The hypothalamic–pituitary–adrenal (HPA) axis plays a key role in adaptation to environmental stresses. Parvicellular neurons of the hypothalamic paraventricular nucleus secrete corticotrophin releasing hormone (CRH) and arginine vasopressin (AVP) into pituitary portal system; CRH and AVP stimulate adrenocorticotropic hormone (ACTH) release through specific G-protein-coupled membrane receptors on pituitary corticotrophs, CRHR1 for CRH and V1b for AVP; the adrenal gland cortex secretes glucocorticoids in response to ACTH. The glucocorticoids activate specific receptors in brain and peripheral tissues thereby triggering the necessary metabolic, immune, neuromodulatory, and behavioral changes to resist stress. While importance of CRH, as a key hypothalamic factor of HPA axis regulation in basal and stress conditions in most species, is generally recognized, role of AVP remains to be clarified. This review focuses on the role of AVP in the regulation of stress responsiveness of the HPA axis with emphasis on the effects of aging on vasopressinergic regulation of HPA axis stress responsiveness. Under most of the known stressors, AVP is necessary for acute ACTH secretion but in a context-specific manner. The current data on the AVP role in regulation of HPA responsiveness to chronic stress in adulthood are rather contradictory. The importance of the vasopressinergic regulation of the HPA stress responsiveness is greatest during fetal development, in neonatal period, and in the lactating adult. Aging associated with increased variability in several parameters of HPA function including basal state, responsiveness to stressors, and special testing. Reports on the possible role of the AVP/V1b receptor system in the increase of HPA axis hyperactivity with aging are contradictory and requires further research. Many contradictory results may be due to age and species differences in the HPA function of rodents and primates. The hypothalamic–pituitary–adrenal (HPA) axis is a key adaptive neuroendocrine system. Regulation of glucocorticoid secretion through adrenocorticotropic hormone (ACTH) is critical to life and essential to maintain the mammalian response to stressor  of the PVN is a key center of the central nervous system, integrating the neuroendocrine effects of stress, and a key part of the HPA axis. On the one hand, the CRH neuron is under the regulatory influence of numerous afferent nerve pathways that carry information about the stressor. In addition, it is regulated by glucocorticoids and it is the central link of the autoregulation mechanism in the HPA axis.The CRH neuron receives projections from ascending catecholaminergic pathways including noradrenergic projections from the A2 noradrenergic cell group within the nucleus of the solitary tract and the locus ceruleus. It also receives input from areas of the limbic system, notably the bed nucleus of the stria terminalis, the hippocampus, and the amygdala  and the low-affinity glucocorticoid receptors (GR), which are expressed in the brain and on the corticotrophs of the pituitary  and a number of peripheral tissues   revealed that age-related dysfunctions of the HPA axis are associated with adaptive behavior of animals  receptors  the possible increase of the AVP production in the PVN for aged rodents, (b) the possible lack of any age changes in the AVP secretion in basal and stress conditions, and (c) the possible reduced basal AVP production along with the CRH hypersecretion.Only a few studies have addressed age-related changes in vasopressinergic regulation of HPA axis stress reactivity in humans and non-human primates  to young and old female rhesus monkeys at different times of day (09:00 and 15:00 h). The response of the pituitary–adrenal axis to the injection of CRH revealed a circadian rhythm with a more pronounced response in the afternoon; this rhythm was not affected by aging The role of CRH and AVP in the stimulation of ACTH secretion varies depending upon the species. For humans, non-human primates, and rats CRH seems to be a more important secretagogue than AVP, in humans, all parvicellular neurons of the PVN, which produce CRH in the basal conditions, produce AVP as well, whereas in rats not more than half produce AVP.(2)AVP is an important regulator of the ACTH response to acute stress. AVP contributes to the acute ACTH secretion to stress in a context-specific manner. AVP is needed for the acute ACTH secretion for most of the known stressors.(3)Current data on the role of AVP in the regulation of HPA axis responsiveness to chronic stress in adulthood are contradictory and require further research.(4)The importance of the vasopressinergic regulation of stress responsiveness of the HPA axis is elevated during the fetal development, in neonatal period, and in the lactating adult.(5)(a)Aging is associated with increased variability in several parameters of HPA axis function including basal state, responsiveness to stressors, and special testing. This increased variability in the aged compared to normal adults has been observed in some form in multiple species including rodents, non-human primates, and humans.(b)For the most experiments on rodents, the hyperactivation of the HPA axis was observed at all levels of the HPA organization with aging under the basal and stress conditions.(c)With healthy aging of non-human primates and humans the HPA hyperactivation is usually associated with the increase of the cortisol level in the evening time, the slight changes in the regulation of the HPA axis by glucocorticoid feedback with relative hypercortisolemia due to the decline in secretion of the adrenal antagonists of cortisol – DHEA and DHEAS.(6)(a)the possible increase of the AVP production in the PVN for aged rodents and humans,(b)the possible lack of any age changes in the AVP secretion in basal and stress conditions,(c)the possible reduced basal AVP production along with the CRH hypersecretion.Reports on the possible role of the AVP/V1b receptor system in the increase of HPA axis hyperactivity with aging are contradictory, suggesting(7)Age-related changes in response of the HPA axis to the moderate acute restraint stress were observed in rhesus monkeys with much higher increase of ACTH and cortisol secretion in young monkeys in response to the stress imposed at 15:00 h. In addition, these age changes were associated with age-related disturbances in vasopressinergic regulation.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Gene regulation underlies fungal physiology and therefore is a major factor in fungal biodiversity. Analysis of genome sequences has revealed a large number of putative transcription factors in most fungal genomes. The presence of fungal orthologs for individual regulators has been analysed and appears to be highly variable with some regulators widely conserved and others showing narrow distribution. Although genome-scale transcription factor surveys have been performed before, no global study into the prevalence of specific regulators across the fungal kingdom has been presented.In this study we have analysed the number of members for 37 regulator classes in 77 ascomycete and 31 basidiomycete fungal genomes and revealed significant differences between ascomycetes and basidiomycetes. In addition, we determined the presence of 64 regulators characterised in ascomycetes across these 108 genomes. This demonstrated that overall the highest presence of orthologs is in the filamentous ascomycetes. A significant number of regulators lacked orthologs in the ascomycete yeasts and the basidiomycetes. Conversely, of seven basidiomycete regulators included in the study, only one had orthologs in ascomycetes.This study demonstrates a significant difference in the regulatory repertoire of ascomycete and basidiomycete fungi, at the level of both regulator class and individual regulator. This suggests that the current regulatory systems of these fungi have been mainly developed after the two phyla diverged. Most regulators detected in both phyla are involved in central functions of fungal physiology and therefore were likely already present in the ancestor of the two phyla. Gene regulation is of major importance for physiology of all organisms, and has been intensively studied in fungi. It ensures that the required genes are switched on and act under the circumstances they are needed, and allows fungi to respond to changing conditions. Thirty-seven classes of regulator proteins have been identified in fungi, such asSaccharomyces cerevisiae,,].].RegulatClick here for filePresence of homologs of the 64 selected regulators in 108 fungal genomes. Presence or absence of homologs of each regulator are tabulated for the 108 fungal genomes analysed.Click here for fileGene IDs of the homologs of the 64 regulators. Gene IDs are displayed as indicated in the genome downloads. In the case of mutiple homologs, the gene ID’s are in the same cell separated by a comma.Click here for file


The analyses of genome sequences have led to the proposal that lateral gene transfers (LGTs) among prokaryotes are so widespread that they disguise the interrelationships among these organisms. This has led to questioning of whether the Darwinian model of evolution is applicable to prokaryotic organisms. In this review, we discuss the usefulness of taxon-specific molecular markers such as conserved signature indels (CSIs) and conserved signature proteins (CSPs) for understanding the evolutionary relationships among prokaryotes and to assess the influence of LGTs on prokaryotic evolution. The analyses of genomic sequences have identified large numbers of CSIs and CSPs that are unique properties of different groups of prokaryotes ranging from phylum to genus levels. The species distribution patterns of these molecular signatures strongly support a tree-like vertical inheritance of the genes containing these molecular signatures that is consistent with phylogenetic trees. Recent detailed studies in this regard on the Thermotogae and Archaea, which are reviewed here, have identified large numbers of CSIs and CSPs that are specific for the species from these two taxa and a number of their major clades. The genetic changes responsible for these CSIs (and CSPs) initially likely occurred in the common ancestors of these taxa and then vertically transferred to various descendants. Although some CSIs and CSPs in unrelated groups of prokaryotes were identified, their small numbers and random occurrence has no apparent influence on the consistent tree-like branching pattern emerging from other markers. These results provide evidence that although LGT is an important evolutionary force, it does not mask the tree-like branching pattern of prokaryotes or understanding of their evolutionary relationships. The identified CSIs and CSPs also provide novel and highly specific means for identification of different groups of microbes and for taxonomical and biochemical studies. The understanding of prokaryotic relationships is one of the most important goals of evolutionary sciences. These relationships have been difficult to understand due to the simplicity and antiquity of prokaryotic organisms and disagreements in viewpoints among evolutionary biologists regarding the importance of different factors when grouping prokaryotes. Although earlier studies in this regard were based on morphology or physiology Cowan, , the fieThe comparative genomic analyses have revealed that phylogenetic relationships deducted based upon different genes and protein sequences are not congruent and lateral gene transfer (LGT) among different taxa is indicated as the main factor responsible for this lack of concordance , or CSIs, in protein sequences comprises an important category  and a number of its sub-phylum level taxa .In addition to the CSIs that are specific for particular prokaryotic taxa, several of the identified CSIs have also proven useful in clarifying the branching order and interrelationships amongst different bacterial phyla Gupta, . One exaThermotoga except T. lettingae  within prokaryotes are currently identified solely on the basis of their branching in the 16S rRNA trees. Because the phylogenetic trees are a continuum, based upon them it has proven difficult to clearly define or delimit the boundaries of different taxonomic groups. Additionally, for virtually all of the higher prokaryotic taxa, no molecular, biochemical or physiological characteristics are known that are unique to them. Hence, a very important aspect of microbiology that needs to be understood is that in what respects do species from different main groups of bacteria differ from each other and what, if any, unique molecular, biochemical, structural or physiological characteristics are commonly shared by species from different groups? In this context, the large numbers of CSIs and CSPs for different taxonomic clades of bacteria that are being discovered by comparative genomic analyses provide novel and valuable tools for taxonomic, diagnostic, and biochemical studies  Based upon these markers different prokaryotic taxa can now be identified in clear molecular terms rather than only as phylogenetic entities. (2) Based upon them the boundaries of different taxonomic clades can also be more clearly defined. (3) Due to their high degree of specificity and predictive ability, they provide important diagnostic tools for identifying both known and unknown species belonging to these groups of bacteria. (4) The shared presence of these CSIs by unrelated groups of bacteria provides potential means for identifying novel cases of LGTs. (5) Functional studies on these molecular markers should help in the discovery of novel biochemical or physiological properties that are distinctive characteristics of different groups of prokaryotes.Lastly, it should be acknowledged that the number of genes which harbor rare genetic changes such as these CSIs is generally small in comparison to the total number of genes that are present in any genome. However, the genes containing these CSIs are involved in different essential functions and they are often are amongst the most conserved proteins found in various organisms. Although, the criticism could be levied that the inferences based upon small numbers of genes/proteins containing these CSIs are not representative of the entire genomes (Dagan and Martin, The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Chronic pancreatitis (CP) is a progressive inflammatory disease in which the pancreatic secretory parenchyma is destroyed and replaced by fibrosis. The presence of intraductal pancreatic stone(s) is important for the diagnosis of CP; however, the precise molecular mechanisms of pancreatic stone formation in CP were left largely unknown. Cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel expressed in the apical plasma membrane of pancreatic duct cells and plays a central role in  Chronic pancreatitis (CP) is a progressive inflammatory disease of the pancreas, and is characterized by pancreatic exocrine and endocrine dysfunction resulting from tissue damage caused by inflammation. The pancreatic exocrine gland is composed of two types of cells, duct cells and acinar cells. Duct cells secrete fluid and For a diagnosis of CP  of the pancreas. Cytoplasmic mislocalization of the CFTR chloride channel results in aberrant The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Drosophila fly. However, not much is known about the mechanisms leading to coherent circadian oscillation in clock neuron networks. In this work we have implemented a model for a network of interacting clock neurons to describe the emergence (or damping) of circadian rhythms in Drosophila fly, in the absence of zeitgebers. Our model consists of an array of pacemakers that interact through the modulation of some parameters by a network feedback. The individual pacemakers are described by a well-known biochemical model for circadian oscillation, to which we have added degradation of PER protein by light and multiplicative noise. The network feedback is the PER protein level averaged over the whole network. In particular, we have investigated the effect of modulation of the parameters associated with (i) the control of net entrance of PER into the nucleus and (ii) the non-photic degradation of PER. Our results indicate that the modulation of PER entrance into the nucleus allows the synchronization of clock neurons, leading to coherent circadian oscillations under constant dark condition. On the other hand, the modulation of non-photic degradation cannot reset the phases of individual clocks subjected to intrinsic biochemical noise.Circadian rhythms in pacemaker cells persist for weeks in constant darkness, while in other types of cells the molecular oscillations that underlie circadian rhythms damp rapidly under the same conditions. Although much progress has been made in understanding the biochemical and cellular basis of circadian rhythms, the mechanisms leading to damped or self-sustained oscillations remain largely unknown. There exist many mathematical models that reproduce the circadian rhythms in the case of a single cell of the  Drosophila melanogaster the expression of the circadian clock genes occurs within approximately 150 clock neurons. The molecular mechanisms of these fundamental oscillators consist mainly of two interlocked transcriptional feedback loops involving per, tim, clk, vri and pdp1 genes per expression, and the PER-TIM complex then inhibits the activity of clk. Furthermore, clk is regulated negatively by the VRI protein and positively by the protein PDP1. In the second loop, vri and pdp1 are directly activated by the CLK protein. After its synthesis, the PER protein is phosphorylated at several residues. This leads to a time delay between the rise of mRNAs and that of the PER acting as transcriptional repressor for the clk gene. Thus alternating protein production, gene repression, and protein degradation may lead to self-sustained oscillations. The circuit is further complicated by the influence of the kinase doubletime on degradation and transport of the PER protein Most living organisms present rhythmic phenomena whose periods range from few milliseconds to years. Circadian oscillation is an important example of this kind of phenomenon. Several recent observations have suggested that the circadian rhythm at the molecular level results from a gene regulatory network Drosophila, the clock neurons have been divided into two major groups: the lateral neurons (LN) and the dorsal neurons (DN). The lateral neurons are subdivided into three subgroups: the large and small ventrolateral neurons  neuropeptide, which is specifically expressed in the ventral lateral neuron group  averaging the period and phase obtained for each individual clock neuron over the clock neuron population; (ii) first averaging the The overall degree of synchronization over a specified time interval is analyzed by computing the parameter zeitgeber the clock neurons are synchronized, but in free running (DD condition) there is a loss of synchronization. Nevertheless, the molecular oscillations of each clock neuron are little affected by the absence of the zeitgeber. Now we will test the hypotheses regarding the effects of interneuron interaction on synchronization:Drosophila, we look for a region in the We assume that the input signal zeitgebers.In addition, we have also determined the period and phase of the oscillations of the individual clock neurons by fitting the time course of We have also done numerical simulations for two other values of or,  see . For   that allow us to explain the observed behavior in In contrast with With our model we have studied the degree of synchronization of oscillators, and the period and phase of the oscillation, at the network level, in the space of parameters for some alternative hypotheses. In particular, we have investigated the effect on the synchronization when (i) Our results indicate that for zeitgebers when the input feedback signal The present network model is able to display circadian oscillation even in the absence of external Our results indicate that mechanisms based on a positive feedback acting over the rate of entrance of the phosphorylated PER into the nucleus could be essential for maintaining the circadian oscillation under free-running condition. This fact suggests a putative way of action for the neuropeptide PDF, which could be acting as an agent that promotes the entrance of the phosphorylated PER into the nucleus.


