Background Due to the low participation in colorectal cancer screening, public preference for colorectal cancer screening modality was determined.
Background
Due to the low participation in colorectal cancer screening, public preference for colorectal cancer screening modality was determined.Methods A cross-sectional survey was performed of healthy ambulatory adults in a pediatrics primary care office and neighboring church. Overall preference was ranked for each of four colorectal cancer screening modalities: Faecal Occult Blood, Fiberoptic Sigmoidoscopy, Barium Enema and Colonoscopy. Four additional domains of preference also were ranked: suspected discomfort, embarrassment, inconvenience and danger of each exam.
Methods
A cross-sectional survey was performed of healthy ambulatory adults in a pediatrics primary care office and neighboring church. Overall preference was ranked for each of four colorectal cancer screening modalities: Faecal Occult Blood, Fiberoptic Sigmoidoscopy, Barium Enema and Colonoscopy. Four additional domains of preference also were ranked: suspected discomfort, embarrassment, inconvenience and danger of each exam.Results 80 surveys were analyzed, 57 of which were received from participants who had experienced none of the screening tests. Fecal Occult Blood Testing is significantly preferred over each other screening modality in overall preference and every domain of preference, among all subjects and those who had experienced none of the tests.
Results
80 surveys were analyzed, 57 of which were received from participants who had experienced none of the screening tests. Fecal Occult Blood Testing is significantly preferred over each other screening modality in overall preference and every domain of preference, among all subjects and those who had experienced none of the tests.Conclusions Efforts to increase public participation in colorectal cancer screening may be more effective if undertaken in the context of public perceptions of screening choices.
Conclusions
Efforts to increase public participation in colorectal cancer screening may be more effective if undertaken in the context of public perceptions of screening choices.

Background Screening for colorectal cancer lessens the risk of dying from that disease [ 1 ]. Knowledge of this fact has not solved all the problems related to screening. The optimal modality of screening is still the subject of debate [ 1 - 3 ]. More problematic is the very low participation of the general public in recommended screening [ 4 ]. In contrast to breast cancer screening, in which the Healthy People 2000 Goal of the U.S. National Institutes of Health was surpassed, at 64% participation by women over 40 years of age, only 20% of Americans over age 50 had fecal occult blood testing within the past year (This is the best estimate of actual screening, rather than diagnostic endeavors for symptoms for which endoscopy or radiologic imaging might be done.), and 34% had a sigmoidoscopy within the past 5 years [ 5 , 6 ] Even if screening is appropriately performed, it is far from certain that a positive screen will be followed by appropriate diagnostic testing, as has been shown in follow-up surveys of fecal occult blood testing [ 7 ]. Most publication concerning colorectal cancer screening relates to the choice of screening modality; discussing accuracy, efficacy and cost, since the most inexpensive technique, faecal occult blood testing, is inaccurate in the detection of colorectal neoplasia, though effective in significantly diminishing disease specific mortality [ 8 ], and the most accurate technique, colonoscopy, is expensive and not without danger [ 3 ]. The choice is not an easy one for clinicians, much less patients or the asymptomatic public. Therein may lie one of the problems with public participation in screening. Unlike cancers of the breast, cervix, prostate or lung, where a single screening modality dominates current recommendations for each, there are four different and relatively independent screening tests for colorectal cancer that are currently recommended by the American Cancer Society, National Cancer Institute and United States Preventative Services Task Force: faecal occult blood test (FOBT), fiberoptic sigmoidoscopy (FS), barium enema (BE), and colonoscopy (C) [ 1 ]. The absence of a single recommendation may lead from indecision to inaction on the part of clinicians or patients. However the greatest problem related to screening remains the low level of participation by those for whom it is intended: asymptomatic individuals over the age of 50 years with no specific risk factors for colorectal cancer, i.e., no past history of colorectal polyps, cancer, rectal bleeding, colitis, change in bowel habits, iron deficiency anemia, weight loss or a close family member with colorectal cancer. We agree with Dr. Woolf [ 2 ], that strategies to improve public compliance with recommended colorectal cancer screening might be more effective if they include an awareness of what the public thinks about the tests being recommended. Previous studies have not surveyed asymptomatic participants' preference over the whole range of screening choices, focusing instead on symptomatic patients undergoing diagnostic evaluation such as colonoscopy and barium enema [ 9 - 11 ] or patients ailing from extracolonic diseases whose motivation for screening might be very different than the healthy population for whom screening is intended [ 12 - 18 ]. Among these latter studies there has been a general preference noted for FOBT (table  1 ). We have in this report chosen to focus our survey differently and uniquely; first to inform healthy, ambulatory and younger people, and not ailing patients, concerning only the preparation and conduct of each screening test. Secondly, in order to determine how their perceptions of the conduct of each test might affect their participation, participants were then asked to rank not just their overall preference based upon the preparation and conduct of the tests alone, but four other domains of preference for each screening modality: perceived physical discomfort, inconvenience, embarrassment and danger. Test accuracy was not included in the preamble on test performance, first, because we wanted to isolate perceptions of the physical conduct of the screening test, and second, because test accuracy has been part of many of the previous surveys, often presented with considerable bias. Randomized trials of decision aids have also shown that description of a test's ability to detect colorectal cancer has not been successful in increasing participation in screening [ 15 - 17 ]. Lastly, despite the current enthusiasm for screening colonoscopy by organizations that do colonoscopy as the complete screening test [ 19 ], as mentioned above, the choice of screening modality is still regarded as controversial.
Background
Screening for colorectal cancer lessens the risk of dying from that disease [ 1 ]. Knowledge of this fact has not solved all the problems related to screening. The optimal modality of screening is still the subject of debate [ 1 - 3 ]. More problematic is the very low participation of the general public in recommended screening [ 4 ]. In contrast to breast cancer screening, in which the Healthy People 2000 Goal of the U.S. National Institutes of Health was surpassed, at 64% participation by women over 40 years of age, only 20% of Americans over age 50 had fecal occult blood testing within the past year (This is the best estimate of actual screening, rather than diagnostic endeavors for symptoms for which endoscopy or radiologic imaging might be done.), and 34% had a sigmoidoscopy within the past 5 years [ 5 , 6 ] Even if screening is appropriately performed, it is far from certain that a positive screen will be followed by appropriate diagnostic testing, as has been shown in follow-up surveys of fecal occult blood testing [ 7 ].Most publication concerning colorectal cancer screening relates to the choice of screening modality; discussing accuracy, efficacy and cost, since the most inexpensive technique, faecal occult blood testing, is inaccurate in the detection of colorectal neoplasia, though effective in significantly diminishing disease specific mortality [ 8 ], and the most accurate technique, colonoscopy, is expensive and not without danger [ 3 ]. The choice is not an easy one for clinicians, much less patients or the asymptomatic public. Therein may lie one of the problems with public participation in screening. Unlike cancers of the breast, cervix, prostate or lung, where a single screening modality dominates current recommendations for each, there are four different and relatively independent screening tests for colorectal cancer that are currently recommended by the American Cancer Society, National Cancer Institute and United States Preventative Services Task Force: faecal occult blood test (FOBT), fiberoptic sigmoidoscopy (FS), barium enema (BE), and colonoscopy (C) [ 1 ]. The absence of a single recommendation may lead from indecision to inaction on the part of clinicians or patients.However the greatest problem related to screening remains the low level of participation by those for whom it is intended: asymptomatic individuals over the age of 50 years with no specific risk factors for colorectal cancer, i.e., no past history of colorectal polyps, cancer, rectal bleeding, colitis, change in bowel habits, iron deficiency anemia, weight loss or a close family member with colorectal cancer. We agree with Dr. Woolf [ 2 ], that strategies to improve public compliance with recommended colorectal cancer screening might be more effective if they include an awareness of what the public thinks about the tests being recommended. Previous studies have not surveyed asymptomatic participants' preference over the whole range of screening choices, focusing instead on symptomatic patients undergoing diagnostic evaluation such as colonoscopy and barium enema [ 9 - 11 ] or patients ailing from extracolonic diseases whose motivation for screening might be very different than the healthy population for whom screening is intended [ 12 - 18 ]. Among these latter studies there has been a general preference noted for FOBT (table  1 ).We have in this report chosen to focus our survey differently and uniquely; first to inform healthy, ambulatory and younger people, and not ailing patients, concerning only the preparation and conduct of each screening test. Secondly, in order to determine how their perceptions of the conduct of each test might affect their participation, participants were then asked to rank not just their overall preference based upon the preparation and conduct of the tests alone, but four other domains of preference for each screening modality: perceived physical discomfort, inconvenience, embarrassment and danger. Test accuracy was not included in the preamble on test performance, first, because we wanted to isolate perceptions of the physical conduct of the screening test, and second, because test accuracy has been part of many of the previous surveys, often presented with considerable bias. Randomized trials of decision aids have also shown that description of a test's ability to detect colorectal cancer has not been successful in increasing participation in screening [ 15 - 17 ]. Lastly, despite the current enthusiasm for screening colonoscopy by organizations that do colonoscopy as the complete screening test [ 19 ], as mentioned above, the choice of screening modality is still regarded as controversial.Methods Participants were a convenience sample of parents or grandparents of children visiting a general pediatrics office (usually for well child visits or minor ailments), personnel working in that office, or parishioners attending a church social gathering, all aged 18 and over. An introductory letter described the purpose of the survey. This was followed by a brief description of the preparation and performance of each commonly used screening test for colorectal neoplasia: faecal occult blood testing (FOBT), fiberoptic sigmoidoscopy (FS), air contrast barium enema (BE) and total colonoscopy (C). The relative accuracy of each exam was not discussed. Six questions followed. The first asked the participant to rank each test in order of overall preference. The second asked the participant to rank each test according to how much that test might cause physical discomfort, the third, inconvenience; the fourth embarrassment, the fifth, the relative danger of the exam. The sixth question asked participants which of the four tests they had previously experienced, along with their gender and age. No further symptom or medical history was obtained and surveys were only numbered consecutively with no personal identifiers. (see appendix for letter and survey) Based upon a related survey concerning subject preference for tests of colonic inflammation [ 20 ], a sample size of 50 individuals was estimated. Eighty four questionnaires were distributed in order to assure receipt of an adequate number of usable responses from individuals who had experienced none of the screening tests. The questionnaire is shown in the Appendix. Analyses Data were analyzed using SPSS 11.0. Analyses focused on comparisons between ranks assigned each test on preference and the other assessed attributes, and included Friedman's test for ranks (to test the hypothesis that ranks differed for different tests) and the Wilcoxon signed-ranks test (to test the hypothesis that pairs of tests were differently ranked.) We also considered whether those rank orders might differ between participants who have and have not received any of these tests, and how gender and age affected preferences.
