The duration of bronchoscopy examinations varies considerably depending on the diagnostic and therapeutic procedures used. It can last more than 20 minutes if a complex diagnostic work-up is included. With wide access to videobronchoscopy, the whole procedure can be recorded as a video sequence. Common practice relies on an active attitude of the bronchoscopist who initiates the recording process and usually chooses to archive only selected views and sequences. However, it may be important to record the full bronchoscopy procedure as documentation when liability issues are at stake. Furthermore, an automatic recording of the whole procedure enables the bronchoscopist to focus solely on the performed procedures. Video recordings registered during bronchoscopies include a considerable number of frames of poor quality due to blurry or unfocused images. It seems that such frames are unavoidable due to the relatively tight endobronchial space, rapid movements of the respiratory tract due to breathing or coughing, and secretions which occur commonly in the bronchi, especially in patients suffering from pulmonary disorders.The use of recorded bronchoscopy video sequences for diagnostic, reference and educational purposes could be considerably extended with efficient, flexible summarization algorithms. Thus, the authors developed a prototype system to create shortcuts  of bronchoscopy video recordings. Such a system, based on models described in previously published papers, employs image analysis methods to exclude frames or sequences of limited diagnostic or education value.The algorithm for the selection or exclusion of specific frames or shots from video sequences recorded during bronchoscopy procedures is based on several criteria, including automatic detection of "non-informative", frames showing the branching of the airways and frames including pathological lesions.The paper focuses on the challenge of generating summaries of bronchoscopy video recordings. Bronchoscopy examinations last from several to 20 or more minutes. Depending on the approach, video recordings of the procedure vary considerably in length. In some bronchoscopy suites only meaningful shots and sequences are recorded for documentation. However, due to the growing pressure of quality assurance and liability problems, it may be preferred to record the entire procedure. This means that images of varying quality are recorded. It is a common finding in videos recorded during endoscopic procedures that the meaningful part of the recording includes frames which are blurred or carry no significant information. Frames which are of poor quality because of blurring or for other reasons have been named by some authors as "non-informative" frames. According to , the perEfficient summarization of video recordings of bronchoscopic procedures is also highly relevant for the development of medical video libraries for bronchoscopists. This strategy should cover the issue of exclusion of non-informative frames, as well as inclusion of those sequences and frames which are crucial for documenting the normal appearance of the endobronchial environment or presenting pathological lesions revealed during examination. Thus, automatically generated summaries could be of considerable value in supporting long-term archiving of video resources or efficient access to medical video library resources. The second option may be enhanced with ad-hoc adjustment of the summarization criteria.Selecting the most relevant shots from the whole video sequence is one of the most essential problems in bronchoscopy video summarization. The perception of the problem is not fully agreed upon among medical specialists. A mechanism to facilitate this process should include an algorithm enabling the automatic analysis of the shots forming the video and including those carrying essential information about the examination.As mentioned above, the process covers a number of aspects related to the analysis of the content of the video sequence, allowing for identification of meaningful shots and scenes  and otheUnfortunately, current medical digital video libraries do not include summary subsystems. The challenge of summarizing video sequences with medical content has rarely been studied by other authors , 10], , . VilarinThe authors assumed that the summary must be considerably shorter (ten or more times) than the whole video sequence. However, the final rate of the initial sequence and summary lengths should depend on the aim of the summary preparation. Long-term archiving could require shorter summaries in comparison to short-term storage or presentations of the procedures for educational purposes. The general approach resulting from the authors' experience and consultations with professional film editors assumed that the volume of the summary should be reduced around twelve times  when comThis work is an extension of the earlier book chapter . New sigThe authors developed a model of a prototype system for generating summaries of bronchoscopy video recordings. The model assumes an application of image analysis methods for excluding frames without informative value and selecting those which could have added value for diagnostic or educational purposes. It originates from previous research activities conducted within the BRONCHOVID project focused on the development of a computer system supporting bronchoscopy laboratories , 15], , , 17], ,  and 19]19]. RelaThe paper is structured as follows: the "Methods" section presents the algorithm developed to summarize bronchoscopy videos; the "Results and Discussion" section presents the implementation of the algorithms; and the "Conclusions" section concludes the paper and gives an insight into further development.The algorithm for the selection or exclusion of specific frames or shots from video sequences recorded during bronchoscopy procedures is based on several criteria. The main effect of this algorithm will be the inclusion of shots consisting of frames tagged with inclusion criteria and the exclusion of frames tagged with exclusion criteria.A primary criterion for exclusion from the summary is related to information in a specific frame. The authors assumed that "non-informative" frames may be important for bronchoscopic assessment only in relatively rare cases. An overall poor quality of the whole recorded video due to independent conditions, e.g. profuse bleeding or the presence of specific excretions in the endobronchial space, may be an example of such a situation. The following criteria were considered for inclusion:• markers  from medical treatment,• frames annotated by the physician performing the bronchoscopy for reference purposes,• frames showing the branching of the airways (ramifications),• frames including pathological lesions detected automatically with the available algorithms of image recognition, complemented with representations of intermediate frames of the shots, and• representative sample of frames between branching points (the ratio of "informative" frames included in the summary should be adjusted according to the purpose of the summary generation).Methods which enable the application of these criteria are described below.Video recordings of endoscopic procedures performed within airways include frames of both adequate and inadequate quality for assessment by an endoscopist. Frames of inadequate quality are called by some authors blurred or "non-informative"  histograms with neural networks, MPEG-7 descriptors, and DCT (Discrete Cosine Transform) have been developed and tested. From all these methods, the authors selected the algorithm based on DCT due its highest sensitivity, specificity and F-measure of identification of "non-informative" frames within test sets prepared by endoscopists. This algorithm of detection of "non-informative" frames is based on the fact that images which do not contain numerous edges (as in the case of most types of "non-informative" frames) are easier to compress using algorithms based on DCT, such as used in the JPEG algorithm. Such frames reveal considerably narrower spectra in the frequency domain than frames which contain numerous edges. This feature of DCT allows it to be used as a simple yet effective edge detection algorithm. The DCT-based algorithm does not allow for localization of the edges in the image, but this is not necessary for the detection of "non-informative" frames.Examples of spectra obtained from "non-informative" and "informative" frames were demonstrated in Figure The algorithm of DCT-based "non-informative" frame detection is presented in Figure The evaluation has been performed on a set of 1538 frames, manually annotated as "non-informative" (669 images) and "informative" (869 images) by the experienced bronchoscopist. The set acted as a ground-truth. Then, the images were evenly (but randomly) split to: the training set and the testing set , labelling, and measuring the properties of image regions were successfully utilized.The algorithm is based on an observation that relatively large, dark (non-illuminated) areas seen within the lumen of the trachea or bronchi can be easily detected and counted. The presence of two or more such areas allows for the identification of a frame showing a view of a branching point of the airway tree. The algorithm first finds all dark objects, and then filters the results to pick out the objects surpassing the threshold value of the dimension. The basic concepts of image opening Automatic detection of pathological lesions is another criterion for frame inclusion in summaries of video recordings of bronchoscopy examinations. The summarization system may utilize available algorithms of automatic detection and specifically those developed within the BRONCHOVID project including DWT (Discrete Wavelet Transform), MPEG-7 standard , and colAt the time of submission of the paper, the module of video recording summarization was in the process of pilot implementation. The system uses a web-based GUI .The algorithm of GUI summarization is shown in Figure The paper focuses on the challenge posed by generating summaries of bronchoscopy video recordings. The main rationale is improved efficiency of the archiving processes, as well as multi-purpose video resource browsing and presentation in educational and reference context in medical environments. The paper presented a summarization model. In later work we intend to publish the results of testing the system with clinical material. A prototype of the software described in the paper was developed by a broader project aiming at the platform supporting data management in bronchoscopy laboratories. The concept of the summarization algorithm currently implemented and tested in pilot settings was based on several assumptions resulting from previous experience in video summarization and the specific requirements of the medical community. The pilot implementation should provide feedback from end-users, enabling an assessment of the feasibility of the described approach.The BRONCHOVID system was implemented in its pilot version in the Bronchoscopy Laboratory of the Department of Pulmonology, Jagiellonian University Medical College in Krakow. The Laboratory performs about 1,200 bronchoscopy procedures yearly. The bronchoscopy procedures are performed by 5 experienced pulmonary medicine specialists.The BRONCHOVID system was used during the pilot period for:- registration of the selected bronchoscopies,- testing of the functionalities enabling annotation of the frames within registered videos,- testing query function within the resources accumulated through pilot period,- generation of summaries of registered bronchoscopy videos,- download of selected shots from registered videos in commonly used formats for external usage, e.g. for educational purposes.Currently, the scenario of the system usage starts from the system initiation just before the insertion of the bronchoscope to upper respiratory tract of the patient. The recording of the procedure is usually started by a nurse employed in the laboratory on request from the physician performing bronchoscopy. The whole procedure is recorded and the process is terminated after removing bronchoscope from the patient's respiratory system. The patient's data are entered after the procedure as the information on status of respiratory tract and findings during bronchoscopy are available then.The anticipated system usage assumes recording of all procedures performed in the laboratory. Recorded bronchoscopy videos are planned to be kept in the full version for the period of 12 months. Afterwards, an automatic summary generation will be initiated and resulting video summaries will be kept for longer period. The videos demonstrating specific lesions or especially valuable in terms of educational and training impact will be kept in unabbreviated version for longer periods.The authors declare that they have no conflicting interests.Mikołaj Leszczuk contributed to "Methods" (partly) and "Results and Discussion". Mariusz Duplaga contributed to "Background", "Methods" (partly) and "Conclusions".Mikołaj Leszczuk, PhD, is an assistant professor at the Department of Telecommunications, AGH University of Science and Technology (AGH-UST), Krakow, Poland. He obtained his MSc in Electronics and Telecommunications in 2000 and PhD in Telecommunications in 2006, both from AGH-UST. He is currently lecturing in Digital Video Libraries, Information Technology, and Basics of Telecommunications. In 2000 he visited Universidad Carlos III de Madrid  for a scientific scholarship. Between 1997-1999 he was employed by several Comarch holding companies as Manager of the Research and Development Department, President of the Management Board, and Manager of the Multimedia Technologies Department. He has participated actively as steering committee member or researcher in several national and European projects, including: INDECT, BRONCHOVID, GAMA, e-Health ERA, PRO-ACCESS, Krakow Centre of Telemedicine, CONTENT, E-NEXT, OASIS Archive, and BTI. His current activities are focused on e-Health, multimedia for security purposes, P2P, image/video processing , development of digital video libraries (particularly on video summarization), indexing, compression, and streaming subsystems. He has been a chairman of the "e-Health in Common Europe" conferences sessions. He has been a member of the IEEE Society since 2000. He has served as an expert for the European Framework Programme and Polish State Foresight Programme, as well as a reviewer for several scientific conferences and journals.Mariusz Duplaga, graduated from the Medical Faculty at the Jagiellonian University Medical College in Krakow in 1991, and completed his doctoral thesis in medicine in 1999, specializing in internal medicine and respiratory medicine. Between 1995-2003 he made working visits to several NHS centres in the UK; University College London, UK; SINTEF, Trondheim, Norway; Municipal Epidemiological Centre, Barcelona, Spain; University of Antwerp, Belgium; and CHRU in Lille, France. He is currently working as a senior researcher at the Institute of Public Health at the Jagiellonian University  and the Department of Pulmonology, Medical Faculty, Jagiellonian University. Since 2002 he has been a project manager at the Centre of Innovation, Technology Transfer and University Development, Jagiellonian University. He has been a site leader or research participant in several research projects on medicine and IT use in health and social care: AIANE (BIOMED II); Medical Data Management (USAID); Hospital Data Management (PHARE); Krakow Centre of Telemedicine (SCI-TECH II); BIOAIR (5FP), PRO-ACCESS (5FP); HEALTHWARE (6FP); e Health ERA (6FP); MATCH ; and MPOWER (6FP). He has participated as a project coordinator or researcher in several projects funded by the Polish Scientific Research Committee and the Ministry of Health in the areas of telemedical services, telemonitoring in severe asthma, and epidemiology of allergic diseases. Between 2000-2003 he took part in establishing the Krakow Centre of Telemedicine, and served as President of the Polish Association of Medical Internet. Between 2000-2002 he served as a delegate of the Polish Scientific Committee and the Ministry of Health to the EC Information Society Technologies Working Party on Health and Persons with Special Needs. In 2008 he served as an expert at the National Centre of Research and Development within the Ambient Assisted Living Programme. His main areas of research and development include: endoscopy, image processing, e-Health/telemedicine, e-inclusion, and support for persons with special needs, chronic care, telemonitoring, and computer-aided interventions.1 The dilation of the erosion with various sizes of morphological structuring elements (image processing term)B The erosion of the dilation with various sizes of morphological structuring elements (image processing term)


Playing video games is a common recreational activity of adolescents. Recent research associated frequent video game playing with improvements in cognitive functions. Improvements in cognition have been related to grey matter changes in prefrontal cortex. However, a fine-grained analysis of human brain structure in relation to video gaming is lacking. In magnetic resonance imaging scans of 152 14-year old adolescents, FreeSurfer was used to estimate cortical thickness. Cortical thickness across the whole cortical surface was correlated with self-reported duration of video gaming (hours per week). A robust positive association between cortical thickness and video gaming duration was observed in left dorsolateral prefrontal cortex (DLPFC) and left frontal eye fields (FEFs). No regions showed cortical thinning in association with video gaming frequency. DLPFC is the core correlate of executive control and strategic planning which in turn are essential cognitive domains for successful video gaming. The FEFs are a key region involved in visuo-motor integration important for programming and execution of eye movements and allocation of visuo-spatial attention, processes engaged extensively in video games. The results may represent the biological basis of previously reported cognitive improvements due to video game play. Whether or not these results represent a-priori characteristics or consequences of video gaming should be studied in future longitudinal investigations. The rapid growth of video game popularity in adolescents has generated concern among practitioners, parents, scholars and politicians. For violent video games, detrimental effects have been reported in social domains, namely increases in aggression and reductions of empathy and prosocial behaviour Brain mapping studies have established that extensive experience with certain skills can alter brain activity during performance of that skill Although behavioural studies have demonstrated effects on visual and cognitive skills, research on the structural correlates of frequent video game playing is still scarce. Of note is a study by Lövden et al. In a first structural study exploring the neural correlates of video game playing on the same data set as the present study we used voxel-based morphometry (VBM) to compare frequent (more than 9 h/week) with infrequent (less than 9 h/week) video game playing adolescents To explore the association between spontaneous video game playing and cortical thickness, we analysed data from 152 14-year old adolescents from the IMAGEN project 152 healthy 14-year old adolescents  were participants of the IMAGEN project, a European multi-centre genetic-neuroimaging study in adolescence t(150) = 1.4, p = 0.16). The images were obtained using a three-dimensional T1-weighted magnetization prepared gradient-echo sequence (MPRAGE) based on the ADNI protocol .For logistical reasons, structural images were collected on two scanners - a General Electric Signa Excite 3 T scanner  and a Siemens Verio 3 T . The participants scanned on the GE and Siemens scanners consisted, respectively, of 63 participants who played 14.4 hours per week on average (SD = 13.9) and 89 participants playing 11.4 hours per week on average (SD = 12.2); this difference was not significant . Local cortical thickness was estimated based on the difference between the position of equivalent vertices in the pial surface and grey-white matter interface. The surface of the grey-white matter border was inflated and differences between participants in the depth of gyri and sulci were normalized. Each participant's reconstructed brain was morphed and registered to an average spherical surface. In order to obtain difference maps of cortical thickness, the data were smoothed on the level of the sphere using a Gaussian smoothing kernel with a full-width half maximum of 15 mm. We used a multiple regression approach to explore the association between cortical thickness and self-reported average video gaming hours per week. To control for the effects of age, sex and scanner these variables were entered as additional regressors of no interest in the whole cortical surface multiple regression analysis. The resulting maps were initially thresholded with p<0.001. Then we performed Monte Carlo simulation cluster analysis in FreeSurfer qdec comprising the synthesis of white Gaussian noise on the estimated surface, smoothing and clustering to correct for multiple comparisons using a cluster threshold of p<0.01. Only clusters that survived this correction for multiple comparisons are reported.First, we used the Tt(150) = 5.03, p<0.001). Participants indicating that they do not play video games during an average week were exclusively female. The group of participants reporting video game playing consisted of 54 females and 72 males. According to the CSV-S scoring schema 6 participants were classified as addicted and 13 as excessive users.On average the participants reported playing video games for an average of 12.6  hours during a typical week. There was a significant difference in hours of video game playing between males and females, with females playing less frequently (t(150) = 4.56, p<0.001; FEF: t(150) = 5.07, p<0.001); on the GE scanner cortical thickness values were higher compared to Siemens, therefore scanner was entered as a covariate of no interest in the main analysis.Cortical thickness differed between scanners  and left frontal eye fields , we found that the time playing video games correlated positively with cortical thickness in the left dorsolateral prefrontal cortex in left middle frontal gyrus extending into left superior frontal gyrus  = −0.123, p = 0.13; FEF: r(152) = −0.15, p = 0.065), whereas no significant difference was observed between female and male participants (DLPFC: t(150) = −0.32, p = 0.749; FEF: t(150) = −0.20, p = 0.839).To explore the effects of the nuisance variables age, sex and scanner we computed the associations between these variables with cortical thickness extracted from the clusters in DLPFC and FEF. Age was only marginally associated with cortical thickness  = 6.36, p<0.05; partial eta square: η2 = 0.051) when controlling for sex, age and scanner, but no significant effect in FEF  = 0.54, p = 0.464).We compared cortical thickness in participants that were classified as excessive (n = 13) or addicted (n = 6) video gamers to the remaining participants in a post-hoc comparison. We found a significant difference in DLPFC (r(149) = 0.317, p<0.001; FEF: r(149) = 0.289, p<0.001).Socioeconomic background, approximated by means of the highest education of the parents, did not influence the association between video gaming hours per week and cortical thickness in DLFPC and FEF; when partialing out parental education the correlations were still significant (DLPFC: r(74) = −0.007, p = 0.95). However, we did not assess BMI at age 14 and can therefore not report results of concurrent video game behaviour and BMI.Although one might be tempted to assume a positive association between body mass index (BMI) and video gaming, we did not find an association between self-reported video game hours at age 14 and BMI at age 16 . Reductions in cortical thickness associated with video gaming frequency were not observed.Prefrontal cortex has been described as the substrate of executive control Interestingly, the FEFs have also been implicated in perceptual decision-making studies on monkeys Although our approach to explore the structural basis of video gaming was purely exploratory in nature, the fact that we found higher cortical thickness jointly in left DLPFC and left FEF could suggest that these morphometric correlates are related to training effects in perceptual decision-making and allocation of attention. Perceptual decision-making involves different processes, namely the intake and accumulation of sensory evidence, subsequent categorization and decision-making based on this input and subsequent actions The presented findings complement previous VBM results on a similar sample in which we have shown that frequent (>9 h/week) compared with infrequent (<9 h/week) video gamers have higher grey matter volume in the left ventral striatum Moreover, the observed results fit well to our recent finding of training-related grey matter volume increases in the right DLPFC The fact that we found a significant difference of DLPFC cortical thickness between gamers classified as excessive or addicted gamers based on the CSV-S score, argues in favour of an effect that sets in once a certain intensity of video gaming is reached. For studies aiming to use video games as a tool for training, the present study may be seen as an indication that a considerable amount of training is needed to potentially detect structural effects, provided that the effects observed are a cause of the video gaming. Interestingly, previous research on online gaming addiction in an adolescent sample has shown decreases of cortical thickness in lateral orbitofrontal cortex among other regions Future research may focus on the direct assessment of the relationship between cortical thickness in left DLPFC and FEF and perceptual decision-making as well as its association with the different video game genres such as action video games, strategy games, platformers etc., Moreover it would have been interesting to know which game genres the adolescents played most, since in particular action video games have been associated with improvements in cognitive performance; therefore future studies should carefully screen how many hours per week are devoted to which type of video game. Likewise, longitudinal studies should be conducted to elucidate the causal effects of video gaming on cortical thickness in DLPFC and FEF. Furthermore, it would be interesting to assess structural correlates of cumulative video gaming hours over the lifetime instead of current video game frequency and the additional assessment of physical activity and BMI.


Plasmodium species. Due to their higher prevalence, much of the research concentrates on Plasmodium falciparum and Plasmodium vivax. In Burkina Faso, where P. falciparum co-exists with Plasmodium malariae and Plasmodium ovale, there is not much data about the prevalence of the latter two species across human population. Moreover, interactions between co-infecting Plasmodium species are not documented. The aim of the current research is to determine species-specific prevalence and temporal distribution. The potential interactions between co-infecting Plasmodium species amongst the child-aged population in Burkina Faso are also discussed.Malaria can be caused by five The study took place in the Sudanese savannah zone in Burkina Faso in a rural village, Laye. Surveys were conducted during the wet season across four years, 2007 to 2010. Volunteers aged three to 15 years with parental signed consent were enrolled. Ten children per week were screened for any history of pain, fever. Parasitological data were obtained by blood slide processing.Plasmodium species were recorded during this study with an average prevalence of 70.7%. Species temporal distribution showed an increase of P. malariae parasite prevalence from 0.9% in 2007 to 13.2% in 2010. Within a season, P. falciparum occurred in the overall study period while P. malariae and P. ovale were highly prevalent after the rainy part of this period. Species-specific infection analysis showed that in a comparison of mono-infections, P. malariae gametocyte prevalence and median density were higher than those of P. falciparum . Likewise, in P. falciparum co-infections with P. malariae or P. ovale, gametocyte prevalence was also higher than in P. falciparum mono-infection. However, in P. falciparum mixed infection with P. malariae, P. falciparum gametocyte prevalence and median density as well as asexual form density decreased compared to P. falciparum mono-infection while for P. malariae mono-infection, only asexual form density significantly vary.Three sympatric Plasmodium species than P. falciparum with a significant variation of P. malariae gametocyte carriers and gametocyte density across years. Molecular tools and entomological studies are needed to highly assess species-specific contribution to malaria transmission.These data revealed high gametocyte prevalence in other  Malaria remains a huge burden for human populations living in tropical areas. More than two million malaria cases were recorded in 2010, with the heaviest mortality rates in children living in sub-Saharan Africa. DespitePlasmodium species which include Plasmodium falciparum, Plasmodium malariae, Plasmodium ovale, Plasmodium vivax and, more recently, Plasmodium knowlesi[Plasmodium falciparum is the most prevalent in Africa and the most pathogenic of these, but in most malaria endemic regions multiple sympatric species are found and co-infection within individual human hosts or the mosquito vector population is common. In Africa, P. malariae is the species most frequently found in sympatry with P. falciparum[Plasmodium inter-species interactions have been the focus of interest of number of studies[P. falciparum co-occurred with P. malariae, field studies reveal that this co-occurrence can reduce disease severity[P. falciparum gametocyte production[Currently, malaria can be caused by five  knowlesi. Plasmodalciparum. Plasmod studies-11. The  studies,13 and a studies. The eff studies and adve studies. Indeed,severity,17, giveseverity or boostoduction,9.P. falciparum co-exists with P. malariae and P. ovale, there is not much data about the interaction of co-infecting species. In fact, only a few studies even report the prevalence of the last two species across human population[P. malariae and P. ovale[P. ovale malaria burden in sub-Saharan Africa[P. falciparum gametocyte is important with a substantial submicroscopic part[P. malariae or P. ovale to this gametocytaemia should be assessed. The aim of the current study was to determine Plasmodium species-specific parasite and gametocyte prevalence, their temporal distribution and potential interaction across a child-aged population from a rural village in Burkina Faso.In Burkina Faso particularly, where pulation,19-21. Mn Africa,23. Morepic part, the rol′W). This village is situated in a Sudanese savannah zone with one rainy season from June to October with some fluctuation across years. In the village, health care facilities are available and it is also a part of the demographic surveillance system (DSS) used by the malaria research centre of Burkina Faso for epidemiological studies. Residents live by subsistence farming in this Sudanese savannah area with seasonal holo-endemic malaria. Malaria prevalence is highest in the rainy season from June to October and peaks around September. Plasmodium falciparum is responsible for the major proportion of malaria infections[Anopheles gambiae complex members and Anopheles funestus groups with other minor vectors[The study took place in Laye, a small rural village located 30 km north of Ouagadougou, Burkina Faso , the national malaria research centre, and enrolled for parasite detection. In situ, they were asked for any history of pain and examined by a physician. Axillary temperature was taken and a blood sample by finger prick was collected.The blood slide processing was made from finger-prick blood of each individual. The slides were left to air dry and stained with 5% Giemsa for 35 min. One hundred high-power fields (HPF) were examined, and the number of malaria parasites of each species and stage was recorded. The number of parasites per ml of blood was calculated, assuming 200 white blood cells per high-power field and a fixed white cell count of 8,000/μl. Each blood slide sample was read independently by two microscopists. The mean of the results of both microscopists was taken as the parasite density. In the event of a discrepancy between the two readers, in terms of species, presence or absence of malaria parasites, or if parasite densities differed by more than 30%, a third reader was involved. In this case, the arithmetic mean of the two closest readings was used as the final value for parasite density. A slide was considered negative if no parasite stage were seen after the examination of 100 fields.®) according to relevant regulations of Burkina Faso’s Health Ministry. Asymptomatic subjects were followed up by the field worker in the week.The study protocol was reviewed and approved by the ethics committee for biomedical research of the Ministry of Health of Burkina Faso (code N° 2006–032). The study procedures, benefits and risks were explained to the children’s parents or legal guardians and their signed consent was obtained. After each assay, symptomatic subjects were treated with the combination of artemether-lumefantrine , the country meteorological data collection and reporting system. The monthly mean rainfall was use for analysis.Plasmodium density. The potential interaction was assessed by comparing species-specific mono-infection to mixed infection. Statistical analyses were performed in R 2.10.1 using the R Commander Package[P-value of 0.05 or lower was considered statistically significant.Comparison of prevalence was done using the Pearson’s Chi square test or Fisher’s exact test with contingency tables. For parasite density, the non-parametric Wilcoxon rank test for two samples or Kruskal-Wallis test for more than two samples was used. Spearman test of correlation was used to assess the link between rainfall and  Package. P-valuevs 47.1% . Across years, gender distribution . On average, across years, 18.8% of the study population presented with fever and 76.3% of these fever cases were coupled with Plasmodium infection.Some 830 children  participated in the study. The mean age in the study group was 8.1 ± 1.7 years. Children of both genders took equal part in this study: 52.9%  P. falciparum, P. malariae and P. ovale were identified. Across years, the average Plasmodium infection prevalence was 70.7%. Plasmodium falciparum was the predominant species with a prevalence of 68.19% followed by P. malariae (6.51%) and P. ovale (1.08%). Several mixed infections were reported with co-infection of P. falciparum and P. malariae (4.34%) and co-infection of P. falciparum with P. ovale (0.72%). No co-infections of P. malariae with P. ovale were observed, though with their low overall infection prevalence this is not surprising.In the study period, three parasite species: Plasmodium infection prevalence showed slight variation with gametocyte prevalence being significantly different across the four seasons . Plasmodium malariae infection prevalence was also variable across years  with an increase from 0.9% in 2007 to 13.2% in 2010  in 2010. However, P. falciparum and P. ovale infection prevalence do not significantly vary between the transmission seasons.In addition, from 2007 to 2010, P. falciparum being present throughout the study period while P. malariae and P. ovale often occurred following the rainy part of the study period . However, P. malariae and P. ovale density were not significantly correlated with rainfall .Within season, species distribution was different with  Figure A. In add Figure B. MoreovP. malariae infections than in P. falciparum infections . The median gametocyte density shows the same trend with higher values being observed in P. malariae infections than in P. falciparum infections . No significant difference was found between P. ovale gametocytes carriage or median gametocyte density and either of the other Plasmodium species.Species-specific mono-infection and mixed infection characteristics are given in Table P. ovale mono-infections  than for P. malariae  or P. falciparum . Variables such as gender, prevalence of fever, and asexual form median density, did not show significant difference across mono-infections.For age variation, the median age was significantly higher for P. falciparum mono-infections to its mixed infections, the study report that gametocyte prevalence and median gametocyte density were lower in mono-infections than co-infections with P. malariae . However, the median age of infected-children was higher in P. falciparum mono-infections than in co-infections with P. malariae .Interestingly, significant differences were observed between parasite species mono-infections and their mixed infections for variables such as gametocytes prevalence or density, asexual forms density, and infected children median age. By comparing P. falciparum mixed infection with P. ovale, gametocyte prevalence and asexual form density were higher in mixed infections than in P. falciparum mono-infections . Other variables did not shown significant variation.When looking at P. malariae and P. ovale mono-infections and their mixed infections with P. falciparum, no significant difference was found between P. malariae mono (n = 18) and mixed infections (n = 36), while P. ovale had a higher median density of asexual forms in mixed infections compared to mono-infections . Table For Plasmodium falciparum gametocyte prevalence, gametocyte median density as well as the median asexual form density in mono-infections was higher than those in mixed infections with P. malariae   or gametocyte density (23.5 vs 40.0 gametocytes/μl) in comparison with mono-infection . However, P. falciparum asexual form median density was higher in its co-infection with P. ovale  compared to mono-infection  .To assess species interaction, species-specific characteristics in mono- and mixed infections were compared. P. malariae-infected children, only asexual forms median density shows a significant difference  between mono-infections and mixed infections (Table Plasmodium ovale does not show any significant variation between mono- and mixed infections.Among s Table . PlasmodP. falciparum, P. malariae and P. ovale were observed in the study site, with P. falciparum being the most prevalent species. Plasmodium falciparum infection is widely prevalent across the entire study period with some monthly fluctuation while P. malariae and P. ovale individually peak at the end of the rainy part of the study period. Similar fluctuation between P. malariae and P. falciparum densities has been reported by several other studies[P. falciparum does not seem to be effective against P. malariae[. It has also been suggested that P. malariae can be found at higher prevalence when transmission and overall infection rates are lower and it is alleviated from the suppressive effect of P. falciparum[P. ovale occurrence. This finding revealed a kind of alternation in the relative contribution of each species to the total parasite indexes that occurred in the study area[Three sympatric species,  studies,27. Offs malariae. It has alciparum,18. A siudy area.P. malariae prevalence throughout the four-year study period allows speculation on positive selection of this parasite by medication. In fact, in the study site and its surrounding villages many research activities occurred with treatment of symptomatic children[P. malariae infected-children because of this species low density. As a result, P. malariae remains in circulation despite the treatment and its transmission goes up in the population. More, with the absence of P. falciparum due to drug, P. malariae prevalence and density goes up because of the suppressive effect of P. falciparum[P. malariae prevalence.The significant increase of children,29,30 orchildren,32. Thesalciparum,18. In aP. malariae-infected children during the study period, suggests that specific attention should be paid to this parasite. Indeed, gametocytes are the currency of transmission from human to mosquito for maintaining the malaria transmission cycle. The presence and infectiousness of gametocytes in circulation determines the success of transmission from humans to mosquitoes. For now, P. malariae gametocyte density and mosquito infection are not well documented. Nevertheless it is well known that lower Plasmodium density as well as submicroscopic density is infectious to mosquitoes[P. malariae is known to cause chronic infections which can last for years and might re-occur decades after initial exposure when people have long since left endemic regions[P. malariae asexual forms density and gametocytes prevalence when P. falciparum is present. With vaccine leading to the absence of P. falciparum, the inhibitory effect on P. malariae may disappear. Then, parasitaemia and gametocyte carriage of P. malariae could increase and maintain severe malaria infection. Within the context of vaccine being developed against P. falciparum[In addition, the high proportion of gametocyte carriers and gametocyte density observed among squitoes,33. Alth regions. Any levalciparum, this fiP. falciparum- and P. malariae-specific gametocyte prevalence, gametocyte and asexual form densities were higher in mono-infection as compared to mixed infections. In summary, the implications of these observations may have a profound repercussion in the outcome of disease control. If the simultaneous infection by other species inhibits P. falciparum-gametocyte production[Plasmodium species other than P. falciparum, this inhibitory effect may disappear[P. falciparum[et al.[P. falciparum and P. vivax are associated with a reduction in the prevalence of P. falciparum gametocytes. In the same way, Marques et al.[P. falciparum gametocytes predominated in single infections. In contrast, it has been reported from studies conducted in Columbia and Kenya that P. malariae infection enhanced production of P. falciparum gametocytes[The current data reveal that oduction and if cisappear. This fialciparum,36. Indees et al. found inetocytes,9. TheseThen, variability in the interactions between species under different transmission intensities, coupled with different sympatric species combinations may contribute to observed differences in the epidemiology and clinical presentations of malaria between endemic regions,37.Plasmodium species. Much study report that parasite prevalence under microscopy is 2.5-fold lower compared to prevalence found with molecular method and this fold difference was consistent across the different transmission levels in individual studies[Finally, prevalences and densities recorded in the current study may underestimate the real part of each  studies-40 or me studies. In lighP. falciparum and other species prevalence. These data revealed high gametocyte prevalence in other Plasmodium species than P. falciparum. The high proportion of gametocyte carriers and gametocyte density across P. malariae-infected children as well as the increase observed across years, presents a great epidemiological issue in the context of a vaccine being developed against P. falciparum. The relevance of these data should be taken into account when general control strategies are planned.Three species of malaria parasite are in circulation in the study area, with a fluctuation of The authors declare that they have no competing interests.AG, WMG, ABT, AD participated in data collection and laboratory procedures. AG, WMG, GBK, MMR, N’FS and KDV conceived and designed the experiments. AG, GBK, analysed the data and wrote the manuscript. All authors reviewed and revised the manuscript. N’FS and KDV coordinated and participated to fund acquisition. All authors read and approved the final manuscript.


In a systematic review of cohort studies of adolescent drinking and later outcomes, Jim McCambridge and colleagues show that although studies suggest links to worse adult physical and mental health and social consequences, existing evidence is of poor quality. Although important to public policy, there have been no rigorous evidence syntheses of the long-term consequences of late adolescent drinking.This systematic review summarises evidence from general population cohort studies of drinking between 15–19 years old and any subsequent outcomes aged 20 or greater, with at least 3 years of follow-up study. Fifty-four studies were included, of which 35 were assessed to be vulnerable to bias and/or confounding. The principal findings are: (1) There is consistent evidence that higher alcohol consumption in late adolescence continues into adulthood and is also associated with alcohol problems including dependence; (2) Although a number of studies suggest links to adult physical and mental health and social consequences, existing evidence is of insufficient quality to warrant causal inferences at this stage.There is an urgent need for high quality long-term prospective cohort studies in order to better understand the public health burden that is consequent on late adolescent drinking, both in relation to adult drinking and more broadly. Reducing drinking during late adolescence is likely to be important for preventing long-term adverse consequences as well as protecting against more immediate harms.Please see later in the article for the Editors' Summary The effects of alcohol intoxication (drunkenness), dependence , and the associated biochemical changes, have wide-ranging health and social consequences, some of which can be lethal. Worldwide, alcohol causes 2.5 million deaths  and 69.4 million  of disability-adjusted life years (DALYs). Unintentional injuries alone account for about one-third of the 2.5 million deaths, whereas neuro-psychiatric conditions account for almost 40%. There is also a causal relationship between alcohol consumption and more than 60 types of disease and injury; worldwide, alcohol is estimated to cause about 20%–30% cases of esophageal cancer, liver cancer, cirrhosis of the liver, homicide, epilepsy, and motor vehicle crashes. There is increasing evidence that, in addition to the volume of alcohol consumed, the pattern of drinking has an effect on health outcomes, with binge drinking found to be particularly harmful. As the majority of people who binge drink are teenagers, this group may be particularly vulnerable to the damaging health effects of alcohol, leading to global concern about the drinking trends and patterns among young people.Although there have been many published cohort studies reporting the longer term harms associated with adolescent drinking, the strength of this evidence remains unclear, which has implications for the objectives of interventions. For example, if adolescent drinking does not cause later difficulties, early intervention on, and management of, the acute consequences of alcohol consumption, such as antisocial behaviour and unintentional injuries, may be the most appropriate community safety and public health responses. However, if there is a causal relationship, there needs to be an additional approach that addresses the cumulative harmful effects of alcohol. The researchers conducted this systematic review of cohort studies, as this method provides the strongest observational study design to evaluate evidence of causality.The researchers conducted a comprehensive literature review to identify relevant studies that met their inclusion criteria, which were: (1) data collection from at least two points in time, at least 3 years apart, from the same cohort; (2) data collection regarding alcohol consumption between the ages of 15 and 19 years old; and (3) inclusion of a report of at least one quantitative measure of effect, such as an odds ratio, between alcohol involvement and any later outcome assessed at age 20 or greater. The majority of these studies were multiple reports from ten cohorts and approximately half were from the US. The researchers then evaluated the strength of causal inference possible in these studies by assessing whether all possible contributing factors(confounders) had been taken into account, identifying studies that had follow-up rates of 80% or greater, and which had sample sizes of 1,000 participants or more.Using these methods, the researchers found that, overall, there is consistent evidence that higher alcohol consumption in late adolescence continues into adulthood and is also associated with alcohol problems, including dependence. For example, one population-based cohort showed that late adolescent drinking can cause early death among men, mainly through car crashes and suicides, and there was a large evidence base supporting the ongoing impacts of late adolescent drinking on adult drinking behaviours—although most of these studies could not strongly support causal inferences because of their weak designs. The researchers also concluded that although a number of studies suggested links with late adolescent drinking to adult physical and mental health and social consequences, this evidence is generally of poor quality and insufficient to infer causality.The results of this study show that that the evidence-base on the long-term consequences of late adolescent drinking is not as extensive or compelling as it needs to be. The researchers stress that there is an urgent need for high quality long-term prospective cohort studies in order to better understand the public health burden associated with adolescent drinking in general and in relation to adult drinking. However, there is sufficient evidence to suggest that reducing drinking during late adolescence is likely to be important for preventing long-term adverse consequences as well as protecting against more immediate harmful consequences harms.http://dx.doi.org/10.1371/journal.pmed.1000413.Please access these Web sites via the online version of this summary at global incidence of alcohol consumptionThe World Health Organization has information about the alcohol and young peopleThe US-based Marin Institute has information about BBC also has a site on late adolescent drinkingThe  Alcohol is responsible for approximately 4% of the global burden of disease There have been many cohort studies of the longer term harms associated with adolescent drinking. Some studies suggest that individuals “mature out” of late adolescent drinking patterns If adolescent drinking does not cause later difficulties with which it may be associated, early intervention on and management of the acute consequences of alcohol consumption, such as antisocial behaviour and unintentional injuries Adolescent alcohol involvement and the potential for subsequent harm have been conceptualised and studied in many different ways. We sought therefore to evaluate the possible effects of any behavioural measure of adolescent alcohol consumption on any adult outcome. The durability of any observed effects is an important study theme due to the likely implications for public health.The data collection process is illustrated in Citation searching used both backward and forward procedures, with the bibliographies of relevant studies checked and Science Citation Index used for subsequent citations of these papers. Three journals were hand searched: Addiction Abstracts; Addiction; and Journal of Studies on Alcohol and Drugs. The latter two have been published continuously during 1964 to 2008 and were selected following piloting. A data collection protocol was developed and the entire process was undertaken twice, on the second occasion by a research assistant blinded to the outcome of the first. All subsequent study tasks were also duplicated. Only peer-reviewed published data were used and further unpublished information was not sought from authors. Finally, experts, including the authors of included primary studies, were contacted to identify additional studies that had been missed.The following selection criteria were applied independently by two researchers. Studies of drinking behaviour were included if they collected data on at least two points in time, were at least 3 y apart, and from the same cohort. Data collection regarding alcohol consumption was required between the ages of 15 and 19 y old (or between 9th grade at school or first year of university if age not specified). Drinking is normative in this age group and approaches peak levels towards the end of this age range and into the early 20s in most high income countries Quality appraisal of included studies was undertaken to evaluate the potential for bias and the adequacy of control for confounding. We gave particular attention to socioeconomic deprivation and other early life sources of vulnerability, as well as indications of other adolescent behavioural problems, in assessing confounding. We designated studies as having stronger capacity for casual inference in relation to the aims of this review if residual confounding in these areas was assessed as unlikely to be important by two reviewers and they had at least one of the following characteristics: (1) follow-up rates of 80% or greater; or (2) sample sizes of 1,000 participants or more. These characteristics identify two forms of bias at the individual study (attrition bias) and at the review level , respectively. Also if a study had both these characteristics, it was deemed to have stronger capacity for causal inference if both reviewers agreed there was reasonable control of confounding even though residual confounding was nevertheless still likely. We considered that adjustment for some factors while leaving major individual psychosocial confounders uncontrolled, did not constitute reasonable control of confounding. This subset of studies with stronger capacity for causal inference is individually discussed in the narrative presentation of results in order to summarise the evidence base. Two researchers agreed on all bar two studies (Kappa 0.91) n = 35) were multiple reports from ten cohorts (see n = 19) originated from separate cohorts (see n = 35) published since 2001. Approximately half of all reports (n = 26) were from US studies, ten were from Sweden, eight from Britain, four from New Zealand, three from Australia, two from Finland, and one from the Netherlands. More than half (n = 30) originated from school-based cohorts. Birth cohorts were more likely to be the subject of multiple studies (n = 11/14). Nineteen (35%) studies, based on eight different cohorts, were assessed as having stronger capacity for causal inference  was high (OR = 13.7 [5.3–35.5]) compared to moderate drinkers, as were deaths due to liver cirrhosis and pancreatitis , though there were few such cases Alcohol consumption was categorised slightly differently in the 25-y follow-up, complicating direct comparisons with earlier data More than 20 studies provided evidence of associations between late adolescent alcohol consumption and subsequent drinking in adulthood, with one study reporting no associations based on a limited measure of alcohol involvement , effects of an age 16 latent class variable on all drinking frequency and quantity outcomes at age 21 survived extensive adjustment for covariates. These controls eliminated apparent relationships between age 16 drinking and most other outcomes Kandel and colleagues p<0.001). They were also stronger for males than females in heavy drinking (regression coefficients approximately three times larger than any other), whereas there was no evidence of gender difference in monthly consumption frequency Both monthly frequency of consumption and heavy episodic drinking at age 18 were related to the same measures at 22, 26, and 35 y in the nationally representative US Monitoring the Future Cohort Study (MFCS) All studies assessing alcohol problems or dependence in adulthood found statistically significant associations with late adolescent drinking. Among seven studies with stronger capacity for causal inference, three were drawn from the SCS and two from the CHDS cohorts.Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) alcohol dependence at age 21, were larger than on any other alcohol-related outcome In CHDS, effects of age 16 alcohol consumption latent class on p<0.01] and 0.08 [p<0.001], respectively). Unlike effects on alcohol consumption, however, the effects of adolescent heavy drinking on alcohol problems at 35 were no longer larger than other possible component causes including parental drinking, theft/property damage, marijuana, and other illicit drug use at age 18  Similar to the findings on alcohol consumption, the RAND female study At approximately age 34, heavy drinking (>250 g per week) young men at age 19 were 2.3 (1.8–2.9) times more likely to have been hospitalised for alcoholism than low risk drinkers (<100 g per week) in the SCS SCS mortality data have already been presented. Among Stockholm County conscripts, heavier alcohol consumption was not associated with drinking and driving offences after 7–8 y with adjustment for confounders p<0.001) The CHDS found no effect of age 16 drinking latent class on court convictions or property offences by age 21 p>0.5 after adjustment) at age 21 assessed in CHDS There were no age 16 alcohol effects on any of the mental health outcomes  and abstainers An observed association between age 16 drinking patterns and DSM-IV nicotine dependence at age 21 disappeared after adjustment for covariates in CHDS In CHDS age 16 drinking latent class was not associated with age 21 cannabis and other illicit drug dependence after control for confounding No effects of adolescent drinking on any educational outcomes  at age 21 remained after adjustment for confounding in CHDS The CHDS found no effect of age 16 drinking latent class on months unemployed, sexually transmitted infections, or pregnancy by age 21 Evidence from studies not assessed as having stronger capacity for inference broadly agreed with the findings presented above. There was consistent evidence of effects on subsequent alcohol consumption and related problems. There were similarly mixed findings on possible mental health, tobacco smoking, and educational consequences. There are two principal exceptions: Although no effects on pregnancy among young women were found in CHDS, contrary findings emerged from two other cohorts This systematic review has investigated whether late adolescent alcohol consumption is a time-limited activity without significant longer term consequences or whether it impacts upon adult health and well being. It is clear that the evidence base on long-term consequences is not as extensive nor as compelling as it could be. There are sparse data of sufficient quality to warrant making causal inferences on the broader health and social consequences of late adolescent drinking on the basis of the data evaluated here.There is evidence from a single population-based cohort that late adolescent drinking can cause early death among men, principally through car crashes and suicides Caution is also required because of the limitations of the present study. Our approach to the investigation of confounding in individual studies was necessarily constrained by weaknesses of the literature as a whole and by the comprehensive nature of our appraisal of possible consequences. For example, there are few studies that address family influences, both siblings and parents. Similarly, there was only a single study included that investigated genetic inheritance Bias was considered in relation to sample size and study attrition in our appraisal of study quality. Whilst this latter variable is long established as important to the evaluation of cohort studies, thinking about the former has been more recently advanced, and thus deserves elaboration and consideration of the impact on review findings. Small study effects have been recently observed within meta-analyses of trials Two other important forms of bias were not directly involved in the determination of study quality. Almost all adolescent behavioural data were self-reported. These data are most likely to involve underestimation of true levels of drinking and its consequences for reasons of social desirability, though the possibility of exaggeration should also not be ignored Publication bias exerts influence in the opposite direction Studies from a range of different national and cultural contexts have been included here and identified as providing a stronger basis for causal attribution, though these are entirely restricted to Anglophone and Northern European countries. There are no included studies from low- and middle-income countries, nor from any country with a Mediterranean drinking culture. Previous meta-analytic study in this area has identified national context to be particularly important to findings on alcohol consumption from cohort studies Because there have been no previous systematic reviews of this literature, the research question addressed here is unusually broad. This approach led us to specify an end date for formal inclusion in the review, and inevitably further studies have since been published. For example, Huurre and colleagues Notwithstanding the limitations of the evidence base and of this review, and attenuations over time in the strength of the direct effects, late adolescent alcohol consumption appears a probable cause of increased drinking well into adulthood, through to ages at which adult social roles have been achieved. Heavier drinking seems most likely, however, to be only one component in a complex causal process, whose contribution has probably been overestimated in previous studies because of uncontrolled confounding, setting aside the uncertainties induced by self-reported data. The importance of these data is highlighted in the context of work showing strong stability of drinking patterns through the fourth and fifth decades of life In this study it seems that alcohol consumption confers additional risk of alcohol problems both on those who are already more vulnerable in various ways to poorer health and psychosocial outcomes, and strikingly also among those who are not otherwise vulnerable. Possible effects on adult alcohol problems and dependence including hospitalisation identified here result from heavier drinking in adolescence without necessarily involving problems at younger ages. If these effects are confirmed, there are two important implications: (1) Reducing late adolescent alcohol consumption in the general population may be expected to make a long-term contribution to reducing the incidence of adult alcohol problems; (2) In more vulnerable populations, late adolescent drinking may be one cause among many of later difficulties, and its effects may be more severe and long-lasting The lack of convincing evidence of effects on nonalcohol outcomes is the product of an absence of evidence rather than strong evidence indicating no effects. A priori, one might expect that effects on nonalcohol outcomes would be weaker simply because they are less direct. To this extent, any such effects would be less durable and may be more likely to occur in high risk subgroups. There is also the possibility of reverse causation in relation to many of these consequences as the initiation of drinking in adolescence may have been preceded by many of the nonalcohol outcomes considered here. Only careful studies of adolescence may address this possibility.There is also a clear need for high quality long-term prospective cohort studies in order to better understand the public health burden that is consequent on late adolescent drinking, both in relation to adult drinking and more broadly. A number of the cohorts included here were originally formed for prevention trials, and obtained some short-term evidence of benefit Click here for additional data file.


It was originally described as an inhibitor of cancer cell proliferation. However, many recent studies have shown that p21 promotes tumor progression when accumulated in the cell cytoplasm. So far, little is known about the correlation between cytoplasmic p21 and drug resistance. This study was aimed to investigate the role of p21 in the cisplatin resistance of ovarian cancer.P21RT-PCR, western blot and immunofluorescence were used to detect p21 expression and location in cisplatin-resistant ovarian cancer cell line C13* and its parental line OV2008. Regulation of cytoplasmic p21 was performed through transfection of p21 siRNA, Akt2 shRNA and Akt2 constitutively active vector in the two cell lines; their effects on cisplatin-induced apoptosis were evaluated by flow cytometry. Tumor tissue sections of clinical samples were analyzed by immunohistochemistry.p21 predominantly localizes to the cytoplasm in C13* compared to OV2008. Persistent exposure to low dose cisplatin in OV2008 leads to p21 translocation from nuclear to cytoplasm, while it had not impact on p21 localization in C13*. Knockdown of cytoplasmic p21 by p21 siRNA transfection in C13* notably increased cisplatin-induced apoptosis through activation of caspase 3. Inhibition of p21 translocation into the cytoplasm by transfection of Akt2 shRNA into C13* cells significantly increased cisplatin-induced apoptosis, while induction of p21 translocation into the cytoplasm by transfection of constitutively active Akt2 in OV2008 enhanced the resistance to cisplatin. Immunohistochemical analysis of clinical ovarian tumor tissues demonstrated that cytoplasmic p21 was negatively correlated with the response to cisplatin based treatment.Cytoplasmic p21 is a novel biomarker of cisplatin resistance and it may represent a potential therapeutic target for ovarian tumors that are refractory to conventional treatment. Ovarian cancer is the sixth most common cancer among women and it leads to the highest mortality per year than any other cancers of the female reproductive system ,2. CisplP21 was the first identified inhibitor of cyclin/cyclin-dependent kinase (CDK) complexes . PreviouGiven that chemoresistance is a biological trait of tumor malignancy and has a direct influence on a patient's prognosis, this study was designed to explore whether cytoplasmic p21 correlated with cisplatin resistance in ovarian tumors. In addition, we sought to determine whether interfering with cytoplasmic p21 could enhance the susceptibility of cancer cells to cisplatin. Here, we report that in the cisplatin-resistant cell line C13*, p21 is predominantly localized to the cytoplasm, while in the cisplatin-sensitive cell line OV2008, p21 is mainly restricted to the nucleus. Additionally, the exposure to low-dose cisplatin in OV2008 induced translocation of most p21 protein from nuclear to cytoplasm. Knockdown of cytoplasmic p21 by transfection of p21 siRNA into C13* cells notably enhanced their sensitivity to cisplatin. Inhibition of p21 translocation into the cytoplasm by Akt2 shRNA transfection in C13* cells significantly enhanced their sensitivity as well. Conversely, the accumulation of p21 in the cytoplasm by transfection of active Akt2 in OV2008 conferred resistance to cisplatin in OV2008 cells. Further analysis of clinical ovarian tumor samples by immunohistochemistry revealed that p21 was predominantly localized in the nucleus in the drug sensitive group. In contrast, p21 is mainly localized in the cytoplasm in the drug resistant group.2.The cisplatin-resistant ovarian cancer cell line C13* and its parental variant OV2008 were provided by Doctor Benjamin K. Tsang . Cells were maintained in RPMI-1640 supplemented with 2 mM L-glutamine, 100 U/ml penicillin, 100 mg/ml streptomycin and 10% fetal bovine serum (FBS) at 37°C in a humidified atmosphere containing 5% COFrom 2004 through 2007, 40 patients who were diagnosed with ovarian carcinoma and received standard cisplatin-based intravenous chemotherapy after surgery at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology were included in the study after obtainment of oral and written informed consents. Paraffin-embedded tumor tissue sections of each patient were prepared by the Department of Clinical Pathology. Information on histopathologic diagnosis was extracted from medical records and reviewed by a specialist in gynecologic pathology. The patients were selected and divided into treatment response and treatment non-response groups according to the CA125 criteria proposed by the Gynecological Cancer Intergroup (GCIC) . BrieflyAntibodies against Akt, Ser473-phosphorylated Akt and p21 were purchased from Cell Signaling Technology, Inc. . β-actin antibody and secondary goat anti-rabbit and goat anti-mouse alkaline phosphatase antibodies were purchased from Santa Cruz Biotechnology . Anti-caspase 3 antibody was purchased from Biolegend Co. . RPMI-1640, FBS, Lipofectamine 2000 and Trizol reagent were purchased from Invitrogen Co. . Cisplatin, MTT, DMSO, G418 and DAPI dye were obtained from Sigma Chemical Co. . The NE-PER cytoplasmic protein extraction kit was purchased from Pierce Co. . The annexin-V/PI apoptosis detection kit was purchased from Promoter Biotech Ltd. .A constitutively active Akt expression vector (AAkt2) and short hairpin RNA targeting Akt2 (Akt2Sh) were described previously ,35. The For RNAi targeting, C13* cells cultured in 6-well plates were transfected with indicated plasmids using Lipofectamine 2000. After 6 hours of incubation, the transfection solution was removed, and was replaced with fresh complete growth medium. 48 hours post-transfection the cells were assayed for the expression of p21 and treated with cisplatin for further experiment.OV2008 cancer cells were stably transfected with AAkt2 vector, C13* cancer cells were stably transfected with Akt2sh, using Lipofectamine 2000. Their corresponding empty vectors, i.e., pcDNA3.1 and pEGFPC1, were transfected as negative control. The cells were selected with G418. The concentration of G418 for selection and maintenance was 600 μg/μl. After three weeks the G418-resistant cell pools were established and seeded into 100 mm dishes for further propagation.Total RNA was isolated from each group of cells using Trizol Regent, according to the manufacturer's instruction. Real-time PCR amplifications were carried out using DNase I (Promega)-treated total RNA. Reactions were performed in a Stratagene MX3000P system using the Real-time PCR Master Mix . P21 primer sequences were as follows: sense, 5'-CCT CTT CGG CCC GGT GGA C-3': anti-sense, 5'-CCG TTT TCG ACC CTG AGA G-3'. GAPDH primer sequences were as follows: sense, 5'-ACG GAT TTG GTC GTA TTG GG-3'; anti-sense, 5'-TGA TTT TGG AGG GAT CTC GC-3'.3VO4, 1 mM phenylmethylsulfonyl fluoride, 25 mg/ml leupeptin and 25 mg/ml aprotinin. The lysates were cleared by centrifugation, and the supernatants were collected. Cytoplasmic proteins were extracted using the N-PER cytoplasmic protein extraction kit according to manufacturer's instructions. Equal amounts of protein lysate were used for western blot analyses. Specific signals were visualized with NBT/BCIP.Total proteins were extracted by lysing cells in buffer containing 50 mM Tris pH 7.4, 150 mM NaCl, 0.5% NP-40, 50 mM NaF, 1 mM NaCells were seeded into 96-well plates, treated with different concentrations of cisplatin for 24 hours and then assessed using 3--2, 5-diphenyltetrazolium bromide. Cell viability was determined by measuring the optical absorbance of cells at 570 nm wavelength and normalizing the values to the corresponding controls.Cells were harvested, washed with PBS and stained with the annexin-V/PI apoptosis kit according to manufacturer's instructions. Analysis of apoptotic cells was performed using a FACScan flow cytometer, and the data were analyzed using cell fit software.Cells were trypsinized and plated onto chamber slides for 12 hours. After fixation in acetone, the slides were blocked with BSA, incubated with p21 antibody and rhodamine-conjugated secondary antibody and counterstained with DAPI. Slides were then observed on a confocal laser-scanning microscope . P21 staining was categorized as negative, nuclear or cytoplasmic according to a standard described before . Briefly2O2 to inhibit endogenous peroxidase. Slides were then blocked with 5% normal serum and incubated with anti-p21 antibody. For qualitative identification of specific antibody staining, the DAKO Envision+ system was used, according to manufacturer's instructions, as described below. After detection with chromogen diaminobenzidine, sections were counterstained with hematoxylin and mounted. For the negative control, all incubation steps were identical except that PBS was used instead of primary antibody. The immunoreactivity of p21 was categorized as negative, nuclear or cytoplasmic according to the standard decribed before [Paraffin-embedded tissue sections were deparaffinized. After antigen retrieval, slides were incubated with 3% Hd before .Western blot images were captured and quantified using the ChemiImager 5500 system from the Alpha Innotech Corporation .2) test. Results expressed as mean ± SD were analyzed using the Student t test. Differences were considered significant when p < 0.05. Data were analyzed using SPSS software version 13.0 .All experiments were repeated three times. The relationship between patients' clinical characteristics and results of p21 immunohistochemistry was assessed using the chi-squared . The difference between cisplatin-induced viability inhibition of the two cell lines peaked at 51.9% with 20 μM cisplatin (p < 0.05). By flow cytometry, we observed that cisplatin treatment increased apoptosis of OV2008 and C13* cells in a time-dependent manner  in the nucleus functions as a tumor suppressor by binding to cyclin/CDK complexes and proliferating cell nuclear antigen [It is well known that p21 antigen ,16. Howe antigen ,32 have  antigen . This stThe cisplatin-resistant cell line C13* used in this study was established after in vitro challenge of OV2008 cells, a line derived from one ovarian carcinoma patient without prior chemotherapy, with cisplatin ,39. SincZhou et al. reported that activation of phosphatidylinositol 3-kinase (PI3K)/Akt signaling can stimulate cytoplasmic accumulation of p21 . There aCaspase 3 activation is considered to be a key cellular component of the terminal and irreversible phase of apoptotic death caused by DNA damaging agents. In our experiments using flow cytometry, we found that the levels of cleaved caspase 3 (17 kDa) were proportional to the rate of apoptosis. Previously, it was reported that p21 could bind to procaspase 3  and prevBy immunohistochemical analysis we found that a large proportion of tissues from treatment non-response tumors stained positive for cytoplasmic p21 (5 to 8) when compared to tissues from the treatment response group (2 to 25) (p = 0.027). We also showed that there was no significant difference in the level of cytoplasmic p21 staining between high stage and low stage ovarian tumors (p = 0.691), and between patients of different ages (p = 0.677). Furthermore, we compared cytoplasmic p21 levels in serous and non-serous tumors because the number of mucous and other types of tumors was limited. However, information on the prognosis and survival of the patients was not available; therefore, our investigation could not make a statistical analysis between cytoplasmic p21 and disease-free or survival rates.Our in vitro experiments demonstrate cytoplasmic p21 is a novel biomarker in cisplatin resistance, and regulation of cytoplasmic p21 could alter the response of ovarian tumor cell lines to the drug. This finding supplements our previous studies ,12,34 ansiRNA: small interference RNA; shRNA: short hairpin RNA; CDK: cyclin-dependent kinase; PI3K: phosphatidylinositol 3-kinase; PTEN: phosphatase and tensin homolog; XIAP: X-linked inhibitor of apoptosis; MKP3: mitogen-activated protein kinase phosphatase 3; MDR: multidrug resistance protein.The authors declare that they have no competing interests.XX and QM carried out the immunofluorescence staining, participated in functional assay and drafted the manuscript. XL, TJ, PC and HX participated in nucleus p21 siRNA sequence designing and silencing efficiency. KL, YF and DW performed cell viability assay, western blot and RT-PCR. YW, SL and ZH collected clinical data, and carried out flow cytometry and immunohistochemistry assay. RL and TZ performed statistical analysis. GX participated in the data interpretation and provided expertise in molecular biological techniques. SW was responsible for writing and revising the manuscript. JZ, DM and LM participated in the design and coordination of the study. All authors have read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/11/399/prepubFigure S1. Representative western blot depicting the Akt and p-Akt protein levels between C13* and OV2008 cells. Total protein was extracted from C13* and OV2008, and western blot was applied to compare the Akt and p-Akt expression between the paired cell lines.Click here for file


Bentham Science Publishers would like to thank and appreciate the co-operation from all reviewers for their constructivecomments and feedback on the manuscripts submitted to Current Cardiology Reviews. Their efforts have contributed greatly tothe high quality and continuous growth of the journal. Given below is the list of reviewers who reviewed articles for the Journalduring 2012.Prof. W. Hueb (Brazil)Dr. J. Zhu (China)Dr. A. Fiorentini Dr. B. Balci (Turkey)Dr. P. M. Eckman (USA)Dr. P. Yu (USA)Dr. A. Bobik, Dr. K. Werdan (Germany)Prof. L H Kuller (USA)Prof. C. D. Arepalli (USA)Dr. T. Carrel (Switzerland)Dr. R. Grant (South Africa)Prof. J. M. Legramante Prof. M. Esco (USA)Dr. X – Y. Yu (China)Prof. D. Hou (USA)Prof. J. Zhang (USA)Prof. M. Endoh (Japan)Prof. G. Bajraktari (Kosovo)Prof. J. P. Veinot (Canada)Prof. G. Deep (USA)Dr. V. Rani (India)Dr. H. R. Weiss (USA)Prof. A. Mistri (United KingdomProf. J. L. Mehta (USA)Prof. G. Samasca (Romania)Prof. S. Micovic (Serbia)Prof. M. Balghith (Saudi Arabia)Prof. N. Ranjan (India)Prof. X. Guo (USA)Prof. W. Deng (USA)Prof. S. Haber (USA)Prof. R. Cheung (USA)Dr. R. Berg (USA)Dr. Goldberg (Pennsylvania)Dr. R. Wessel (USA)Dr. J. A. Ambrose (USA)Dr. G. Dangas (USA)Dr. G. Dangas (USA)Dr. D. Alexopoulos (Greece)Prof. Y.H. Lip (United Kingdom)Prof. A. Skanes (Canada)Prof. D. Sánchez-Quintana (Spain)Prof. L. Roten (France)Prof. D. Redfearn (Canada)Prof. J. Caldwell (Canada)Prof. P. Sommer (Germany)Prof. A. Natale (USA)Prof. Y. Khaykin (Canada)Prof. B. Gorenek (Turkey)Prof. G. Kudaiberdieva (Turkey)Prof. M. A. Mamas (United Kingdom)Prof. A. Baranchuk (Canada)Prof. R.A. Malik (United Kingdom)


Identifying the anthropometric measures of successful and less successful handball players may be helpful in developing a talent identification and development model, allowing for the determination of key physical capacities required for elite performance. The purpose of the study was to describe the anthropometric characteristics, including age, standing stature, body mass and body mass index (BMI) in handball players who participated in the 2013 Men’s Handball World Championships. Secondly, the objective was to identify the possible differences in these parameters in terms of individual playing positions . Rosters with handball player’s age, standing stature, and body mass were obtained from the International Handball Federation website. The research material included 409 handball players (24 teams). National teams were organized by their ranks and sub-grouped using their continents and playing positions. The results of the analyses of variance demonstrated significant differences in age , standing stature , and body mass  among the groups (G1–G6). Players in G1 had the highest standing stature and body mass, while players in G6 had the lowest age and body mass values. The backs and line players were the tallest. In addition, the measurement of body mass showed that the line players had the highest body mass and BMI values. In conclusion, this study presented anthropometric data that differentiated levels of success in male handball teams playing in the 2013 world championships. This information should serve as a reference for the average standing stature, body mass, and BMI of handball players for particular positions at the professional level. Handball is an Olympic team sport which has been played since the 1972 Games in Munich with further major international competitions encompassing world championships, continental championships, and international tournaments, as well as major club championships being played throughout the world. From the point of view of physical performance, handball is a complex, intermittent sport game, played over 60 minutes, which requires efforts of maximum intensity in a short period of time, where players jump, run, and throw the ball at a high velocity, followed by low intensity recovery periods. Clearly, given the physical challenges of the game it requires significant physical preparation in order to compete successfully . HandbalThus, the main aim of this study was to describe the anthropometric profile of elite handball players who participated in the world championships from five different continents and compare these characteristics based on different playing positions .www.ihf.info). All team rosters and all players who were registered for the tournament were included. This comprised a total of 24 teams, with 409 handball players. For the purpose of analysis, the age, standing stature, body mass, and playing position of all 409 male handball players from 24 countries and 5 continents were recorded and body mass index (BMI) of the players calculated. National teams were organized by their ranks and sub-grouped using their continents and playing positions.The anthropometric characteristics of the handball players who participated in the 2013 World Men’s Handball Championship were analyzed. Rosters with player’s age, standing stature, and body mass were obtained from the International Handball Federation website .All results are reported as a mean ± SD. The Kolmogorov-Smirnov test was used to verify the normality of the distribution. In addition, differences of age, body height, body mass and body mass index across groups (G1–G6), playing positions and continents were analyzed with oneway analysis of variance (ANOVA). When a significant difference was revealed, the Dunnett’s T3 or Scheffe’s post hoc test was used to specify where the difference occurred. When the homogeneity of variance was established, the Scheffe’s post hoc test was used; otherwise, we applied the Dunnett’s T3 post hoc test. Effect size was calculated using Partial Eta Squared . Playing position-adjusted partial correlation coefficients were calculated to investigate the association between team rank and age and anthropometric characteristics. The level of significance was set at Anthropometric characteristics of male handball players from the 2013 World Championships, grouped according to their ranks, are presented in 2=0.028), standing stature , and body mass  among the groups , standing stature , body mass , and BMI  among the positions. The backs and line players were taller than other players. In addition, the measurement of body mass showed that the line players had the highest body mass and BMI values , standing stature , and body mass , but BMI did not differ among the continents . Hasan ePearson correlations or multiple regressions are often used to identify which anthropometric characteristics or physical capabilities can predict athletic performance . StrengtIn conclusion, this study presented anthropometric data on more and less successful male handball teams that participated in the 2013 World Championships. Furthermore, this study confirms and expands on previous data about anthropometric differences among playing positions and continents in handball. The measurement of anthropometric characteristics provides an insight into the current status of handball players, allowing coaches to evaluate typical characteristics of elite performers. This information should serve as a reference for what the average standing stature, body mass, and BMI of handball players may be for positions at the professional level. This date can be used to develop a model of elite handball performance which can be used to supplement talent identification programs, and also in the construction of effective player development programs.


Although videos of surgical procedures are useful as an educational tool, the recording of trauma surgeries in emergency situations is difficult. We describe an inexpensive and practical shooting method using a commercially available head-mounted video camera.We used a ContourHD 1080p Helmet Camera . This small, self-contained video camera and recording system was originally designed for easy videography of outdoor sports by participants.We were able to easily make high-quality video recordings of our trauma surgeries, including an emergency room thoracotomy for chest stab wounds and a crush laparoptomy for a severe liver injury.There are currently many options for recording surgery in the field, but the recording device and system should be chosen according to the surgical situation. We consider the use of a helmet-mounted, self-contained high-definition video camera-recorder to be an inexpensive, quick, and easy method for recording trauma surgeries. The number of trauma victims in developed countries has become much smaller during recent years. In addition, the success of non-operative management of many injuries has diminished the number of operations performed by trauma surgeons ,2. As a A variety of methods are currently available for capturing video of surgical procedures, such the operation of light mounted cameras, the use of head-mounted cameras (head-cams) designed for hospital environments, and laparoscopic cameras -7. Howevhttp://store.contour.com/), which can shoot crisp, smooth video at either 720p at 60 frames per second (fps) or 1080p at 30fps. This video camera was originally introduced for ease of use when recording outdoor sports. The supplied battery allows approximately 2 hours of recording, an internal 16GB microSD card can hold roughly 4 hours of full HD  video, and the weight is only 123g. The camera is equipped with two laser pointers mounted on the lens assembly, so the field of view can be checked and easily aligned, regardless of the camera’s mounted position, simply by rotating the lens assembly. The camera is mounted on the head with a band and is focused on the surgical field so that the camera will record whatever is in the surgeon’s view  scan, taken after hemodynamic stabilization, showed an extravasation of contrast material from the right lobe of the liver, a facial fracture, and a pelvic fracture. Soon after the CT scan, his hemodynamic status deteriorated again, with drop in systolic blood pressure to 68 mmHg. At crush laparotomy, 3 L of blood was found, with lacerations of the right lobe and left lateral segment of the liver (see Figure The details of surgical techniques and a patient’s clinical status are hard to convey in writing, even when figures and photographs are included, and this is especially pertinent concerning intricate surgical handwork and hemorrhagic status. Current advances in video technology have enabled surgeons to make recordings of their operations and document procedures; these recordings can later be used for teaching, research, auditing, and patient education -6. High-Laparoscopic video is easy to record but capturing video during open surgeries is challenging. Although there are currently many options for recording surgery fields -7,11, noSeveral medical head-cams are currently on the market and can accurately record surgeons’ views, but because these are connected to a video monitor, surgeon mobility is restricted and equipment preparation is usually required. As a result, this type of equipment is unsuitable for recording emergency procedures such as an emergency thoracotomy in the emergency room. In addition, medical equipment built for hospital-use tends to be very costly, but the rapid pace of technological development means that such equipment may soon become outdated, reducing the value of significant capital expenditures. Therefore, the simplest and most cost-effective method is to employ a commercially available item .Commercially available head-cams without a video monitor are inexpensive and allow quick and easy recording of trauma surgeries. Also, in addition to the advantages offered by head-cams during emergency in-hospital procedures, they can be useful during the provision of pre-hospital care. However, for recording video during surgical procedures, commercially available head-cams have two major problems.The first problem is that the view of the operator and that of the camera may be different and since no monitor or display is used, there is no way to verify the congruence of these views. The ContourHD model described in this paper has a built-in pair of laser pointers that indicate the plane of the camera’s view, but this feature is only used temporarily, to orient the camera lens appropriately prior to the start of recording. The second problem is that these head-cams operate in a fixed mode, with no zoom function. Therefore, although a general view is effectively captured, providing closer views of detailed procedures requires the use of video editing software that has a zoom function. However, new devices are being developed to mitigate these problems.Decision making is very difficult when attending to major trauma . The attWe described a simple and cost-effective method of recording trauma surgery. Although many options for recording surgical fields are available, each has its distinctive characteristics, advantages, and disadvantages. Recording devices that best meet the needs of the surgical situation should be chosen.Written informed consent for publication of the case report details and accompanying audiovisual material was obtained from all patients, copies of which are available for review by the Editor-in-Chief of this journal.This report was presented at World Trauma Congress, August 2012 in Rio de Janeiro. This report has neither been published nor is it being considered for publication elsewhere.This report has neither been presented nor is it being considered for publication elsewhere.The authors declare that they have no competing interests.S.M conducted literature searches and conceived of this technique. S.M wrote the manuscript, which was critically revised by K.S and M.K. All authors read and approved the final manuscript.Emergency thoracotomy in the emergency room with pericardium incision.Click here for fileCrush laparotomy, showing significant hemorrhaging from the abdominal cavity.Click here for filePringle’s maneuver and vacuum assisted closure after perihepatic packing.Click here for file