To investigate the importance of incorporating adaptive designs of randomised phase II trials into the protocol and patient information sheets using NEO-ESCAPE as an illustrative example.NEO-ESCAPE was a randomised two arm phase II study in inoperable ovarian cancer designed as an external pilot to inform a future phase III randomised controlled trial. The primary objective was to assess the feasibility of two new extended chemotherapy regimens with 44 patients required on each arm. If one or both treatment arms proved feasible, the trial would continue to recruit to the feasible treatment arm(s) to improve the estimates of outcomes to be used in the phase III trial. Stopping rules were essential to enable pre-planned decisions on the futility of continuing to the required 44 patients on each arm. Simulations to assess futility were used in the decision making process.At the first pre-planned interim analysis when 56 patients had been recruited (28 on each arm) and 21 patients  had finished treatment, it was clear that one arm of the trial would not meet the feasibility criteria on completion of recruitment. On the advice of the Independent Data Monitoring Committee, this arm of the study closed to recruitment but follow-up for these patients continued.Closure of one arm of the study resulted in a temporary halt of the trial while the protocol was amended to a single arm study, the patient information sheet was updated and all the relevant ethics, MHRA and Research and Development approvals were obtained. This temporary two month halt in recruitment to the study carried not only a loss of potential patients during the closed period but also a loss of momentum of centres on re-opening of the study and hence resulted in a delay in completing recruitment.Our experiences with this phase II study emphasise the need for full details of any adaptive designs, including all anticipated scenarios and subsequent actions, to be fully incorporated into the protocol and patient information sheet to avoid the need for a temporary halt of recruitment. A detailed statistical analysis plan is also essential in ensuring optimal decision making within these types of studies. The dilemma remains on how best to achieve a seamless transition in the adaptive element whilst not confusing patients with too much information about each possible future adaptation.


Results of the survey show that the overall attitude of the Malaysian stakeholders towards GM products was cautious. Although they acknowledged the presence of moderate perceived benefits associated with GM products surveyed and were moderately encouraging of them, they were also moderately concerned about the risks and moral aspects of the three GM products as well as moderately accepting the risks. Attitudes towards GM products among the stakeholders were found to vary not according to the type of all GM applications but rather depend on the intricate relationships between the attitudinal factors and the type of gene transfers involved. Analyses of variance showed significant differences in the six dimensions of attitude towards GM products across stakeholders' groups.Public acceptance of genetically modified (GM) foods has to be adequately addressed in order for their potential economic and social benefits to be realized. The objective of this paper is to assess the attitude of the Malaysian public toward GM foods  and GM medicine (GM insulin). A survey was carried out using self-constructed multidimensional instrument measuring attitudes towards GM products. The respondents ( There has been significant advancement in modern biotechnology worldwide in the past ten years. Current biotechnology products mostly focus on the commercialization of biopharmaceuticals  followedIn Malaysia, biotechnology has been identified as one of the five core technologies that will accelerate the country's transformation into a highly industrialized nation by 2020 . Most ofThe advancement in gene technology for the production of GM crops and biopharmaceuticals has been so rapid in the past fifteen years, making it the object of an intense and divisive debate worldwide. The acceptance of gene technology varies from country to country and across different applications of the technology . Past suThe studies of public attitudes towards biotechnology and GM foods have many similarities with risk perception studies. The psychometric approach suggests that the public do not perceive technological risk according to a single dimension related to predicted injuries or fatalities akin to a risk assessor's viewpoint but interpret risk as a multidimensional concept, concerned with broader qualitative attributes , 36. WitThe objective of this paper is to assess and compare the attitudes of the Klang Valley stakeholders towards two GM foods: genetically modified (GM) soybean , GM palm oil , and GM insulin (involving the transfer of human genes into bacteria). GM soybean and GM insulin are already available in the Malaysian market while GM palm oil is a high priority area of research in Malaysia.A survey was carried out between June 2004 and February 2005. The people in the Klang Valley region were chosen as the targeted population as it is the centre of the country's economic and social development  as well as the respondents in this region meet the requirement of diverse background stated in the model.N = 1017) were adults (age 18 years old and above) stratified according to various interest or stakeholder groups listed in f = 0.25) at P = 0.05 and u = 12, a sample of 22 subjects per group is required to obtain a power of 0.80 [In this study, the stakeholder-based survey approach recommended by Aerni  was adop of 0.80 . So each of 0.80 , for anyThe questionnaires were handed out personally to respondents by biotechnology graduate enumerators who were trained to be neutral on their stance of GM products. Before answering, the respondents were given an introduction to basic concepts and examples of GM foods and GM medicine. They were also exposed to the real scenario of GM products debate on the possible benefits and risks and regulation of GM products, and they were given the chance to enquire further. This approach was suggested by Kelley  to assesThe multidimensional instrument measuring attitudes towards GM foods and medicine used in this study was constructed based on earlier research . The insInitially, reliability  tests were carried out using SPSS version 12.0 to assess the consistency and unidimensionality of the constructs. Analyses of variance (ANOVAs) were also carried out using the same statistical package. Confirmatory factor analysis was carried out using Analysis of Moment Structure (AMOS) software version 19 with maximum likehood estimation to validate the measures.χ2 = 608.2, df = 208, P < 0.001). Chi-square statistical significant test is not very useful in indicating the fit of the model in this study due to the large sample size [A single step SEM analysis as proposed by Hair Jr et al.  was carrple size . Other fple size , NFI, CFple size , 50 are Three types of reliabilities measured in this paper are the internal consistency , item reliability, and construct reliability. The Cronbach's alpha coefficients for majority of the constructs were considered good (above 0.70) . The corTwo validity measures were tested in this paper. The convergent validity was assessed by the factor loadings and composite reliability . The staAttitudes towards GM foods  and GM insulin were analyzed based on six dimensions: familiarity, perceived benefits, perceived risks, risk acceptance, moral concerns, and encouragement.F = 4.26, P < 0.001), GM palm oil , and GM insulin  across stakeholders. The biology students scored the highest weighted average in terms of familiarity with the three GM products  and post hoc tests showed that their rating of GM insulin differed significantly from majority of other stakeholders except for the producers , GM palm oil , and GM insulin  across stakeholders. Post hoc analyses of the beneficial aspects of the three surveyed GM applications highlighted the significant difference in opinion of the biology students compared to the media and the general public , GM palm oil , and GM insulin . Post hoc test showed the media's rating of GM insulin as significantly differed from the biologists, policy makers, and biology students , GM palm oil , and GM insulin  across stakeholders. The media was noticeably the most critical with the lowest rating for GM soybean and GM palm oil. Post hoc tests showed that their acceptance of risk for GM soybean, GM palm oil, and GM insulin were significantly different from the biology students and additionally differed with the Buddhist scholars with respect to the acceptance of risk related to the two GM foods , and GM palm oil , and GM insulin . Post hoc tests confirmed that the Buddhist and Christian scholars significantly perceived the moral aspects of the GM applications surveyed as higher than the majority of stakeholders except for the media and Hindu scholars , GM palm oil , and GM insulin  across stakeholders. Post hoc tests showed significant difference in the support of the biology students towards all three GM products compared to the Buddhist and Christian scholars, additionally differed with the Islamic scholars with respect to GM soybean and GM insulin, displayed higher rating than the general public in their opinion of GM palm oil, and showed higher rating of GM insulin compared to the Hindu scholars  followed by GM insulin (weighted average 4.44) and GM soybean  was the most supported but, on the other hand, the other type of GM food (GM soybean) was the least supported compared to GM insulin . When a Overall, the Malaysian stakeholders were the most supportive of GM palm oil  followed by GM insulin  and GM soybean . The weighted averages for overall encouragement in this study are slightly higher than the mean score of Malaysians' attitude towards agricultural biotechnology  in the ISAAA-UIUC 2003a) report. Across Asia, the support for GM foods and medicines was not very encouraging too. Data on public attitude in other Asian countries is rather limited for comparison and those available used different questionnaires. The urban shoppers in Seoul also perceived the benefits of GM foods as moderate too  03a repor. In a moComparing across stakeholders, the biology students were clearly the most enthusiastic about GM foods and GM insulin surveyed as well as claiming to be the most familiar with those products. This could be because they were still studying and therefore were actively seeking information related to their courses. It is typical of the biology courses in Malaysia to focus on the theory, concepts, and applications/development of GM products rather than on the risk aspects. So it is to be expected that the biology students would be highly enthusiastic about the potentials of GM products. On the other hand, the media subjects were noticeably the most critical of GM foods and GM insulin. This finding again supported the earlier study by ISAAA-UIUC , where tThe NGOs in the Klang Valley region were not strongly against GM foods and GM insulin. Their perception of the risks related to the three GM applications surveyed was in the moderate range, acknowledging moderate benefits and moderately encouraging the three GM applications comparable to the majority of the other stakeholders. This is a favourable finding for the country and in contrast with Aerni's study . Aerni  reportedSurprisingly and as cause for concern, the biotechnologists and policy makers claimed to have only moderate familiarity with GM foods and GM insulin surveyed and their weighted averages were in the same category  with the majority of the other stakeholders with the exception of the biology students. Even more worrying is the ignorance of the policy makers who are responsible for making decisions regarding modern biotechnology issues in Malaysia. They professed to have low familiarity with GM soybean and although their familiarity with GM palm oil and GM insulin were in the moderate category, they were within the lowest three ranking together with the religious scholars groups. The reason behind this could be because biotechnologists tended to focus their activities on research and development of new products while the policy makers are mostly biotechnology related academicians or researchers who also share the same priorities.Attitude of the scientists (biotechnologists and biologists), policy makers, and the producers in the Klang Valley region seemed to be cautious towards GM products. Although their attitudes were inclined towards the positive side compared to the other stakeholders except for the biology students, they also seemed to have some reservations about GM foods and GM insulin. The attitude towards GM products scenario is rather common worldwide. Torres et al.  stated tAmong the stakeholders, the Buddhist and Christian scholars were highly concerned about the moral aspects of GM foods and GM insulin surveyed while the Hindu scholars perceived the moral aspects of GM insulin as high. Aerni  found thThe politicians and the general public were found to have moderate attitude towards GM foods and GM insulin. The consumers in the Philippines were more positive towards GM crops  but it sDespite significant developments in modern biotechnology and GM foods worldwide and in Malaysia, the Klang Valley stakeholders' overall attitude towards GM foods and GM insulin was found to be cautious. Although they acknowledged the presence of moderate perceived benefits associated with GM foods and GM insulin surveyed and were moderately encouraging of them, they were also moderately concerned about the risks and moral aspects of the three products as well as moderately accepting the risks. Results from this study revealed that acceptance of modern biotechnology products by the stakeholders varies not so much according to the type of applications or products but rather on the intricate relationships between all the factors, familiarity, benefit to consumers, and the moral aspects or the type of gene transfers involved. If the biotechnology application offers high and clear benefit to consumers and is of low moral concern, the risk associated with it would be highly compensated (acceptable) and the application would be highly encouraged. It is suggested that biotechnologists and industries assess the benefit, risk, and moral aspects of new GM food and GM applications/products to gauge public acceptance of the applications before embarking on R&D and commercialization to avoid the loss of huge amount of financial and labour investments if the products turn out to be unacceptable to consumers. Labelling GM foods and GM products is also recommended to increase consumers' confidence in the products besides the need to make available scientific evidence on the safety of modern biotechnology products by independent researchers.The research findings serve as a useful database for understanding public acceptance of GM foods in a developing country to understand the social construct of public attitude towards GM foods. A more in-depth study needs to be carried out to evaluate the reasons for the low familiarity of the Malaysian public especially among the biotechnologists and policy makers on GM foods and to explore the cautious attitude of the scientists (biotechnologists and biologists), policy makers, and the producers in the Klang Valley region towards GM foods and products. There is also a need to understand the religious perspectives of various religions on the moral aspects of genetic modification as well as looking at the actual reasons behind the critical nature of the people in media.


Successful removal of metalwork requires a skilled surgeon and the correct instruments. We describe a simple method for the removal of an AO (Arbeitsgemeinschaft für Osteosynthesefragen) unreamed tibial nail in the absence of the correct extraction bolt. The threaded rods from the Taylor Spatial Frame fit into the proximal end of the nail perfectly, allowing for the easy extraction of the nail. The addition of a hexagonal post  allows t


We describe the case of a 68-year-old male with autopsy-confirmed sporadic CJD (CJDs) who had undergone 2 colonoscopies prior to this diagnosis.The involved endoscopy centre had multiple colonoscopes and gastroscopes that are cleaned and disinfected in the same automatic washers/disinfectors (AWD). There was no system in place to track the use and disinfection of individual endoscopes.Four questions arise:- Is it necessary to dispose of colonoscopes potentially contaminated by CJDs?- Is it necessary to dispose of the AWD where the endoscopes were washed?- Is it necessary to dispose gastroscopes at risk of contamination during the disinfection process in the AWD?- Is it necessary to inform the patients who were exposed to these endoscopes ?We estimated that this situation occurs approximately 17 times each year in Switzerland. To answer these questions requires data on the presence of CJDs prions in the colon, the risk of contamination of the endoscopes, the risk of prion transmissions to other patients via the endoscopes, and the procedures of cleansing and disinfection. Finally, it is also necessary to take into account psychological, financial and ethical implications for the endoscopy centre and the patients exposed to the potentially contaminated endoscopes.This complex situation highlights the need for guidance recommendations in this area.None declared.


Presently, different studies are conducted related to the topic of biomass potential to generate through anaerobic fermentation process alternative fuels supposed to support the existing fossil fuel resources, which are more and more needed, in quantity, but also in quality of so called green energy. The present study focuses on depicting an optional way of capitalizing agricultural biomass residues using anaerobic fermentation in order to obtain biogas with satisfactory characteristics.. The research is based on wheat bran and a mix of damaged ground grains substrates for biogas production.The information and conclusions delivered offer results covering the general characteristics of biomass used , the process parameters with direct impact over the biogas production  and the daily biogas production for each batch relative to the used material.All conclusions are based on processing of monitoring process results , with accent on temperature and pH influence on the daily biogas production for the two batches. The main conclusion underlines the fact that the mixture batch produces a larger quantity of biogas, using approximately the same process conditions and input, in comparison to alone analyzed probes, indicating thus a higher potential for the biogas production than the wheat bran substrate.Adrian Eugen Cioabla, Ioana Ionel, Gabriela-Alina Dumitrel and Francisc Popescu contributed equally to this work AEC and FP performed the experimental research and elaborate the paper. II coordinated the whole research including the drawing of the conclusions and coordinated the final form of the paper. GAD performed the mathematical approach and analyze. All authors read and approved the final manuscript.


Dentigerous cysts, commonly encountered in the practice of dentistry, are benign odontogenic cysts associated with crowns of unerupted and/or impacted permanent teeth. They frequently occur during the second and third decades of life. Treat-ment modalities range from enucleation to marsupialization, which may be influenced by the age of the patient, severity of impaction, and root form of associated tooth/teeth. The purpose of this report is to describe the successful outcome of con-servative surgical management of a large dentigerous cyst associated with an impacted mandibular second premolar in a young patient. Maxillary and mandibular premolars have also been associated with dentigerous cysts.7 Dentigerous cysts have also been reported in association with impacted deciduous teeth.9Dentigerous cyst or follicular cyst is an odontogenic cyst associated with the crown of an impacted, embedded, unerupted or developing tooth. The cyst which encloses the crown of an unerupted tooth is attached to the cervical region of the tooth. It is the second most common type of odontogenic cysts accounting for 14% to 24% of all jaw cysts.10 The usual radiographic feature is characterized by a symmetric, well-defined, usually unilocular radiolucent lesion surrounding the crown of an unerupted tooth. Generally there is a distinct, dense periphery of reactive bone (condensing osteitis) with a radiolucent center. These cysts can also manifest as multilocular entities and occasionally may be associated with resorption of the roots of adjacent erupted teeth.13Clinically, patients with dentigerous cysts are generally asymptomatic. They are often described as an incidental radiographic finding on routine radiographs or when films are obtained to determine why a tooth has failed to erupt or when an acute inflammation or infective exacerbation occurs.2 marsupialization,5 and decompression of the cyst via fenestration.6Dentigerous cysts are generally treated by surgical means. The most common surgical modalities used are total enucleation,This case study describes a conservative surgical approach combined with routine orthodontic treatment of a dentigerous cyst associated with a mandibular second premolar in an adolescent.An 11-year-old female was referred by her dentist in Community Medical Center to the Orthodontic Section, Department of Dentistry, Hamad Medical Corporation, Doha, Qatar, with the chief complaint of a swelling on the left side of her lower jaw since three months earlier. The swelling had been growing slowly over the period and was associated with no pain or discharge. The overall general physical health of the patient was good with nonspecific general medical history, without any contraindication to dental treatment.The extraoral examination revealed a symmetrical orthognathic facial profile with no signs of neurological deficit in the lower half of the face. There was no sign of any regional lymphadenopathy. Intraoral examination revealed a mixed stage of dentition, bilateral Class I molar relationships and Class I incisors. A hard, non-tender, non-fluctuant swelling of 2.5 × 2 cm was evident in the lower left vestibule, extending from the distal surface of the left permanent canine to the distal surface of ipsilateral first permanent molar. The swelling was associated with expansion of buccal and lingual cortical plates and covered by healthy-appearing and freely-moving mucosa. The teeth adjacent to the swelling were quite firm and not associated with any decay. A panoramic radiographic examination (OPG) revealed the presence of all the permanent teeth without any decayed or supernumerary teeth. There was a well-circumscribed unilocular radiolucent lesion in the body of the mandible on the left side, which was associated with the crown of a vertically impacted second premolar. The root of the impacted second bicuspid was developed approximately up to half of its usual length and the apex was quite wide open. The cystic structure appeared to have originated from the second bicuspid with inferior and distal displacement of the same tooth. The corresponding deciduous tooth (second molar) was still present with normal crown and roots.A clinical diagnosis of a dentigerous cyst involving the crown of the impacted left mandibular second bicuspid was made with the differential diagnosis of an inflammatory cyst, a keratocyst and a unilocular ameloblastoma.Aims and objectivesConsidering the age of the patient, her occlusal status, size of the cyst, position, and developmental stage of the root of the involved tooth a conservative treatment modality was decided upon. The main objectives of the treatment were clinical and radiographic elimination of the pathologic entity and to bring the involved permanent tooth into its proper position.Treatment planExtraction of the left mandibular second deciduous molar and decompression of the cyst through the extraction socket.Histopathologic examination of the cystic lining.Trans-lingual arch to hold the permanent first molars bilaterally in their current position and to maintain the space for unerupted left bicuspids.Follow-up of the progress of eruption of the impacted second bicuspid with periodic radiographs.Fitting of a fixed orthodontic appliance for final alignment of teeth in due course if needed.Treatment progressThe left second deciduous molar was extracted under local anesthesia  and the socket was used to establish a communication between the cyst cavity and the oral cavity. An incisional biopsy was obtained from the cyst wall for histopathologic examination, which confirmed the initial diagnosis of a dentigerous cyst without evidence of any dysplastic changes. A BIPP (bismuth iodoform paraffin paste) gauze pack was inserted into the cyst cavity and secured with a suture. One week after surgery, the pack was removed and repacking was done with another BIPP gauze pack, which was kept in place for another week. Two weeks after surgery, the patient was sent back to an orthodontist for the fabrication of trans-lingual arch and for further follow-up.However, the patient could not return for further follow-up and treatment as she was out of the country. She reported eight months after the initial surgery and at this stage the clinical examination revealed inadequate space for the unerupted second premolar. The panoramic view (OPG) showed a favorable change in the position of the impacted premolar with increasedradiopacity of cystic lesion, suggesting osteogenesis. A fixed14The aim of treatment for dentigerous cysts is complete elimination of pathology and maintenance of dentition with minimal surgical intervention. Recently-defined criteria for selecting the treatment modality refer to the cyst size and location of the cyst, patient age, dentition involved, stage of root development, position of the involved tooth in the jaw and its relation to the adjacent teeth, and involvement of adjacent vital structures.14 This approach is favored in cases involving impaction of a single tooth, such as a wisdom tooth in an adult, which has no function; however, it is not often in the patient’s best interests. In particular, extractions of associated teeth in children may have functional, esthetic, and psychological consequences. Thus a conservative surgical approach was chosen for this patient, which consisted of the removal of one deciduous tooth and an incisional biopsy for histological examination, considered essential to confirm the diagnosis. Many authors have emphasized the importance of maintaining the opening between the cyst and the oral cavity artificially not only to heal the cystic lesion but also to prevent the formation of a fibrous scar which can impair eruption of the involved teeth.10 However, in this case no such attempt was made to maintain the patency of the cyst opening into the oral cavity except for keeping the surgical pack in place for only two weeks. This finding supports the hypothesis that simple decompression of the cyst and further root development would allow for the spontaneous relocation of the associated tooth.Surgical treatment of dentigerous cysts usually includes enucleation of the lesion along with the removal of associated teeth.7 the optimal timing for the initiation of surgical treatment of a cyst-associated tooth is when the tooth has the ability to erupt. Radiographically the roots of these teeth should show at least 2/3 of root formation with an open apex. Although optimal timing correlates with the 2/3 of root development, in this case the radiograph showed approximately 1/2 of root development. The decision was made to administer treatment at this stage considering the initial position of the involved tooth in relation to the lower border of the mandible and to allow for further root development by an early release of intra-cystic pressure.According to Miyawaki et al,6 However in this case an early initiation of orthodontic treatment was essential as there was inadequate space for the impacted second premolar due to drifting of adjacent teeth into the extraction site of the second deciduous molar.It has also been well-documented by many authors in different case studies that complex orthodontic treatment can be avoided by maintaining the space in the arch for underlying involved tooth.It took a total of 37 months to finish the treatment, which emphasizes the importance of close supervision by the operators. The result also highlights the potential for healing of the cystic lesion after its decompression, particularly in young children. As revealed by the panoramic view, there was complete radiologic healing of the cystic lesion, including the filling of cystic cavity with normal trabecular bone at the end of the treatment .This case report presents a number of points which are noteworthy:A simple and conservative surgical approach should be preferred for a large dentigerous cyst in an adolescent in the mixed dentition period. This not only preserves the function and esthetic values but also prevents the child from psycho-social trauma due to tooth loss.The capacity to regenerate bone is greater among children than among adults and teeth with open apices have great eruptive potential. Thus, large dentigerous cysts in children can be treated differently and conservative treatment with tooth preservation should always be considered.This case report also provides a commentary on the optimal timing to initiate surgical treatment of a cyst-associated tooth. It supports the concept of initiation of treatment when radiographic analysis of the roots and apex of these teeth shows at least 1/2 - 2/3 of root formation with an open apex.A panoramic (OPG) film is a common and reliable tool for the diagnosis and assessment of progress in healing of a mandibular dentigerous cyst along with the change in the position of the associated tooth.However, this conservative approach does require close cooperation on the part of both the patient and the dental practitioners in order to monitor the healing of the lesion and change in the position of the involved tooth. The result can be the elimination of pathology and maintenance of the dentition.


The study aimed to evaluate the level of burnout among the clinical dental students in two Jordanian universities.A total of 307 students from the two schools were surveyed using Maslach Burnout Inventory survey. Scores for the inventory’s subscales were calculated and the mean values for the students’ groups were computed separately. Kruskal-Wallis and Mann-Whitney tests were carried out and the results were compared at 95% confidence level.The results showed that the dental students in both Jordanian universities suffered high levels of emotional exhaustion and depersonalization compared to reported levels for dental students in other countries. The dental students of the University of Jordan demonstrated a significantly higher (p < 0.05) level of emotional exhaustion than their counterparts in the Jordan University of Science and Technology.The findings indicated that dental students in the Jordanian universities presented considerable degrees of burnout manifested by high levels of emotional exhaustion and depersonalization. Studies targeting students health and psychology should be carried out to determine the causes of burnout among dental students. The curricula of the dental schools in the two universities should be accordingly improved to minimize burnout among the students.Burnout; Emotional exhaustion; Depersonalization; Personal accomplishment; Maslach Burnout Inventory Dentistry is a profession demanding physical and mental efforts as well as people contacts.Excessive contact and handling of people can result in a condition known as Burnout. Burnout, therefore, is defined as ‘a syndrome of emotional exhaustion and cynicism that occurs frequently among individuals who do ‘people-work’ of some kind’ . BurnoutThe rate of burnout among dentists and its effect on their lives have been previously investigated by many researchers . It has Many researchers studied the existence of stress among dental students ,7-12, a In a study aimed at testing the rate of burnout among German dental students of three universities , it was The perceived stress among dental students had been attributed to factors such as fear of failure , the loaThe aim of this study was to determine the presence and level of burnout among the clinical dental students in the University of Jordan and in the Jordan University of Science and Technology, and also to compare the results with those of other countries.The extent of burnout in 307 clinical dental students of the University of Jordan (UJ) and Jordan University of Science and Technology (JUST) was assessed by employing the Maslach Burnout Inventory - Human Services Survey (MBI-HSS) . The invThe employed inventory is an effective tool of proven reliability and validity in detecting the presence and assessing the degree of burnout in human services workers.The English version of the inventory was used since English is the teaching language in the two Jordanian dental schools.The clinical students (fourth and fifth year) of both dental schools of UJ  and JUST  were asked to complete the inventory during one lecture at each of the universities during the second semester after the midterm examinations. The instructions were explained thoroughly to the students by the researchers. The response was totally anonymous to ensure confidentiality.The total score for each of the three subscales was calculated for each student by calculating the sum of responses to the items in the subscale. Mean values were then calculated for each student group separately. Shapiro-Wilk test of normality indicated that the data was not normally distributed in many instances. Consequently, non-parametric statistical tests were used in comparing the results of the four student groups. Kruskal-Wallis one-way analysis of variance (ANOVA) based on ranks was used in determining whether any significant differences existed among the student groups. Multiple comparisons among the different groups were performed using Mann-Whitney rank sum test. The various data sets were rigorously treated statistically at 95% level of confidence. Statistical analysis was carried out using the Statistical Package for Social Sciences .The responses for the 4th and 5th year students of each university were described in terms of means, standard deviations, variances, minimum and maximum values  and Fig.Cut-off values above which a subscale score was deemed high were obtained by correcting the values indicated in the MBI-Scoring Key to compensate for the difference in scoring scale.Female students in UJ had higher degrees of emotional exhaustion (p < 0.05) than their male counterparts while no significant differences were found between males and females of both universities neither in depersonalization nor in personal achievement scores .Pairwise comparisons have shown that the 4th year UJ students exhibited significantly higher degrees of burnout (p < 0.05) in the three subscales than their 5th year counterparts. On the other hand, no significant differences were found between 4th and 5th year students in JUST. Comparisons between universities have shown that UJ students had significantly higher degrees of emotional exhaustion (p < 0.05) than their counterparts in JUST .The results showed that almost all of the students of both the 4th and 5th years in the two dental schools of the two Jordanian universities suffered high degrees of emotional exhaustion. In a previous study  it was rComparisons between the two dental faculties of the two Jordanian universities revealed that UJ students had significantly higher scores of emotional exhaustion than JUST students. Although the clinical training scheme was similar in both universities, there were some differences which were possibly in favour of JUST students. The dental faculties of both universities adopted a clinical training system which obliged the students to successfully finish a minimum amount of clinical requirements in order to pass any clinical course. Nevertheless, the minimum clinical requirements of UJ dental faculty were more in terms of quantity and variety of clinical tasks than those of JUST for 4th or 5th year students. This accounted for more physical and mental efforts of the UJ students as opposed to that of their counterparts in JUST. In addition, UJ students had to find their own patients due to the absence of patients records filing system. The dental faculty of JUST, on the other hand, organized the students patient records and distributed them according to the students needs. This had increased the number of patients the UJ students had to interact with, which consequently increased the emotional exhaustion level in those students.Clinical sessions were longer and less frequent in JUST dental faculty. As a result, UJ students were more stressed trying to finish their procedures in time. Not to mention, that more clinical sessions per week meant more patients contacts, which in turn, increased the level of emotional exhaustion.The availability of the staff during the clinical sessions might also have played a role. In JUST, the staff to student ratio was very favourable for both the learning experience and the students mental health. As each clinical instructor handled less number of students, the students received longer time and better attention from the staff. Moreover, JUST provided an Allied Dental Sciences program, whose students assisted the clinical dental students during their sessions by putting four-handed dentistry into practice. The dental faculty at the UJ did not offer any allied dental sciences programs. This has obliged the dental students of the UJ to look for and find their own patients and to handle them entirely by themselves, unassisted by ancillary personnel.Depersonalization may be the most critical aspect of burnout in a health care profession like dentistry. Perceiving the patient as an impersonal object rather than a human being might result in detrimental negligence in treatment procedures and disregard of the psychological aspect of treating the patients. Fifth year students had significantly higher scores of depersonalization than 4th year students in both dental schools. No significant differences were found between students of the two schools in the same academic level. These findings might suggest that depersonalization increased with increased patient contact.Longitudinal studies are necessary to confirm such suggestion, but increasing the student as well as the instructors awareness to such problem is imperative to avoid further development of the problem in the future clinical career of the students.High scores of personal achievement mean more involvement with the patients, more satisfaction with the profession, and consequently, lower degrees of burnout. The lower scores of personal achievement in 5th year students, revealed in this study, should be viewed as another sign of increasing burnout which was related to increased patient contact in terms of frequency and duration. This scale of burnout is extremely important and should be closely monitored during the clinical training period of dental students and even after their graduation to ensure that the lack of personal achievement has diminished.The findings of this study indicated that dental students in the Jordanian universities suffered considerable degrees of burnout as manifested by high degrees of emotional exhaustion and depersonalization.Longitudinal studies that include pre-clinical dental students as well as young graduates should be carried out to determine how the patterns of burnout vary during the students academic clinical training period and further in their professional lives.Analytical studies targeting students health and psychology should be carried out regularly to determine the causes and factors related to the high degrees of burnout among dental students.The curricula of the dental schools in the two universities should be accordingly improved to minimize burnout among the students.Dental students as well as instructors should be informed about burnout and its elements, to increase their awareness which can alleviate the problem.


During the past two decades, the identification of new scientific developments to improve outcomes in gastrointestinal disorders has been attractive to many researchers. Pharmaceutical industries are now more motivated to introduce novel therapeutic remedies in the treatment of gastrointestinal disorders. Such disorders have increased at an exponential rate in various patient communities and both natural and synthetic compounds have been investigated for their potential biological activity in the treatment of these gastrointestinal disorders.Several interesting works were assessed in this special issue. Amongst them five articles were chosen based on their critical findings in gastrointestinal disorders.β-catenin and COX-2 in colon tumors. The Schiff base metal derivatives also may enhance the expression of HSP70 and suppress the expression of BAX proteins in an acute hemorrhagic gastric ulcer model. Another animal study assessed the hepatoprotective activity of the ethanolic extract of rhizomes of Z. officinale against thioacetamide-induced hepatotoxicity in rats. The floating dosage form of an anticancer drug was prepared in another study entitled “Preparation and Characterization of a Gastric Floating Dosage Form of Capecitabine.” The work characterized the sustained release tablet in terms of total floating time, dissolution, friability, hardness, drug content, and weight uniformity to compare the prepared formulation with the commercial tablet in terms of drug release, and to evaluate the stability of the formulation.The effects of rikkunshito on the decrease in food intake were assessed after induction of stress in mice and showed improvement in the decrease of food intake probably via serotonin 2B receptor antagonism of isoliquiritigenin. In another work, the preventive effect of inositol hexaphosphate extract of rice bran on colon cancer was assessed. The results showed significant reduction in the expression of By presenting these articles, we hope that this issue incorporates new scientific evidence and emerging developments as the basis of rational treatment in medicinal practice using novel therapeutics  in the treatment of gastrointestinal disorders.Mahmood Ameen AbdullaIbrahim BanatPatrick Naughton


Chemical and physical processes occurring at the surfaces of the minute grains found in interstellar dust clouds are crucial in the formation of the many different atomic and molecular species found in the interstellar medium. These surface processes include not only relatively simple processes, such as the formation of dihydrogen gas from the atomic hydrogen prevalent in the interstellar medium, but also the assembly of small molecules, such as water and carbon dioxide and their catalysis into bigger, more complex species. When the dust grains coalesce into planetary accretion discs, these molecules may be retained and become trapped in the planets as they form. Direct measurements, laboratory studies, theoretical investigations and mathematical models all serve to improve our understanding of these complex processes.This Theme Issue is the outcome of a Royal Society International Scientific Seminar on ‘Surface science in the interstellar medium’, which brought together an interdisciplinary group of scientists to explore how their complementary expertise in chemistry, physics, astronomy, computing and mathematics could be exploited to provide a fuller picture of this fascinating area of research. The papers presented here showcase a wide variety of state-of-the-art techniques used to shed light on the formation of the interstellar dust clouds and the surface-mediated reactions that convert simple atoms into increasingly complex molecules. They illustrate how this combination of expertise can unravel a range of complex physico-chemical processes occurring under the extreme conditions prevalent in the interstellar medium.I would like to dedicate this Theme Issue to the memory of Prof. Michael J. Drake, a friend and colleague who was one of the driving forces behind the organization of the Royal Society meeting, but tragically died shortly afterwards. Mike had a profound interest in surface processes occurring in the interstellar medium. Having spent half a life-time teaching his students the accepted versions of the origin of our planetary water, which increasingly did not fit the available evidence, Mike suggested an alternative hypothesis, where water was already present at the surfaces of interstellar dust grains when they accreted to form our planet. Although this hypothesis fitted with all available evidence, it would only work if the adsorption of water to the dust grains was sufficiently strong to survive the harsh conditions in the accretion disc. Mike then had the insight to look outside his own field and to computer simulations to test his hypothesis. Simulations of water adsorption at dust grain models have shown that the kind of highly fractal surfaces found on interstellar dust grains are indeed suitable for the strong retention of water under the extreme temperatures and pressure conditions prevalent in the accretion disc during planetary formation. Some of this work is illustrated in this Theme Issue, which I trust is a fitting memorial to Mike's contributions to the field.


The reverse sural artery flap is a generally accepted means of soft tissue reconstruction for defects of the distal third of the legs. The routine sacrifice of the sural nerve with its consequential temporary loss of sensation on the lateral aspect of the foot can be of concern to early rehabilitation of some patients.rd and the middle 3rd of tibia. A reverse sural artery flap was raised without transecting the sural nerve to cover the distal part of the defect.This is a case report of a 24 years old male who had Gustillo and Anderson type IIIB injury involving the upper part of the distal 3The distal part of the exposed bone was covered with the reverse sural artery flap without loss of sensation at anytime to the lateral part of the foot.The reverse sural artery flap can be raised to cover the upper portion of the distal leg without severing the sural nerve. Reconstruction of soft tissue defects of middle third have not being as challenging as that of the lower third of the leg, the heel and the hind foot. While the upper and middle third is amenable to many options of fasciocutaneous and muscle flaps, the distal third had mainly the option of free flap up until 1992 when Masquelet et al, exterioThis case report highlights the use of nerve sparing reverse sural artery flap as a possible option for covering the upper part of the distal tibia and the mid tibia.Mr. A. J is a 22 years old iron welder who presented with one hour history of pain, deformity and inability to bear weight on the left lower limb following a motorcycle accident. There was no history of symptoms suggestive of injuries to other parts of the body.He was conscious on presentation with stable vital signs. The essential finding was a wound on the anterio-medial aspect of the left leg measuring 23cm x 12cm exposing the middle and part of the distal tibia and fibula. There were fractures of the left tibia and fibula. The posterior tibial and dorsalis pedis arterial pulsation were palpable and the cutaneous sensation over L5 and S1 were preserved.rd of the tibia with some bone loss and segmental fracture of the fibular both at the proximal and the middle 3rd. Patient had wound debridement with application of external fixator. . Patient was resuscitated and investigated. Radiogram revealed oblique fracture of the distal 3. Figure He subserd of the leg posteriorly. It was then transposed as an island flap to cover the distal part of the exposed middle tibia and the upper part of distal tibia. To enhance mobilization, the point at which the sural nerve pierces the fascia was gently cut about 4cm distally and the peroneal communicating nerve was transected at the lateral border of the flap. Hemisoleus flap was raised to cover the remaining exposed mid tibia bone  which held on 21st- 27th May, 2011 at the Vancouver Convention Centre, Vancouver British Columbia Canada.Paper presented at the 16The authors declare that they have no competing interests.EEE conceived the study, participated in the design and coordinated the surgeries and drafting the manuscript. NOC participated in the surgery and drafting of manuscript. OJE, AS and AFO participated in literature search, sequence alignment and drafting of the manuscript. All authors read and approved the final manuscript.


Teaching of microscopy in the pharmacy curricula in Europe has almost vanished, although adulterations and mistakes in identification of herbal substances have caused several problems during the last decade. Thus, profound knowledge in the macroscopic and microscopic authentication of herbal drugs is an indispensable prerequisite in quality control.This book provides an excellent overview over macroscopical and much more detailed over microscopical features of more than 140 herbal substances used in European phytotherapy. Those drugs with existing HMPC-, WHO- and ESCOP-monographs have been prioritized. In each of the presented monographs the precise botanical name of the respective plant (under inclusion of recent systematic findings), a photograph of macroscopic characteristics, a short compilation of the most important compounds and the use of the herbal substance is given. Additionally, six clear coloured charts of the most important microscopical characteristics are shown and described in detail. The drugs are arranged according to the plant part used  and presented in alphabetical order based on the German names. Finally, some instructions for investigations under use of colouring reagents for specific compounds, a glossar and charts explaining the structure of several plant organs follow. This book is highly recommended to all interested pharmacists whether in public pharmacies or in quality control of herbal substances in industry as well as especially for students, because it provides a detailed insight into this more and more neglected field. The in-depth microscopical part makes the book a valuable teaching tool and excellently suitable for self-learning.


Alcohol and other drugs are frequently used in combination . Based o® (cimetidine), and Zantac® (ranitidine), interact with alcohol metabolism leading to a higher level of blood alcohol concentration (BAC)  may help explain why polydrug use is dangerous to fetal development. Pharmacokinetic interaction is the process that occurs when two or more drugs are in the system at the same time. Although the pharmacokinetics of individual drugs may be well characterized, when the drugs are combined, one drug can seriously and unpredictably alter the concentration, bioavailability (the rate of a drug entering the bloodstream), and net effect of the other drug. Alternatively, the combination of drugs can alter the bioavailability of either or both drugs or form a metabolite more toxic than either of the parent compounds. For example, several well-known over-the-counter medications, such as aspirin, Tagameton (BAC) . BAC levon (BAC) , 1990, aIn another example of the effects of combined drug use, As a final example, the interaction of alcohol and cocaine has been shown to be more harmful than the use of each drug individually because of the formation of the highly toxic metabolite cocaethylene . CocaethPotential harm to the developing fetus resulting from polydrug use during pregnancy is an important area of drug abuse research. Exploring the effects of each drug alone on the developing fetus does not capture the essence of the clinical condition. Studies on interactive effects of polydrug use fill a void in the scientific literature and highlight the importance of recognizing polydrug use during pregnancy as a significant maternal risk factor for fetal and child development and health. Research on how alcohol interacts with other drugs and how such interactions may adversely affect the developing brain will lead to a better categorization of the known detrimental effects from gestational polydrug use and a more focused understanding of the methods to avert or treat the outcomes.


This work entails scaling a biophysical model of the neocortex using parallel NEURON  while ruIndividual simulations consisted of stimulation and completion of a single memory pattern within 1 second of cortical activity. Preliminary results show near linear speedups of the computational part of the simulation, but degradation of file I/O performance as the number of cores increase. Since each core writes out spiking activity after the simulation, the performance decline may be due to the ratio of core to I/O nodes and the large number of output files. With this performance analysis, further work will include measuring and scaling memory storage capacity with the described second variation of the biophysical neocortical model.