Methods
Participants were a convenience sample of parents or grandparents of children visiting a general pediatrics office (usually for well child visits or minor ailments), personnel working in that office, or parishioners attending a church social gathering, all aged 18 and over. An introductory letter described the purpose of the survey. This was followed by a brief description of the preparation and performance of each commonly used screening test for colorectal neoplasia: faecal occult blood testing (FOBT), fiberoptic sigmoidoscopy (FS), air contrast barium enema (BE) and total colonoscopy (C). The relative accuracy of each exam was not discussed. Six questions followed. The first asked the participant to rank each test in order of overall preference. The second asked the participant to rank each test according to how much that test might cause physical discomfort, the third, inconvenience; the fourth embarrassment, the fifth, the relative danger of the exam. The sixth question asked participants which of the four tests they had previously experienced, along with their gender and age. No further symptom or medical history was obtained and surveys were only numbered consecutively with no personal identifiers. (see appendix for letter and survey)Based upon a related survey concerning subject preference for tests of colonic inflammation [ 20 ], a sample size of 50 individuals was estimated. Eighty four questionnaires were distributed in order to assure receipt of an adequate number of usable responses from individuals who had experienced none of the screening tests. The questionnaire is shown in the Appendix.Analyses Data were analyzed using SPSS 11.0. Analyses focused on comparisons between ranks assigned each test on preference and the other assessed attributes, and included Friedman's test for ranks (to test the hypothesis that ranks differed for different tests) and the Wilcoxon signed-ranks test (to test the hypothesis that pairs of tests were differently ranked.) We also considered whether those rank orders might differ between participants who have and have not received any of these tests, and how gender and age affected preferences.
Analyses
Data were analyzed using SPSS 11.0. Analyses focused on comparisons between ranks assigned each test on preference and the other assessed attributes, and included Friedman's test for ranks (to test the hypothesis that ranks differed for different tests) and the Wilcoxon signed-ranks test (to test the hypothesis that pairs of tests were differently ranked.) We also considered whether those rank orders might differ between participants who have and have not received any of these tests, and how gender and age affected preferences.Results 80 of 84 surveys were available for analysis; twenty nine from men and 51 from women. The mean age of the participants was 38.3 years (range 18 – 54 years; St. Dev. 8.19 years; median 40 years). Eight subjects had previously had a colonoscopy, five a barium enema, seven a sigmoidoscopy and 17 had stool collected for various reasons. Fifty seven subjects had experienced none of the screening tests. The mean rankings for preference among the entire sample are presented in Table  2  and among only those individuals who had experienced none of the tests are presented in the Table  3 , score "1" being the most preferred and "4" the least. In each case, mean rankings were found to vary by test (Friedman's test, 3 df), and FOBT was significantly preferred over the second-ranked test (FS) by Wilcoxon signed-ranks test. Median scores were determined for each domain for both the whole survey group and the naive subgroup. For each domain and in each group the results were the same, with ranks of 4,3,2 &1 for C, BE, FS and FOBT respectively, 1 being most preferred, except for embarrassment in both groups in which C and BE each had a median rank 3. The results hold up for each gender subgroup in all cases except that men didn't consider FOBT significantly less inconvenient than FS. Age was not significantly correlated with ranking of FOBT (that is, the ranking given didn't change with age) by Spearman's rho. Rho values ranged from -0.10 to +0.16, none significant. Splitting the groups into ages 18–39 (n = 39) and 40+ (n = 40), the results are the same for both groups except that for those over 40, preference for FOBT vs. FS and inconvenience of FOBT vs. FS did not reach significance by two-tailed test (p = .079 and p = .057 respectively)
Results
80 of 84 surveys were available for analysis; twenty nine from men and 51 from women. The mean age of the participants was 38.3 years (range 18 – 54 years; St. Dev. 8.19 years; median 40 years). Eight subjects had previously had a colonoscopy, five a barium enema, seven a sigmoidoscopy and 17 had stool collected for various reasons. Fifty seven subjects had experienced none of the screening tests. The mean rankings for preference among the entire sample are presented in Table  2  and among only those individuals who had experienced none of the tests are presented in the Table  3 , score "1" being the most preferred and "4" the least. In each case, mean rankings were found to vary by test (Friedman's test, 3 df), and FOBT was significantly preferred over the second-ranked test (FS) by Wilcoxon signed-ranks test.Median scores were determined for each domain for both the whole survey group and the naive subgroup. For each domain and in each group the results were the same, with ranks of 4,3,2 &1 for C, BE, FS and FOBT respectively, 1 being most preferred, except for embarrassment in both groups in which C and BE each had a median rank 3.The results hold up for each gender subgroup in all cases except that men didn't consider FOBT significantly less inconvenient than FS. Age was not significantly correlated with ranking of FOBT (that is, the ranking given didn't change with age) by Spearman's rho. Rho values ranged from -0.10 to +0.16, none significant. Splitting the groups into ages 18–39 (n = 39) and 40+ (n = 40), the results are the same for both groups except that for those over 40, preference for FOBT vs. FS and inconvenience of FOBT vs. FS did not reach significance by two-tailed test (p = .079 and p = .057 respectively)Discussion A recent review of colorectal cancer screening stated that, "At present there is no preferred CRC screening strategy"[ 1 ]. This presents the perspective of a group of impartial physicians. However from the perspective of those who should take part in CRC screening in the future, a clear preference for FOBT over each other screening modality is expressed in this survey. Each domain of preference similarly ranks FOBT as significantly most preferred. Among previous surveys there are four randomized controlled trials of the use of decision aids that were designed with the intent of altering participation in screening. Three of these presented choices of screening modality or scenario to both intervention and control groups [ 15 - 17 ]. These studies therefore provided information of participant preference for specific screening modality, though again the participants, primary care  patients , were quite different from the group reported herein. Only one of those reports offered all four of the screening modalities that we did in our study [ 16 ], the other two offering only a choice between FOBT and FS [ 15 , 16 ]. Nevertheless a uniform preference for FOBT was reported in these studies as well (Table  1 ). None of the test interventions were particularly effective in increasing participation in screening, an endpoint not assessed in our study. The fourth randomized trial randomized non-patients, relatives of gastroenterology patients, to be offered either FS or C and measured differential participation, which was equal in the two groups [ 20 ]. In the survey most similar to the present study, Pignone surveyed 146 patients in a general medicine clinic [ 18 ] and questioned participants after four sequential levels of information were given. Only two screening options were presented, FOBT & FS. Information included in sequence 1) the risk of colorectal cancer, 2) description of the conduct of the test, 3)accuracy of the tests, 4) cost. Previous screening participation was queried but not an exclusion. Less than 5% of those approached refused participation and no data were presented on the screening naïve participants in his sample. FOBT was preferred at each level of investigation, though both tests together were preferred after level 2 (Table  1 ). Participants were also asked for reasons for their preferences. The reasons most often given related to cost, ease of performance and being done alone. Among some physicians there is a growing popularity for the use of definitive diagnostic testing as a screening tool, that is, colonoscopy [ 19 ]. Though expensive and not without danger, reimbursement for the test is declining and the procedure is getting safer. It has obvious theoretical advantages of offering precise diagnostic capabilities, through biopsy, for those with positive screens. Most important, colonoscopy has the best potential for cancer prevention by adenoma removal – which is not possible with any other test [ 22 , 23 ]. This, properly applied, might even result in cost savings in the global cost of caring for colorectal cancer. But the public has to want to participate in this program and there is little evidence in this current survey and previous studies, especially those done in primary care settings [ 13 - 18 ], that this is likely. The concerns expressed herein about safety, embarrassment, inconvenience and discomfort all must be addressed in future efforts to increase screening participation. A potentially significant development related to these issues is that the principal disadvantage of FOBT, its inaccuracy in detecting colorectal neoplasia, might be overcome. Recently developed stool tests show an ability to diagnose cancer with much greater reliability [ 24 ]. Perhaps these gene based stool tests may establish the potential for adenoma discovery by non-invasive testing as well.
Discussion
A recent review of colorectal cancer screening stated that, "At present there is no preferred CRC screening strategy"[ 1 ]. This presents the perspective of a group of impartial physicians. However from the perspective of those who should take part in CRC screening in the future, a clear preference for FOBT over each other screening modality is expressed in this survey. Each domain of preference similarly ranks FOBT as significantly most preferred.Among previous surveys there are four randomized controlled trials of the use of decision aids that were designed with the intent of altering participation in screening. Three of these presented choices of screening modality or scenario to both intervention and control groups [ 15 - 17 ]. These studies therefore provided information of participant preference for specific screening modality, though again the participants, primary care  patients , were quite different from the group reported herein. Only one of those reports offered all four of the screening modalities that we did in our study [ 16 ], the other two offering only a choice between FOBT and FS [ 15 , 16 ]. Nevertheless a uniform preference for FOBT was reported in these studies as well (Table  1 ). None of the test interventions were particularly effective in increasing participation in screening, an endpoint not assessed in our study. The fourth randomized trial randomized non-patients, relatives of gastroenterology patients, to be offered either FS or C and measured differential participation, which was equal in the two groups [ 20 ]. In the survey most similar to the present study, Pignone surveyed 146 patients in a general medicine clinic [ 18 ] and questioned participants after four sequential levels of information were given. Only two screening options were presented, FOBT & FS. Information included in sequence 1) the risk of colorectal cancer, 2) description of the conduct of the test, 3)accuracy of the tests, 4) cost. Previous screening participation was queried but not an exclusion. Less than 5% of those approached refused participation and no data were presented on the screening naïve participants in his sample. FOBT was preferred at each level of investigation, though both tests together were preferred after level 2 (Table  1 ). Participants were also asked for reasons for their preferences. The reasons most often given related to cost, ease of performance and being done alone.patientsAmong some physicians there is a growing popularity for the use of definitive diagnostic testing as a screening tool, that is, colonoscopy [ 19 ]. Though expensive and not without danger, reimbursement for the test is declining and the procedure is getting safer. It has obvious theoretical advantages of offering precise diagnostic capabilities, through biopsy, for those with positive screens. Most important, colonoscopy has the best potential for cancer prevention by adenoma removal – which is not possible with any other test [ 22 , 23 ]. This, properly applied, might even result in cost savings in the global cost of caring for colorectal cancer.But the public has to want to participate in this program and there is little evidence in this current survey and previous studies, especially those done in primary care settings [ 13 - 18 ], that this is likely. The concerns expressed herein about safety, embarrassment, inconvenience and discomfort all must be addressed in future efforts to increase screening participation. A potentially significant development related to these issues is that the principal disadvantage of FOBT, its inaccuracy in detecting colorectal neoplasia, might be overcome. Recently developed stool tests show an ability to diagnose cancer with much greater reliability [ 24 ]. Perhaps these gene based stool tests may establish the potential for adenoma discovery by non-invasive testing as well.Competing interests The author(s) declare that they have no competing interests.
Competing interests
The author(s) declare that they have no competing interests.Authors' contributions RLN conceived of the study, designed the questionnaire and supervised its administration. AS organized the domains of preference and performed the statistical analyses. Both authors participated in the writing of the manuscript.
Authors' contributions
RLN conceived of the study, designed the questionnaire and supervised its administration.AS organized the domains of preference and performed the statistical analyses.Both authors participated in the writing of the manuscript.Pre-publication history The pre-publication history for this paper can be accessed here:
Pre-publication history
The pre-publication history for this paper can be accessed here:


Current journal requirements forcing clinical trials to be registered [ 1 ] are insufficient and are unlikely to solve the problem of negative trials never even making it to a journal. Most of the patients consenting to clinical trials do so out of altruism. It is a great betrayal of their trust to suppress clinical trial data. I suggest that institutional review boards refuse to allow human experimentation unless the protocol is filed in a central (online) repository. The primary data should also be required to be in the public domain (say, within 1–2 years after completion). Data obtained by appealing to altrusitic instincts, similar to money in public charities, are not proprietary information, nor can physicians cash out the trust of their patients. In reality, it is the pharmaceutical industry that stands to gain the most if data are made public as such data inform future research and help smaller, innovative companies avoid redundancy. Voluntarily sticking to higher standards of ethics will raise societal respect for the industry (currently being battered for greed) and attract a more talented workforce, and may even help the current efforts to reform the tort law.


Background Recently, several members of a vertebrate protein family containing a six trans-membrane (6TM) domain and involved in apoptosis and cancer (e.g. STEAP, STAMP1, TSAP6), have been identified in Golgi and cytoplasmic membranes. The exact function of these proteins remains unknown.
Background
Recently, several members of a vertebrate protein family containing a six trans-membrane (6TM) domain and involved in apoptosis and cancer (e.g. STEAP, STAMP1, TSAP6), have been identified in Golgi and cytoplasmic membranes. The exact function of these proteins remains unknown.Methods We related this 6TM domain to distant protein families using intermediate sequences and methods of iterative profile sequence similarity search.
Methods
We related this 6TM domain to distant protein families using intermediate sequences and methods of iterative profile sequence similarity search.Results Here we show for the first time that this 6TM domain is homolog to the 6TM heme binding domain of both the NADPH oxidase (Nox) family and the YedZ family of bacterial oxidoreductases.
Results
Here we show for the first time that this 6TM domain is homolog to the 6TM heme binding domain of both the NADPH oxidase (Nox) family and the YedZ family of bacterial oxidoreductases.Conclusions This finding gives novel insights about the existence of a previously undetected electron transfer system involved in apoptosis and cancer, and suggests further steps in the experimental characterization of these evolutionarily related families.
Conclusions
This finding gives novel insights about the existence of a previously undetected electron transfer system involved in apoptosis and cancer, and suggests further steps in the experimental characterization of these evolutionarily related families.

Background A family of vertebrate proteins containing a six transmembrane domain (6TM) has been recently implicated in apoptosis and cancer. Up to date, this family contains four vertebrate members: STEAP, STAMP1/STEAP2, TIARP and TSAP6/pHyde. STEAP (six-transmembrane epithelial antigen of the prostate) was the first described member of this family and identified as a prostate-specific cell-surface antigen overexpressed in cancer, located at the cell-cell junction of the secretory epithelium of prostate, and found as well in both colon and bladder cancer cell lines [ 1 , 2 ]. STAMP1 (six transmembrane protein of prostate 1), also known as STEAP2, also overexpressed in prostate cancer, has been located in the trans-Golgi network and shuttles to plasma membranes, which suggest a role in the secretory/endocytic pathways [ 3 , 4 ]. TIARP (Tumor necrosis factor-alpha-induced adipose-related protein) is a cell surface protein induced by TNF-α and IL-6, probably implicated in resistance to insulin [ 5 , 6 ]. TSAP6 (tumor suppressor activated pathway-6), also known as pHyde [ 7 - 10 ], is a p53 inducible protein which regulates apoptosis and the cell cycle via direct interaction with Nix (a pro-apoptotic Bcl-2 related protein) and Myt1 kinase (a negative regulator of the G2/M transition) [ 9 ]. TSAP6 has been shown to be interacting with TCTP (Translationally controlled tumor protein) and could be implicated in its secretion [ 10 ]. In this work we present evidence of remote homology of this family to other two families: the mainly eukaryotic Nox and the bacterial YedZ (Fig.  1 ), both involved in redox functions [ 11 - 17 ]. The Nox family is involved in the production of reactive oxygen species (ROS) [ 11 , 12 ]. The first member of the family (gp91phox) was discovered in phagocytes and contains an N-terminal transmembrane heme binding domain and two C-terminal domains with binding sites for both flavin adenine dinucleotide (FAD) and NADPH (Fig.  2 ) [ 11 - 13 ]. Originally, ROS were thought to be used just as a mechanism of host defence. The discovery of gp91phox homologues in several other tissues has suggested their implication in many other functions, such us signal transduction, cancer, mitogenic signalling, cellular growth, angiogenesis, and modification of extracellular matrix proteins [ 11 - 14 ]. Regarding the bacterial YedZ family, the only experimentally characterized member so far is the  Escherichia coli  YedZ protein, which binds a single heme and is involved in electron transfer to the molybdopterin cofactor in YedY, its operon neighbour gene [ 16 - 18 ]. The exact function of the operon YedZ/YedY remains unknown.
Background
A family of vertebrate proteins containing a six transmembrane domain (6TM) has been recently implicated in apoptosis and cancer. Up to date, this family contains four vertebrate members: STEAP, STAMP1/STEAP2, TIARP and TSAP6/pHyde. STEAP (six-transmembrane epithelial antigen of the prostate) was the first described member of this family and identified as a prostate-specific cell-surface antigen overexpressed in cancer, located at the cell-cell junction of the secretory epithelium of prostate, and found as well in both colon and bladder cancer cell lines [ 1 , 2 ]. STAMP1 (six transmembrane protein of prostate 1), also known as STEAP2, also overexpressed in prostate cancer, has been located in the trans-Golgi network and shuttles to plasma membranes, which suggest a role in the secretory/endocytic pathways [ 3 , 4 ]. TIARP (Tumor necrosis factor-alpha-induced adipose-related protein) is a cell surface protein induced by TNF-α and IL-6, probably implicated in resistance to insulin [ 5 , 6 ]. TSAP6 (tumor suppressor activated pathway-6), also known as pHyde [ 7 - 10 ], is a p53 inducible protein which regulates apoptosis and the cell cycle via direct interaction with Nix (a pro-apoptotic Bcl-2 related protein) and Myt1 kinase (a negative regulator of the G2/M transition) [ 9 ]. TSAP6 has been shown to be interacting with TCTP (Translationally controlled tumor protein) and could be implicated in its secretion [ 10 ].In this work we present evidence of remote homology of this family to other two families: the mainly eukaryotic Nox and the bacterial YedZ (Fig.  1 ), both involved in redox functions [ 11 - 17 ]. The Nox family is involved in the production of reactive oxygen species (ROS) [ 11 , 12 ]. The first member of the family (gp91phox) was discovered in phagocytes and contains an N-terminal transmembrane heme binding domain and two C-terminal domains with binding sites for both flavin adenine dinucleotide (FAD) and NADPH (Fig.  2 ) [ 11 - 13 ]. Originally, ROS were thought to be used just as a mechanism of host defence. The discovery of gp91phox homologues in several other tissues has suggested their implication in many other functions, such us signal transduction, cancer, mitogenic signalling, cellular growth, angiogenesis, and modification of extracellular matrix proteins [ 11 - 14 ]. Regarding the bacterial YedZ family, the only experimentally characterized member so far is the  Escherichia coli  YedZ protein, which binds a single heme and is involved in electron transfer to the molybdopterin cofactor in YedY, its operon neighbour gene [ 16 - 18 ]. The exact function of the operon YedZ/YedY remains unknown.Escherichia coliMethods To do the sequence analysis of the new domain we took advantage of the possibility of connecting distant protein families via intermediate sequences [ 19 ] and methods of iterative profile sequence similarity search: HMMer [ 20 , 21 ] and PSI-BLAST [ 22 ] over the Uniprot 90% non redundant sequence database [ 23 ]. We used NAIL to view and analyse the HMMer results [ 24 ]. The alignment of transmembrane regions using standard substitution matrices might be inaccurate because of the different roles played by amino acids in globular proteins and in transmembrane media [ 25 ]. In the case of the ACRATA domain, the regions to be aligned mostly consist of amino acids located in transmembrane regions (Fig.  1 ). For this reason, we used a method based on a hidden Markov model (HMMer hmmalign), which does not rely on a general substitution matrix [ 20 , 21 ], using as a guide both the transmembrane predictions from TMHMM [ 26 , 27 ] and the results of multiple sequence alignment using T-Coffee [ 28 , 29 ]. The genomic neighborhood of the bacterial sequences (YedZ family) was analyzed to find potentially related genes in operons using STRING [ 17 , 18 ].
Methods
To do the sequence analysis of the new domain we took advantage of the possibility of connecting distant protein families via intermediate sequences [ 19 ] and methods of iterative profile sequence similarity search: HMMer [ 20 , 21 ] and PSI-BLAST [ 22 ] over the Uniprot 90% non redundant sequence database [ 23 ]. We used NAIL to view and analyse the HMMer results [ 24 ]. The alignment of transmembrane regions using standard substitution matrices might be inaccurate because of the different roles played by amino acids in globular proteins and in transmembrane media [ 25 ]. In the case of the ACRATA domain, the regions to be aligned mostly consist of amino acids located in transmembrane regions (Fig.  1 ). For this reason, we used a method based on a hidden Markov model (HMMer hmmalign), which does not rely on a general substitution matrix [ 20 , 21 ], using as a guide both the transmembrane predictions from TMHMM [ 26 , 27 ] and the results of multiple sequence alignment using T-Coffee [ 28 , 29 ]. The genomic neighborhood of the bacterial sequences (YedZ family) was analyzed to find potentially related genes in operons using STRING [ 17 , 18 ].Results The global hidden Markov profile [ 20 , 21 ] generated for STEAP and related vertebrate proteins (STEAP family, henceforth) localized the first bacterial sequence (SpTrembl Q7VKI9 from  Haemophilus ducreyi ) with an E-value of 0.63. This protein belongs to the large YedZ family of bacterial oxidoreductases. The corresponding YedZ global profile detected the STEAP family (most similar member: SpTrembl Q8IUE7, human STAMP1) with an E-value of 0.00087. The global profile of STEAP and YedZ detected the Nox family with an E-value of 0.032 and the corresponding Nox global profile localized the YedZ family with an E-value of 0.007 (Fig.  3 ). Only the regions from transmembranes 3 to 5 were considered to build the profiles because the transmembranes 1, 2 and 6 are highly variable among families. We have named this 6TM domain the ACRATA domain after  A poptosis,  C ancer and  R edox  A ssociated  T ransmembr A ne domain. To investigate the consistency of our results we performed iterative database searches using the PSI-BLAST program [ 22 ]. We used as query the most conserved region of the ACRATA domain in  E. coli  YedZ protein (residues 71–166). These searches detected all of the ACRATA domain-containing families after 15 iterations (using a cut-off of E = 0.005 for the inclusion of retrieved sequences in the profile). None of these profile searches retrieved new unrelated sequences, and reciprocal searches produced convergent results. Therefore, we have concluded that ACRATA is a previously undetected, conserved domain that is commonly found in members of the STEAP, YedZ and Nox protein families. The similarity between these proteins was suspected before [ 30 ]. However, no alignment, domain definition or substantial statistical evidence was provided to demonstrate the evolutionary relationships of these proteins. The complete conservation of two histidines in all ACRATA domain containing proteins (Fig.  1 ) indicates that the STEAP protein family could bind at least an heme group, as was previously experimentally characterized for Nox and YedZ families [ 13 , 16 ], or for other analogous proteins such as cytochromes [ 31 ].
