitae, which involved selection for faster and slower pre-adult development, the selection regimes yielded faster developing lines with faster circadian clocks (τ ~ 22.6 h), and slower developing lines with slower circadian clocks (τ ~ 30.9 h)[D. melanogaster unresolved. In order to investigate the role of circadian clocks in development time without confounding pleiotropic effects of clock genes one would need to assay development time of flies from similar genetic background under short and long day lengths, wherein their clocks would entrain by speeding up or slowing down oscillations.Circadian clocks have been implicated in affecting life history traits such as pre-adult development time, and adult lifespan -5. It is periods . The pre = 28 h) . The cor = 28 h) ,7. Moreonts τ = 1 h develoD. melanogaster (LL1.. 4) under five different light regimes: LL, DD, LD cycles of 10:10 h (T20), 12:12 h (T24), and 14:14 h (T28). The average periodicity of eclosion rhythm in T20, DD, T24, and T28 was, 20 h, 23.5 h, 24 h and 28 h, respectively, while eclosion was arrhythmic under LL [D. melanogaster.In the present study we assayed pre-adult development time and pre-adult survivorship of four large out-bred laboratory populations of F4,12 = 2411.97, p < 0.001) . The development time of males and females was shortest under LL, followed by T20, DD, and T24 &T28, in that order , and light regime × sex interaction (F4,12 = 6.56, p < 0.05). Multiple comparisons using 95% CI showed that females developed faster than males under all five light regimes and the difference in male-female development time was greatest under T28 regime, followed by DD, T24, LL and T20 regimes. In addition, eclosion appeared to be bimodal under T28, and the pattern of bimodality was more prominent in females than in males  = 1923.295, p < 0.001] and females [H (4, N = 2709) = 2061.568, p < 0.001]. The Kruskal-Wallis test thus confirmed the results obtained in ANOVA. Although eclosion waveforms under no two light regimes were similar, the dissimilarity was even more striking under T24 and T28. The test revealed that mean development time of males was shortest under LL, followed by T20, DD, T24, and T28, in that order. While the mean development time of females followed a similar trend, it did not differ significantly between T24 and T28.ANOVA on pre-adult development time data revealed a significant main effect of light regime (T20, T24 and T28, as reported in one of our previous studies on the same populations were 23.5 h, 20 h, 24 h and 28 h, respectively, while eclosion was arrhythmic under LL [T20, T24 and T28) showed a significant positive correlation with the mean period of eclosion rhythm under the corresponding environments , the ancestral populations of the flies used in the present study, we had reported shortest development time under LL regime, followed by LD 12:12 h, and DD [T20, DD, and T24 and T28, in that order. As opposed to LL, eclosion under DD is gated in a circadian manner, and as a result flies took longer to develop compared to that in LL. We believe that the slight discrepancy in the results of our two studies could be due to the fact that different set of flies (about 100 generations apart) with different clock periods were used in the two experiments. The periodicity of JB populations under DD was greater than 24 h, whereas those of LL populations was lesser than 24 h. Thus, consistent with our proposal, development time of JB populations was greater under DD compared to development time in LD 12:12 h regime, whereas those of LL populations was shorter in DD compared to those under LD 12:12 h.In several insect species adult eclosion is gated in a manner that it occurs only during a narrow window of time, generally around dawn when environmental humidity is the highest . In D. m neurons , and it  neurons . Develop, and DD . In the T20, DD, T24, and T28) showed a significant positive correlation with the mean period of eclosion rhythm under the corresponding light regimes; i.e. shorter period of eclosion rhythm under T20 was associated with faster pre-adult development, followed closely by DD, whereas flies took longest to develop under the light regimes wherein their eclosion periodicities were 24 h and 28 h, suggesting that development in D. melanogaster is regulated by eclosion rhythm. The peak of eclosion under three periodic light regimes closely matched phase relationships of eclosion rhythm relative to LD cycles, suggesting that phases of eclosion rhythm also play a key role in the regulation of development time [D. melanogaster is not entirely regulated by the periodicity of the environment and/or the periodicity of eclosion rhythm. These results are in agreement with the findings of previous studies, where the duration of pre-adult development was positively correlated with clock period [The mean development time under four different light regimes , at constant temperature of 25°C (± 1°C), and constant humidity of 70 ± 5%, on a 21 day discrete generation cycle (henceforth will be referred as LL1, 2, 3, 4 populations). These populations were maintained at moderate larval densities of ~ 60–80 larvae per 8 dram vial (9.0 mm height × 2.4 mm diameter) containing banana-jaggery food medium (henceforth banana food). The ancestry and maintenance of these populations has been described in detail in an earlier paper [3). From these petri plates, 60–80 eggs are collected into each of 40 vials in which larvae then develop into adults. Adults eclosing from these vials are transferred to plexiglass cages on 12th day after egg lay. On the 18th day after egg lay, adult flies are supplied with banana food supplemented with live yeast paste for two days, after which eggs are collected to initiate the next generation and the adults discarded. The breeding population typically consists of about 1500 flies.The four populations of er paper . In brieT20), 12:12 h (T24), and 14:14 h (T28). Thus a total of 200 vials were set up for the assay . These vials were introduced into five different light regimes at 20:00 h, when lights went off simultaneously in all LD regimes. Fluorescent white light of intensity ~ 100 lux was used during light phase, whereas in dark phase red light of λ >650 nm was used. Temperature and relative humidity in the five light environments monitored continuously using a Quartz Precision Thermo-Hygrograph, Isuzu Seisakusho Co, LTD, were found to be comparable. The vials were monitored for eclosion of adult flies after the pupae became dark. Eclosing adults were collected every 2 h, sexed, and counted until all the flies eclosed.From the running culture of each population (LL1..4), eggs laid on banana medium over a 2 h window were collected for the assay. Exactly 30 eggs were dispensed into 8 dram vials containing ~ 6 ml banana food and 50 such vials were set up from each population. Ten vials from each population were introduced into continuous light (LL), continuous dark (DD), light-dark (LD) cycles of 10:10 h , in which replicate populations were treated as random blocks, and light regime and sex were treated as fixed factors.In order to detect differences in the eclosion profiles of the flies under different light regime, development time data of individual flies from all four replicate populations were pooled and compared using Kruskal-Wallis test.Pre-adult survivorship was calculated as the fraction of eggs that successfully developed into adults in each vial. The mean pre-adult survivorship values of each population in each light regime were used as data in a mixed model ANOVA, with replicate populations as random blocks, and light regime as a fixed factor.DAP and AD were involved in collecting eggs, collecting and counting flies for pre-adult development time, estimating pre-adult survivorship, data entry and analyses. VKS conceived of the study and participated in its design and coordination. MKC and AJ gave valuable comments and suggestions throughout the study. All authors read and approved the manuscript.


Public health practitioners and researchers for many years have been attempting to understand more clearly the links between social conditions and the health of populations. Until recently, most public health professionals in English-speaking countries were unaware that their colleagues in Latin America had developed an entire field of inquiry and practice devoted to making these links more clearly understood. The Latin American Social Medicine (LASM) database finally bridges this previous gap. brings important information, originally known mostly within professional networks located in Latin American countries to public health professionals worldwide via the Internet. The LASM database uses Spanish, Portuguese, and English language trilingual, structured abstracts to summarize classic and contemporary works.This public health informatics case study describes the key features of a unique information resource intended to improve access to LASM literature and to augment understanding about the social determinants of health. This case study includes both quantitative and qualitative evaluation data. Currently the LASM database at The University of New Mexico This database provides helpful information for public health professionals on the social determinants of health and expands access to LASM. Public health practitioners have long recognized the connections between patients' socioeconomic conditions and their health -8. Yet tAmerican Journal of Public Health that focused on LASM [Until recently, however, most of the knowledge base in this discipline has remained largely unknown outside Latin America. Language barriers and disincentives to distribute this information more widely are two major reasons for this lack of awareness. Some readers might have first learned about Latin American social medicine (LASM) through recent critical reviews  or throu on LASM ,11.LASM traces its historic origins to European researchers such as Rudolf Virchow and the belief systems of indigenous cultures. Both the European and indigenous sources of current social medicine practices emphasized the importance of linking social conditions to health status. Contemporary social medicine in Latin America continues to emphasize these linkages between social conditions and the health of populations. Social medicine professionals participate in a wide array of settings in Latin America and represent diverse specialties. Their integration into healthcare systems has varied by era and country .Innovative approaches to disseminating work in LASM have become increasingly available due to Internet technology. The project "Enhanced Access for Latin American Social Medicine" at The University of New Mexico with funding from the U.S. National Library of Medicine seeks to make information on the connections between social conditions and health problems available to a wide audience. The project has sought to bridge the prior information gap primarily through delivering structured abstracts of social medicine publications in Spanish, English, and Portuguese via the Internet on the LASM database beginning in 2001. Other goals of this project include: publishing full text social medicine electronic journals on behalf of medical societies in Latin America; and, maintaining a repository for key classic and contemporary social medicine publications.Structured abstracts are posted in three languages in the LASM database at The University of New Mexico for both the classic and contemporary social medicine literatures. The first phase of this project involved preparing and posting the structured abstracts of 25 landmark books, 50 book chapters, and 100 journal articles from the classic social medicine literature in Spanish, Portuguese, and English.A peer selection committee identified and agreed upon the specific selections of classic books, book chapters, and journal articles to be abstracted for this project. Table The contemporary literature summarized in the LASM database has been drawn primarily from the 12 journals currently or previously published in Latin America. Table Saúde em Debate (Brazil) and SaluCo Bulletin (Cuba), are available from the host website. The host website also posts structured abstracts of important articles from these full text journals.As a pilot, the project has made two social medicine journals available in electronic full text format. Several issues of these journals, The LASM database encompasses several broad themes within LASM. Subject areas include the history, theories, methodologies, and organizational dimensions of social medicine. Other subjects pertain to institutional analysis, social/critical epidemiology, and strategic planning. Table The LASM database is a web application developed using the Cold Fusion application server. The data are stored in a Microsoft SQLServer relational database. The data sources are the original Latin American publications, which are summarized in Spanish, Portuguese, and English languages in structured abstract format. The English-language structured abstracts are quality checked by the principal investigator, who reviews the abstracts for substantive content, and then by the librarian investigator who reviews the structured abstracts for final quality assurance purposes. Each record contains fields for author, title (book, book chapter, or article), place of publication, publisher and structured abstracts in each language. Records contain volume, number, and pagination when applicable. All records contain terms the from Medical Subject Headings (MeSH) system, a controlled vocabulary developed and maintained by the National Library of Medicine. Users can search the database on controlled fields of author, title, and MeSH terms in any of the three available languages. Full text abstract searching is also available. In addition to the abstract searching facilities, the LASM database can be browsed alphabetically by title. The browsing interface offers a convenient way to become familiar with the extent and diversity of the LASM literature.From January 2002 through December 2003, a total of 17, 853 visits were made to the website hosting the LASM database. The largest numbers of visits in descending rank order originated from Brazil, Mexico, Argentina, Spain, and Colombia. A preliminary, qualitative evaluation has been favorable. Following completion of this project, we will conduct and publish a comprehensive summative evaluation. A total of 250 structured abstracts in Spanish, Portuguese, and English had been posted to the LASM database as of June 30, 2004. The host website presents more detailed information about this project, as well as the structured abstracts themselves.The LASM database comprises a dynamic and searchable web application containing structured abstracts in English, Portuguese, and Spanish. It is designed using industry standard web application design principles, but its content is unique to the LASM domain.A database searching design and utility problem unique to the LASM database, and other web applications like it, relates to the problem of web-based multilingual searching. Widely available search engines cannot preprocess a multilingual language translation of search terms (e.g. retrieving results containing the Spanish word "pública" for the English search term "public"). Additionally, search engines do not recognize that the unaccented "publica" (as it might be entered by an English speaker as a search string) might be the same word as the Spanish accented "pública" and therefore will not return the user's expected search result. Key combinations and modifiers that are used to create special and accented characters in word processing programs like Microsoft Word often do not work in browser based search and form fields. Our primary instruction to users for constructing search terms containing special and accented characters (i.e., diacritics) suggests that they use a separate text editor that accepts keyboard modifiers to construct special and accented characters to build the search term and then copy and paste the completed search string into the field. On our search pages we also list common special and accented characters in Spanish and Portuguese that users can copy and paste into browser based search fields.Although there are no other alternatives for entering special and accented characters into browser form fields, both methodologies are somewhat cumbersome. Therefore, to improve the searching utility of the LASM database we also preprocess entered search strings to allow the search engine to perform selected character substitution on the entered search string and attempt to solve the accented character problem from the search engine side. All search strings are first passed through a regular expression routine, which substitutes single character search engine wildcards for the following characters: A, E, I, O, U, a, e, i, o, u, N, C, n, c. This effectively removes potential special and accented character misspellings. To return to the previous example, a user might enter the search string "publica" ("public" in English) in a search field as an attempt to find article titles that contain the Spanish or Portuguese word "pública". Properly spelled, "Pública" uses the accented character "ú" rather than "u" (ASCII 163 rather than ASCII 117). Unfortunately, current search engines are not intelligent enough to infer that "pública" is a match for the search string "publica". Therefore, the literal search for publica (unaccented) will not return any search results that contain "pública" although there are hundreds of instances of the word "pública" in the LASM database.In the case of "publica", the preprocessed search string that is finally submitted to the search engine is "p*bl***". The search engine will return all seven-letter word matches that contain the letters p, b, and l in the first, third, and fourth positions respectively. The net effect of this technique is to under-specify the search result. That is, the search engine may possibly return records that contain other words that happen coincidentally to match the submitted search string. On the other hand, the returned result set can be guaranteed to contain the desired search result.Problems created from under-specifying the search are limited based on experience gained from using this technique. The positional constraints of submitted characters within the search string generally are restrictive enough to prevent most problems. Specifically, within a limited domain search surface like the LASM database, the likelihood of the occurrence of most alternative word matches is very low.The character substitution methodology described here is not perfect, and many other alternative strategies for addressing the multilingual search problem have been explored by LASM technical staff. Most of the alternative strategies considered, however, involved much higher costs in terms of acquiring or developing specialized search engine capabilities or much higher abstract preparation costs. Therefore, we chose the character substitution strategy as a compromise between implementation cost and search utility.Internet technology via websites and web browsers has created numerous opportunities for public health colleagues to inform one another and to collaborate across wide geographic space. The LASM database clearly demonstrates the efficacy of the Internet for communicating its informative structured abstracts posted in the Spanish, Portuguese, and English languages. This database provides useful information that would otherwise be unavailable for public health professionals on the social determinants of health. Furthermore, it expands access to LASM through its inclusion of both the classic and contemporary literature.. As the data reported above indicate, the LASM database already has been accessed steadily since its initial small-scale publicity began in 2002. We hope that public health readers will utilize the LASM database to improve their research, teaching, and practice.Anyone with access to the World Wide Web and a web browser can access all structured abstracts in the LASM database Neither the authors nor any support personnel possess competing interests related to the LASM database or to this article's publication.JE conceived of and wrote the initial version of this article, served as an early collaborator on and helped design the project, was responsible as an investigator for acquiring journals for the Latin American social medicine collection, provided quality assurance editing on structured abstracts, played a major role in the formative evaluation of the project, and coordinated all revisions to this article. HW initiated and designed the project, served as principal investigator, obtained funding, translated and edited abstracts in the English-language, and edited this manuscript. HSB served as co-principal Investigator, helped design this project, obtained funding, and led the effort for the formative evaluation of this project. JT helped administer the project and edited this manuscript. CI coordinated the project, wrote Spanish-language structured abstracts, and provided reference materials for this article. KW and JT developed all programming aspects of the website including the search strategies, managed the web interface and underlying database and contributed the text for portions of this article.The pre-publication history for this paper can be accessed here:


Daily energy expenditure consists of three components: basal metabolic rate, diet-induced thermogenesis and the energy cost of physical activity. Here, data on diet-induced thermogenesis are reviewed in relation to measuring conditions and characteristics of the diet.Measuring conditions include nutritional status of the subject, physical activity and duration of the observation. Diet characteristics are energy content and macronutrient composition.Most studies measure diet-induced thermogenesis as the increase in energy expenditure above basal metabolic rate. Generally, the hierarchy in macronutrient oxidation in the postprandial state is reflected similarly in diet-induced thermogenesis, with the sequence alcohol, protein, carbohydrate, and fat. A mixed diet consumed at energy balance results in a diet induced energy expenditure of 5 to 15 % of daily energy expenditure. Values are higher at a relatively high protein and alcohol consumption and lower at a high fat consumption. Protein induced thermogenesis has an important effect on satiety.In conclusion, the main determinants of diet-induced thermogenesis are the energy content and the protein- and alcohol fraction of the diet. Protein plays a key role in body weight regulation through satiety related to diet-induced thermogenesis. Diet induced thermogenesis (DIT) can be defined as the increase in energy expenditure above basal fasting level divided by the energy content of the food ingested and is commonly expressed as a percentage. It is, with basal metabolic rate and activity induced thermogenesis, one of the three components of daily energy expenditure. Although DIT is the smallest component, it could play a role in the development and/or maintenance of obesity. De Jonge and Bray  evaluateMethodological issues include: was the baseline appropriate, what was the energy content and nutrient composition of the test food consumed, what was the duration of the postprandial measurement period, and what was the error associated with the calculation of DIT from the measured energy expenditure. Weststrate et al  investigHere, the focus is on DIT as a function of the energy content and nutrient composition of the test food consumed and the duration of the postprandial measurement period in adult subjects with a normal bodyweight. The review is based on literature published over the last 15 years.The experimental design of most studies on DIT is a measurement of resting energy expenditure before and after a test meal, with a ventilated hood system. The observation is started after an overnight fast, where subjects are refrained from eating after the last meal at 20.00 h at the latest. Thus, with observations starting between 08.00 and 09.00 h the next morning, the fasting interval is at least 12 h. Postprandial measurements are made for several hours where subjects have to remain stationery, most often in a supine position, for the duration of the measurements. In some studies, measurements are 30 min with 15 min intervals allowing i.e. for sanitary activities.The use of a respiration chamber to measure DIT has the advantage of reproducing more physiological conditions over a longer period of time while regular meals are consumed throughout the day ,6. The DStudies on DIT were selected from Medline. Studies were selected when information was presented on energy intake, diet composition with respect to carbohydrate, protein fat and alcohol of the test food, duration of the postprandial measurement, and DIT.Reported intra-individual variability in DIT, determined with ventilated-hood systems, is 6 to 30% ,8. ReporThe mean pattern of DIT throughout the day is presented in figure Fifteen studies on DIT with information on energy intake, on diet composition and on the postprandial measurement period were selected from literature Table . Five stFor a comparison of DIT between studies as a function of the nutrient composition of the test food consumed, the energy content of the test food was divided by the length of the measurement interval after food consumption and expressed in MJ/h. Only three of the 22 studies presented in table The main determinant of DIT is the energy content of the food, followed by the protein fraction of the food. The thermic effect of alcohol is similar to the thermic effect of protein.Diet induced thermogenesis is related to the stimulation of energy-requiring processes during the post-prandial period. The intestinal absorption of nutrients, the initial steps of their metabolism and the storage of the absorbed but not immediately oxidized nutrients . As suchTheoretically, based on the amount of ATP required for the initial steps of metabolism and storage, the DIT is different for each nutrient. Reported DIT values for separate nutrients are 0 to 3% for fat, 5 to 10% for carbohydrate, 20 to 30% for protein , and 10 Of the studies presented in table The higher DIT value of alcohol and protein compared with carbohydrate and fat has implications for the effect of these nutrients on energy balance. However, the main effect on energy balance does not seem to be primarily linked to the lower bioavailability of alcohol-and protein energy than that of fat and carbohydrate. Alcohol energy is largely additive to the normal diet but does not seem to affect energy balance positively . ProteinAlcohol forms a significant component of many diets and it supplements rather than displaces daily energy intake. Alcohol consumption as an aperitif has even been shown to result in a higher subsequent intake with no intake compensation afterwards . Yet, alThe main effect of protein on energy balance is thought to be DIT related satiety. Satiety scores were higher during meals with a high-protein/high-carbohydrate diet, as well as over 24 h, than with a high-fat diet . The obsIn conclusion, the main determinants of diet-induced thermogenesis are the energy content and the protein-and alcohol fraction of the diet. Protein plays a key role in body weight regulation through satiety related to diet-induced thermogenesis.


In view of clinical observations and laboratory results that support a central role of the spleen in idiopathic thrombocytopenic purpura (ITP) pathophysiology, we studied the effect of splenectomy on type-1 and type-2 cytokine gene expression in an adult ITP case, refractory to conservative treatment.6/L within 10 days after the operation. Two consecutive blood samples were obtained from the patient, 3 and 7 months after the splenectomy for the purposes of this study. A control group consisted of 11 healthy adults. Peripheral blood mononuclear cells were prepared from each blood sample and cultured in vitro for 8 h with the addition of the mitogens phorbol myristate acetate and ionomycin. Total cellular RNA extracted from 106 cells was submitted to semiquantitave reverse transcriptase-polymerase chain reaction (RT-PCR) for the amplification of IL-2, IFN-γ, IL-4, IL-5, and IL-10 metagraphs. The PCR products were run on ethidium-stained agarose gels, photographed and quantified by densitometry.The patient was subjected to splenectomy 9 months after the diagnosis with complete response, attaining platelet counts over 150 × 106/L to 265 × 106/L. The change of type-2 cytokine expression (IL-4, IL-5, IL-10) was slight and the Th2 activity (IL-4+IL-5) remained largely unchanged. The Th1/Th2 ratio, that reflects the pathogenic disease-specific T-cell immune deviation, was accordingly reduced 7 months post-splenectomy (Th1/Th2 = 1.3) compared to 3 months (Th1/Th2 = 3.5).A steep decrease of type-1 cytokine expression (IL-2, IFN-γ) and their calculated sum expressing Th1 activity was observed at 7 months post-splenectomy compared to 3 months post-splenectomy, in parallel with a rise of platelet count from 190 × 10The reduction of the Th1/Th2 cytokine ratio that was observed over time after splenectomy was accompanied by full clinical remission. Nevertheless, the persistence of a type-1 polarization, even after several months following spleen removal, is suggestive of a more basic abnormality of the immune function in these patients. Adult autoimmune thrombocytopenic purpura (ITP) is a chronic acquired organ-specific autoimmune thrombocytopenic syndrome . The lowThe spleen is considered to be the primary site of the autoimmune response where initiation, maintenance and regulation of the autoimmune attack take place. The spleen is the site of autoreactive T- and B-cell interaction and activation, and autoreactive anti-platelet antibody production . Platelein vitro cultures [+CD4+, CD3+CD8+, CD3+HLADR+, and CD3+CD25+ cells increases significantly in ITP patients refractory to splenectomy [Splenectomy is followed by reduction of autoantibody peripheral blood titre ,13. Splecultures . The percultures . The numenectomy . Changesenectomy .Splenectomy is the most clinically effective therapeutic intervention in ITP patients, resulting in complete remission in two thirds of the patients with more than 60% maintaining the therapeutic effect in the long term ,18. IrreGiven the important immunoregulatory role of the spleen, we looked at the effects of splenectomy on immune activation and immune deviation indices in the peripheral blood of an ITP patient after splenectomy in association with peripheral platelet counts.6/L). Following clinical exclusion of causes of secondary thrombocytopenia [A 42 year old woman presented in October 1999 in Patras University Hospital (PUH) with lower limb purpura and low platelet count . Informed consent was obtained from the patient. PUH abides by the Helsinki declaration on ethical principles for medical research involving human subjects.in vitro for 8 h with the addition of 20 ng/ml phorbol myristate acetate (PMA) and 1 μM ionomycin (Sigma, St-Louis, MI).Peripheral blood mononuclear cells (PBMC) were prepared from each blood sample by centrifugation over a Ficoll-Paque gradient (Pharmacia, Sweden). The cells were cultured 6 cells was submitted to semiquantitative RT-PCR for the amplification of IL-2, IFN-γ, IL-4, IL-5, and IL-10 metagraphs [Total cellular RNA extracted from 10tagraphs . Primerstagraphs .6/L to 265 × 106/L. Regarding type-2 cytokine gene expression, IL-4 increased, IL-5 decreased, and IL-10 remained unchanged, whereas the change in Th2 activity (IL-4 units plus IL-5 units) was slight (Figure A sharp decrease in the expression of the type-1 cytokines IL-2 and IFN-γ and their calculated sum expressing Th1 activity was observed at 7 months after splenectomy compared to 3 months after splenectomy (Figure The above results show that in this patient type-1 polarization persists after removal of the spleen and attainment of clinical remission. This may mean that the spleen is not exclusively responsible for the coordination or the maintenance of the pathological immune response in this patient, provided that no accessory splenic tissue exists. Other disease centres may control the autoimmune reaction as well, such as the liver or the bone marrow. Alternatively, it is possible that ITP is the manifestation of a general immune system malfunction that pre-existed before the development of thrombocytopenia and persists after removal of what seems to be the effector of a manifestation of an autoimmune proclivity.Unfortunately, a pre-splenectomy sample was not available for analysis. As a result, no conclusions can be drawn about the effect of splenectomy on the direction of change of Th1 activity. Based on phenotypic studies showing increased presence of T lymphocytes with activated phenotype after splenectomy in ITP patients , it is pThe clinical remission may be due to the removal of a major platelet destruction site, although the underlying immune activity that drives the destruction may remain unaffected. Complete remission does not mean that increased platelet destruction has stopped after splenectomy. Platelet life span may still be shortened in this patient and/or her normal platelet count may be even higher than what was achieved after splenectomy.The pathological immune activity seems to decrease over time after splenectomy, as reflected by the lower Th1/Th2 ratio that is indicative of the degree of immune polarization. This may be explained by reduced stimulation of the immune system by activated spleen reticuloendothelial cells that present platelet antigens to T helper lymphocytes. In this way, it may be hypothesized that removal of one vital component of the self-attacking immune process can break the vicious circle that culminates in even greater immune activation, polarization, and platelet destruction. Removal of a major site of autoimmune activity may have abrogated recruitment of naïve T-cells. As a result, overall autoimmune activity wears off, as existing activated Th1 effector cells perish leaving behind a much smaller population of peripheral memory cells that retain the initial Th phenotype.Another consideration that stems from the results of this case study is that immune polarization and immune deviation of the pathological response depend more on upregulation of type-1 mediators rather than on suppression of type-2 cytokines, or that type-2 response is inadequate to control excess type-1 response in active disease.Clinical improvement after splenectomy is associated with reduced but not normalized immune activation and polarization in the patient studied. However, the spleen seems not to be absolutely necessary for the maintenance of the autoimmune reactivity.The authors declare that they have no competing interests.FPP prepared the case report, performed the experiments and drafted the manuscript. AM conceived of the study, participated in its design and coordination and co-wrote the manuscript. Both authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:


A healthcare provider's recommendation to undergo screening has been shown to be one of the strongest predictors of completing a colorectal cancer (CRC) screening test. We sought to determine the relationship between the general quality of self-rated patient-provider communication and the completion of CRC screening.A formative study using qualitative data from focus groups and quantitative data from a cross-sectional survey of church members about the quality of their communication with their healthcare provider, their CRC risk knowledge, and whether they had completed CRC screening tests. Focus group participants were a convenience sample of African American church members. Participants for the survey were recruited by telephone from membership lists of 12 African American churches located in rural counties of North Carolina to participate in the WATCH (Wellness for African Americans Through Churches) Project.Focus Groups. Six focus groups (n = 45) were conducted prior to the baseline survey. Discussions focused on CRC knowledge, and perceived barriers/motivators to CRC screening. A theme that emerged during each groups' discussion about CRC screening was the quality of the participants' communication with their health care provider. Survey. Among the 397 participants over age 50, 31% reported CRC screening within the recommended guidelines. Participants who self-rated their communication as good were more likely to have been screened (36%) within the recommended guidelines than were participants with poor communication (17%) . Participants who had adequate CRC knowledge completed CRC screening at a higher rate than those with inadequate knowledge (p = 0.011). The percentage of participants with CRC screening in the recommended guidelines, stratified by communication and knowledge group were: 42% for good communication/adequate knowledge; 27% for good communication/inadequate knowledge; 29% for poor communication/adequate knowledge; and 5% for poor communication/inadequate knowledge.Participants who rated their patient-provider communication as good were more likely to have completed CRC screening tests than those reporting poor communication. Among participants reporting good communication, knowledge about colorectal cancer was also associated with test completion. Interventions to improve patient-provider communication may be important to increase low rates of CRC screening test completion among African Americans. Colorectal cancer (CRC) screening among average risk adults 50 years and older can decrease the incidence and mortality rates for CRC -7. NatioA healthcare provider's recommendation to undergo screening has been shown to be one of the strongest predictors of completing a CRC screening test -17, and . The WATCH Project was a church-based colorectal cancer prevention study designed to increase fruit and vegetable consumption, reduce fat intake, increase moderate physical activity, and increase CRC screening among church members. In this study of patient-provider communication and CRC screening, we used data from two different sources: 1) focus groups of African American men and women, and 2) surveys of church members. The Institutional Review Board from the University of North Carolina at Chapel Hill approved this study.Data for this study were obtained as part of a larger study, the WATCH (Wellness for African Americans Through Churches) Project As part of the formative data collection in early 1998, we conducted six focus groups of African American adults. There were three focus groups of African American adult men and three of African American adult women. The focus groups comprised of a convenience sample drawn from members of African American churches located in central North Carolina. The focus groups were conducted in the churches, lasted approximately 60 minutes, were tape recorded, transcribed, and reviewed for accuracy. A $15 incentive and refreshments were provided for the participants. The focus groups were led by sex-matched African American moderators and explored issues associated with colon cancer, CRC screening (barriers and motivators), nutrition, and physical activity. The information from the focus groups was used to develop the questionnaires and to help guide the intervention strategies used in the culturally appropriate colon cancer prevention program.The second source of participants for the survey study was the baseline intervention sample for the larger WATCH project. The telephone survey collected information focused on general health status, nutrition, physical activity, patient-provider communication, CRC risk knowledge and screening behaviors. The baseline survey was completed, on average, in approximately 40 minutes and was administered by trained interviewers prior to the intervention. The baseline telephone surveys were conducted between October 1998 and October 1999.In this study, a history of CRC screening was defined as the self-report of undergoing a fecal occult blood test (FOBT), flexible sigmoidoscopy, or colonoscopy within the recommended time period. Participants were asked whether they had each of the CRC screening tests, and if they responded yes, the participants were asked when they had their last test. The items in the survey included a brief explanation of each screening test. Items were described as follows: FOBT, "which is stool slides"; sigmoidoscopy, "which is a tube inserted in the rectum to look at the colon and the bowel"; and colonoscopy, "which is a tube inserted in the rectum to look at the entire intestine, usually given in a hospital or specialist's office." Responses included, "less than 1 year"; "1–2 years"; "3–5 years"; or "more than 5 years."CRC screening was considered to be within the recommended time period based on an algorithm using ACS guidelines considering which test and how recent the test was performed (e.g. a person who reported having FOBT within the past year was considered within the recommended time period). Participants were considered to have been screened within the recommended time period if they had a FOBT within the preceding year, and sigmoidscopy within the preceding 5 years. Although current CRC screening guidelines recommend colonoscopy every 10 years for average-risk adults, we examined colonoscopy use in the past 5 years because of the limitations of the survey instrument. Self-report of CRC screening behavior has been demonstrated to be a reliable endpoint for intervention trials .Analyses of data from this study included factor analysis, analysis of variance, and logistic regression and were conducted using SPSS, version 10.1. Logistic regression analyses were performed to evaluate whether the level of perceived patient-provider communication was significantly related to CRC screening behavior in this population. Sociodemographic variables were identified as potential covariates if there was plausible theoretical or empirical evidence that the variable might be associated with the communication variable or with CRC screening. Variables that were significantly associated with communication level (p < 0.05) were retained and tested as covariates in the logistic models. Only the sex of the participant, receiving healthcare at a doctor's office versus a clinic/emergency room, and knowledge of CRC risk were significantly associated with communication and only these three covariates were entered into the initial logistic model. Variables in the model were evaluated by the Wald test and interpreted using odds ratios and confidence intervals. The overall fit of each model was evaluated using the Hosmer-Lemeshow Goodness of Fit test and by examining classification tables .Several major themes associated with CRC emerged from the personal experiences expressed about the medical community during the focus groups. One of the themes discussed by the participants in each focus group was patient-provider communication. Selected comments by focus group members about CRC and patient-provider communication are listed in Table Originally, 2480 names were obtained from the 12 church rosters located in five rural counties in North Carolina. Many members were ineligible  or we were unable to contact them by telephone, and 239 members who declined to participate in the WATCH Project. There were 850 church members who participated in the WATCH Project and completed the baseline survey. The adjusted response rate was 66% using a calculation method, suggested by the Council of American Survey Organizations (CASRO) , that acThe participants in this study were the 397 church members who participated in the WATCH Project and were 50 years and older. The characteristics of the 397 participants are shown in Table Factor analysis of the five communication items was performed from the baseline survey responses and two factors were identified; one with three items and the other with two items. The second factor was dropped because it had only two items and did not add reliability to the scale. The three communication items about shared decision-making and patient satisfaction demonstrated good reliability  and were summed to calculate a communication score. The communication score was used to categorize the participants into three groups: good, fair, and poor communication with providers. Participants were categorized as having "good" communication if they perceived receiving enough information from their provider, being involved in medical decisions, and thinking that their provider understood their health needs almost all the time or always. Participants who rated all three items 'sometimes', 'rarely', or 'never' scored "poor" on the communication scale, and individuals who rated the items with a mix of the above listed responses were assigned to the "fair" group.In terms of quality of communication, 75% 298/397) responded positively to all 3 questions and were considered have "good" communication; 10% (42/397) responded positively to none of the 3 questions and were considered to have "poor" communication; and 13% (50/397) had fair results. Participants in the good communication group were more likely to be female (p = 0.031), and were more likely to receive their healthcare at a doctor's office versus a clinic/emergency room/health department (p = 0.028). None of the other sociodemographic factors listed in Table 97 responOnly 45% (175/389) of the participants reported that their providers had recommended CRC screening, and just 31% (120/389) of all participants reported being screened within the recommended time interval. Of the individuals who reported being screened, 65% (78/120) stated that their doctor had recommended CRC screening, compared with 36% (97/269) of those who did not report screening.Knowledge of CRC was assessed using seven items Table  with a mKnowledge about CRC was considered adequate (knowledge score > = 4) for 57% (228/397) and inadequate for 43% (197/397). Participants with adequate CRC knowledge were more likely to have completed a CRC screening test within the recommended time period compared to those with inadequate CRC knowledge (21% vs. 10%). Adequate knowledge was associated with a higher level of education (p < 0.001), a higher level of income (p < 0.001), having health insurance (p < 0.001), and having Medicare/ Medicaid as one's health insurance (p < 0.001).Results of the logistic regression analyses are shown in Table CRC screening within recommended guidelines by perceived communication and knowledge is listed in Table Our study found that participants had higher rates of CRC screening when their self-rated communication with their healthcare provider was classified as perceived as more positive. In addition, we found that participants who self-rated their communication as good and who had adequate CRC knowledge completed recent CRC screening at higher rates than those with good communication and inadequate knowledge. In addition, screening rates are higher with both good communication and adequate CRC knowledge than when only one factor is present. These findings suggest that both good patient-provider communication and CRC knowledge are important for CRC screening. Because of the cross-sectional nature of our study, we cannot determine causality, and it is possible that CRC knowledge improves by going through the screening process.Improving CRC screening rates in the African American population may require strategies that address both improving physician-patient communication skills and increasing CRC knowledge. Good patient-provider communication is fundamental to a patient's perceived quality and satisfaction with their healthcare. Better communication, including the use of shared decision making, is associated with trust between patients and providers . HoweverThe association between the lack of physician recommendations for cancer screening tests and low patient utilization of those tests has been documented in previous investigations ,19,27-30The results of our study and other previously published work ,35-39 suAlthough the results from our cross-sectional study have implications for developing colorectal cancer prevention programs, it must be recognized that prospective longitudinal studies are needed that specifically address the effect of patient-provider communication on CRC screening. Because of its cross-sectional design, we cannot infer causal relationships. In addition, since all participants were recruited from 12 churches, there may be some clustering of exposures and outcomes by physician that may affect the results; we did not measure this effect. Patient-provider communication was measured by using only three self-reported communication items, which may not fully capture the full extent of the patient-provider relationship. In addition, we do not know whether our participants had racially discordant or concordant physicians, and we did not have information regarding the physician's beliefs or practices about CRC screening or the physicians' assessment of the quality of communication with the patients. The outcome measure of having undergone CRC screening was self-reported, and these results were not validated. Finally, because of the relatively small number of participants and the use of convenience sampling, results from this study may not be generalizable.The findings from this cross-sectional study suggest that not only do patients need to be informed about their CRC risk and the importance of screening tests but that having good communication with their healthcare provider may also important. The burden of having good communication in the patient-provider relationship is the responsibility of both individuals. Both the patient and the provider should strive to improve their communication skills so that patients who want to participate in the decision about how to be screened for colorectal cancer may do so effectively.Because culturally distinct factors may contribute to poor communication and mistrust for African-Americans, specific new strategies need to be developed . BeliefsThe author(s) declare that they have no competing interests.M.L.K. participated in the conception of the study, the analyses, the interpretation of the results, writing the first draft and revising the manuscript. A.S.J. participated in the conception of the study, performed the statistical analyses, participated in the interpretation of the results, and the editing of the manuscript. M.P.P. participated in the interpretation of the results and the writing of the manuscript. M.H., E.J., and V.O. assisted with the qualitative analysis and surveys. M.K.C. participated in the conception of the study, the statistical analyses, interpretation of the results, and the writing of the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:


Essential hypertension is a common, polygenic, complex disorder resulting from interaction of several genes with each other and with environmental factors such as obesity, dietary salt intake, and alcohol consumption. Since the underlying genetic pathways remain elusive, currently most studies focus on the genes coding for proteins that regulate blood pressure as their physiological role makes them prime suspects.The present study examines how polymorphisms of the insertion/deletion (I/D) ACE and M235T AGT genes account for presence and severity of hypertension, and embeds the data in a meta-analysis of relevant studies.The I/D polymorphisms of the ACE and M235T polymorphisms of the AGT genes were determined by RFLP (restriction fragment length polymorphism) and restriction analysis in 638 hypertensive patients and 720 normotensive local blood donors in Weisswasser, Germany. Severity of hypertension was estimated by the number of antihypertensive drugs used.No difference was observed in the allele frequencies and genotype distributions of ACE gene polymorphisms between the two groups, whereas AGT TT homozygotes were more frequent in controls (4.6% vs. 2.7%, P = .08). This became significant (p = 0.035) in women only. AGT TT genotype was associated with a 48% decrease in the risk of having hypertension , and this risk decreased more significantly in women . The meta-analysis showed a pooled odds ratio for hypertension of 1.21 (TT vs. MM, 95% CI: 1.11 to 1.32) in Caucasians. No correlation was found between severity of hypertension and a specific genotype.The ACE I/D polymorphism does not contribute to the presence and severity of essential hypertension, while the AGT M235T TT genotype confers a significantly decreased risk for the development of hypertension in the population studied here. This contrasts to the findings of meta-analyses, whereby the T allele is associated with increased risk for hypertension. Essential hypertension is a common, polygenic, complex disorder resulting from interaction of several genes with each other and with environmental factors such as obesity, dietary salt intake, and alcohol consumption. Since the underlying genetic pathways remain elusive, currentThe Renin-Angiotensin System (RAS) has a central role in regulating blood pressure and sodium homeaostasis. Genes encoding components of RAS, including angiotensinogen (AGT), angiotensin-converting enzyme (ACE), angiotensinogen II type-1 receptor (AGTR1), and renin, have been extensively investigated as genetic determinants of essential hypertension . PolymorIn 1992, the M235T AGT TT polymorphism was first reported to be associated with hypertension . This fiThe inconsistent results might be explained in part by the genetic and environmental heterogeneity among different ethnic groups . On the The present study investigates the relationship between variants of the I/D ACE gene and M235T AGT gene, and the presence and severity of essential hypertension in a large homogeneous German population. The effect of a combination of ACE and AGT gene polymorphisms on hypertension was also examined.The design of the study followed the guidelines proposed by Cooper et al , and the2 or dialysis), 15 were due to diabetic nephropathy, 5 to chronic pyelonephritis, 1 to chronic glomerulonephritis, 1 light chain deposits, 1 polycystic kidney disease, and 14 of unknown cause (no biopsy obtained). The severity of hypertension was estimated based on the number of antihypertensive medications used, a surrogate marker for the severity of hypertension[This cross-sectional study comprised a total of 1358 individuals from Weisswasser, a county town of 25,000 in Saxony, Germany. After giving informed consent, 720 normotensive subjects were selected from local blood donors and 638 hypertensive patients from the local renal care center. All hypertensive patients included in the study had been diagnosed as suffering from primary hypertension by the attending consultants on first contact with the clinic. Hypertensives were defined as those who received at least one antihypertensive medication. At the time of blood sampling, 34.2% were diabetic (6 type 1, 212 type 2), and 65.1% were suffering from kidney disease. Of the 37 patients with K/DOQI stage 5 (Kidney failure: GFR, 15 ml/min/1.73 mRFLP (restriction fragment length polymorphism) and restriction analysis were used to determine the frequencies of the I/D polymorphisms of the ACE gene, and homo-/ heterozygoty of the M235T AGT gene,21. ACE AGT M235T polymorphism was studied by first amplifying a 104 bp long fragment of the AGT gene using the following primer sequences: sense- 5'CCGTTTGTGCAGGGCCTGGCTCTCT3', and antisense: 5'CAGGGTGCTGTCCACACTGGACCCC3'.Tth 111I.The M -> T point mutation at position 235 creates a detection site for the restriction enzyme t test for continuous data and Pearson's χ2 test for categorical data. Allele frequencies were calculated with the gene-counting method. χ2 test was used for assessment of the Hardy-Weinberg equilibrium for the distribution of genotypes. Odds ratios were calculated with a 95% confidence interval. A P < .05 was considered significant.Statistical analysis was carried out using SPSS personal computer statistical package (version 11.5, SSPS Inc, Chicago, IL). Demographic characteristics were compared by 2 test using P-value < 0.05. The Mantel-Haenszel odds ratios were calculated by applying both fixed effect model and random effect model in case of heterogeneity.A meta-analysis was performed using Review Manager 4.2 (The Cochrane Collaboration) to further examine the association of the AGT M235T gene polymorphisms with essential hypertension in Caucasians. A systematic literature search in PubMed Medline for articles published between April 2002 and June 2004 was carried out using the following MESH-headings: "angiotensinogen/genetics", "hypertension/genetics", "blood pressure/genetics", and "adult". The search was limited to articles published in English and studies on Caucasian human subjects. Only 2 studies were left after strict examination according to the exclusion criteria listed in . A totalDemographic data are summarized in Table AGT M/T genotyping was successful in 637 hypertensives and 720 normotensives, and ACE I/D genotype was analyzed in 636 hypertensive and 719 control subjects. The roles of age and gender in the association between hypertension and ACE and AGT gene polymorphisms were examined by comparing the effects of ACE and AGT genotypes for hypertension in men and women, young and elderly subjects respectively. "Young" was defined as "age < 50 years old", and "elderly" was characterized as "age ≥ 50 years old".No differences were observed in ACE allele and genotype frequency distribution between hypertensives and controls with respect to gender and age, and no deviations from Hardy-Weinberg equilibrium were observed in any of subgroups P > 0.1). ACE genotypes I/I, I/D and D/D were of almost identical frequency within both groups  compared with those with MM genotype Figure . The stuThe effect of eight combinations  on hypertension was examined. No statistically significant association was observed between any combination above and hypertension in all subjects combined. Nonetheless, in women, both genotypes of TT, DD/ID and TT, II/ID were significantly associated with lower prevalence of hypertension  and a more significant association was found in women , compared to men. This is in stark contrast to findings from previous studies, including two German datasets [AGT 235 T-allele and/or TT genotype significantly increased the risk for essential hypertension in Caucasians: odds ratio T vs. M was 1.20 (95% CI: 1.11 to 1.29) [Surprisingly, the cross-sectional study presented here shows a higher prevalence of the T/T M235T AGT gene in the control group compared to the hypertensive group. AGT TT genotype was associated with a datasets ,32, and datasets ,22,47, wto 1.29) , odds rato 1.29)  includedto 1.29) AGT T allele among normotensives was higher than that among hypertensives (0.36 vs. 0.33). This was inconsistent with one previous meta-analysis in Caucasians, which showed that among controls, the mean allele frequency for the AGT T allele was 0.41 (95% CI: 0.34 to 0.48), and among cases, increased to 0.45 (95% CI: 0.38 to 0.52) [AGT T allele among hypertensives (0.33) was outside the lower border of the 95% confidence interval (0.38 to 0.52) reported in [Although no significant difference was observed in AGT T allele frequency distribution between hypertensives and controls with respect to age and gender, the frequency of the to 0.52) . In the orted in . This maThe AGT genotype distribution is not in Hardy-Weinberg equilibrium (P < 0.001) while no deviations from Hardy-Weinberg equilibrium are observed on the ACE genotype distribution in the same population. This may be explained by a shift toward a higher frequency of MT individuals (62.4%) instead of TT individuals (3.7%) in this specific population.The study population presented here contains a large proportion (65%) of patients with renal disease. While selection of participants based on patient records excluded those patients that had symptoms suggesting the diagnosis of secondary hypertension at first contact, the possibility remains that at least a part of the study population suffers from renal rather than essential hypertension. It should be noted, however, that the majority of studies included in the presented meta-analysis does not give specific information regarding renal function of hypertensives, and the largest study  is populAnother possible explanation is that the AGT T allele frequency may decrease with age, which was reported from the United Arab Emirates . The preA number of studies -54 examiThe effect of a combination of RAAS genes' polymorphisms on blood pressure has been investigated in the participants to the Olivetti Heart Study , in whicAlthough in most surveys the prevalence of hypertension appears to be equal in women and men , sex-speIn addition to the factor declared above, the result may be influenced by the study design and the composition of the sample population. The study design itself may influence the results. As mentioned above, this study was a cross-sectional study where subjects were assessed at a single time, and at that time most of the controls were younger than 50 years old. Animal studies have shown that hypertension genes may be activated for only certain periods during the life history of an organism . Hence, The population can be described as static population with a mixed Germanic-Slavonic background. Due to the location  and political and historical setting , the population may be assumed as homogeneous. Several recent studies -61 have In the meantime, it should be noted that the present study was carried out on an unusually large population . Given Despite the limitations mentioned, this cross-sectional study does not support the notion that the ACE I/D polymorphism contributes to the prevalence and severity of essential hypertension. However, the M235T TT genotype of AGT gene was detected to confer a significantly decreased risk for the prevalence of hypertension in women from this particular population. Despite the large sample size, the present study fails to revise the odds ratio in a meta-analysis of a total of 25 studies on the association between the AGT M235T polymorphisms and hypertension in caucasians. This observation may reflect a very specific local inheritance pattern of the AGT genotypes. If this holds true, studies aiming at drug development based on genomic traits must be scrutinized rigorously as therapeutic recommendations may be valid for selected subpopulations only.The author(s) declare that they have no competing interests.M.N. designed and initiated the study, analyzed the samples and wrote part of the manuscript. A-L.Z. and M.L. did the statistical analysis. A.M. devised the concept for meta-analysis and wrote the manuscript. L.P. created the figures. M.N. and A.M. should be considered as joint co- authors.The pre-publication history for this paper can be accessed here: