The purpose of this study was to confirm that women with latent toxoplasmosis have developmentally younger fetuses at estimated pregnancy week 16 and to test four exclusive hypotheses that could explain the observed data.Toxoplasma-free and 185 Toxoplasma-infected pregnant women.In the present retrospective cohort study we analysed by the GLM  method data from 730 P = 0.014). Pregnancy of Toxoplasma-positive compared to Toxoplasma-negative women was by about 1.3 days longer, as estimated both from the date of the last menstruation (P = 0.015) and by ultrasonography (P = 0.025).At pregnancy week 16 estimated from the date of the last menstruation, the mothers with latent toxoplasmosis had developmentally younger fetuses based on ultrasound scan (Toxoplasma-positive women. The phenomenon was only detectable in multiparous women, suggesting that the immune system may play some role in it.The most parsimonious explanation for the observed data is retarded fetal growth during the first weeks of pregnancy in  Toxoplasma gondii, is probably the most widespread human parasitosis. In immunocompetent humans, postnatally acquired toxoplasmosis is either inapparent, or accompanied by cervical lymphadenopathy with fever, joint pain, headache and tiredness [Toxoplasmosis, a zoonosis caused by a protozoan, iredness ,2. The airedness . The mosiredness . Approxiiredness .Toxoplasma have more sons [Toxoplasma antibodies (and therefore probably recent infection) gave birth to 250 boys per 100 girls. Moreover, slower fetal development was observed at estimated pregnancy week 16 in women with latent toxoplasmosis based on ultrasonography [Toxoplasma-infected women. The aims of the present study were to confirm the retarded fetal development in an independent retrospective cohort study, and to test four exclusive hypotheses that could explain the observed data:For pregnant women with latent toxoplasmosis neither pathological changes in newborns nor health damage due to toxoplasmosis in mothers have been reported. It was speculated about possible effects of latent toxoplasmosis on the risk of abortion ; howeverore sons . In a laIn infected women the fetal development is slower but the delivery does not take place until the fetus reaches the usual birth parameters, e.g. birth weight and length. Therefore infected women are likely to have longer pregnancy as estimated both from the date of the last menstruation and based on ultrasonography.Toxoplasma-free women independently of the child's size at birth. Therefore infected women are likely to have the same pregnancy length as Toxoplasma-free women estimated based on the date of the last menstruation and shorter pregnancy estimated based on the first ultrasonography. Infants of infected women are likely to have lower birth weight.In infected women, the fetal development is slower but pregnancy duration is still 280 days on average as in In infected women, ovulation occurs in the later phase of the menstruation cycle. Therefore the first ultrasonography shows correctly the fetal age, pregnancy duration estimated based on ultrasonography is the same as in women without toxoplasmosis but the pregnancy duration estimated from the date of the last menstruation is longer.Toxoplasma-infected and Toxoplasma-free women at pregnancy week 16 when the male and female fetuses are studied separately.Women with and without toxoplasmosis differ from each other in the secondary sex ratio  and the Toxoplasma to decide which of the four above mentioned hypotheses best corresponds to the empirical data.In our cohort study, we analysed clinical records of 1,035 pregnant women tested for the presence of anamnestic antibodies against Toxoplasma was diagnosed with the indirect immunofluorescence test (IIFT) at dilutions between 1:8 and 1:1024. The samples with specific fluorescence visible in a 1:16 or higher dilution was considered as Toxoplasma-positive. In the study set, 208 women tested Toxoplasma-positive . Clinical records comprised maternal antibody titres, age, number of previous deliveries, number of previous abortions, newborn's sex and birth weight and length, date of the last menstruation, pregnancy length estimated based on the first ultrasonography (mostly between pregnancy weeks 8 and 12), and bioparameter data from fetal ultrasonography  done approximately at pregnancy weeks 20 and 30. The data on the last menstruation can be affected by stochastic errors; however, stochastic errors cannot be responsible for false positive results.The experimental set consisted of clients of two private clinics (Centres of Reproductive Medicine in Prague 5 and Prague 8). The experimental design was a cohort study. With the help of the personnel from these clinics, anonymous data was collected on the progress of 1,053 pregnancies. The original data set included records of all clients tested for toxoplasmosis from 1996–2004 who were Czech citizens and inhabitants of the city of Prague. Women were serologically tested for toxoplasmosis at about pregnancy week 16. The presence of anamnestic antibodies against Toxoplasma-infected. The data set included 642, 342, 58, 10 and 1 records concerning newborns from the first, second, third, fourth and fifth pregnancy, respectively. Data on the twins were excluded from the data set. Given that some records were incomplete, 66 women with missing data were excluded from the respective analyses. For example, some women were excluded because of the missing data on pregnancy length estimated based on ultrasonography at pregnancy week 16 (43 cases), suspected acute toxoplasmosis, i.e. high IgM and IgA titres (2 cases) or probable error in the date of the last menstruation when the difference in pregnancy length estimated based on ultrasonography and from the date of the last menstruation was greater than 20 days (21 cases).The average maternal age was 30 (19–44). Thirty-six women gave birth to twins, with 7 of them being ® 6.0 software. The study was approved by the IRB of the Faculty of Science, Charles University, and complied with the current laws of the Czech Republic.The influence of toxoplasmosis on pregnancy length at pregnancy week 16 estimated based on the first ultrasonography was evaluated by the GLM  method. Independent variables in the model were the binary variable TOXO and continuous variables maternal age and pregnancy length estimated from the last menstruation. The GLM model was also used for studying the effects of toxoplasmosis (independent variable TOXO) and maternal age (independent continuous variable), on the newborn's birth length and weight, fetal bioparameters measured by ultrasonography at pregnancy weeks 20 and 30, and pregnancy length. The continuous variable pregnancy length estimated from the date of the last menstruation was included into the model used for testing the effect of toxoplasmosis on fetal bioparameters. Women with preterm delivery (pregnancy length less than 266 days ), were eToxoplasma-infected subjects had a shorter pregnancy (111.56 days) than 730 Toxoplasma-free subjects (112.59 days) . The continuous predictors in the model were also significant: maternal age , and presumptive pregnancy length estimated from the date of the last menstruation . The same model was used for evaluating the effects of toxoplasmosis separately in women with male and female offspring. In both cases the influence of latent toxoplasmosis on pregnancy length was significant in one-tailed tests . The separate tests for primiparous and multiparous women showed that the effect of toxoplasmosis was significant for multiparous women , while for primiparous women this effect was not significant  , birth weight  and in the subset of multiparous women: birth length , birth weight .Toxoplasmosis had no effect on fetal bioparameters measured by ultrasonography at pregnancy weeks 20 and 30 in both the whole study set Table  and the Toxoplasma-infected women had longer pregnancy than Toxoplasma-free women   , . To estimate influence of available confounding variables and interactions, we also analysed two models with independent variables TOXO, newborn's SEX and PARITY , and the dependent variable pregnancy length estimated either based on ultrasonography or from the date of the last menstruation. The effect of TOXO on pregnancy length estimated both based on ustrasonography and from the date of last menstruation was significant . On the other hand, no effect of interaction, including TOXO-PARITY and TOXO-newborn's SEX, was significant in any model.Toxoplasma-infected and Toxoplasma-free women. As for our four proposed hypotheses, the obtained data confirm hypothesis No. 1 that assumes the slower fetal development in women with toxoplasmosis with the determination of pregnancy length based on fetal bioparameters. Hypotheses No. 2 and 3 can be rejected on the basis of the observed differences in pregnancy length between Toxoplasma-infected and Toxoplasma-free women and Hypothesis No. 4 was disproved on the basis of positive results of the analysis performed separately for the male and female offspring.The results confirmed the already reported differences in the early fetal development between Toxoplasma could directly retard the fetal development or could shift the moment of the implantation of the blastocyst or reduce the stringency of embryo quality control, thus allowing fetuses with mild developmental disorders to escape it. Retarded fetal development could be a result of subclinical health impairment in Toxoplasma-infected women. Chronic pathogenic processes can affect the circulation of blood in the uterus and maternal part of the placenta with consequent fetal malnutrition [Toxoplasma-infected women. In its early phase, the fetal development is most susceptible to environmental disturbances [Toxoplasma-infected and Toxoplasma-free women were strongest early in pregnancy, and turned out to be nonsignificant at pregnancy weeks 20 and 30.The slower fetal development in infected women can be explained at least by three principally different proximal mechanisms. utrition . Toxoplaurbances . It is iToxoplasma-infected women. Immunological memory is suspected to be responsible for the differences between the first pregnancy and the following ones [Toxoplasma-infected women could be less immunized by antigens on the surface of the blastocyst during the first pregnancy and consequently, the blastocyst implantation in later pregnancies could be delayed.The influence of toxoplasmosis on pregnancy was only observed in multiparous women and remained nonsignificant in primiparous women. It suggests that the maternal immune system could play some role in the proximate mechanism of impairment of the fetal development in ing ones ,14. Two ing ones . Toxoplaing ones ,17 that Toxoplasma could weaken or switch off the mechanism of spontaneous abortion, normally responsible for removal of embryos with developmental defects . Some components of the immune system probably play a role in the effector arm of this quality control process. Toxoplasmosis is known to be associated with suppression of the immune system [Toxoplasma-infected mothers could bear to full term more children with developmental defects. This could explain the smaller fetal size at the first ultrasonography as well as longer pregnancy in Toxoplasma-infected women. The stronger effect of toxoplasmosis in multiparous women can result from the previous immunization by trophoblast or embryonic antigens leading to generally higher stringency of quality control mechanisms. In Toxoplasma-free multiparous (and therefore immunized) women, most fetuses with any developmental defect are likely to be aborted. In Toxoplasma-infected women whose immunization against trophoblast and embryonic antigens is lower (due to Toxoplasma induced immunosuppression), a higher percentage of defective embryos are likely to survive.The other hypothesis suggests that e system . Due to Toxoplasma infection [Toxoplasma infection is in fact only statistically associated with some unknown socioeconomic or possibly even infection factor that is responsible for the observed effects. On the other hand, most toxoplasmosis-associated effects such as changes in novelty seeking, activity, reaction times and the secondary sex ratio have been already confirmed by experimental infection of laboratory mice or rats [Toxoplasma on the organism of its host seem to be the most parsimonious explanation for the observed phenomena.Most previous studies assumed that the latent toxoplasmosis-associated behavioural and physiological changes are a product of nfection . It cann or rats ,20. TherThe effect of latent toxoplasmosis on pregnancy is rather low. The relatively high statistical significance is partly caused by the large size of the studied sample (n = 915); it must be stressed, however, that the effect size estimated on the basis of the eta squared is less than 1%. The difference in pregnancy length of 1.3 days seems to be of no importance for clinical practice. However, the slightly retarded fetal development could not be the only effect of latent toxoplasmosis on pregnancy. Nothing is known either about the possible influence of latent toxoplasmosis in the mother on the postnatal development of her child. Latent toxoplasmosis affects as many as 84% of women in some populations , while tToxoplasma-infected women is slower, but the delivery does not take place until the fetus reaches the usual birth parameters, e.g. birth weight and length. The maternal immune system probably plays a role in the proximate mechanism of impairment of the fetal development in Toxoplasma-infected women.The obtained data confirmed that the fetal development in The author(s) declare that they have no competing interest.Both authors contributed equally to this work and read and approved the final manuscript.The pre-publication history for this paper can be accessed here:


Ultrabithorax (aUbx) in the millipede Glomeris and the centipede Lithobius are expressed in patterns complementary to that of the Ubx sense transcripts. A similar complementary expression pattern has been described for non-coding RNAs (ncRNAs) of the bithoraxoid (bxd) locus in Drosophila, in which the transcription of bxd ncRNAs represses Ubx via transcriptional interference. We discuss our findings in the context of possibly conserved mechanisms of Ubx regulation in myriapods and the fly.Antisense transcripts of Ubx and Antennapedia (Antp) has been reported previously for a myriapod and a number of crustaceans. In this paper, we show that Ubx/Antp bicistronic transcripts also occur in Glomeris and an onychophoran, suggesting further conserved mechanisms of Hox gene regulation in arthropods.Bicistronic transcription of aUbx in all investigated myriapods, whereas in other arthropod classes, including the Onychophora, aUbx is not expressed. Of the two splice variants of Ubx/Antp only one could be isolated from myriapods, representing a possible further synapomorphy of the Myriapoda.Myriapod monophyly is supported by the expression of  Drosophila, the initially established expression patterns of the Hox genes are maintained by the trithorax (trxG) and Polycomb group (PcG) factors . A b1 Figure . We expeaUbx in members of other arthropod classes and an onychophoran. Sense probes of the same length as the antisense probes used for the detection of Ubx in Tribolium (Insecta), the two known Ubx paralogs in Cupiennius (Chelicerata) [Ubx in Euperipatoides (Onychophora) failed to detect any transcripts. In all cases, positive controls detecting the Ubx signal were successfully probed with antisense probes in parallel experiments (data not shown).We investigated the possible expression of icerata) , and UbxUltrabithorax are presently known from four myriapod species: the geophilomorph Strigamia maritima (Chilopoda) [L. atkinsoni and L. forficatus ([G. marginata (Progoneata) [Ubx is transcribed and the expression pattern of the antisense transcripts (aUbx) is complementary to that of the sense transcript   ; the litficatus ( and thisgoneata) . In all t; Ubx)  is involved in the regulation of the other. Striking similarities to the situation in myriapods can be found in Drosophila, in which transcription of bxd non-coding RNAs (ncRNAs) upstream of Ubx prevents transcription of the latter. This repression is probably caused by transcriptional interference as the bxd transcript(s) elongate into the region of Ubx promoters and prevent the binding of the transcription machinery [bxd ncRNAs are expressed in a complementary pattern to that of Ubx, causing a mosaic-type expression pattern of Ubx within its overall expression domain [The fact that achinery ,30. As an domain ,6aUbx, is expressed in a complementary pattern to that of Ubx. Like the bxd ncRNAs in Drosophila, aUbx also precedes expression of Ubx, and also as in Drosophila, expression of Ubx in myriapods occurs in the anterior of each segment and expression of bxd and aUbx occur in the posterior of each segment .bxd ncRNAs in Drosophila and aUbx in myriapods is that aUbx (or its promoter) is located on the complementary DNA strand in myriapods and not oriented in a tandem position to Ubx on the same strand. How can this disparity be explained if we assume that aUbx expression in myriapods is homologous to bxd expression in Drosophila?The most obvious difference between the expression of Ubx locus back in the stem lineage leading to the myriapods, placing the aUbx (bxd) promoter on the complementary strand  are conserved and thus are most probably of strong developmental importance, thus they are unlikely to have been separated in this way. A single inversion event putting Ubx alone on the complementary strand can also be excluded because of the presence of Ubx/Antp bicistronic transcripts that are very unlikely to be a result of a trans-splicing event (discussed below) [bxd/aUbx promoter site evolved on the complementary strand located between Antp and Ubx  ,32. An ax Figure . FunctioDrosophila and myriapods has been discussed in the previous section. However, although this possibility appears to be likely, aUbx or its transcription could nevertheless also act differently. We therefore summarize and discuss some of those mechanisms in the light of our data.A number of theories have been suggested over the past few years to explain how noncoding antisense transcripts or bidirectional transcription may regulate the expression of the coding unit RNA, a source for small interfering RNAs that would mediate RNA interference (RNAi) . The combx dsRNA .aUbx is expressed significantly earlier than Ubx may also have important implications on the regulatory mechanisms discussed. It would guarantee the immediate binding of incorrectly expressed Ubx to pre-existing aUbx in an RNAi-based mechanism, or provide a head start for transcription of aUbx in cases of transcriptional interference. In the case of epigenetic modification, it would prevent the later transcription of Ubx by silencing its promoter(s).The fact that Ubx. This sequence most probably represents a minisatellite  common in bacterial and metazoan genomes [Ubx. The finding of an SSR could generally also be of interest for investigating population genetics in Glomeris [We discovered a repetitive sequence of exactly 21 bp Figure  in the 3 genomes . It may  genomes . AlternaGlomeris .Ubx and Antp (Ubx/Antp) are present in myriapods and crustaceans suggests that this represents a conserved state of at least the Mandibulata or potentially the Arthropoda. Despite this, we failed to isolate Ubx/Antp fusion transcripts from the beetle T. castaneum. The latter may merely represent a loss in higher insects that finally allowed the Hox complex to split between Ubx and Antp, as is the case in Drosophila melanogaster [Tribolium, the Hox cluster is still intact [Ubx/Antp in the stem lineage of the insects or hexapods. If the hexapods have evolved from a crustacean ancestor (as in the Pancrustacea theory), a loss of Ubx/Antp may be present in the suggested recent sister-group crustacean orders Remipedia and/or Cephalocarida [Ubx/Antp fusion transcripts in an onychophoran shows that the evolutionary origin of bicistronic transcription of Ubx and Antp dates back to the common ancestor of onychophorans and euarthropods, suggesting that Ubx/Antp is also likely to occur in chelicerates.The finding that bicistronic transcripts of nogaster ; howeverl intact . Alternalocarida . The preInterestingly, only the short splice variant II Figure  has beenUbx/Antp splice variant II in onychophorans, crustaceans and myriapods argues against a mere genomic rearrangement in a population of Ubx as suggested for the centipede Strigamia [The presence of the trigamia , but ratUbx/Antp are not (Daphnia) or only partially (only Ubx in Artemia) translated. Expression of the translated monocistronic transcripts, and therefore the protein, differs significantly from expression of Ubx/Antp [Ubx/Antp under control of the Ubx promoter interferes with the proper transcription of monocistronic Antp in these crustaceans.In crustaceans, bicistronic transcripts of Ubx/Antp . It is tUbx/Antp in arthropods and onychophorans suggests their involvement in the regulation of Ubx, Antp or both Hox genes. In particular, repression of Antp via Ubx/Antp transcription appears likely, not least because the transcript is apparently spliced in such a way that it lacks most of its coding capacity (variant II).The conserved appearance of Glomeris and Euperipatoides, it is unclear whether the detected expression patterns of Ubx and Antp are a result of mono-or bicistronic transcription. However, in both, as in crustaceans [Ubx/Antp transcript is probably under control of the Ubx promoter, as the expression pattern of Ubx/Antp is identical with that of Ubx (not shown). Thus, it is possible Ubx/Antp contributes to or even replaces monocistronic Ubx expression in Glomeris and Euperipatoides as it does in Artemia [Ubx and Antp [Ubx/Antp, it might not correlate with the protein pattern. Specific antibodies to detect UBX and ANTP protein are not available, and the crossreacting antibody FP6.87 [Glomeris (data not shown). Further investigation is thus needed to unravel the role of Ubx/Antp transcription in arthropods.For staceans , the Ubx Artemia . If partand Antp  is a resy FP6.87  does notUbx expression is likely to be involved in the delayed outgrowth of the walking legs posterior to T3 in Glomeris by repressing Distal-less (Dll) as shown for other arthropods [aUbx, a possible repressor of Ubx (as discussed above), is strongly expressed in the tips of the legs in T2 and T3 further supports this view, suggesting that the absence of Ubx is indeed crucial for the accelerated development of walking legs in T1 to T3 in Glomeris [Ubx from the distal part of the legs possibly caused or supported by aUbx could represent a developmental novelty in the 'battle' of appendage growth in Ubx-expressing segments. In Strigamia and Lithobius, Ubx seems not to repress Dll, possibly because of a number of phosphorylation sites in the C-terminal end of the protein that interfere with the assumed repressor function of Ubx on Dll [Ubx or, in other words, to express aUbx.thropods -46. The Glomeris . The exx on Dll ,45. ConsUbx and Antp regulation are found across the Arthropoda. Repression of Ubx transcription, and thus formation of a complex segmental pattern of Ubx expression, may depend on transcriptional interference as shown for Drosophila, and suggested and visualized by aUbx expression in Glomeris. Furthermore, bicistronic transcription of Ubx and Antp and subsequent splicing of these transcripts as shown for Crustacea, Myriapoda and Onychophora, but possibly not Insecta, suggests that Ubx/Antp transcription is an important ancestral feature of Hox gene regulation as well. As shown for Crustacea, runthrough transcription and subsequent nontranslation of Ubx/Antp may compete with the proper transcription of the (translated) monocistronic Ubx and Antp transcripts [Ubx/Antp transcription might contribute to a defined protein expression pattern within areas of ubiquitously expressed Hox gene mRNA. Presence of aUbx transcription and the possible lack of Ubx/Antp splice variant I in myriapods represent possible synapomorphies for the Myriapoda.A number of conserved aspects of nscripts , and thuThe authors declare that they have no competing interests.Euperipatoides.RJ carried out the experiments, wrote the first draft of the manuscript and was mainly responsible for the experimental outline. GEB was involved in drafting the final version of the manuscript and discussed the experimental outline. GEB also initiated work on


Primary neoplastic lesions presenting with a mucocele of the appendix are very rare and can be divided into benign variants of mucinous adenomas or cystadenomas, mucinous tumours of uncertain malignant potential or mucinous cystadenocarcinomas. Most of these tumourous mucoceles are asymptomatic and are found incidentally. The major complication of neoplastic mucinous appendiceal tumours is the development of a pseudomyxoma peritonei due to spreading of mucin-producing cells within the abdominal cavity.A 44-year-old man presented with a history of non-specific symptoms of right upper abdominal pain. Abdominal ultrasound and computed tomography scan identified a cystic mass consistent with the morphological characteristics of an echinococcal hydatid cyst. After completing systemic albendazole therapy, an explorative laparotomy revealed a cystic tumour of the appendix. Ileocaecal resection was performed and pathology reports confirmed the diagnosis of a mucinous cystadenoma of the appendix. The postoperative course was uneventful.Here we present the case of a man with a mucinous cystadenoma of the appendix mimicking cystic hydatid disease. We discuss the importance of re-evaluation and differential diagnostic reflections in cases of appendiceal mucocele. Mucocele of the appendix is a rare cystic dilatation of the appendiceal lumen caused by mucinous secretions and consecutive retention of mucus. It can be caused by either non-neoplastic or primary epithelial neoplastic disease ,2. The nHere we report a case of a man with a mucocele caused by a mucinous cystadenoma mimicking cystic hydatid disease and discuss the importance of differential diagnostic reflections in cases of appendiceal mucocele.A 44-year-old man presented with a history of non-specific symptoms of right upper abdominal pain for 6 years. Abdominal ultrasound (US) revealed a cystic mass containing low level internal echoes and sonic shadowing. Computed tomography (CT) revealed, in the axial and coronal views, a cystic mass with curvilinear calcifications extending from segment six of the right hepatic lobe into the right lower quadrant, consistent with the morphological characteristics of an echinococcal hydatid cyst Figure  and 1B. During exploration of the abdominal cavity the cystic mass, which measured 17.5 cm in length and 4.5 cm in diameter, was identified as a cystic antecaecal appendix with a smooth serosal surface involving the base of the appendix Figure . Due to The incidence of mucoceles of the appendix is reported to be 0.2% to 0.3% . ApproxiCross sectional imaging such as CT is superior to US in the evaluation of mucoceles of the appendix because it demonstrates the topographic anatomical relationship between the caecum and the mucocele. In addition, CT is more sensitive than US in the detection of mural calcifications within the mucinous neoplasm. The appearance at CT scanning is characterized by a well-encapsulated cystic structure with either an enhancing smooth thin or thick wall, with or without mural calcification. The detection of mural curvilinear calcifications is highly suggestive of the diagnosis, but is detectable in less than 50% of cases . Kim et Several diseases including hydrosalpinx, ovarian cysts or renal cysts have been reported as mimicking appendiceal mucocele in their US and CT appearance as well as in their uncharacteristic clinical symptoms ,11. To ochinococcus granulosus, has an uneven geographical distribution in Europe, presenting with well-defined single or multiple cysts on CT scan that may be uniloculated or multiloculated and either thin or thick walled. Calcification, daughter cysts and germinal membrane detachment may also be present. Usually no rim enhancement is evident unless the hydatid cyst is superinfected [Cystic hydatid disease, caused by Einfected . Cystic infected .Although serodiagnosis was negative, in our case the morphological appearance on CT, the localization with topographic relation to the right liver lobe and the medical history made the diagnosis of a cystic hydatid disease most likely. It is worth noting that the sensitivity and specificity of serodiagnostic tests for Echinococcosis have been reported to range between 80% and 90% and therefore results might be negative despite hydatid disease being present .New therapeutic approaches in the treatment of hydatid disease include percutaneous punction of the cystic lesions followed by aspiration of the internal fluid and injection of alcohol containing solutions, and re-aspiration. This so-called PAIR procedure should be repeated several times . In thisThe case presented shows the importance of re-evaluation and differential diagnostic reflections in cases of the very rare entity of mucocele of the appendix. In particular, in cases with high suspicion for hydatid disease but with negative serodiagnosis, surgical exploration is recommended rather than the interventionally performed PAIR procedure.CT: computed tomography; PAIR: puncture aspiration injection re-aspiration; US: ultrasound.The authors declare that they have no competing interests.Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.AK and JSAE performed the surgery, conducted the acquisition, analysis and interpretation of data and drafted the manuscript, LWP performed the analysis and interpretation of the computed tomography scans, SB performed the pathological analysis, WTK made substantial contributions to the conception, acquisition and interpretation of data and revised the manuscript critically. All authors read and approved the final manuscript.


Phase III trials have demonstrated the efficacy of human papillomavirus (HPV) vaccines in preventing transient and persistent high-risk (hr) HPV infection and precancerous lesions. A mathematical model of HPV type 16 infection and progression to cervical cancer, parameterised to represent the infection in Finland, was used to explore the optimal age at vaccination and pattern of vaccine introduction. In the long term, the annual proportion of cervical cancer cases prevented is much higher when early adolescents are targeted. Vaccinating against hr HPV generates greater long-term benefits if vaccine is delivered before the age at first sexual intercourse. However, vaccinating 12 year olds delays the predicted decrease in cervical cancer, compared to vaccinating older adolescents or young adults. Vaccinating males as well as females has more impact on the proportion of cases prevented when vaccinating at younger ages. Implementing catch-up vaccination at the start of a vaccination programme would increase the speed with which a decrease in HPV and cervical cancer incidence is observed. Human papillomavirus (HPV) is a common sexually transmitted agent  and persIn phase III trials, two HPV virus-like particle vaccines have been shown effective in preventing incident and persistent HPV16 and 18 infection and associated precancerous lesions, with reported efficacies in the region of 90–100% . These iIn earlier work, we used sexual behaviour data along with HPV seroprevalence trends in pregnant women to parameterise a mathematical model of HPV16 occurrence in Finland , we compared the predicted proportion of cervical cancer caused by HPV16 prevented by vaccination of 70% of female subjects introduced in 2008. For simplicity, we assumed that the vaccine has 100% efficacy with lifelong duration of protection and that the vaccine had no effect on those already infected. The additional proportion of cervical cancer cases prevented by vaccinating male as well as female subjects at different coverages, and by different strategies of catch-up vaccination at the start of a campaign was also examined. We assumed 3 years of catch-up vaccination at the start of a vaccination campaign aimed at 12-years-old, corresponds to vaccinating at ages 12, 13, 14 and 15 in the first year of the campaign. We explored four catch-up vaccination strategies corresponding to 3, 6, 9 and 12 additional years age cohorts vaccinated in the first year.The model predicts that vaccinating young adolescents at 12 years of age, compared with 15-years-old, delays the impact of immunisation on HPV16-associated cervical cancer incidence . Before The predicted impact of vaccinating male subjects in addition to female subjects depends upon the age of vaccination and the coverage. At younger ages, the number of additional cases prevented is greater . In the Three years of catch-up vaccination at the start of a campaign also has more impact at younger ages of vaccination  because cumulative number of cases of HPV16-associated cervical cancer prevented by 2055 both with and without the 3-year catch-up is highest if vaccination occurs at age 15 , which is present in at least half of the cervical cancers. There may be differences in the oncogenic potential of the different hrHPV types, but with appropriate parameters the same model could be used to explore other types. More significantly, we have assumed complete naturally acquired immunity on clearance of infection. The age of incidence of HPV infection and cervical neoplasia suggest that a naturally derived type-specific immunity occurs, and observational studies suggest that there is also cross reactive natural immunity , but theWe assume the vaccine is 100% effective with lifelong duration of protection. A lower vaccine efficacy would result in reduced proportions of cases prevented but the difference between vaccination strategies would not be affected. However, if duration of protection is lower the proportion of cases prevented by different strategies may be altered, particularly if the duration of protection means that the vaccinated cohort would cease to be protected by the time they reach the age of peak incidence. In addition, the vaccine was assumed to have no effect on individuals already infected with HPV. Although it has not yet been shown conclusively that vaccines have any therapeutic effect, if they significantly reduce infectiousness in those already infected, vaccination at older ages would prevent more cases than we have observed as a result of reductions in transmission. This is an important consideration that needs further research.vs both sexes. The current analysis allows qualitative insights into how to focus vaccination campaigns, but more detailed work is required to determine the feasibility and costs of such campaigns.So far the cost-effectiveness of HPV vaccination has not really been considered in relation to implementing HPV into the national vaccination programme (


Helicobacter pylori is one of the most genetically diverse of bacterial species, and since the 5'-end of cagA gene and the middle allele of vacA gene of H. pylori from different populations exhibit considerable polymorphisms, these sequence diversities were used to gain insights into the genetic affinities of this gastric pathogen from different populations. Because the genetic affinity of Arab strains from the Arabian Gulf is not known, we carried out genetic analysis based on sequence diversities of the cagA and the vacA genes of H. pylori from 9 ethnic Arabs in Kuwait. The analysis showed that the Kuwaiti isolates are closely related to the Indo-European group of strains, although some strains have a tendency to form a separate cluster close to the Indo- European group, but clearly distinct from East Asian strains. However, these results need to be confirmed by analyses of neutral markers (house-keeping genes in a multi-locus sequence typing [MLST]) platform. The profiling of virulence-associated genes may have resulted from ecologically distinct populations due to human migration and geographical separation over long periods of time. Helicobacter pylori, the Gram-negative, spiral, microaerobic bacterium, infects more than half of the world's population  (cagA 5'-end), [GenBank:GU212667 to GenBank:GU212669 and GenBank:GU441847]  and  .In the previous study on the antibiotic susceptibility of patients . Of thescagA gene that had been used to distinguish East Asian and European strains [vacA middle region from various parts of the world revealed the existence of 3 distinct groups . Such analyses have been carried out for H. pylori isolates from various ethnic groups in India [in India  and Iranin India . These sH. pylori infecting individuals in different continents. The profiling of virulence-associated genes like cagA and vacA provide examples in which evolutionary dynamics might have been shaped by local differences in environmental conditions and host physiology and may have resulted in ecologically distinct populations due to human migration and geographical separation over long periods of time. The remarkable differences found to-date between various Asian and European H. pylori populations in at least a few loci along with the present data from Kuwaiti strains should encourage further analyses of strains from relatively understudied geographic areas and human ethnic groups like Middle Eastern regions where human migration and geographical separation over long periods of time are prominent. Such "geographic genomics" may unearth new genes that affect human infection, increase our understanding of bacterium-host interactions in colonisation and disease, and impart new insights into the evolution of this diverse and globally distributed human pathogen.The Arab population in the Middle East is a distinct ethnic race. Although the region is geographically separate, it established contacts with other regions of the world through colonisation and trade hundreds of years ago. Our study has shown that the strains that infect ethnic Arab Kuwaiti population is closely related to the Indo-European strains although some strains have a tendency to form a separate cluster close to the Indo- European group but far away from East Asian strains. This suggests a common ancestry of strains circulating in Kuwait, India and the European countries. The ancestry of these strains is different from that of the strains circulating in the Far East since they formed a distinct cluster. Human migration and geographical separation over long periods of time may have resulted in ecologically distinct populations of The authors declare that they have no competing interests.MJA and AKM conceived the study and drafted the manuscript. HMA, RD and RoD carried out the work. All authors read the manuscript and approved the final draft.


An analysis of ribosomal protein pseudogenes in the four mammalian genomes reveals no correlation between number of pseudogenes and mRNA abundance. The availability of genome sequences of numerous organisms allows comparative study of pseudogenes in syntenic regions. Conservation of pseudogenes suggests that they might have a functional role in some instances.We report the first large-scale comparative analysis of ribosomal protein pseudogenes in four mammalian genomes . To this end, we have assigned these pseudogenes in the four organisms using an automated pipeline and make the results available online. Each organism has a large number of ribosomal protein pseudogenes . The majority of them are processed (generated by retrotransposition). However, we do not see a correlation between the number of pseudogenes associated with a ribosomal protein gene and its mRNA abundance. Analysis of pseudogenes in syntenic regions between species shows that most are conserved between human and chimpanzee, but very few are conserved between primates and rodents. Interestingly, syntenic pseudogenes have a lower rate of nucleotide substitution than their surrounding intergenic DNA. Moreover, evidence from expressed sequence tags indicates that two pseudogenes conserved between human and mouse are transcribed. Detailed analysis shows that one of them, the pseudogene of RPS27, is likely to be a protein-coding gene. This is significant as previous reports indicated there are exactly 80 ribosomal protein genes encoded by the human genome.Our analysis indicates that processed ribosomal protein pseudogenes abound in mammalian genomes, but few of these are conserved between primates and rodents. This highlights the large amount of recent retrotranspositional activity in mammals and a relatively larger amount of it in the rodent lineage. We calcWe calculated the number of nucleotide substitutions per site since the human-chimpanzee divergence and human-mouse divergence for each pair of corresponding syntenic pseudogenes using the Kimura 2-parameter model . Pairs oWe used EST data from dbEST for verifying if human and mouse pseudogenes in syntenic regions are transcribed . For eviEST: expressed sequence tag; RP: ribosomal protein.SB performed the bioinformatic analyses, DZ, YL, GF, RR and PC helped with various details of the analyses, AF performed manual analyses of syntenic pseudogenes in human and mouse, and NC provided pseudogene assignments using PseudoPipe. This work was performed in the laboratory of MG. All authors read and approved the final manuscript.The following additional data are available with the online version of this paper. Additional data file RPS27L/Rps27l locus in human and mouse.Figures 5 and 6: the variation in the number of pseudogenes identified when the percent identity cutoff and e-value cutoff is varied. Figure 7: the results of manual annotation of the Click here for fileProcessed pseudogenes associated with each RP gene for human, mouse, chimpanzee and rat.Click here for file


There are only a few reports on laparoscopic pyeloplasty in kidney abnormalities and only one case for laparoscopic pyeloplasty in a duplicated system. Increasing experience in laparoscopic techniques allows proper treatment of such anomalies. However, its feasibility in difficult cases with altered kidney anatomy such as that of duplicated renal pelvis still needs to be addressed.We present a case of a 22-year-old white Caucasian female patient with ureteropelvic junction obstruction of the lower ureter of a completely duplicated system that was managed with laparoscopic pyeloplasty. Crossing vessels were identified and transposed. The procedure was carried out successfully and the patient's symptoms subsided. Follow-up studies demonstrated complete resolution of the obstruction.Since laparoscopic pyeloplasty is still an evolving procedure, its feasibility in complex cases of kidney anatomic abnormalities is herein further justified. Despite the emergence of endoscopic techniques and the recent development of laparoscopic approaches, many patients with ureteropelvic junction (UPJ) obstruction are still managed through open pyeloplasty. It is probably because of technical difficulties and the need for intracorporeal knot tying that this procedure has not yet been adopted worldwide as the initial treatment of choice in UPJ obstruction. However, increasing experience has gradually identified laparoscopic pyeloplasty as the optimum procedure since it combines success rates similar to that of open surgery with the low morbidity of laparoscopic approaches . Both opSince the efficacy of laparoscopic pyeloplasty for UPJ obstruction co-existing with a duplicated collecting system has been reported in one adult patient , a seconThe patient, a 22-year-old white Caucasian woman, presented with a long history of recurrent left colicky flank pain. An ultrasound scan revealed a dilated left kidney. Intravenous pyelography studies indicated left renal pelvis duplication with concomitant ureter duplication. Furthermore, UPJ obstruction was apparent in the lower of the two systems Figure . DespiteAfter general anesthesia induction, the patient received a single dose of intravenous second-generation cephalosporin and a second one 8 hours postoperatively. In addition, subcutaneous heparin was also administered at the same time, and a urethral Foley catheter was placed.The patient was then placed in a lateral decubitus position and was ready to be securely stabilized on the operating table. Using the Hasson technique, pneumoperitoneum was established by insertion of a 10 mm port, 2 cm laterally to the umbilicus. A three-port technique was utilized and two additional laparoscopic ports were inserted below the costal margin and at the ipsilateral lower quadrant along the midclavicular line. After Toldt line incision, the duplicated UPJ was identified along with the two ureters located medially to the lower pole of the kidney.After cranial mobilization of the lower ureter, accessory crossing vessels were identified at the level of the UPJ. Crossing vessels ran anteriorly to both ureters which originated from the upper and lower moiety, respectively. During the procedure, the normal upper moiety ureter was identified and protected from inadvertent accidental injury. After mobilization of the renal pelvis, the UPJ was circumferentially transected, the ureter spatulated towards the lower pole of the kidney over 2 cm and the renal pelvis reduced appropriately. Before the initiation of the anastomosis, the ureter was transposed to the opposite (anterior) side of the crossing vessels. A classic Hynes-Anderson dismembered pyeloplasty was performed using two 4-0 absorbable running sutures for both anterior and posterior anastomosis. Intracorporeal knot tying was performed in a free-hand fashion. When the posterior part of the anastomosis was concluded, a guidewire was inserted through a trocar in the ureter reaching the bladder and antegrade stenting (using a double J stent) was performed. A 14F suction drain was finally placed through one of the port sites.Overall, operative time was 260 minutes and blood loss was minimal (approximately 30 ml). The drain was free of output on the third postoperative day, when it was removed and the patient discharged. Four weeks postoperatively, the ureteral stent was removed. Currently, 18 months postoperatively, the patient is doing well and is free of any symptoms. Intravenous pyelography studies at 6 months revealed a normal UPJ, free of signs of obstruction (Figure Even though open pyeloplasty remains the standard of treatment for UPJ obstruction management with success rates exceeding 90% ,4, recenFurther to its widespread utilization in large series, laparoscopic pyeloplasty has been reported to be efficient in difficult cases such as persistent UPJ obstruction after failed open pyeloplasty and some kind of salvage endoscopic approach . Bove anDespite the efficacy of laparoscopic pyeloplasty in UPJ obstruction in our patient, other techniques are also feasible. Kumar and colleagues  recentlyIn addition to this series of reports we herein add a confirmation of laparoscopic pyeloplasty as a feasible option for management of adult UPJ obstruction in a completely duplicated collecting system. The case presented is novel in that it reports on the efficacy of laparoscopic pyeloplasty in the lower segment of a duplicated system in the presence of crossing vessels. In their report on UPJ obstruction management in a duplicated collecting system, Sahai and co-workers  did not Further, compared to the report of Sahai and colleagues , our casAfter surgery, the patient's subjective symptoms as well as imaging studies have significantly improved arguing in favor of the procedure's success. Postoperative course and final cosmetic result were also excellent, an issue of importance for a young female patient.In conclusion, we argue for the feasibility of laparoscopic pyeloplasty for UPJ obstruction management in a duplicated collecting system, also in the setting of co-existing crossing vessels. This report further supports the trend of endoscopic surgery utilization even in cases complicated by modified renal anatomy.UPJ: ureteropelvic junction.The authors declare that they have no competing interests.KGS was the main surgeon and made substantial contribution to conception and design, provided all operative details and photographic material in the present work while substantially contributing to manuscript preparation and revision. IA contributed in patient care, acquisition of data and has been involved in drafting the manuscript. IA, TK, GC contributed in patient care, data analysis, literature review and multiple revisions of the manuscript while CC cooperated in design, and critically revising of the final version of the manuscript. TK was especially involved with the initial draft as well as final draft corrections and correspondence. All authors have given final approval of the version to be published.Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.


Recent projections suggest that by the year 2030 depression will be the primary cause of disease burden among developed countries. Delivery of accessible consumer-focused evidenced-based services may be an important element in reducing this burden. Many consumers report a preference for self-help modes of delivery. The Internet offers a promising modality for delivering such services and there is now evidence that automated professionally developed self-help psychological interventions can be effective. By contrast, despite their popularity, there is little evidence as to the effectiveness of Internet support groups which provide peer-to-peer mutual support.Members of the community with elevated psychological distress were randomised to receive one of the following: (1) Internet Support Group (ISG) intervention, (2) a multi-module automated psychoeducational and skills Internet Training Program (ITP), (3) a combination of the ISG and ITP, or (4) an Internet Attention Control website (IAC) comprising health and wellbeing information and question and answer modules. Each intervention was 12 weeks long. Assessments were conducted at baseline, post-intervention, 6 and 12 months to examine depressive symptoms, social support, self-esteem, quality of life, depression literacy, stigma and help-seeking for depression. Participants were recruited through a screening postal survey sent to 70,000 Australians aged 18 to 65 years randomly selected from four rural and four metropolitan regions in Australia.To our knowledge this study is the first randomised controlled trial of the effectiveness of a depression ISG.Current Controlled Trials ISRCTN65657330. It has been projected that depression will be the leading cause of disease burden in 2030 . LifetimIt is likely that the undertreatment of depression is due in part to lack of availability and accessibility of services , an unwiThere is some evidence that self help interventions delivered online can be effective in reducing depressive symptoms . In partResearch into the effectiveness of online interventions for depression has been focused primarily on applications designed to deliver psychological skills training. However, the widespread availability of the Internet has stimulated the development of a large number of online 'mutual support' or 'self help support' groups. Such support groups have been estimated by Eysenbach to be used by 'millions' of consumers daily  and therA recent systematic review of depression ISGs identified no randomised controlled trials of the effectiveness of the groups, for individuals with depression, in reducing depressive symptoms or in improving other psychological, mental health, service-related or other outcomes . HoweverIt is possible however, that the primary effect of depression support groups is on outcomes other than symptomatology. For example, it is often claimed that support groups increase consumer empowerment and social support ,24. HoweOne potential limitation of fully automated online programs is the likelihood of substantial dropout during their unguided use . AutomatA final limitation of available research is that the majority of randomised controlled studies of e-mental health programs have employed wait list control groups . A smallThe primary objectives of the study are to (i) evaluate the efficacy of a depression Internet Support Group (ISG) and an automated psychoeducational and skills Internet Training Program (ITP) for reducing depressive symptoms relative to a plausible Internet Attention Control condition (IAC); to evaluate the relative efficacy of the ITP, ISG and combined ITP and ISG interventions; and (iii) to ascertain if the adherence rates and magnitude of improvement in depressive symptoms is greater for the ISG and ITP interventions combined than for either condition alone.Secondary objectives of the study are to (i) evaluate the effect of the two experimental interventions on anxiety, disability, social support, loneliness, self-esteem, empowerment, loneliness, depression literacy, stigma and help seeking in people with elevated depressive sympotms; and (ii) to compare the outcomes of these interventions in rural and metropolitan residents.Members of the community with elevated levels of depressive symptoms were randomised in a 2 by 2 quasi-factorial design to receive either the ISG, the ITP, a combination of the ISG and IPT or a plausible internet-based attention control (IAC) . The study protocol is registered with the Controlled Clinical Trials registry (ISRCTN65657330).Participants in the ANU WellBeing Study have been recruited via postal invitation and survey of 70,000 adults aged between 18 to 65 years who were randomly selected from the electoral rolls of four rural and four metropolitan Australian electoral divisions. Registration on the electoral roll is compulsory for all Australian citizens. Participants were selected from the division list using the 'select cases' random selection facility in SPSS. The metropolitan samples comprised registrants from one electoral division in Canberra, The Australian Capital Territory; two electoral divisions in Melbourne, Victoria ; and one division in Sydney, NSW (Bennelong). The rural divisions were located in Victoria  and New South Wales . Divisions were selected from those which had a moderate (51%) to high proportion (>62.2%) of households with internet access . ParticiThe screening survey was accompanied by a letter and brochure which described both an enclosed 'WellBeing' screening survey and an intervention project ("The Wellbeing Promotion Study"). The participant was informed that the WellBeing survey was designed to 'find out more about the mental health of Australians in the city as well as in rural areas' and that the WellBeing Promotion Study was designed to 'look at the usefulness of self help internet programs for improving emotional well being and preventing or reducing the symptoms of depression'.Survey respondents who met the eligibility criteria for the WellBeing study  to one of the four trial conditions and were sent an information sheet about the project and the intervention conditions together with a consent form. At this point, however, neither they, their interviewer nor the project coordinator were informed of their randomisation status. Randomisation prior to consent and completion of the pre-intervention was undertaken for pragmatic reasons as the trial required the participants in the internet support groups to commence simultaneously. Undertaking stratified randomisation post-consent and post-baseline survey would have either introduced a significant delay between screening and baseline measures and the commencement of the intervention or reduced the available pool of participants.Those participants who returned consent forms were sent a letter informing them of the condition to which they had been randomised together with a 14 or 15 page user guide containing a week by week overview of their intervention, a 'Frequently Asked Questions' section and a 'Technical Tips' page.Recruitment to the WellBeing Study was conducted in three waves  between August 2008 and May 2009. A subsample of 7000 surveys  were employed to pilot the survey and protocol. After the successful completion of the intervention phase of the pilot, a further 28,000 surveys were sent to residents in the above divisions. Since these screening surveys did not yield the target sample size for the study, a further 35,000 surveys were sent to the divisions of Bennelong, Higgins, Murray and Riverina.The study involved four intervention conditions comprising the two intervention programs presented singly and in combination and an attention-control website administered over a 12 week period. Although a module could not be accessed until the week scheduled for its delivery, it remained open for the remainder of the 12 week intervention period and for 12 months from the commencement of the intervention. Participants in the attention control condition were provided with access to the ITP after the 6-month follow-up assessment. The ITP, ISG and IAC conditions employed the e-couch, WellBeing Board and HealthWatch websites respectively. The weekly content of each intervention websites is summarised in Table http://ecouch.anu.edu.au. The intervention comprised a depression literacy module together with five interactive self help tools designed to reduce depressive symptoms.This automated online psychological intervention is a research version of the depression stream of the online application e-couch The depression literacy module contained information about the symptoms and types of depression and their diagnosis, sources of help, information about the prevalence and disability burden associated with depression, depression risk factors, and evidence-based medical, psychological and lifestyle treatments for depression based on updated systematic reviews and clinical practice guidelines. The self help module comprised online versions of treatments amendable to delivery online and known to be effective in face-to-face therapy, bibliotherapy or computerised or Internet delivery. These included: (a) cognitive behaviour therapy; (b) interpersonal therapy; (c) applied relaxation; and (d) physical activity. An example page from the research version of e-couch is illustrated in Figure The WellBeing Board is a research ISG which uses a bulletin board format to facilitate discussions. It was developed for the trial based on the primary author's experience in running a public ISG and a thematic analysis of a randomly selected subset of topics on that board. The WellBeing board was divided into three main categories: Your Wellbeing, Feeling Better and General. Each week one, or in the case of weeks 8 and 11, two new forums or topics were introduced for each category in turn , gender , and location of residence . Randomization schemes with a fixed block size of four were generated for each strata using the web site Randomization.com Table Depressive symptoms: The primary outcome measure was the Centre for Epidemiological Studies Depression scale . This 2baseline and in at least one subsequent survey to evaluate improvement or change in mental health, other outcomes and potential moderating or mediating factors:The following secondary measures were used at Anxiety severity: The Penn State Worry Questionnaire (PSWQ)[Quality of life: The EUROHIS QOL - 8 item index [Disability: 'Days Out of Role' questions adapted from the US National Comorbidity Survey [Self esteem: Rosenberg Self-esteem Scale [Perceived social support: The 8-item Medical Outcomes Study Social Support Survey (MOS)/Emotional/informational support subscale [Loneliness: The UCLA Loneliness Scale [Stigma: Depression Stigma Scale , a measure of personal, negative attitudes to depression [Depression knowledge: (i) a short 11-item version of the Depression Literacy Scale  which of the above medication, psychological, lifestyle and alternative treatments or activities they had used or people they had consulted for depression in the past 3 months [Empowerment: Power-powerlessness subscale of the Empowerment Scale [Perceived utility of the Internet: Two questions assessed participant's beliefs about the utility of the Internet for preventing and understanding depression ; "I am confident that a website could help people understand depression better" ).re (PSWQ); Qualityem index ; Disabily Survey ; Self esem Scale ; Perceivsubscale . This scss Scale ; Stigma:pression ,42; Depry scale; ); (ii) 3y scale; ; Help se3 months ; Empowernt Scale . This scSatisfaction and perceived benefits/negatives: Satisfaction with the interventions was measured using 10 previously employed self-report items ) together with a series of questions based on items developed in a UK study of depression ISG users [Perceived negative effects were measured with items specifically developed for the purposes of this study .); Participation in healthcare: A three item measure, modified from a study of a physical health internet support group [Adherence: measured in two ways for each individual: (i) completion of post-test surveys; (ii) number of modules completed ; (iii) frequency of logins and number of weeks logged onto the WellBeing ISG and activity level on each website .In addition, the following measures were employed at one or more points post-intervention with a view to assessing their experience of the program: SG users  . In addition, severity of general anxiety, depression and stress was measured using The Depression Anxiety Stress Scale , self reported professional help seeking for any such problem and perceived usefulness of seeking professional help for these problems were also collected. A series of purpose designed items were included in the screening survey to assess participant self reported need for information about depression. Finally, an item was included to measure participant randomisation preference at baseline.A number of other measures were collected in the screening survey. These included DASS-21; ), sociale  and pan- Panic; ) scale. a priori contrasts of treatment arms conducted within the framework of omnibus test of condition by time mixed model repeated measures analysis. It is planned that the unique effect of the combined treatments will be tested by appropriate contrasts. It is possible that the combinations of treatment (e-couch and ISG) will prove no better than the individual programs. Conversely, cumulative effects or potentiation (synergy) may be observed. The target sample size ensured that the study is powered to detect an effect of .25 in either direction.The WellBeing trial aimed to recruit and randomise 500 participants to four conditions (125 per group). The primary analysis will be undertaken on an intent-to-treat basis. Mixed-model repeated measures (MMRM) analyses will be used because this method has been demonstrated to be superior to using the last observation carried forward method for handling missing data in longitudinal designs . For anaTo our knowledge this study is the first RCT of the effectiveness of a depression ISG, the first to systematically investigate if participating in a peer-to-peer ISG improves adherence and outcomes and the first to investigate the comparative effectiveness for rural and metropolitan consumers of an automated psychological intervention. In addition, there have been no previous studies of effect of an automated online self-help program on consumer empowerment.A second novel contribution of this trial is its use of a purpose constructed plausible, web-based attention control containing authoritative information. At the time of writing, we were not aware of any published RCTs of the efficacy of e-mental health interventions which employed such a control. As already noted, depression or mental health education websites are not the preferred control condition for studies of interventions for mental disorders as there is evidence that such information may improve mental health. We did consider referring control group users to existing websites with a 'wellbeing' theme. However, these websites were typically characterised by one or a number of limitations in that they contained content that: included potentially active components (such as exercise interventions); incorporated advertisements, which raises ethical issues when used in the context of a research trial; were typically not evidence-based, a further ethical concern; might change or be removed from the Internet; and was not subject to the control of the research team. Moreover, external websites could not be seamlessly integrated into our automated research trial processes and accordingly it would not have been possible to automatically track trial participant access and usage of these sites.The trial was commenced in August 2008. Participants recruited in the pilot and wave 1 stages of the study have completed the 12-month follow-up. Participants recruited in the wave 2 stage have completed the 6-month follow-up with 12 month follow up due to be completed in May 2010.KG and HC are directors of e-hub at the ANU which developed the E-couch program and runs depression and anxiety internet support groups. However, neither author derives personal financial benefit from the operation of e-hub.KG conceived, designed and supervised the study, and drafted the paper. DC drafted the paper and served as trial manager of the study. HC designed the study and edited the paper. AM designed the study, provided statistical and methodological advice, undertook the randomisation process and edited the paper. KB contributed to the design of the protocol, oversaw the IT implementation of the project and edited the paper. All authors have read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-244X/10/20/prepub


A mismatch between individual physical capacities and physical work demands enhance the risk for musculoskeletal disorders, poor work ability and sickness absence, termed physical deterioration. However, effective intervention strategies for preventing physical deterioration in job groups with high physical demands remains to be established. This paper describes the background, design and conceptual model of the FINALE programme, a framework for health promoting interventions at 4 Danish job groups  characterized by high physical work demands, musculoskeletal disorders, poor work ability and sickness absence.A novel approach of the FINALE programme is that the interventions, i.e. 3 randomized controlled trials (RCT) and 1 exploratory case-control study are tailored to the physical work demands, physical capacities and health profile of workers in each job-group. The RCT among cleaners, characterized by repetitive work tasks and musculoskeletal disorders, aims at making the cleaners less susceptible to musculoskeletal disorders by physical coordination training or cognitive behavioral theory based training (CBTr). Because health-care workers are reported to have high prevalence of overweight and heavy lifts, the aim of the RCT is long-term weight-loss by combined physical exercise training, CBTr and diet. Construction work, characterized by heavy lifting, pushing and pulling, the RCT aims at improving physical capacity and promoting musculoskeletal and cardiovascular health. At the industrial work-place characterized by repetitive work tasks, the intervention aims at reducing physical exertion and musculoskeletal disorders by combined physical exercise training, CBTr and participatory ergonomics. The overall aim of the FINALE programme is to improve the safety margin between individual resources  and physical work demands, and thereby reduce the physical deterioration in a long term perspective by interventions tailored for each respective job-group.The FINALE programme has the potential to provide evidence-based knowledge of significant importance for public health policy and health promotion strategies for employees at high risk for physical deterioration.ISRCTN96241850, NCT01015716 and NCT01007669 Work ability reflects the relation between the capacity and demands of the worker . When thWorkers with high physical work demands are well documented to be at elevated risk for impaired work ability -13, muscPrevious initiatives applying individual counselling and education among employees with high physical work demands have not been able to show positive effects for improving work ability . In contIn the last decade, more focus has been on the workplace as a convenient arena for health promoting initiatives  such as In the FINALE programme, health impairing effects originating from a mismatch between individual capacities and physical work demands  is defined as physical deterioration. The overall aim of the FINALE programme is to evaluate effects on 1) the balance between individual capacities  and physical work demands , and 2) the resulting effects on physical deterioration  from tailored interventions to the individual capacities, physical work demands and health profile of employees from 4 job groups . The consequent main outcomes are musculoskeletal disorders, work ability, physical capacity, body mass index (BMI), kinesiophobia, rate of physical exertion during work and sickness absence. The primary outcome is specifically tailored to each respective intervention.The FINALE programme consists of 3 randomized controlled trials (RCT) and 1 exploratory case-control study involving several workplaces.Table The FINALE programme is conducted in different regions of Denmark. In specific, the industrial workers are recruited from a single large workplace in the Southern region. The health care workers are recruited from public health-care centres in a county of Jutland. The cleaners are recruited from several large work-places (both private and public) situated in Zealand employing at least 30 cleaners. The construction workers are primarily working in the Southern region.The conceptual model of the FINALE programme is illustrated in figure A novel approach of the FINALE programme is that the type of physical exercise training is tailored to the physical exposure at work, physical capacities and health profile of each respective job group. For decades, high physical capacities have been considered important for preserving work ability among workers with high physical demands , and worPsychosocial factors are well accepted to have an important role for perception, experience and behaviours regarding musculoskeletal disorders ,59. BecaParticipatory ergonomic initiatives involve active participation and cooperation between the workers and management in the process of recognizing risk factors in the workplace, and to choose the best solution to reduce the risks . ParticiHowever, the effectiveness of ergonomic interventions in general has been questioned . This maObesity is a considerable public health problem, being associated with chronic diseases like type 2 diabetes, cardiovascular disease and mortality -83. In tA structured self-administered questionnaire with validated measures (the FINALE questionnaire) was applied in all intervention studies. The questionnaire involved sociodemographic measures , lifestyle behaviour and health  based method was applied in two of the RCT (cleaners and construction workers). Each week, the participants received 4 questions on their mobile phone during the entire intervention period. The participants received the questions on Wednesday, with a reminder on Sunday. The 4 questions concerned 1) neck-shoulder pain intensity last 7 days , 2) low-back pain intensity the last 7 days , 3) work ability the last 7 days , and 4) hours of leisure time physical activity the last 7 days. The questions were inspired from the Standardized Nordic Questionnaires for the analysis of musculoskeletal disorders , the WorThe objective measures of the RCTs are height, body weight, hip/waist-ratio, percentage body fat with impedance recording, blood pressure, muscular strength of neck, shoulder, trunk flexion and extension , posturaIn all 3 RCTs, the recruitment and randomization of participants were done in according to the same principles. For each respective RCT, the participants were recruited from managers' lists of employees, which included their civil registration number with linked information about age and sex. All eligible employees were invited to an information meeting during their working hours and asked to fill out a screening questionnaire and to give consent or not to enrol in the study.For minimising contamination, a restricted cluster randomisation was applied for allocating the employees into the intervention and reference groups. Each workplace or worksite was considered a stratum. Clusters depended on work teams - where possible - were made up from groups in which employees had lunch, worked in close proximity to each other, or worked to the same manager. Clusters were matched on sex, age, job seniority or job type with varied block sizes. The randomization process was concealed, and performed after the baseline measures, and those assessing the outcomes were blinded to group assignment.The common main outcomes of the interventions composing the FINALE programme are the measures for physical deterioration; musculoskeletal disorders, work ability and sickness absence. However, the primary and secondary outcomes are specifically tailored for each respective intervention.The title of this study is "Preventing deterioration among cleaners". The project is ethically approved by The Committees on Biomedical Research Ethics of the Capital Region of Denmark on the 13th May 2008 (ref: H-C-2007-0033) and qualified for registration in the International Standard Randomised Controlled Trial Number Registry (ISRCTN96241850). The main aim of the study is to evaluate the effect of interventions with physical exercise training and CBTr among cleaners on musculoskeletal disorders, physical capacity, kinesiophobia, work ability and sickness absence.The participants are cleaners working at least 20 hours per week. The intervention is a 1 year RCT, taking place during the working hours of the cleaners. The previously described self-reported and objective measures are obtained before the intervention period, after the first phase (3 months) and after the second phase (12 months). Exclusion criteria to the project are pregnancy, angina pectoris and life-threatening diseases according to safety regulations for physical evaluation methods . PrimaryThe cleaners are randomized into I) Physical exercise training , II) CBTr or III) Reference group Figure . I) The The title of this study is "Physical exercise, dietary counseling and cognitive behavioral training as a combined intervention to reduce weight and to increase workability in health care workers". The project is ethically approved by The Central Denmark Region Committees on Biomedical Research Ethics on the 7th may 2009 (ref: M-20090050), and qualified for registration in the International Standard Randomised Controlled Trial Number Registry (NCT01015716). The main aim of this study is to evaluate the effect of a 1-year lifestyle intervention aiming at reducing body weight, increasing work ability and reducing sickness absence among health care workers.The participants are health care workers employed at the municipality of Randers in Denmark. The intervention is a 1 year RCT, mainly taking place during working hours, but also with some physical exercise training during leisure time. The previously described self-reported and objective measures are obtained before the intervention period, after the first phase (3 months) and after the second phase (12 months).Exclusion criteria to the project are pregnancy, angina pectoris and life-threatening diseases according to safety regulations for physical evaluation methods . The priThe title of this study is "Effects of specified work site physical activity intervention on musculoskeletal disorders among employees with physically heavy work". The study protocol is approved by the Ethical Committee in region Southern Denmark (S-20090058), and qualified for registration in Clinical Trials.gov (NCT01007669). The aim of the study is twofold:1. to outline the extent of musculoskeletal disorders in workers with heavy work load in relation to physical and metabolic fitness through a health check, which includes also assessment of general physical activity and working condition.2. to evaluate the effect of individually adjusted exercise programs on muscular strength, aerobic capacity, musculoskeletal disorders, work ability and sickness absence.The participants are construction workers working at least 20 hours per day. The project is a RCT study with two arms  and a power of 0.8 and a statistical significance level of 0.05. Mean and SD was based on interventions studies of muscle strength in neck/shoulder [The power analysis in the FINALE - Construct study was based on a minimal relevant difference of 10% in muscular strength and aerobic capacity  is generally considered to enhance the risk for physical deterioration, defined as musculoskeletal disorders, poor work ability and sickness absence. However, effective interventions for preventing physical deterioration in job groups at high risk remain to be established. The aim of the FINALE programme, being an umbrella for 4 tailored interventions among job groups with high risk for physical deterioration, is to evaluate the effects of balancing the relation between individual capacities and physical work demands on physical deterioration. The background, design, conceptual model and interventions of the FINALE programme have been described.A strength of the FINALE programme is that it constitutes 3 RCTs tailored to the physical work demands, physical capacities and health profile of different job groups characterized by a high risk for physical deterioration. This feature of the FINALE programme enhances the probability for enabling evidence-based information for public health policy and health promotion strategies among employees in job groups with high risk for physical deterioration. Another strength of the FINALE programme is that all interventions take place at workplaces, providing a high external validity of the findings. An additional strength is that several workplaces with different characteristics  from different regions of Denmark are included in the FINALE programme. Moreover, numerous subjective and objective work and health-related measures are collected. Because the same FINALE-questionnaire and many common objective measures are included in the studies, the data from all interventions can potentially be merged and analysed.A limitation of the FINALE programme is that only simple measures of process evaluation such as proportion of workers in uptake, actual start of the programme and actual completion of the RCT are collected. Moreover, no economical cost-effectiveness evaluations are included. Another limitation is that the intervention among industrial workers is an exploratory, not well controlled study.The study population of the FINALE programme  is well documented to have a high risk for physical deterioration. If proven effective, the specific tailored interventions to the different job groups can provide meaningful scientifically based information for public health policy and health promotion strategies for employees in these job groups at high risk for physical deterioration. This knowledge can be beneficial for occupational health professionals, supervisors, companies and employees in these job groups. Because the interventions are carried out during ordinary circumstances at a wide range of Danish workplaces, it is expected that the findings can be transferred and interventions implemented in other workplaces with high physical demands.The authors declare that they have no competing interests.AH led the writing of the manuscript, and wrote the first draft of the abstract, background, methods and discussion. All authors contributed to the design and protocol of parts of the FINALE programme. KS is responsible for conception and design of the FINALE study and wrote the grant application, with contributions from MBJ, JRC, GS, JEA. MBJ and KS wrote the specific information about the FINALE - Clean study. JRC and KO wrote the specific information about the FINALE - Health study. BG and GS wrote the specific information about the FINALE - Construct study. AH and KS wrote the specific information about the FINALE - Indust study. All authors read and approved the manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2458/10/120/prepub


The presence of subcutaneous emphysema, pneumomediastinum and pneumoperitoneum simultaneously is a rare complication of upper gastrointestinal endoscopy that usually indicates free perforation to the peritoneal cavity or the retroperitoneal space.We report an unusual case of a self-limited subcutaneous emphysema, pneumomediastinum and pneumoperitoneum following an unsuccessful ERCP for removal of a common bile duct stone.There was no radiological evidence of peritoneal or retroperitoneal perforation. This complication is distinct from pneumomediastinum and pneumoperitoneum due to perforation, and must be recognized, because it is benign and needs no surgical or radiological intervention. Endoscopic retrograde cholangiopancreatography (ERCP) is a standard invasive technique for revealing and management of a wide spectrum of distal bile duct disorders. The rate of significant complications is very low if it isn't combined with endoscopic sphincterotomy. Subcutaneous emphysema, pneumomediastinum and pneumoperitoneum after endoscopy indicate free perforation resulting from instrumental trauma. We present a case of subcutaneous emphysema, pneumomediastinum and pneumoperitoneum after ERCP without an obvious retroperitoneal or peritoneal perforation.th day after admission. Progressively, the signs of subcutaneous emphysema resolved. The patient was discharged on the 10th hospital day without complains and without radiographic signs of pneumomediastinum and pneumoperitoneum.A 78 year old Caucasian male referred to our department because of a history of recurrent jaundice and periodical appearance of right upper quadrant pain. The patient had undergone a post-Billroth II gastrectomy for peptic ulcer disease and cholecystectomy 48 and 7 years ago respectively. On admission, physical examination was unremarkable and laboratory evaluation showed no abnormalities with liver function tests being normal. Ultrasonography (U/S) of the liver revealed a common bile duct stone with no dilation of the common bile duct. Computed tomography (CT) showed the same findings as well. Magnetic resonance imaging (MRI) and magnetic resonance cholangiopancreatography (MRCP) revealed the existence of a common bile duct stone and confirmed the U/S and CT findings. The patient underwent an ERCP with the purpose to remove the offending stone and to perform endoscopic sphincterotomy. A long afferent limb of the Billroth II gastroenterostomy made locating the duodenal papilla technically difficult. After several attempts with no success, the procedure was abandoned for a few days later. The whole procedure had no obvious mediate complications. Immediately after the examination and for the rest of the day, there were no abnormal signs or symptoms. The morning after, the patient complained for crepitus in the soft tissues of the supraclavicular fossae and neck. Physical examination confirmed this finding. Plain radiographs of the chest and abdomen revealed subcutaneous emphysema, pneumomediastinum and pneumoperitoneum Figure . An esopThe presence of pneumomediastinum implies that there is or have been a breach of an air-containing mediastinal structure. Air in the mediastinal tissues may originate from the respiratory tract, such as after blunt or penetrating trauma to the facial bones, pharynx, hypopharynx, trachea and main stem bronchi. Dental procedures – using compressed air – may result to facial and neck subcutaneous emphysema and pneumomediastinum. Severe straining, Valsalva maneuver and free perforation of the gastrointestinal tract may be responsible of the appearance of pneumomediastinum and subcutaneous emphysema .In free perforation of the gastrointestinal tract, the air may enter from the peritoneal cavity to the mediastinum through the esophageal hiatus and the foramen of Morgagni. However, pneumomediastinum without evidence of perforation has been described after esophagogastroscopy , endoscoThe most likely explanations for the simultaneous presence of pneumoperitoneum, pneumomediastinum and subcutaneous emphysema in our patient are: (a). The endoscopic tip injured the mucosa of the gastric mucosa or the long afferent limb of the Billroth II gastroenterostomy, allowing insufflated air to enter the wall and dissect along the perineural and perivascular sheaths to reach the mediastinum. (b). High pressure in the closed long afferent limb of the Billroth II gastroenterostomy may have contributed by forcing air through the mucosal break into the interstitial tissues.Maunder et al described the anatomic route by which peritoneal air results in pneumomediastinum and pneumothoraces . The sofAnother explanation has been given by Kirschner, who described and categorized the clinical occurrence of peritoneopleural transphrenic passage of fluids or gases through, either congenital or acquired pores in the diaphragm as porous diaphragm syndromes .Our patient experienced a mild retrosternal discomfort radiating into the neck. He did not experience respiratory difficulty. The physical examination can reveal crepitus; "Hamman's crunch" (crepitant sound heard at auscultation that varies with heartbeat), ecchymosis, masses, and erythema may be present in the face, neck, or torso. Typically, the history and physical examination are sufficient to determine the mechanism and timing of the injury and the patient's physiologic response.The best tests to evaluate pneumomediastinum, pneumoperitoneum and subcutaneous emphysema are those that rapidly help to determine the location and size of perforation (if it exists), estimate the degree of contamination and help the clinician to develop a plan of treatment. A chest x-ray and plain abdominal x-rays define the findings, but because of being relatively insensitive, CT of the neck, chest and abdomen should be performed. CT can help to identify the source of mediastinal air. Contrast enhanced fluoroscopy of the pharynx and the esophagogastric region may help detecting the perforation. A water-soluble contrast study with diatrizoate meglumine (Gastrographin) is used to define an esophageal or gastric perforation, but a small leak or tear may seal spontaneously and be missed by this investigation in approximately 10% of the cases. If there is a high suspicion of perforation, a contrast study with dilute barium can detect smaller leaks [When patients undergo evaluation for pneumomediastinum, the initial management is conservative. They should receive nothing by mouth; gastric aspiration and intravenous broad-spectrum antibiotics are appropriate. Total parenteral nutrition may be indicated. Repeated chest x-rays will document improvement and ensure that progression to pneumothorax will not be missed. If perforation is demonstrated in the imaging studies, surgical repair is indicated ,13.Our case suggests that pneumomediastinum, pneumoperitoneum and subcutaneous emphysema without free esophageal perforation or perforation in the peritoneal cavity or the retroperitoneal space following endoscopy is benign, self-limited and need no surgical or radiological intervention.The authors declare that they have no competing interests.AK, ST and AG designed the study protocol; SN, KI and EN carried out the clinical assessment; ST, AK and AG drafted the manuscript. All authors read and approved the final manuscript. ST and AG are guarantors of the paper.We have obtained written, informed consent from the patient for open access publication of this case report. A copy of the written consent is available for review by the Editor-in-Chief of this journal.


The combined effect of the chemotherapeutic agent ICRF-159 and irradiation were evaluated using the Lewis lung tumour (LL). At a daily dose of 25 mg/kg, ICOF given alone prevented the progressive growth of LL. Daily pretreatment also potentiated the effects of radiation (600 rad) on tumour growth, provided the pretreatment kinetics of the tumour permitted a response to radiation alone. Single acute doses of the drug failed to alter the growth of LL, and when combined with radiation failed to enhance the radiation effect. Fractionation of the drug  before irradiation, however, results in immediate effects on tumour growth which are more than additive. The results suggest that a low dose of ICRF-159 for extended periods is more effective in enhancing radiotherapy than a high dose provided acutely.


Arabidopsis thaliana allows more detailed analysis of genome content and organisation than ever bafore possible in plants. The genome shows a surprisingly high level of genetic redundancy, with as many as 75% of gene products showing signficant homology to another protien of A. thaliana. Many duplicated genes occur in arrays of conserved order and indicate that A. thaliana is likely to have had a tetraploid ancestor. Analysis of the divergence of duplicated genome segments leads to the prediction of two major modes of plant genome evolution: macro-scale duplication and rearrangement of chromosomes and micro-scale translocation, duplication and loss of individual genes or small groups of genes.The rapidly accumulating genome sequence data from the plant