Results
The global hidden Markov profile [ 20 , 21 ] generated for STEAP and related vertebrate proteins (STEAP family, henceforth) localized the first bacterial sequence (SpTrembl Q7VKI9 from  Haemophilus ducreyi ) with an E-value of 0.63. This protein belongs to the large YedZ family of bacterial oxidoreductases. The corresponding YedZ global profile detected the STEAP family (most similar member: SpTrembl Q8IUE7, human STAMP1) with an E-value of 0.00087. The global profile of STEAP and YedZ detected the Nox family with an E-value of 0.032 and the corresponding Nox global profile localized the YedZ family with an E-value of 0.007 (Fig.  3 ). Only the regions from transmembranes 3 to 5 were considered to build the profiles because the transmembranes 1, 2 and 6 are highly variable among families. We have named this 6TM domain the ACRATA domain after  A poptosis,  C ancer and  R edox  A ssociated  T ransmembr A ne domain.Haemophilus ducreyiACRATATo investigate the consistency of our results we performed iterative database searches using the PSI-BLAST program [ 22 ]. We used as query the most conserved region of the ACRATA domain in  E. coli  YedZ protein (residues 71–166). These searches detected all of the ACRATA domain-containing families after 15 iterations (using a cut-off of E = 0.005 for the inclusion of retrieved sequences in the profile). None of these profile searches retrieved new unrelated sequences, and reciprocal searches produced convergent results. Therefore, we have concluded that ACRATA is a previously undetected, conserved domain that is commonly found in members of the STEAP, YedZ and Nox protein families. The similarity between these proteins was suspected before [ 30 ]. However, no alignment, domain definition or substantial statistical evidence was provided to demonstrate the evolutionary relationships of these proteins.E. coliThe complete conservation of two histidines in all ACRATA domain containing proteins (Fig.  1 ) indicates that the STEAP protein family could bind at least an heme group, as was previously experimentally characterized for Nox and YedZ families [ 13 , 16 ], or for other analogous proteins such as cytochromes [ 31 ].Discussion Experimental evidence show that Nox and YedZ families share heme binding capabilities and also involvement in electron transfer chains [ 11 - 13 , 16 ]. For the STEAP family, the electron transfer capability is consistent with the presence of an N-terminal cytoplasmic NADP oxidoreductase coenzyme F420 dependent domain, being the only exception the STEAP protein itself (Fig.  2 ). Therefore we conclude that ACRATA domain is a heme binding 6TM domain that originated before the onset of eukaryotes (ancestral, YedZ), transmitted by vertical descent in a conventional manner (Nox family), and further expanded in vertebrates (STEAP family) (Fig.  4 ). Although the mechanism of action of the ACRATA domain could be the same in all the proteins containing it, its variable cellular role is made conspicuous by the different effects produced by the modifications in the expression of the corresponding genes. For example, the knock-out of the whole YedYZ operon seems not to affect  E. coli  in a number of conditions tested (Brokx, S.J. and Weiner, J.H. personal communication). Very differently, changes in the expression patterns of human genes containing the ACRATA domain could be related with apoptosis or cancer [ 1 - 14 ]. The well known functional flexibility of oxidoreductases is exemplified in bacterial proteins such as cupredoxins and cytochromes, normally involved in electron transfer during respiration but that can enter in eukaryotic cells to induce apoptosis or inhibition of cell growth [ 32 ], or in the Nox family, with functions as different as host defence in phagocytes or extracellular matrix modification [ 11 , 12 ].
Discussion
Experimental evidence show that Nox and YedZ families share heme binding capabilities and also involvement in electron transfer chains [ 11 - 13 , 16 ]. For the STEAP family, the electron transfer capability is consistent with the presence of an N-terminal cytoplasmic NADP oxidoreductase coenzyme F420 dependent domain, being the only exception the STEAP protein itself (Fig.  2 ). Therefore we conclude that ACRATA domain is a heme binding 6TM domain that originated before the onset of eukaryotes (ancestral, YedZ), transmitted by vertical descent in a conventional manner (Nox family), and further expanded in vertebrates (STEAP family) (Fig.  4 ).Although the mechanism of action of the ACRATA domain could be the same in all the proteins containing it, its variable cellular role is made conspicuous by the different effects produced by the modifications in the expression of the corresponding genes. For example, the knock-out of the whole YedYZ operon seems not to affect  E. coli  in a number of conditions tested (Brokx, S.J. and Weiner, J.H. personal communication). Very differently, changes in the expression patterns of human genes containing the ACRATA domain could be related with apoptosis or cancer [ 1 - 14 ]. The well known functional flexibility of oxidoreductases is exemplified in bacterial proteins such as cupredoxins and cytochromes, normally involved in electron transfer during respiration but that can enter in eukaryotic cells to induce apoptosis or inhibition of cell growth [ 32 ], or in the Nox family, with functions as different as host defence in phagocytes or extracellular matrix modification [ 11 , 12 ].E. coliConclusions We have described for the first time a 6TM domain present in three protein families (STEAP, YedZ and Nox): the ACRATA domain. The common functions of the proteins of those families suggest that this domain is involved in electron transfer, mediated by its heme binding capability. We hypothesize that STEAP, STAMP1, TSAP6, and TIARP have this function, and that they form part of electron transfer systems involved in cellular regulation, apoptosis, and cancer. Additional experimental approaches using different members of the ACRATA domain-containing families are required to confirm these hypotheses.
Conclusions
We have described for the first time a 6TM domain present in three protein families (STEAP, YedZ and Nox): the ACRATA domain. The common functions of the proteins of those families suggest that this domain is involved in electron transfer, mediated by its heme binding capability. We hypothesize that STEAP, STAMP1, TSAP6, and TIARP have this function, and that they form part of electron transfer systems involved in cellular regulation, apoptosis, and cancer. Additional experimental approaches using different members of the ACRATA domain-containing families are required to confirm these hypotheses.Abbreviations STEAP, six-transmembrane epithelial antigen of the prostate; STAMP1, six transmembrane protein of prostate 1; TSAP6, tumor suppressor activated pathway-6; TIARP, Tumor necrosis factor-alpha-induced adipose-related protein; TCTP, Translationally controlled tumor protein; Nox, NADPH oxidase; ROS, reactive oxygen species; TM, Trans-membrane; FAD, flavin adenine dinucleotide; HMM, Hidden Markov Models;
Abbreviations
STEAP, six-transmembrane epithelial antigen of the prostate;STAMP1, six transmembrane protein of prostate 1;TSAP6, tumor suppressor activated pathway-6;TIARP, Tumor necrosis factor-alpha-induced adipose-related protein;TCTP, Translationally controlled tumor protein;Nox, NADPH oxidase;ROS, reactive oxygen species;TM, Trans-membrane;FAD, flavin adenine dinucleotide;HMM, Hidden Markov Models;Competing interests The author(s) declare that they have no competing interests.
Competing interests
The author(s) declare that they have no competing interests.Authors' contributions LSP, AMR, and MAA carried out the sequence analysis of the domain. LSP and MAA provided with the initial input of the research. LSP, AMR, AV, CMA, and MAA authored the manuscript.
Authors' contributions
LSP, AMR, and MAA carried out the sequence analysis of the domain.LSP and MAA provided with the initial input of the research.LSP, AMR, AV, CMA, and MAA authored the manuscript.Pre-publication history The pre-publication history for this paper can be accessed here:
Pre-publication history
The pre-publication history for this paper can be accessed here:


Background It is a high priority that health care providers have effective communication skills. It has been well documented that the doctor-patient relationship is central to the delivery of high quality medical care, and it has been shown to affect patient satisfaction, to decrease the use of pain killers, to shorten hospital stays, to improve recovery from surgery and a variety of other biological, psychological and social outcomes. This study sought to quantify the current knowledge of interns in Iran about communication skills.
Background
It is a high priority that health care providers have effective communication skills. It has been well documented that the doctor-patient relationship is central to the delivery of high quality medical care, and it has been shown to affect patient satisfaction, to decrease the use of pain killers, to shorten hospital stays, to improve recovery from surgery and a variety of other biological, psychological and social outcomes. This study sought to quantify the current knowledge of interns in Iran about communication skills.Methods A cross-sectional study using a self-report questionnaire was conducted among interns. Data analysis was based on 223 questionnaires. The internal consistency of the items was 0.8979.
Methods
A cross-sectional study using a self-report questionnaire was conducted among interns. Data analysis was based on 223 questionnaires. The internal consistency of the items was 0.8979.Results Overall, knowledge levels were unsatisfactory. Results indicated that interns had a limited knowledge of communication skills, including identification of communication skills. In addition, there was a significant difference between the mean scores of interns on breaking bad news and sex education. The confidence of males about their communication skills was significantly higher than for females. Analysis of the total scores by age and sex showed that there was a statistically significant main effect for sex and the interaction with age was statistically significant. Free response comments of the interns are also discussed.
Results
Overall, knowledge levels were unsatisfactory. Results indicated that interns had a limited knowledge of communication skills, including identification of communication skills. In addition, there was a significant difference between the mean scores of interns on breaking bad news and sex education. The confidence of males about their communication skills was significantly higher than for females. Analysis of the total scores by age and sex showed that there was a statistically significant main effect for sex and the interaction with age was statistically significant. Free response comments of the interns are also discussed.Conclusions It is argued that there is a real need for integrating a communication skills course, which is linked to the various different ethnic and religious backgrounds of interns, into Iranian medical curricula. Some recommendations are made and the limitations of the study are discussed.
Conclusions
It is argued that there is a real need for integrating a communication skills course, which is linked to the various different ethnic and religious backgrounds of interns, into Iranian medical curricula. Some recommendations are made and the limitations of the study are discussed.

Background The expectations of the public have been dramatically increased and the majority of them are familiar with their rights in the health care system. As a consequence, it is a high priority that health care providers have effective communication skills. It has been well documented that the doctor-patient relationship is central to the delivery of high quality medical care. It has been shown to affect patient satisfaction, to decrease the use of pain killers, to shorten hospital stays, to improve recovery from surgery and a variety of other biological, psychological and social outcomes [ 1 - 4 ]. Lack of knowledge of communication skills, or an inability to use them effectively, can be distressing and is potentially hazardous for patients. It may also be a cause of stress for medical students arriving on the ward for the first time [ 5 ]. There is a large body of evidence indicating the importance of students' knowledge of communication skills and [ 6 , 7 ] how behaviours learned from communication skills training transfer into the clinical setting and such training is known to have long term effects on students behaviour [ 8 - 11 ]. However, little is known about the importance of communication skills in the practice and training of doctors in Iran, where the culture differs greatly from that of the West. Sensitivity to religious matters is particularly important in Iranian doctor-patient relationships where Islam is more than a religion; it is a way of life. It controls politics, local laws, behaviour and many other aspects of daily life. It gives guidance in all spheres of human activity from birth to death. Therefore doctors coming into contact with religious patients need to be aware that there are numerous potential barriers to good communication [ 12 ]. A major criticism of current medical training in Iran is that communication skills have not been embedded in the curriculum of Iranian medical students, despite the richness and variety of evidence from elsewhere concerning the importance of communication skills. Concerns over poor doctor-patient communication amongst Iranian doctors led to an exploration of the current situation [ 13 ]. In this paper we investigate the knowledge level of interns about communication skills to gain a clearer picture of some challenges relating to health care promotion, especially patient satisfaction and adherence to treatment. Two questions guided the study: (a) How do interns assess their knowledge about communication skills? (b) Is there a significant difference between the level of knowledge among male and female interns?
Background
The expectations of the public have been dramatically increased and the majority of them are familiar with their rights in the health care system. As a consequence, it is a high priority that health care providers have effective communication skills. It has been well documented that the doctor-patient relationship is central to the delivery of high quality medical care. It has been shown to affect patient satisfaction, to decrease the use of pain killers, to shorten hospital stays, to improve recovery from surgery and a variety of other biological, psychological and social outcomes [ 1 - 4 ]. Lack of knowledge of communication skills, or an inability to use them effectively, can be distressing and is potentially hazardous for patients. It may also be a cause of stress for medical students arriving on the ward for the first time [ 5 ]. There is a large body of evidence indicating the importance of students' knowledge of communication skills and [ 6 , 7 ] how behaviours learned from communication skills training transfer into the clinical setting and such training is known to have long term effects on students behaviour [ 8 - 11 ].However, little is known about the importance of communication skills in the practice and training of doctors in Iran, where the culture differs greatly from that of the West. Sensitivity to religious matters is particularly important in Iranian doctor-patient relationships where Islam is more than a religion; it is a way of life. It controls politics, local laws, behaviour and many other aspects of daily life. It gives guidance in all spheres of human activity from birth to death. Therefore doctors coming into contact with religious patients need to be aware that there are numerous potential barriers to good communication [ 12 ].A major criticism of current medical training in Iran is that communication skills have not been embedded in the curriculum of Iranian medical students, despite the richness and variety of evidence from elsewhere concerning the importance of communication skills. Concerns over poor doctor-patient communication amongst Iranian doctors led to an exploration of the current situation [ 13 ]. In this paper we investigate the knowledge level of interns about communication skills to gain a clearer picture of some challenges relating to health care promotion, especially patient satisfaction and adherence to treatment. Two questions guided the study: (a) How do interns assess their knowledge about communication skills? (b) Is there a significant difference between the level of knowledge among male and female interns?Methods A quantitative survey was performed at Tehran University of Medical Science (TUMS). A cross-sectional study was conducted using a questionnaire administered to 235 interns. Anonymity was maintained throughout. The subjects received the self-administered questionnaire with a covering letter explaining the project and the subject's rights. 12 subjects did not return the questionnaire and an additional 7 subjects did not give their age and one person did not give his/her sex. Therefore data analysis was based on 223 questionnaires, but covariate-based analysis on fewer. The subjects were asked to complete the questionnaire without referring to source books. The questionnaire consisted of three sections. The first section asked students to give personal details including the demographic items age and gender (summarised in Table  1 ). The second section is related to the educational items: subjects studied or attended in a specific course about communication skills (Table  2 ). The third section asked students to rate their knowledge of communication skills and, if they rated themselves higher than 5, discuss the item briefly in the space provided in order to assess their real knowledge with regard to that communication skill. In addition, they were encouraged to provide additional written comments on the questionnaire. The communication skills knowledge scale (CSKS) developed here consists of 10 items about communication skills. Each item is measured on a 10-point scale, ranging from 1 (low) to 10 (high). Table 1 Distribution of background characteristics Variables Number Percentages Sex Male 132 59.5 Female 90 40.5 Total 222 100 Age Less than 25 114 52.8 25–30 96 44.4 More than 30 6 2.8 Total 216 100 Table 2 Percentage response to educational items by interns Educational item Yes No % % 1. Have you studied a paper in relation to communication skills? (n = 219) 21.9 78.1 2. Have you formally attended communication skills courses? (n = 221) 8.6 91.4 The choice of items was based on the communication skills an intern will need. All items were verified and subjected to content validation by three major experts in communication skills. These experts were given copies of the CSKS and the purpose and objectives of the study. They then evaluated the CSKS on an individual basis. Comparisons were made between these evaluations and the authors then made some minor changes within the CSKS. The CSKS had a high internal consistency ( Cronbach alpha  = 0.8979). The validity of the CSKS can only be examined through logical rather than empirical means. Since the CSKS was not compared to a standardised test, it was impossible to obtain a numerical estimate of the validity of the test. However, based on logical means, i.e., a respectable  Cronbach alpha  and high inter-rater agreements on each item, the authors believe that the test is valid. The questions and responses have been translated from Persian into English for this paper.
Methods
A quantitative survey was performed at Tehran University of Medical Science (TUMS). A cross-sectional study was conducted using a questionnaire administered to 235 interns. Anonymity was maintained throughout. The subjects received the self-administered questionnaire with a covering letter explaining the project and the subject's rights. 12 subjects did not return the questionnaire and an additional 7 subjects did not give their age and one person did not give his/her sex. Therefore data analysis was based on 223 questionnaires, but covariate-based analysis on fewer. The subjects were asked to complete the questionnaire without referring to source books.The questionnaire consisted of three sections. The first section asked students to give personal details including the demographic items age and gender (summarised in Table  1 ). The second section is related to the educational items: subjects studied or attended in a specific course about communication skills (Table  2 ). The third section asked students to rate their knowledge of communication skills and, if they rated themselves higher than 5, discuss the item briefly in the space provided in order to assess their real knowledge with regard to that communication skill. In addition, they were encouraged to provide additional written comments on the questionnaire. The communication skills knowledge scale (CSKS) developed here consists of 10 items about communication skills. Each item is measured on a 10-point scale, ranging from 1 (low) to 10 (high).Distribution of background characteristicsPercentage response to educational items by internsThe choice of items was based on the communication skills an intern will need. All items were verified and subjected to content validation by three major experts in communication skills. These experts were given copies of the CSKS and the purpose and objectives of the study. They then evaluated the CSKS on an individual basis. Comparisons were made between these evaluations and the authors then made some minor changes within the CSKS. The CSKS had a high internal consistency ( Cronbach alpha  = 0.8979).Cronbach alphaThe validity of the CSKS can only be examined through logical rather than empirical means. Since the CSKS was not compared to a standardised test, it was impossible to obtain a numerical estimate of the validity of the test. However, based on logical means, i.e., a respectable  Cronbach alpha  and high inter-rater agreements on each item, the authors believe that the test is valid. The questions and responses have been translated from Persian into English for this paper.Cronbach alphaResults The potential score range from the 10-item CSKS (by summing all 10 item scores) is 10 to 100, with 10 indicating low knowledge. Analysis of the total scores produced a mean score of 51.30 [95 per cent confidence interval (CI) 49.05–53.55]. The subjects' performance on the CSKS suggests a knowledge deficit in communication skills. The mean scores for males and females were respectively 53.6 and 48.2 (P = 0.02). The vast majority of interns (78.1%) had not studied a paper on communication skills. When asked whether they had formally attended communication skills courses, 91.4% of interns reported "no". Of the few interns who reported "yes", these interns specified courses such as CPR, injections and semiology (Table  3 ), which are not formal communication skills courses. Table 3 Courses of communication skills training reported by interns Courses Number CPR 2 EBM 1 Ethics 4 Health 2 Injection 1 Skills lab 3 Semiology 3 Workshop 1 Total 17 The analysis of the scores by topic is shown in table  4 . The possible range of scores for each item was 1 to 10. Mean scores for topics ranged from 2.8 to 6.1. Interns were most confident on "giving and receiving information", and the least confident on "sex education". Table 4 Analysis of results by communication skill Topics Mean P Value Male (SD) Female (SD) Breaking bad news 4.6 (2.0) 3.7 (2.0) 0.02 Dealing with anger/difficult patient 5.0 (2.4) 4.4 (2.2) 0.81 Demonstration of empathy 5.3 (2.3) 5.5 (2.4) 0.56 Giving and receiving information 6.1 (2.3) 5.9 (2.2) 0.46 Non-verbal communication skills 5.3 (2.5) 5.0 (2.0) 0.37 Dealing with patient perception 5.8 (2.4) 5.4 (2.1) 0.22 Shared decision making 5.7 (2.2) 5.4 (2.3) 0.28 Patient-oriented interviewing 5.4 (2.3) 5.3 (2.3) 0.17 Sex education 4.6 (2.7) 2.8 (1.9) 0.00 Closing skills 5.4 (2.4) 4.8 (2.4) 0.08 Total 53.6 (17.4) 48.2 (15.8) 0.02 A two-way between-groups analysis was conducted to explore the impact of sex and age on levels of knowledge, as measured by the CSKS. Subjects were divided into two groups according to their age (less than 25 years, or 25 years and above). There was a statistically significant main effect for sex [F (1, 212) = 4.90, p = 0.02] and the interaction effect [F (1, 212) = 4.06, p = 0.04) did reach statistical significance. However the effect size was small (eta squared = 0.02). The young male interns were more confident than average, while the young female interns were less confident. Free responses included the following comments: ' Nobody has trained us about communication skills. Our knowledge in respect of communication skills is very poor. Your items show that we are very far behind other countries. Our universities are not as advanced as other universities' . 'I feel we are not familiar with the ABC of communication skills' . 'A good guide to communication skills needed' . 'I feel communication skills would be an excellent course since it gives us an idea of how we can handle bad news' . 'Attending doctors are not totally familiar with the aims and use of communication skills in the clinical setting' . 'All our courses only focus on biological issues rather than psychosocial issues'
Results
The potential score range from the 10-item CSKS (by summing all 10 item scores) is 10 to 100, with 10 indicating low knowledge. Analysis of the total scores produced a mean score of 51.30 [95 per cent confidence interval (CI) 49.05–53.55]. The subjects' performance on the CSKS suggests a knowledge deficit in communication skills. The mean scores for males and females were respectively 53.6 and 48.2 (P = 0.02). The vast majority of interns (78.1%) had not studied a paper on communication skills. When asked whether they had formally attended communication skills courses, 91.4% of interns reported "no". Of the few interns who reported "yes", these interns specified courses such as CPR, injections and semiology (Table  3 ), which are not formal communication skills courses.Courses of communication skills training reported by internsThe analysis of the scores by topic is shown in table  4 . The possible range of scores for each item was 1 to 10. Mean scores for topics ranged from 2.8 to 6.1. Interns were most confident on "giving and receiving information", and the least confident on "sex education".Analysis of results by communication skillA two-way between-groups analysis was conducted to explore the impact of sex and age on levels of knowledge, as measured by the CSKS. Subjects were divided into two groups according to their age (less than 25 years, or 25 years and above). There was a statistically significant main effect for sex [F (1, 212) = 4.90, p = 0.02] and the interaction effect [F (1, 212) = 4.06, p = 0.04) did reach statistical significance. However the effect size was small (eta squared = 0.02). The young male interns were more confident than average, while the young female interns were less confident.Free responses included the following comments:' Nobody has trained us about communication skills. Our knowledge in respect of communication skills is very poor. Your items show that we are very far behind other countries. Our universities are not as advanced as other universities' .Nobody has trained us about communication skills. Our knowledge in respect of communication skills is very poor. Your items show that we are very far behind other countries. Our universities are not as advanced as other universities''I feel we are not familiar with the ABC of communication skills' .'I feel we are not familiar with the ABC of communication skills''A good guide to communication skills needed' .'A good guide to communication skills needed''I feel communication skills would be an excellent course since it gives us an idea of how we can handle bad news' .'I feel communication skills would be an excellent course since it gives us an idea of how we can handle bad news''Attending doctors are not totally familiar with the aims and use of communication skills in the clinical setting' .'Attending doctors are not totally familiar with the aims and use of communication skills in the clinical setting''All our courses only focus on biological issues rather than psychosocial issues'Limitations There were a number of limitations to this study. 1. The CSKS has not been normed for a population of interns. 2. Criterion-related validity of the CSKS was not determined, although content validity was established on the instrument. 3. Since it is a self-assessed questionnaire, these may be problems with bias, such as prestige bias.
Limitations
There were a number of limitations to this study.1. The CSKS has not been normed for a population of interns.2. Criterion-related validity of the CSKS was not determined, although content validity was established on the instrument.3. Since it is a self-assessed questionnaire, these may be problems with bias, such as prestige bias.Discussion The very high response rate (95%) of this questionnaire may have reflected general interest, or may have resulted from the advantages of self-assessment which itself may improve performance. The results on the CSKS show that basic knowledge of interns in Iran about communication skills is limited. Researchers have reported similar findings in other countries which reveal a deficit in the knowledge of doctors about communication skills [ 14 ]. The importance of communication skills has long been acknowledged in general practice training [ 15 ] and the need to teach communication skills formally, as part of British undergraduate medical education, has also been recognised [ 16 ]. In Iran, interns' knowledge deficiency may be attributed to the fact that interns have never been trained to consult in the general practice setting, and their skills are limited to making value judgements, often using the only available criterion, comparison with their own style [ 13 ]. This approach to a patient is not cost effective and may lead to negative health outcomes such as patient dissatisfaction, poor adherence to treatment and medical errors [ 17 ]. A few students reported their attendance at courses such as EBM, semiology, skills lab or CPR, which have no relation with communication skills training. This indicates that students are not familiar with the tasks of communication skills [ 18 ]. The vast majority of research studies have been conducted on the outcome of communication skills in the practice and training of doctors in western countries. Even here, despite doctors trained in communication skills and the advocacy of the use of a patient-oriented approach, some evidence suggests that there are difficulties in practice [ 19 , 20 ]. However, research has demonstrated that communication skills training intervention using behavioural, cognitive and affective domains can increase not only potentially beneficial and effective interviewing styles, but also alter attitudes and confer other benefits [ 9 , 21 ]. The results of the study show that there were significant differences between males and females with regard to their reported knowledge of the main communication skills. Women were less confident of their skills. The deficit may partly be an artefact of an inadvertent prestige bias of the male students. The deficit is particularly notable in sex education. There are three possible explanations for this. Firstly, in general, Iranian female interns are very shy to ask patients about sexual issues. Therefore they may feel that sex education skills have no implications for their practice and hence pay less attention to sex education training. Secondly, it may be a systematic error in female respondents, i.e. they may be shy to discuss their knowledge about sex education skills rather than lack knowledge. Thirdly, in the past, sex education was regarded as a taboo in Iran and was not available in schools, especially for girls [ 22 ]. This perhaps acts as an inhibitory factor on the basic knowledge of sex education. Within this context, there is no evidence that shows similar results for gender difference on the knowledge of sex education in the practice and training of doctors. The results on the CSKS suggest that there are areas of weakness in the communication skills confidence of interns, particularly in breaking bad news. While it is well recognised that delivering bad news is a difficult task that requires skills and sensitivity [ 23 ], both female interns and male interns reported that their confidence in breaking bad news is low, especially the female interns. While the interns commented on the need to improve medical students' communication skills, it seems that guidelines on delivering bad news to patients and patients' family members have not been seriously taken into consideration in the practice and training of doctors in Iran. This could be due to interns possessing deep fears regarding delivering bad news to patients' family members, or because they are unaware of the general guidelines about delivering bad news [ 24 ]. Three studies which have attempted to address residents' perception of delivering bad news indicate that residents had experienced discomfort with psychosocial issues related to the conveyance of bad news, such as personal fears and different perceptions of bad news [ 25 - 27 ]. There is a significant difference between the mean score of the interns on breaking bad news. The female interns have reported lower confidence than the male interns. The deficit could be an inadvertent prestige bias of the male students. However, to our knowledge, there is no evidence that underpin such finding. Although Orlander et al's work [ 28 ] demonstrated there were no significant differences between males and females with regard to the type of bad news, residents' knowledge with regard to breaking bad news was not reported by the authors. Therefore, some empirical research is essential. Given the poor levels of confidence about communication skills, particularly sex education skills, revealed in this study, it is concluded that educational programmes are necessary. In sex education skills training, given the complex interplay of cultural and religious beliefs in Iran, particular attention must be paid to multicultural and religious issues. Therefore, further work is needed on gender education and stereotypes in sex education; learning styles; the 'hidden curriculum'; and how far medical schools make organisational and administrative arrangements on the basis of gender and the implication for female and male interns. The enthusiastic response to the questionnaires may suggest that medicine is accepting the need for developing communication skills within the medical curriculum. Medical education in Iran must respond to this challenge. Finally, our findings may be somewhat limited in generalisability because they are derived from only one medical school in Iran. Self-assessment data may suffer from biases such as prestige bias. Despite these caveats, the authors believe the data to be an accurate reflection of current practice in Iran, based on the Iranian authors training experiences, and consistency with previous accounts.
Discussion
The very high response rate (95%) of this questionnaire may have reflected general interest, or may have resulted from the advantages of self-assessment which itself may improve performance. The results on the CSKS show that basic knowledge of interns in Iran about communication skills is limited. Researchers have reported similar findings in other countries which reveal a deficit in the knowledge of doctors about communication skills [ 14 ]. The importance of communication skills has long been acknowledged in general practice training [ 15 ] and the need to teach communication skills formally, as part of British undergraduate medical education, has also been recognised [ 16 ]. In Iran, interns' knowledge deficiency may be attributed to the fact that interns have never been trained to consult in the general practice setting, and their skills are limited to making value judgements, often using the only available criterion, comparison with their own style [ 13 ]. This approach to a patient is not cost effective and may lead to negative health outcomes such as patient dissatisfaction, poor adherence to treatment and medical errors [ 17 ]. A few students reported their attendance at courses such as EBM, semiology, skills lab or CPR, which have no relation with communication skills training. This indicates that students are not familiar with the tasks of communication skills [ 18 ].The vast majority of research studies have been conducted on the outcome of communication skills in the practice and training of doctors in western countries. Even here, despite doctors trained in communication skills and the advocacy of the use of a patient-oriented approach, some evidence suggests that there are difficulties in practice [ 19 , 20 ]. However, research has demonstrated that communication skills training intervention using behavioural, cognitive and affective domains can increase not only potentially beneficial and effective interviewing styles, but also alter attitudes and confer other benefits [ 9 , 21 ].The results of the study show that there were significant differences between males and females with regard to their reported knowledge of the main communication skills. Women were less confident of their skills. The deficit may partly be an artefact of an inadvertent prestige bias of the male students. The deficit is particularly notable in sex education. There are three possible explanations for this. Firstly, in general, Iranian female interns are very shy to ask patients about sexual issues. Therefore they may feel that sex education skills have no implications for their practice and hence pay less attention to sex education training. Secondly, it may be a systematic error in female respondents, i.e. they may be shy to discuss their knowledge about sex education skills rather than lack knowledge. Thirdly, in the past, sex education was regarded as a taboo in Iran and was not available in schools, especially for girls [ 22 ]. This perhaps acts as an inhibitory factor on the basic knowledge of sex education. Within this context, there is no evidence that shows similar results for gender difference on the knowledge of sex education in the practice and training of doctors.The results on the CSKS suggest that there are areas of weakness in the communication skills confidence of interns, particularly in breaking bad news. While it is well recognised that delivering bad news is a difficult task that requires skills and sensitivity [ 23 ], both female interns and male interns reported that their confidence in breaking bad news is low, especially the female interns. While the interns commented on the need to improve medical students' communication skills, it seems that guidelines on delivering bad news to patients and patients' family members have not been seriously taken into consideration in the practice and training of doctors in Iran. This could be due to interns possessing deep fears regarding delivering bad news to patients' family members, or because they are unaware of the general guidelines about delivering bad news [ 24 ]. Three studies which have attempted to address residents' perception of delivering bad news indicate that residents had experienced discomfort with psychosocial issues related to the conveyance of bad news, such as personal fears and different perceptions of bad news [ 25 - 27 ].There is a significant difference between the mean score of the interns on breaking bad news. The female interns have reported lower confidence than the male interns. The deficit could be an inadvertent prestige bias of the male students. However, to our knowledge, there is no evidence that underpin such finding. Although Orlander et al's work [ 28 ] demonstrated there were no significant differences between males and females with regard to the type of bad news, residents' knowledge with regard to breaking bad news was not reported by the authors. Therefore, some empirical research is essential.Given the poor levels of confidence about communication skills, particularly sex education skills, revealed in this study, it is concluded that educational programmes are necessary. In sex education skills training, given the complex interplay of cultural and religious beliefs in Iran, particular attention must be paid to multicultural and religious issues. Therefore, further work is needed on gender education and stereotypes in sex education; learning styles; the 'hidden curriculum'; and how far medical schools make organisational and administrative arrangements on the basis of gender and the implication for female and male interns.The enthusiastic response to the questionnaires may suggest that medicine is accepting the need for developing communication skills within the medical curriculum. Medical education in Iran must respond to this challenge.Finally, our findings may be somewhat limited in generalisability because they are derived from only one medical school in Iran. Self-assessment data may suffer from biases such as prestige bias. Despite these caveats, the authors believe the data to be an accurate reflection of current practice in Iran, based on the Iranian authors training experiences, and consistency with previous accounts.Conclusions Whilst the approach to this research has been shaped by a government-recognised health need, the authors recognise the need for, and welcome, further examination of these findings from multiple perspectives, especially with regards to ethnicity and social issues. Since not enough attention has been focused on individuals as makers of health as a service rather than customers of health care services, it is strongly recommended, therefore, that medical students be trained in the context of psychosocial issues that may influence health behaviour, as has been indicated by one of the participants. It is particularly important that this type of approach be incorporated into the curricula of medical training. This may assist in transferring from the disease-oriented to the patient-oriented approach and ultimately lead to patients understanding more and taking greater responsibility for their own health.
Conclusions
Whilst the approach to this research has been shaped by a government-recognised health need, the authors recognise the need for, and welcome, further examination of these findings from multiple perspectives, especially with regards to ethnicity and social issues. Since not enough attention has been focused on individuals as makers of health as a service rather than customers of health care services, it is strongly recommended, therefore, that medical students be trained in the context of psychosocial issues that may influence health behaviour, as has been indicated by one of the participants. It is particularly important that this type of approach be incorporated into the curricula of medical training. This may assist in transferring from the disease-oriented to the patient-oriented approach and ultimately lead to patients understanding more and taking greater responsibility for their own health.Competing interests The author(s) declare that they have no competing interests.
Competing interests
The author(s) declare that they have no competing interests.Authors' contributions MT and ST carried out the conception, design, initial analysis and interpretation of the data. MT drafted the paper. ODL was involved in revising the draft critically, revising the statistical analysis and gave final approval of the version to be published. AAZ contributed to the collection of data and the reviewing of the manuscript.
Authors' contributions
MT and ST carried out the conception, design, initial analysis and interpretation of the data. MT drafted the paper. ODL was involved in revising the draft critically, revising the statistical analysis and gave final approval of the version to be published. AAZ contributed to the collection of data and the reviewing of the manuscript.Pre-publication history The pre-publication history for this paper can be accessed here:
Pre-publication history
The pre-publication history for this paper can be accessed here: