O. rufipogon as a reference in the characterization. Results indicated relatively rich genetic diversity (He = 0.63-0.65) in Italian rice varieties. Further analyses revealed a close genetic relationship of the Italian traditional varieties with those from northern China, which provides strong genetic evidence for tracing the possible origin of early established rice varieties in Italy. These findings have significant implications for the rice breeding programs, in which appropriate germplasm can be selected from a given region and utilized for transferring unique genetic traits based on its genetic diversity and evolutionary relationships.The characterization of genetic divergence and relationships of a set of germplasm is essential for its efficient applications in crop breeding and understanding of the origin/evolution of crop varieties from a given geographical region. As the largest rice producing country in Europe, Italy holds rice germplasm with abundant genetic diversity. Although Italian rice varieties and the traditional ones in particular have played important roles in rice production and breeding, knowledge concerning the origin and evolution of Italian traditional varieties is still limited. To solve the puzzle of Italian rice origin, we characterized genetic divergence and relationships of 348 rice varieties from Italy and Asia based on the polymorphisms of microsatellite fingerprints. We also included common wild rice  Oryza sativa L., referred to as rice hereafter) is the third largest cereal crop of the world, and provides staple foods and nutrition for nearly one half of the global population [Asian cultivated rice  and 1.6 million tons of total grain production. Nearly all rice varieties grown in Italy are japonica ecotype [Italy is the largest rice production country in Europe, with about 250,000 hectares of cultivation area , although no written document about these is available. The earliest rice cultivation documented in Italy can be traced back to 1468 in the wetlands of Tuscany, near Pisa [Magnaporthe oryzae). To guarantee the continued rice cultivation that was seriously threatened by this fungal disease, new varieties were introduced from China and Japan at the beginning of 19th century. These varieties were characterized by their high yielding and resistance to rice blast. As a consequence, five Italian rice varieties were cultivated in Italy in 1872: Ostiglia, Bertone, Novarese, Francone, and Giapponese. Because of the recrudescence of blast attacks that created a new crisis for Italian rice cultivation, more rice varieties were imported from Asian countries including China, India, and Japan in 1880, which led to a substantial increase in the number of Italian rice varieties in the subsequent years. A milestone of Italian rice cultivation in history was the presence of a set of varieties grouped under the general name of “Chinese Originario” with high yield and strong resistance to blast [The first official documentation of rice introduction to Italy is related to the Spanish Presence in the Kingdom of Naples because of the ties between the Aragon family (The Kings of Naples) and the Sforza family (Dukes of Milan) in the second half of 15 century . Rice maear Pisa . At thatRice production in Italy fluctuated significantly, depending essentially on the national and international varieties used. A number of successful varieties  were bred in 1926 through the systematic selection from “Chinese Originario” or, in a few cases, improved from old American varieties. This illustrates the importance of rice improvement in Italy relying on the introduction of alien germplasm from other countries. A number of recent studies have systematically characterized the existing Italian rice germplasm for its genetic diversity , agronomOryza rufipogon Griff.) accessions were also used as a reference. The primary objectives of this study were to (i) estimate the general genetic diversity of different historical groups of Italian rice germplasm in comparison with that from other sources; (ii) determine genetic divergence of Italian rice germplasm from that of Asian rice germplasm; and (iii) trace the possible origin of Italian rice varieties based on genetic data. The answer of these questions will facilitate the continued genetic improvement of Italian rice for the sustainable rice production in the region.To solve the “puzzles” of Italian rice origin, we characterized a large set of rice germplasm from extensive sources, based on the polymorphisms of microsatellite (SSR) fingerprints at 24 loci across the rice genome. The set of germplasm is represented by 183 Italian rice varieties, including nearly all traditional and modern varieties currently available in Italy, and 165 rice varieties from Asia. In addition, ten common wild rice (Oryza sativa) from Italy and Asian countries were included in this study  represented the modern Italian varieties that were improved under local genetic breeding programs. The third group  included the modern Italian varieties improved under genetic breeding with rice germplasm from North America. These rice varieties covered the entire range of Italian rice cultivation regions and represented nearly all rice germplasm currently available in Italy (http://www.enterisi.it/ris_schede.jsp).A total of 348 rice varieties (is study . InformaO. rufipogon) from Guangdong and Hunan Province of southern China (Wild) were also included as a reference group  the Chinese group that included varieties from different Provinces of this country (encoded as China); (2) the East Asian group included varieties from Japan and South Korea (E Asia); (3) the South Asian group included varieties from India and Sri Lanka (S Asia); and (4) the Southeast Asian group comprised of varieties from different countries in southeastern Asia (SE Asia), including Cambodia, Indonesia, Laos . In addice group . Seeds of sampled rice varieties and wild accessions were germinated in an incubator at the temperature of ~25°C. The total genomic DNA was extracted from about 1g fresh leaf tissues for each seedling, separately, at about the three-leaf stage 10 days after seed germination. The extraction followed a modified cetyltrimethyl ammonium bromide (CTAB) protocol described by . http://www.gramene.org). All the forward primers were labeled by one of the following fluorophore: FAM (blue), ROX (red), or JOE (green) . Twenty-four SSR primer pairs distributed on the two arms of each of the 12 rice chromosomes were selected for analyses from The RiceGenes Database (2+), 0.2mM each of dNTPs, 0.2μM each of SSR primers, 20 ng of genomic DNA and 0.3U of Taq polymerase . The reaction procedure was programmed as following: a denaturation period of 4 min at 94°C followed by 28 cycles of 30 s at 94°C, 30 s at 55°C and 40 s at 72°C, and then 7 min at 72°C for the final extension.The polymerase chain reaction (PCR) was performed in the “2720 Thermal Cycler” . Reactions were carried out in a volume of 10 μL mixture, containing 1×buffer  and internal lane size standard (GeneScan™ -500 LIZ) for fragment separation after denaturing at 94°C for 5 min and then cooled at 4°C. The SSR fragments were separated on a capillary electrophoresis genotyper, ABI 3130xl . The separated SSR fragments were scored as genotypic data using the software Genemapper ver. 3.7 .P); (2) the effective number of alleles per locus (Ne); (3) the observed heterozygosity (Ho); (4) Nei’s unbiased genetic diversity (He) [I). In addition, the number of private alleles per rice group (Npa) was also calculated to estimate the uniqueness of each group. To determine genetic relationships among cultivated rice groups (see definition in sampling of rice germplasm) from various regions, the values of Nei’s unbiased genetic similarity [The genotypic data matrix from all rice varieties and wild accessions generated by the 24 SSR primer pairs was analyzed to estimate the level of genetic diversity. The following five diversity parameters were calculated: (1) the percentage of polymorphic loci (ty (He) ; and (5)milarity  were calmilarity .To illustrate the relationships of different rice groups, an UPGMA dendrogram was constructed based on the unbiased genetic similarity , using tRice germplasm included in this study with different origins presented a relatively high level of overall genetic diversity, although with a considerable degree of variation among rice groups . A totalThe Nei’s unbiased genetic similarity  was calcFor estimate genetic relationships of rice varieties from Italy (three groups) and Asia (four groups), a dendrogram  was consindica and japonica rice varieties as shown in previous studies. The NJ tree did not suggest an obvious variation pattern of the rice varieties from different regions either. However, the Italian traditional rice varieties categorized in Italy-1 , a neighbor joining (NJ) tree was constructed based on the genetic distance of all the individual rice varieties using wild rice as an out-group . In geneindica and japonica) of rice varieties in different regions, which was considered for dividing the whole group into subgroups. The newly divided Asian regions included different Provinces of China, Southeast Asia, East Asia, and South Asia  with Chinese and East Asian varieties as groups. Given the abundant genetic diversity in Italian traditional rice varieties  as a reference, to estimate its genetic variation and relatedness. The total number of alleles (442) detected in these varieties was unexpectedly high, compared with those detected in a previous study where 172 Italian rice varieties and 47 introduced foreign varieties were analysed using 24 SSR loci [O. rufipogon that had a much higher Ho value . We analyzed a large set of rice germplasm including 183 varieties representing nearly all Italian rice germplasm, 165 varieties from Asia, and ten accessions of wild rice  in Italian rice varieties (three groups) is comparable to that (0.59) reported in a previous study on the temporal trends of variation in Italian germplasm [The level of genetic diversity  and locally improved modern  rice varieties share a close affinity, and showed their close linkage with rice varieties from China and East Asia. This finding reveals that the Italian rice varieties produced based on germplasm from similar sources  remain much closer genetic relationships than those with germplasm from different sources such as North American . In addition, Italian rice germplasm as a whole showed a relatively distant genetic affinity with that from South Asia and Southeast Asia, where varieties, it makeindica and japonica differentiation as suggested by other studies [Notably, the Italian traditional and locally improved rice varieties have a close genetic affinity with Chinese and East Asian varieties. When alien germplasm was introduced from North America and used as breeding materials for hybridization, the genetic relationship between Italy-3 and Chinese/East Asian rice varieties became loose due to mixture of North America rice germplasm. Obviously, the evolution and divergence of Italian rice germplasm depend essentially on the introduced exotic rice varieties from different geographical sources and the breeding methods. The NJ tree based on genetic relatedness of individual rice varieties did not show particular groupings of these varieties associated with either  studies ,25, or g studies ,18. HoweUnderstanding genetic relationships of the current Italian rice germplasm has its important implications in rice breeding, through properly selecting and introducing exotic germplasm into Italian rice varieties . The intindica and japonica rice varieties [Our results generally indicated a close relationship of Italian traditional and locally bred modern varieties to Chinese varieties as a whole group. However, China is a large country with the extensive cultivation of diverse types of arieties ,23,24. IOur results based on genetic similarity analysis of Italian traditional varieties  with Chinese rice germplasm represented by different Provinces evidently indicated their close genetic affinity to that from northern rice cultivation regions . These rAlthough the tales such as Marco Polo’s contribution to the introduction of rice from China to Italy may never be fully confirmed, results from this study provide solid genetic evidence to confirm the close linkage between Italian and Chinese rice varieties. Rice varieties from northern China may provide genetically most accessible and useful germplasm for Italian rice breeding because of their close genetic relatedness and abundant genetic diversity, even though rice varieties from other regions in Asia can also provide unique and especially valuable germplasm that has not been represented in the Italian rice gene pool. As the largest rice production country in Europe, Italy holds important and diverse rice germplasm, which guarantees the sustainable rice production and breeding in Italy and neighboring countries. Knowledge concerning the genetic diversity, origin, and evolutionary relationships of Italian rice has important implications for its effective breeding by selecting proper exotic rice germplasm. The early introduced rice varieties such as “Chinese originario” have played an important role in Italian rice production and breeding programs. However, the origin and evolutionary relationships of these early introduced varieties have not been properly documented. Results based on SSR fingerprints of a large set of rice germplasm from Italy and Asia in this study demonstrate a close genetic relationship between Italian and Chinese rice varieties, suggesting the possible origin of Italian traditional rice from northern China. Although the conclusion on Chinese origin of Italian traditional rice still needs supports from further studies, this finding has significant implications for Italian rice improvement by including appropriate exotic germplasm in its breeding programs.Figure S1A Neighbor-Joining (NJ) tree showing individual-based genetic relationships of 348 rice varieties analyzed in this study (see Table 1 and Table S1 for detail information), using wild rice as an out-group (root). The yellow-color highlighted entries indicate the Italian traditional varieties, and the green-color highlighted entries indicate Chinese varieties. The NJ tree was constructed based on the “distance methods” installed in the software PAUP ver. 4.0 [ver. 4.0 .(PDF)Click here for additional data file.Table S1Rice germplasm included in the analysis. Accession numbers and indica (i) or japonica (j) characteristics are indicated in the parentheses following the name of a rice variety. IBS = Institute of Biodiversity Sciences of Fudan University; AAV = Shanghai Agricultural Gene Center; ENR-CRR = Ente Nazionale Risi-Centro Ricerca sul Riso; RNV = Registro Nazionale Varietà 2013.(DOC)Click here for additional data file.


Associations between clinical outcome and patient characteristics, such as tumour gene expression, and inherited variation (single nucleotide polymorphisms) can be difficult to reproduce between ovarian cancer cohorts. Sources of variation include the size and composition of patient cohorts and treatment, which has varied over time and can vary between countries. We have undertaken a review of treatment in patients recruited to the Australian Ovarian Cancer Study (AOCS) to determine the primary treatment patterns and levels of consistency across the cohort. Australian clinical practice guidelines for the management of women with epithelial ovarian cancer were published in 2004  and AOCSAOCS collected fresh tissue, blood, epidemiological/dietary questionnaires and clinical follow-up data for women aged 18-79 diagnosed with invasive (n=1476) and borderline (n=352) cancer, and material and data are available for research, by application. Clinical data was collected through a national research nurse network at pre-specified intervals: at diagnosis, completion of primary treatment and then at 6-monthly intervals. At the end of Feb 2011 primary treatment data was complete on 99% of eligible cases and the median follow-up time was 5.1 years.Most patients with invasive cancer underwent surgery prior to chemotherapy  and a small proportion had an interval debulk  or other procedure (<10%). The vast majority of women with advanced stage cancer (FIGO stage II-IV) received chemotherapy  and of these, over 99% (1110/1116) received a platin-based regimen. The most common regimens were carboplatin/paclitaxel (77%) and carboplatin alone (9%), most women (86%) received 6-8 cycles and 95% of women who received adjuvant chemotherapy began treatment within 6 weeks of surgery.In conclusion, the majority of women in AOCS were treated according to national guidelines, enabling the selection of cases with uniform treatment for projects investigating associations of genomic and genetic features with clinical outcome.


Number of studies indicates on possible role of toxic substances in development of heart malformations during cardiogenesis. The aim of our research is studying of toxic element barium content in different biosubstrates of children with CHD.29 patients  boys and 12  girls), aged from 14 days to 17 years (medium age: 26 month±2 month) old with CHD were examined by the spectral analysis of toxic element barium in intraoperative (23) and autopsy (6) biopsies of endocardium (22), myocardium (26), pericardium (7), aorta (10), skin (8), subcutaneous fat (8), intercostal muscles (24), fascia (2), kidneys (5), brain (2) and hair (9) by methods of the atomic emission spectrometry in the inductively coupled plasma and atomic absorption spectrometry with electrothermal atomization.A comparative analysis of barium level in different biosubstrates demonstrated it’s highest content (числа) in muscle tissue . Whereas in other tissues the concentration was decreased or absent. Barium content exceeded toxic level in heart tissues of 72.4% of patients. The excess degree of barium content depended on biopsy topics, namely, in aorta coarctation place, valve atresia place, septal defect its level was in two, ten or more times higher than in normal heart area or great vessel area. Dependence between the barium excess degree content in the heart tissue and severity of malformation or its combinations was also established: children with exceeding level of barium in the heart tissues had significantly more (p <0.05) of combined complex CHD.Barium affinity to the myocardium, blood vessels smooth muscles and striated skeletal muscles was confirmed. Spectrum of barium content depends on the type and severity of the defect and biopsy point. Received data indicate on possible role of barium in cardiogenesis malformation, that needs deeper investigation.


To study the association between house dust endotoxin levels and respiratory symptoms and allergen sensitizations in children from the urban areas (Guangzhou) and rural areas (Conghua) of Guangdong province, China.20-FEV1) and allergen skin reactions were analysed by logistic regression.Three hundred and seventeen children aged 13-14 years  with self-reported respiratory symptoms and 537 healthy children were selected from 854 school-children according to their response to ISAAC standardized questionnaire. These children attended the school infirmary again to complete a detailed questionnaire and medical examinations including skin prick test (SPT) to 8 common aeroallergens, lung function test, histamine bronchial provocation test and peripheral blood eosinophil counts. House dust samples were collected from living room and mattresses of 156 of these children with the agreement of their parents . The content of endotoxin in house dust was quantified using an endpoint chromogenic kinetic limulus amoebocyte lysate test. Associations between levels of house dust allergens and endotoxin and the provocation dose producing a 20% fall in forced expiratory volume in one second , and a negative association (p<0.01) between endotoxin levels and the wheal sizes of skin response to Dermatophagoides pteronyssinus (Der. p) and Dermatophagoides farinae (Der. f).The prevalence of wheeze symptom, asthma, nasal symptoms and allergic rhinitis in the children of Guangzhou were significantly higher  than the children of Conghua . Endotoxin concentrations in dust samples in homes of Conghua were significantly higher  than those of Guangzhou . Logistic regression analyses showed a positive association between endotoxin levels and PDThese findings suggest that exposure to higher levels of house dust endotoxin might contribute to the lower risk of allergic sensitization in children.


Our objective was to evaluate if the implementation of a multifaceted intervention program for quality improvement in ICUs of nonacademic hospitals would decrease mortality and the catheter-related bloodstream infection rate (CRBSI).®); (6) 3-day workshop to share the coordinating institution quality improvement practices with directors and ICU coordinators from the 17 participant institutions; (7) 3-day nursing visits from the coordinating hospital to perform advice on care practice; (8) basic life support courses, 56 vacancies per hospital, and fundamentals of critical care support, 30 vacancies; and (9) implementation of a web-based system to collect ICU and hospital mortality, SAPS3, standardized-mortality ratio (SMR) and CRBSI after June 2011. We assessed variation of SMR and CRBSI on time using weighted linear regression, and variation of mortality on time using generalized-estimating equations.A clinical practice improvement program involving 17 Brazilian ICUs of nonacademic public hospitals located far from major economic centers under coordination of a not-for-profit private hospital with the support of Brazilian Ministry of Health. We implemented the following interventions: (1) hospital visits to assess the facilities, human resources and processes; (2) workshop with hospital directors and ICU coordinators to elaborate improvement proposals based on the initial visit findings; (3) multidisciplinary videoconference lectures every 3 weeks about critical care medicine assistance and quality issues; (4) website containing project educational material, videoconference recordings, and an evidence-based practice course; (5) subscription of an electronic clinical information resource for all participating hospitals (UpToDateThe results are presented in Table A multifaceted intervention program applied to a network of ICUs in nonacademic public hospitals reduced mortality.


The aim of the study was to evaluate the effect of cumulative dose of glucocorticoids during 3 years on bone mineral density (BMD) and bone turnover (BMT) measurement in children suffering from inflammatory bowel disease (IBD).In cohort of 64 children with IBD (54 children with Crohn disease and 10 with Ulcerative colitis) we measured bone mineral density at the time of diagnosis and two times during follow-up. Bone turnover /osteocalcin (OC) and C-terminal telopeptide of type I collagen (CTx)/ was measured using ELISA same time as BMD. All patient were treated by glucocorticoids with average of cumulative dose 4,46g. The obtained results were analyzed using correlation analysis.± SD). There was no change during the treatment . The level of CTX and osteocalcin paradoxically increased, but there was no statistical significance.At the time of diagnosis we observed the total body BMD Z-score –1,7 (mean In our study we didn’t find correlation between BMD, cumulative dose of glucocorticoids, CTX and osteocalcin during period of 3 years. Insignificant increase of bone markers was established. According to our results we can speculate that bone status impairment of bone mass is independent in children with IBD on treatment with glucocorticoids regarding to inflammation itself.


Population fluctuations are often driven by an interplay between intrinsic population processes and extrinsic environmental forcing. To investigate this interplay, we analyzed fluctuations in coastal phytoplankton concentration in relation to the tidal cycle. Time series of chlorophyll fluorescence, suspended particulate matter (SPM), salinity and temperature were obtained from an automated measuring platform in the southern North Sea, covering 9 years of data at a resolution of 12 to 30 minutes. Wavelet analysis showed that chlorophyll fluctuations were dominated by periodicities of 6 hours 12 min, 12 hours 25 min, 24 hours and 15 days, which correspond to the typical periodicities of tidal current speeds, the semidiurnal tidal cycle, the day-night cycle, and the spring-neap tidal cycle, respectively. During most of the year, chlorophyll and SPM fluctuated in phase with tidal current speed, indicative of alternating periods of sinking and vertical mixing of algal cells and SPM driven by the tidal cycle. Spring blooms slowly built up over several spring-neap tidal cycles, and subsequently expanded in late spring when a strong decline of the SPM concentration during neap tide enabled a temporary “escape” of the chlorophyll concentration from the tidal mixing regime. Our results demonstrate that the tidal cycle is a major determinant of phytoplankton fluctuations at several different time scales. These findings imply that high-resolution monitoring programs are essential to capture the natural variability of phytoplankton in coastal waters. What drives fluctuations in population abundances? In the 1920s the famous zoologist Charles Elton argued that population fluctuations of many birds and mammals are most likely due to climatic fluctuations This interplay between intrinsic population processes and external forcing is exemplified by the plankton of freshwater and marine ecosystems. Theory and experiments have shown that plankton communities can display striking fluctuations, and even chaos, under constant conditions without external forcing Environmental forcing by the tidal cycle is an important driver of phytoplankton variability in coastal waters We hypothesize that these different sources of phytoplankton variability can be distinguished by investigating the time scales of phytoplankton fluctuations. For instance, phytoplankton fluctuations with a periodicity of 6 hours 12 min indicate an alternation between entrainment of sinking phytoplankton into the surface layer during high tidal current speeds and settlement of sinking phytoplankton during tidal slacks. A periodicity of 12 hours 25 min indicates changes in phytoplankton concentration due to horizontal transport of different water masses. A 24 hour periodicity would signal environmental forcing by the day-night cycle , which would be very different from the 24 hour 50 min periodicity of a mixed semidiurnal tide. At longer time scales, the spring-neap cycle and apogee-perigee cycle generate variation in the intensity of tidal mixing that could affect phytoplankton populations.Furthermore, we hypothesize that the impact of environmental forcing on phytoplankton population dynamics will depend on the relative magnitude of intrinsic population growth versus environmental forcing. For instance, settling and resuspension of phytoplankton in shallow coastal waters depends on the vertical mixing intensity generated by wind action and tidal motion To investigate these hypotheses, we analyze phytoplankton fluctuations in a high-resolution time series obtained from an automated mooring station in the coastal North Sea. The mooring measured chlorophyll fluorescence, suspended particulate matter (SPM), nitrate, salinity, temperature and irradiance at a high temporal resolution for a period of nine years. Earlier analysis of the first year of this time series showed that the phytoplankton spring bloom was initiated by an improved light availability in spring, due to a combination of enhanced solar radiation and reduced SPM concentrations We analyzed data of mooring station Warp, located in the coastal waters of the southern North Sea near the Thames Estuary . The maihttp://www.cefas.defra.gov.uk. More information on the methodology and application of SmartBuoys can be found in Kröger et al. At the mooring station an automated measuring platform, called a ‘SmartBuoy’, has been deployed from 30 November 2000 onwards, as part of the United Kingdom’s eutrophication monitoring program in situ Seapoint fluorometer measurements versus extracted chlorophyll concentrations in the water samples had a R2 of 0.86 when averaged over all monthly samples. Although chlorophyll fluorescence is a very convenient measurement technique, it is known that the fluorescence signal can be quenched when cells are exposed to high light Chlorophyll fluorescence was measured with a Seapoint fluorometer (Seapoint Inc.). Fluorescence data were calibrated against chlorophyll concentrations in water samples taken during monthly service visits to the mooring stations. Chlorophyll concentrations were measured by filtering known sample volumes through glass fiber filters  in triplicate. Pigments were immediately extracted in 90% buffered acetone and refrigerated prior to analysis. A Turner Designs Model 10AU filter fluorometer was used to measure the fluorescence of extracted chlorophyll and phaeopigment before and after acidification as described by Tett in situ Seapoint turbidity measurements versus SPM concentrations in the water samples had a R2 of 0.72 when averaged over all monthly samples.Optical backscatter was measured with a Seapoint turbidity meter (Seapoint Inc.), and converted to SPM concentration using calibration against monthly water samples. SPM concentrations in the samples were measured by filtering known sample volumes through pre-weighed 0.4 µm polycarbonate filters and subsequent rinsing with 2×50 mL ultrapure water. Filters were then dried in a desiccator at room temperature and weighed until filter weight remained constant. Calibration curves of The concentration of total oxidisable nitrogen (hereafter referred to as nitrate) was measured with a NAS-3X nutrient analyzer (EnviroTech). Salinity and temperature were measured using an FSI CT sensor . Salinity measurements were calibrated using a Guildline 8400B salinometer, which had been standardized with IAPSO standard seawater. Downwelling PAR was measured at 1 and 2 m depth using two LiCor (LI-192) underwater quantum sensors (LiCor Biosciences).The SmartBuoy measurements went through a Quality Assurance protocol within the SmartBuoy Data Management System, checking all data manually for possible sensor malfunction and biofouling. For instance, fluorescence measurements directly before each monthly service were compared with those directly after monthly service to identify signatures of biofouling. Data that looked suspect were flagged and not used in the analyses.Phytoplankton species composition at the mooring station was determined on an approximately monthly basis. Water samples (150 mL) taken at 1 m depth were preserved with 2.5 mL acidified Lugol’s solution, and analyzed by inverted microscope after 12 hours of settling in a 25-mL glass chamber Tidal data were obtained from a tide gauge at the nearby coastal station Sheerness . Inspectµmol quanta m−2 s−1), to remove possible effects of non-photochemical quenching of chlorophyll fluorescence. We analyzed the hourly averaged and daily averaged time series separately to investigate variability at different time scales.Because the sampling interval of the automated measurements varied between instruments and between years, we calculated hourly averages to obtain a more uniform dataset. We also calculated daily averages of all variables, where the chlorophyll data were confined to measurements made in the dark  to reduce the effect of small-scale variability caused by e.g. measurement noise, intermittent turbulence or local patchiness. We used these small intervals for the moving average filter to avoid smoothing out relevant periodicities of the tidal cycle. Third, we calculated the rates of change from the difference between the data values at time t and time t-Δt, where Δt represents a single time step of one hour or one day. Because we had log-transformed the data, this procedure effectively resulted in a time series of the relative rates of change (‘relative growth rates’) of the measured variables, since.We analyzed the rates of change of the data instead of their concentrations, because concentrations are the result of growth and decay processes during the preceding period whereas instantaneous rates of changes better reflect the conditions at the time of measurement.We used wavelet analysis We applied wavelet coherence, an extension of wavelet analysis, to investigate the ‘coherence’ of two time series http://www.pol.ac.uk/home/research/waveletcoherence/).The statistical significance of periodicities revealed by wavelet analysis was tested by comparing the wavelet power spectrum of our time series against the 95% confidence level of wavelet power spectra generated by red noise, using an autoregressive AR1 model with the same autocorrelation coefficient as our time series Our time series contained several data gaps. Small gaps of at most one data point were filled by linear interpolation. Larger gaps could not be filled by interpolation without affecting the results. Therefore, we calculated separate wavelet power spectra for all subsets of the time series with a sufficient number of consecutive data points. Wavelet analysis can accurately detect periodicities up to ∼25% of the length of a time series Phaeocystis). Most abundant were chain-forming diatoms , and benthic diatoms .Time series of water level, chlorophyll, SPM, nitrate, light intensity, temperature and salinity all displayed strong variability at several different time scales , S8, S9.Light intensity (PAR) at 1 m depth followed the expected seasonal pattern, but with distinct daily and biweekly variation . High liWe first analyzed the tidal data measured at station Sheerness . In lineThe spring-neap cycle is clearly visible in the time series of the tidal range . Close iWavelet analysis of the hourly-averaged chlorophyll concentration of the year 2007 reveals significant periodicities of 6 hours 12 min and 12 hours 25 min during most of the year, and an additional 24-hour periodicity in late spring and summer only . LikewisComparison with the tidal data reveals that chlorophyll concentrations consistently peaked a few hours before high tide and a few hours before low tide . The timTaking the absolute value  transforms the 12 hour 25 min periodicity of the water level to a 6 hour 12 min periodicity in tidal current speed. Indeed, the rate of change in chlorophyll concentration seems to fluctuate in phase with tidal current speed .This phase relationship can be tested by wavelet coherence analysis, which displays the coherence (colors) and phase angles (arrows) between two fluctuating time series. Bold black lines delineate areas of significant coherence. Arrows pointing to the right indicate in-phase fluctuations. This confirms that the rate of change in chlorophyll concentration fluctuated in phase with tidal current speed at a significant 6-hour periodicity . In otheIn Wavelet coherence analysis shows that the chlorophyll concentration fluctuated in phase with the tidal range  and SPM This sequence of events, where a strong decline of the SPM concentration in late April or early May was accompanied by a large spring bloom, was also observed in the years 2001, 2003, 2004 and 2008 , S8, S9.−3 of chlorophyll should contribute 100 mg m−3 of SPM. In view of the measured concentrations of chlorophyll and SPM in our time series, this implies that phytoplankton comprised less than 5% of the SPM concentration throughout the entire year, except during the spring bloom when phytoplankton increased to ∼20% of total SPM. However, during the spring bloom the phytoplankton dynamics diverged from the SPM dynamics, as the decline in SPM concentration was accompanied by a rise in chlorophyll concentration. For these reasons, the in-phase fluctuations of chlorophyll and SPM cannot be explained by the assumption that SPM consisted mostly of phytoplankton particles.Our results show that short-term fluctuations of coastal phytoplankton were dominated by periodicities of 6 hours 12 min, 12 hours 25 min, and to a lesser extent 24 hours, reflecting the typical periodicities in tidal current speed, horizontal displacement of tidal waters, and the day-night cycle, respectively. Likewise, SPM also fluctuated at 6-hour and 12-hour periodicities, in phase with the chlorophyll fluctuations. One possible explanation for the in-phase fluctuations of chlorophyll and SPM could be that SPM is largely composed of phytoplankton. We therefore estimated the relative contribution of phytoplankton to SPM. Assuming a phytoplankton biomass to carbon ratio of 2.5 Cylindrotheca, Paralia, Plagiogrammopsis), which combine a benthic and pelagic life style as they commonly settle on the sediment during weak mixing but are resuspended during intense tidal mixing Instead, we hypothesize that the 6-hour periodicity and in-phase dynamics of chlorophyll and SPM are explained by alternating sinking and vertical mixing of phytoplankton and SPM driven by the tidal cycle. Phytoplankton and SPM both have a particulate nature. Hence, surface concentrations of phytoplankton and SPM will decrease simultaneously due to sedimentation during weak turbulent mixing . Conversely, phytoplankton and SPM will increase simultaneously by resuspension during periods of intense tidal mixing generated by the high current speeds between each high and low tide. This explanation is supported by the in-phase fluctuations of the chlorophyll dynamics and tidal current speed . In fact−1−1Sinking rates of single diatom cells range from near zero to 10 m dSalinity, nitrate and temperature are not subject to sedimentation and resuspension by tidal mixing. Indeed, salinity, nitrate and temperature showed only minor 6-hour periodicity, but fluctuated predominantly at a periodicity of 12 hours 25 min. This periodicity matches the typical time scale of horizontal displacement of water masses moving back and forth by tidal motion. Horizontal transport of different water masses is further confirmed by the observation that salinity fluctuated in phase with water level, while nitrate fluctuated in anti-phase with water level at a 12-hour 25-min periodicity . This reAn additional process contributing to the 12 hour 25 min periodicity might be the vertical excursions of the SmartBuoy, which moved up and down with the water level. This could be particularly relevant in waters with strong vertical gradients of the chlorophyll and SPM concentrations in the upper meters of the water column, where the measurements are made. At station Warp, however, the upper meters of the water column are well mixed . TherefoIn summer, we also found a 24-hour periodicity in chlorophyll fluorescence, but not in SPM. The 24-hour periodicity was less pronounced than the periodicities at 6 hours 12 min and 12 hours 25 min. Wavelet analysis indicates that this 24-hour periodicity is independent of the tidal periodicity, because the peak of the global power spectrum was located at 24 hours sharp rather than at 24 hours 50 min. This day-night cycle is probably caused by non-photochemical quenching of the fluorescence signal during sunny days. Alternatively, this day-night cycle might reflect diurnal variation in convective mixing driven by thermal micro-stratification during the daytime and surface cooling at night. Van Haren et al. Superimposed upon the 6-, 12- and 24-hour periodicities the chlorophyll concentration also fluctuated at a significant 15-day periodicity, in phase with the spring-neap tidal cycle. A possible explanation for the 15-day periodicity in phytoplankton abundance is that the spring-neap cycle modulated the nutrient supply. This mechanism was described by Sharples et al. 2. Hence, the chlorophyll and SPM fluctuations observed at the time scale of the spring-neap cycle will probably not represent small-scale processes restricted to the local neighborhood of station Warp, but may integrate sedimentation and resuspension over a large area. The 15-day periodicity of the SPM concentration confirms recent spectral analyses of remote sensing data of the North Sea, which indicated spring-neap variations in SPM in the East Anglia plume and Rhine plume Instead, the in-phase fluctuations of both chlorophyll and SPM with the tidal range suggest that a large fraction of the phytoplankton and SPM sinks to the sediment or deeper water layers during calm conditions at neap tide, while they are resuspended by strong tidal mixing during spring tide. Station Warp is part of a large shallow outer estuary of more than 100 kmEarlier analysis indicated that the spring bloom at our coastal mooring site is triggered by improved light conditions due to a combination of enhanced solar radiation and reduced SPM concentrations in spring What caused the conspicuous decline of the SPM concentration in mid spring? It might be induced by a strong reduction in tidal range, weakening tidal mixing and thereby enhancing sedimentation of SPM. For instance, the strong SPM decline in early May 2007 occurred when spring tide coincided with apogee of the moon, resulting in a weak spring tide . LikewisThe phytoplankton spring bloom resulted in rapid depletion of inorganic nutrients, which was followed by lower phytoplankton concentrations during the remainder of the summer. This classic pattern was also observed in the earlier study of Weston et al. Prorocentrum micans and Peridinium trochoideum) aggregated near the water surface during slack water, while they became homogeneously distributed when tidal mixing intensified. Conversely, large pelagic diatoms (Coscinodiscus spp.) relied on enhanced turbulent mixing during ebb and flood currents to prevent sinking from the photic zone. In view of these studies, it seems quite plausible that the 6-hour periodicity in chlorophyll concentration observed in our tidal system may also be accompanied by a concomitant 6-hour periodicity in phytoplankton species composition, due to species-specific differences in vertical dispersal by the tidal cycle.Temporal variation in turbulent mixing may result in temporal variation in the phytoplankton community. For instance, Huisman et al. According to the intermediate disturbance hypothesis, biodiversity will be highest in ecosystems exposed to intermediate frequencies of environmental forcing The superposition of several periodic fluctuations in chlorophyll concentration and phytoplankton species composition are a challenge for the design of marine monitoring strategies. Measurements taken at fixed time intervals that are not commensurate with the natural frequencies of the tidal cycle may introduce structural biases in monitoring data. For instance, the semidiurnal tidal cycle takes slightly longer than 12 hours. Hence, if measurements are taken, say, once every day at noon, this may erroneously suggest large changes in phytoplankton concentration over a period of several days, while these data simply represent different phases of the semidiurnal tidal cycle. Likewise, the spring-neap cycle takes slightly longer than 14 days. Hence, if a water body is sampled once every two weeks, then the data may erroneously suggest large changes in phytoplankton concentration and phytoplankton species composition over a period of several months, while these data actually reflect different phases of the spring-neap cycle. To avoid such structural biases, the temporal resolution of the measurements should be sufficiently refined to capture the periodicities in the system. In practice, this implies that chlorophyll concentrations should be measured at minimum time intervals of ∼1 hour to capture the semidiurnal tidal cycle. Alternatively, if resources are limited, one might consider measuring less frequently but always at the same moments with respect to both the semidiurnal and spring-neap tidal cycle. In those marine ecosystems where the tidal cycle is a key determinant of chlorophyll variability, it will be difficult to make sense of phytoplankton data obtained from low-frequency sampling programs ignoring the tidal periodicities.Our results show that careful investigation of the time scales of population fluctuations in relation to environmental forcing can reveal much information on the underlying processes. We found that phytoplankton fluctuations in the southern North Sea reflect different oscillatory modes of the tidal cycle, including variation in tidal current speeds (6 hours 12 min), horizontal water motion (12 hours 25 min) and the spring-neap tidal cycle (15 days). A weaker 24-hour periodicity was also observed. During most of the year, chlorophyll and SPM concentrations fluctuated in phase with the tidal cyle, indicative of alternating periods of sedimentation and resuspension. However, phytoplankton escaped from the spring-neap tidal cycle in spring, when a strong decline in SPM concentration led to improved light conditions. Hence, fluctuations of coastal phytoplankton were strongly driven by external forcing, but intrinsic population processes took over when growth rates were high during the spring bloom. Our findings illustrate that high-resolution monitoring is required to capture this natural variability, which is considered an essential first step for the reliable detection and prediction of the long-term response of coastal phytoplankton to changing environmental conditions.Figure S1Contour plots of water density. The contour plots are based on CTD profiles taken during service visits to the Smartbuoy from August 2004 to July 2006.(TIF)Click here for additional data file.Figure S2Time series measured in 2001. (A) Water level (red line) and tidal range (blue solid line) at station Sheerness. When tidal data at station Sheerness were missing, we show the tidal range at station K13A (blue dashed line) rescaled to match the tidal range at Sheerness. (B) Chlorophyll concentration (green) and SPM concentration (black). (C) Nitrate concentration (dark purple) and light intensity at 1 m depth (pink). (D) Salinity (blue) and water temperature (red). In (B-D), dots show the hourly averages and lines the daily averages.(TIF)Click here for additional data file.Figure S3Time series measured in 2002. (A) Water level (red line) and tidal range (blue solid line) at station Sheerness. When tidal data at station Sheerness were missing, we show the tidal range at station K13A (blue dashed line) rescaled to match the tidal range at Sheerness. (B) Chlorophyll concentration (green) and SPM concentration (black). (C) Nitrate concentration (dark purple) and light intensity at 1 m depth (pink). (D) Salinity (blue) and water temperature (red). In (B-D), dots show the hourly averages and lines the daily averages.(TIF)Click here for additional data file.Figure S4Time series measured in 2003. (A) Water level (red line) and tidal range (blue solid line) at station Sheerness. (B) Chlorophyll concentration (green) and SPM concentration (black). (C) Nitrate concentration (dark purple) and light intensity at 1 m depth (pink). (D) Salinity (blue) and water temperature (red). In (B-D), dots show the hourly averages and lines the daily averages.(TIF)Click here for additional data file.Figure S5Time series measured in 2004. (A) Water level (red line) and tidal range (blue solid line) at station Sheerness. (B) Chlorophyll concentration (green) and SPM concentration (black). (C) Nitrate concentration (dark purple) and light intensity at 1 m depth (pink). (D) Salinity (blue) and water temperature (red). In (B-D), dots show the hourly averages and lines the daily averages.(TIF)Click here for additional data file.Figure S6Time series measured in 2005. (A) Water level (red line) and tidal range (blue solid line) at station Sheerness. (B) Chlorophyll concentration (green) and SPM concentration (black). (C) Nitrate concentration (dark purple) and light intensity at 1 m depth (pink). (D) Salinity (blue) and water temperature (red). In (B-D), dots show the hourly averages and lines the daily averages.(TIF)Click here for additional data file.Figure S7Time series measured in 2006. (A) Water level (red line) and tidal range (blue solid line) at station Sheerness. When tidal data at station Sheerness were missing, we show the tidal range at station K13A (blue dashed line) rescaled to match the tidal range at Sheerness. (B) Chlorophyll concentration (green) and SPM concentration (black). (C) Nitrate concentration (dark purple) and light intensity at 1 m depth (pink). (D) Salinity (blue) and water temperature (red). In (B-D), dots show the hourly averages and lines the daily averages.(TIF)Click here for additional data file.Figure S8Time series measured in 2008. (A) Water level (red line) and tidal range (blue solid line) at station Sheerness. When tidal data at station Sheerness were missing, we show the tidal range at station K13A (blue dashed line) rescaled to match the tidal range at Sheerness. (B) Chlorophyll concentration (green) and SPM concentration (black). (C) Nitrate concentration (dark purple) and light intensity at 1 m depth (pink). (D) Salinity (blue) and water temperature (red). In (B-D), dots show the hourly averages and lines the daily averages.(TIF)Click here for additional data file.Figure S9Time series measured in 2009. (A) Water level (red line) and tidal range (blue solid line) at station Sheerness. When tidal data at station Sheerness were missing, we show the tidal range at station K13A (blue dashed line) rescaled to match the tidal range at Sheerness. (B) Chlorophyll concentration (green) and SPM concentration (black). (C) Nitrate concentration (dark purple) and light intensity at 1 m depth (pink). (D) Salinity (blue) and water temperature (red). In (B-D), dots show the hourly averages and lines the daily averages.(TIF)Click here for additional data file.Figure S10Coherence between fluctuations in light attenuation and SPM on a daily time scale. (A) Time series of the light attenuation coefficient Kd (pink line) and SPM concentration (black line) using daily averaged data of spring 2005. Kd is calculated from PAR measurements at 1 m and 2 m depth. (B) Wavelet coherence spectrum of the two time series in panel A. Color coding indicates the coherence of the two time series. Arrows indicate the phase angle between fluctuations of the two time series. See the legend of (TIF)Click here for additional data file.Figure S11Coherence between fluctuations in water level, salinity and nitrate on an hourly time scale. (A) Time series of water level (red line) and salinity (blue line) on an hourly time scale during 8 days in winter 2007. (B) Wavelet coherence spectrum of the two time series in panel A. Color coding indicates the coherence of the two time series. Arrows indicate the phase angle between fluctuations of the two time series. See the legend of (TIF)Click here for additional data file.Figure S12Coherence between fluctuations in nitrate concentration, tidal range and salinity on a daily time scale. (A) Time series of nitrate concentration (thick purple line) and tidal range (thin blue line) on a daily time scale during spring of 2007. (B) Wavelet coherence spectrum of the two time series in panel A. Color coding indicates the coherence of the two time series. Arrows indicate the phase angle between fluctuations of the two time series. See the legend of (TIF)Click here for additional data file.


The aim of the present study was to evaluate the long term follow-up of patients enrolled in the Italian Registry of cryopirin associated periodic sindrome (CAPS).The Italian CAPS Registry started in 2004 and has currently enrolled 29 patients: 16 with Chronic Infantile Neurologic Cutaneous Articular Syndrome (CINCAs), 8 with Muckles Welles syndrome (MWS) and 5 with Familial Cold Urticaria (FCU). 16 patients were treated with Anakinra (IL-1 receptor antagonist) at 1 mg/kg/day. The Child Health Questionnaire (CHQ-PF 50) was used to assess the health related quality of life.Rapid clinical and laboratory improvement was observed in all patients, but six patients who declined treatment and experienced progressive course of the disease. All the treated patients maintained persistent remission; 5 patients required an increase of the dosage to 300 mg per day. No adverse effects were recorded except injection site reactions.Until today, 8 of the 16 patients initially treated with Anakinra have subsequently switched to Canakinumab  at the initial dose of 150 mg every 8 weeks.IL-1 inhibition seems to be crucial in modifying the natural history of CAPS. Long-term follow up of patients treated with Anakinra established its efficacy and tolerability. The same evaluation will be done for Canakinumab, that appears to be equally effective but whose side effects still need to be evaluated. The bimonthly administration of Canakinumab may be certainly useful, especially in pediatric population, however its long half-life implies a tight surveilance in case of infections.


The objective of this study was to systematically review the medical literature for the prevalence of waterpipe tobacco use among the general and specific populations.We electronically searched MEDLINE, EMBASE, and the ISI the Web of Science. We selected studies using a two-stage duplicate and independent screening process. We included cohort studies and cross sectional studies assessing the prevalence of use of waterpipe in either the general population or a specific population of interest. Two reviewers used a standardized and pilot tested form to collect data from each eligible study using a duplicate and independent screening process. We stratified the data analysis by country and by age group. The study was not restricted to a specific context.Of a total of 38 studies, only 4 were national surveys; the rest assessed specific populations. The highest prevalence of current waterpipe smoking was among school students across countries: the United States, especially among Arab Americans (12%-15%) the Arabic Gulf region (9%-16%), Estonia (21%), and Lebanon (25%). Similarly, the prevalence of current waterpipe smoking among university students was high in the Arabic Gulf region (6%), the United Kingdom (8%), the United States (10%), Syria (15%), Lebanon (28%), and Pakistan (33%). The prevalence of current waterpipe smoking among adults was the following: Pakistan (6%), Arabic Gulf region (4%-12%), Australia (11% in Arab speaking adults), Syria (9%-12%), and Lebanon (15%). Group waterpipe smoking was high in Lebanon (5%), and Egypt (11%-15%). In Lebanon, 5%-6% pregnant women reported smoking waterpipe during pregnancy. The studies were all cross-sectional and varied by how they reported waterpipe smoking.While very few national surveys have been conducted, the prevalence of waterpipe smoking appears to be alarmingly high among school students and university students in Middle Eastern countries and among groups of Middle Eastern descent in Western countries. Tobacco smoking using waterpipe - also known as narguileh, hookah and shisha - is traditional to region of the Middle East Figure 1]. The . The 1].A recent systematic review found that waterpipe tobacco smoking was significantly associated with lung cancer, respiratory illness, low birth weight and periodontal disease . An assoRecent studies have reported relatively high prevalence rates of waterpipe tobacco smoking in Middle Eastern countries, but alsoThe primary objective of our study was to systematically review the medical literature for the prevalence of waterpipe tobacco use among the general population as well as specific populations. A secondary objective was to identify the factors associated with waterpipe tobacco use.No protocol for this review has been published.Inclusion criteria were:• Cohort studies and cross sectional studies• Assessment of the prevalence of use of waterpipe for the purpose of tobacco smoking.• The target population is either the general population or a specific population of interest such as high school students, university students, and pregnant women.• Prevalence of waterpipe smoking reported separately from the prevalence of other forms of smokingExclusion criteria were:• Convenience sampling• Sampling methodology did not clearly lead to a representative sample of the target population .• No measure of prevalenceWe electronically searched the following databases in June 2008, MEDLINE (1950 onwards), EMBASE (1980 onwards), and ISI the Web of Science using no language restrictions. The search strategy was based on related systematic review, a reviewTwo reviewers independently screened the title and abstract of identified citations for potential eligibility. They then used a standardized and pilot-tested form to independently screen the full texts of citations judged potentially eligible by at least one reviewer. They resolved disagreements by discussion or using an arbitrator.Two reviewers used a standardized and pilot-tested form to independently abstract data and resolved disagreements by discussion or using an arbitrator. Abstracted data related to the following:• Study methodology: sampling frame, sampling method, recruitment method, and administration method• Methodological quality: sample size calculation, validity of tool, pilot testing, and response rate• Population: country, target population, setting (location and time period), and numbers sampled, participated, and analyzed• Results including prevalence results  of waterpipe only smoking, waterpipe smoking (regardless of other tobacco products use), cigarette smoking, and factors significantly associated with waterpipe smoking.We calculated the kappa statistic to evaluate the agreement in assessing full texts for eligibility. We stratified data analysis by country and age group. We present the results by the region of the world.Figure The studies varied by whether they reported the prevalence of waterpipe only smokers (n = 5), all waterpipe smokers (n = 37) , and by the types of measure of waterpipe smoking: ever smoker (n = 16), current smoker (n = 34), and regular smoker (n = 3). Five studies reported on group waterpipe smoking while 35 studies reported on individual smoking.Ten studies reported sample size calculation. The instruments used to measure waterpipe use were: self developed instrument with no validation reported (n = 15); self developed instrument based on previously validated instruments, with no validation of the new instrument reported (n = 7); self developed validated instrument (n = 1); previously developed instrument with no validation reported (n = 1); previously validated instrument that measured "forms of smoked tobacco products other than cigarettes" which the authors assumed to be waterpipe smoking (n = 1) and not reported (n = 13). Fifteen studies reported pilot testing the measurement instrument. Twenty-nine studies reported response rate that varied from 18% to 62% for online administered surveys, 46% to 100% for paper-based surveys, and 70% for telephone survey.Additional file two studies of intermediate and secondary school students in Lebanon reported 25% current and 65%-66% ever waterpipe smoking ,,46-48 th%-15%,,46Our findings are consistent with national surveys conducted by the WHO and the Global Youth Tobacco Survey (GYTS) in a number of countries  and the type(s) of measure of waterpipe smoking .The authors declare that they have no competing interests.EAA contributed to drafting the protocol, designing the search strategy, developing the forms, screening, data abstraction, data analysis, and drafting of the manuscript. SKG contributed to data abstraction, data analysis, and drafting of the manuscript. RO and SA contributed to data abstraction. PAJ and RH contributed to screening. JI contributed to drafting the protocol and designing the search strategy. All authors revised the article critically for important intellectual content and approved its final version. All authors had full access to all of the data  in the study and can take responsibility for the integrity of the data and the accuracy of the data analysis. EAA is the guarantor. All authors read and approved the final draft.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2458/11/244/prepubElectronic search strategies. Provides the detailed search strategies used in the systematic reviewClick here for fileExcluded studies. Provides a list of excluded studies and the reason for their exclusionClick here for fileTables describing the characteristics of included studies measuring waterpipe smoking prevalence by world region. Provides tables describing the characteristics of included studies measuring waterpipe smoking prevalence by world regionClick here for fileResults of the Global Youth Tobacco Survey (GYTS) and World Health Organization (WHO) surveys. Provides the prevalence of waterpipe smoking in the GYTS and WHO surveysClick here for file


Superficial siderosis (SS) is a rare disease which affects people in all ages and both sexes, but three times more in men. Pathological etiology is deposition of hemosiderin (a product of the breakdown of blood) in leptomeninges, subpial layer, ependymal surface and other parts of central nervous system (CNS) and typically leads to neurological dysfunction and progressive irreversible signs and symptoms. We present a 33-year-old man with complete deafness in left ear, partial hearing loss in right ear, gait imbalance, bilateral frontotemporal throbbing headache and anosmia resulted from superficial siderosis. His familial history was noncontributory.Neurological examination revealed a good alert patient with no evidence of cognitive impairment, horizontal nystagmus in both eyes with normal saccade and pursuit, normal force and tone of muscle with decreased light touch and pin prink with stocks and gloves pattern, severe dysmetria and moderate dysdiadochokinesia, generalized hyperreflexia, bilateral equivocal plantar reflexes, and ataxic gait with impossibility to perform tandem gait.Audiogram showed bilateral, high-frequency sensorineural hearing loss especially in left side.Magnetic resonance imaging (MRI) findings are shown in 2 It was first described in 1908 by Hamill; but with no access to modern technology and MRI, the only diagnostic way was biopsy.2 Using the results of 270 reported cases of SS in articles from 1908 to 2006 revealed different causes for this disease;2 some of the most frequent ones are Idiopathic (35%), head or neck trauma (13%), AVM (9%), current CNS tumor (15%), previously resected CNS tumor (6%), post CNS surgery (non-tumor) (7%), amyloid angiopathy (3%), brachial plexus injury (6%), and other cause of subarachnoid hemorrhage (6%).5 The probable cause in the presented case was recurrent head trauma in his childhood.Superficial siderosis (SS) is a rare disease affects people in all ages and both sexes but three times more in men.4 and as the result of these depositions and central nervous system involvement; there are progressive, irreversible clinical manifestations of the disease; the most common one is sensorineural hearing loss which over a period of 1 to 12 years progresses to total deafness.2 In our case, hearing loss and loss of sense of smell began at the age of 20 and over 13 years developed to complete deafness and anosmia. The second most common sign is gait imbalance and ataxia which was also in our case a remarkable, slowly progressive problem.After breaking down of erythrocytes or red blood cells exiting in CSF and CNS, hemoglobin and iron-containing heme are released in CSF and in response to this upsurge in heme levels, Bergmann glia and microglia cells produce heme oxygenase-I enzyme which breaks down free heme into biliverdin, carbon monoxide and iron. The deposition of iron in cerebral tissue is the main pathology of superficial siderosis2 The largest review of the literature to date, reported that patients presented with bilateral SNHL (95%), ataxia (88%), and pyramidal tract signs (46%);6 cerebellar dysarthria is common and nystagmus may be present.7 But, sensory symptoms or a sensory level are uncommon.8Using the result of 270 reported cases of SS, the most common features of the disease are hearing loss (81%), ataxia (81%), myelopathy (53%), urinary problems (14%), headache (14%), anosmia (14%), diplopia (4%), bowel problems (3%), and cranial nerve palsies (2%).2 and optic or trigeminal neuropathy9 also are uncommon but have been reported. In approximately one third of the cases in an earlier literature review,2 severe recurrent headaches which were indicative for symptomatic subarachnoid hemorrhage were reported; but was infrequent in recent large studies.10Extraocular nerve palsies11The first step for early detection of SS is via MRI which shows iron depositions in affected tissues as a hypointense band, and characteristic rim of intensity appearing on the cerebellum, with no enhancement These signal loss areas in T2-weighted scans are pathognomonic for the disease, but hyperintense rime is also rarely seen.11 Iron or copper chelators and steroids are other treatments but with little success.12 In one study, using oral deferiprone (a lipid-soluble iron chelator with ability to cross the blood-brain barrier) at a dose of 30 mg/kg per day has been caused reduction of hemosiderin deposition in MRI;13 and the usage of trientine also has been reported to reduce iron concentration in CSF.14There is no successful or specific treatment for SS. With early detection of source of bleeding, the surgery may be helpful.In conclusion, according to our literature review, SS with CNS involvement is a rare disorder which formed because of the deposition of hemosiderin in leptomeninges, subpial layer, ependymal surface and other parts of CNS and leads to neurological dysfunction and progressive irreversible signs and symptoms. In our case, hearing loss and loss of sense of smell began at age of 20 and over 13 years developed to complete deafness and anosmia. There is no successful or specific treatment for SS but Iron or copper chelators and steroids are some treatments with little success.


Identification of the genetic differences between the two lesions may assist in identifying genes that promote the invasive phenotype. To annotate these alterations we analysed 21 breast tumours containing synchronous areas of DCIS and IDC. Tumour cells were microdissected from FFPE tissue and analysed by 300K Molecular Inversion Probe (MIP) copy number arrays. Matched IDC and DCIS showed highly similar copy number profiles (average of 83% of the genome shared). Four regions of loss  and four regions of gain  were recurrently affected in IDC but not in the matching DCIS. CCND1 and MYC showed increased amplitude of gain in IDC. One region of loss (17p11.2) was specific to DCIS. Our data shows that DCIS is an advanced pre-invasive tumour with genetic instability and continues to evolve in parallel with co-existing IDC. In the IDC-specific regions of genomic alteration we have identified novel loci as well as genes with previous links to breast cancer progression.Ductal carcinoma


Methods. A secondary school having girl students in the age group of 12–15 years studying in sixth to ninth standard was selected. Serum ferritin concentration was estimated by ELISA. For assessing the cognitive function mathematics score, one multi-component test for memory, attention and verbal learning and Intelligent Quotient scores of the students were used. Results. Scholastic Performance, IQ and Scores of Mental balance, Attention & Concentration, Verbal Memory and Recognition were decreased in iron deficient girls, both anemic and non anemic as compared to the non iron deficient girls.Iron deficiency anemia is most common nutritional deficiency disorder in India and remains a formidable health challenge. Girls in the period of later school age and early adolescence are prone to develop iron deficiency. Iron deficiency leads to many non-hematological disturbances which include growth and development, depressed immune function in infants; reduces physical work capacity; decreases the cognitive function in both infants and adolescents. Present study was done to know the prevalence of iron deficiency in both the anemic and non anemic school going adolescent girls, to assess the effect of iron deficiency on cognitive functions in anemic iron deficient and non-anemic iron deficient school girls in a village school situated in central India.  Iron deficiency is the third greatest global health risk after obesity and unsafe sex . Anemia Iron deficiency has both physiologic and pathologic causes. Physiologic causes relate to the greater iron demands during periods of growth and development whereas pathologic causes refer to iron losses secondary to a chronic medical condition. In general, iron deficiency results when iron demands by the body are not met by iron absorption. Thus, iron deficiency can result from inadequate intake, impaired absorption, increased requirements, and chronic blood loss.More than half of the world's undernourished population lives in India  and halfIron deficiency is a systemic condition which has many non ematological consequences, which occurs in relation to its severity, like decreased physical work capacity , decreasIn present study, effort has been made to assess the effect of iron deficiency on cognitive functions in anemic iron deficient and in nonanemic iron deficient school going adolescent girls in a village school.The present study was carried out in the Department of Pathology, MGIMS, Sevagram, India from July 2007 to September 2009. Approval was obtained from the Institutional Ethics Committee for the study.A secondary school in the neighborhood, having girl students in the age group of 12−15 years studying in sixth to ninth standard was selected. Necessary permission was taken from the school authority and girls were explained in detail about the study in the school assembly. Participation in the screening programme was voluntary. An explanatory letter and consent form was given to all the girls. Written consent was obtained from parents or guardian for participation in the screening as all participants were minor. Participants completed a questionnaire asking for significant family, medical and menstrual history, parent education, and their dietary habits.Screening for anemia and iron deficiency was done by (1) complete blood count: done by automatic cell counter, that is, Coulter for hemoglobin concentration. (2) estimation of serum ferritin concentration was done by ELISA. For this recommended protocol by the kit used was followed. Established age adjusted values for hemoglobin and serum ferritin were used.Group I—participants who were anemic (Hb < 12 gm%) and iron deficient (serum ferritin less than 12 μg/L).Group II—participants who were nonanemic (Hb ≥ 12 gm%) and iron deficient (serum ferritin less than 12 μg/L).Group III—participants who were nonanemic (Hb ≥ 12 gm%) and noniron deficient (serum ferritin levels of 12 μg/L or more).The participants after screening were divided into three groups.After dividing the participants into three groups, that is, anemic iron deficient (group I), nonanemic iron deficient (group II), and nonanemic noniron deficient (group III), for assessing the cognitive function mathematics score, one multicomponent test for memory, attention and verbal learning, and intelligent quotient (IQ) scores of the students was used.For assessment of scholastic performance, the mathematics score obtained in the final term examination was noted from the report card. The score obtained were from total 100 marks.Multicomponent test of the three groups was assessed after randomization by using PGI test—(Dr. N. N. Wig & Dr. Dwarka Prasad) for testing memory attention and verbal learning  Both parPGI test—(Dr. N. N. Wig & Dr. Dwarka Prasad), consisted of the following ten subtests: (I) remote memory, (II) recent memory, (III) mental balance, (IV) attention and concentration, (V) delayed recall, (VI) immediate memory, and (VII) verbal retention for similar pairs, (VIII) verbal retention with dissimilar pairs, (IX) visual retention, and (X) recognition.For assessing the intelligent quotient of the girl student's, Bhatia battery performance test—(Dr. C. M. Bhatia) for intelligent quotient (I.Q) was used, which includes two subtest Kohl's block design and Pass along test .Statistical analysis: the data was analyzed with SPSS (version 16) statistical software. One-way ANOVAs test 63 of 100 girl students had hemoglobin levels less than 12 gm% and 37 had hemoglobin levels above 12 gm%. Thus, prevalence of anemia in school going adolescent girls was 63%. The overall mean hemoglobin in the study was 11.66 ± 1.27 g/dL.Out of the 63 girl students who had anemia, 56 girls (56%) had Hb values between 10 and 12 gm%, 5 girls (5%) had Hb values between 7 and 10 gm%, and rest of the 2 girls (2%) had Hb values below 7 gm%. Thus, mild anemia (Hb 10–12 gm%) was present in 56% of the study subjects, moderate anemia (Hb 7–10 gm%) in 5%, and severe anemia (Hb < 7 gm%) was present in only 2% of the study subjects.μg/L). So the prevalence of iron deficiency was 67%.Serum ferritin was done in 100 girl students between the age group of 12−15 years, 67 were iron deficient  between nonanemic noniron deficient (group III) and anemic iron deficient (group I), it was significant  between nonanemic noniron deficient (group III) and nonanemic iron deficient (group II).The difference in mathematics score was highly significant (Multicomponent test (MCT) of verbal learning, attention, memory and IQ scores of all the three groups was assessed after randomization. Tests were administered under the guidance of trained research assistant of the Department of Psychological Medicine. The person who was assessing the tests was unaware of the group assignment.P value < 0.0001) and also the scores of mental balance differed significantly  between the nonanemic noniron deficient (group III) and nonanemic iron deficient (group II). The difference in scores of attention and concentration was significant  between non anemic noniron deficient (group III) and anemic iron deficient (group I). And the nonanemic iron deficient (group II) and nonanemic noniron deficient (group III) also showed statistically significant  difference in scores of attention and concentration.The difference in scores of mental balance between the nonanemic noniron deficient (group III) and anemic iron deficient (group I) was significant , and on comparing the scores of Verbal Retention for Similar Pairs between the non-anemic iron deficient (group II) and non anemic non iron deficient (group III) the difference was also statistically significant .Non anemic non iron deficient (group III) and anemic iron deficient (group I) when compared for scores of Verbal Retention for Similar Pairs showed significant difference  and also between the nonanemic iron deficient (group II) and nonanemic noniron deficient (group III) showed statistically significant difference .The difference in scores of verbal retention for dissimilar pairs between the anemic iron deficient (group I) and nonanemic iron deficient (group III) was statistically significant , similarly the difference in scores of recognition between the nonanemic iron deficient (group II) and nonanemic iron deficient (group III) were statistically significant .The scores of recognition between the anemic iron deficient (group I) and nonanemic iron deficient (group III) showed significant difference (For assessing the intelligent quotient (IQ) of the girl students two test, that is, Kohl's block design test and Pass along test were used. After obtaining the test quotient (TQ) from these two tests the IQ was calculated.P value < 0.0001 and also between nonanemic noniron deficient (group III) and nonanemic iron deficient (group II) .The IQ levels differed significantly between nonanemic noniron deficient (group III) and anemic iron deficient (group I) with Thus, the cognitive function scores which included the mathematics score, multicomponent test scores, and IQ scores were less in iron deficient both anemic and nonanemic groups (group I and II) than the noniron deficient nonanemic group (group III).Although all the features of cognition are important but verbal learning and attention and concentration along with memory are particularly more important for academic performance.In present study, iron deficient both anemic and nonanemic students had scored less in mathematics than the normal non iron deficient students. This is in accordance to the study done by Prestonjee  wherein Multicomponent test of verbal learning, attention, and memory of all the three groups was assessed after randomization. The overall total score was less in iron deficient both anemic and nonanemic groups than noniron deficient nonanemic group.Similar findings were also seen in scores of mental balance and verbal retention for similar and dissimilar pairs. There was no difference in score of recent and remote memory, delayed and immediate recall, and visual retention subsets between iron deficient (group I and II) and noniron deficient (group III).The findings suggest that iron deficiency, even in the absence of anemia causes decrease in at least some aspect of cognitive functioning.The present findings are in accordance with the findings of a randomized trial done by Bruner et al.  on nonanThe difference of mean IQ scores between iron deficient both anemic and nonanemic groups (I and II) and nonanemic noniron deficient was statistically significant.Pollitt et al. , SoemantThe findings of the present study are iron deficient school going adolescent females both anemic and nonanemic had low scholastic performance in the form of low mathematics score and low scores in verbal learning, attention, mental balance, and recognition component of multicomponent test along with low IQ scores than their noniron deficient comparers. Iron deficiency independently leads to decreased cognitive scores. Iron deficiency without anemia is the initial stage and as the iron deficiency increases anemia manifests. The cognitive scores were lowest in the iron deficient anemic (group I). In iron deficient without anemia it was slightly more than group I but much less than group III, that is, nonanemic noniron deficient subjects. Prevalence of anemia was 63% while prevalence of iron deficiency anemia in present study was 50%.There is need to initiate programme for supplementation of iron and folic acid to school going adolescent girls for the prevention of hematological and nonhematological consequences of iron deficiency with government and private organizational efforts.


To the Editor: Approximately 3,000 cases of tickborne encephalitis virus (TBEV) disease are registered annually in Europe , aseptic meningitis (3 cases), encephalitis (2 cases), meningoencephalitis (8 cases), and meningoencephalomyelitis (3 cases) (,During the past 20 years, TBEV has reemerged in several European areas that had been disease free (The implementation of a regional active surveillance system allows the highest sensitivity in assessing the epidemiologic features of TBEV infections, which are characterized by highly disease-endemic microfoci in areas free of the problem (


Down syndrome includes learning and memory deficits in all cases, as well as many other features which vary in penetrance and expressivity in different people. While Down syndrome clearly has a genetic cause - the extra dose of genes on chromosome 21 - we do not know which genes are important for which aspects of the syndrome, which biochemical pathways are disrupted, or, generally how design therapies to ameliorate the effects of these disruptions. Recently, with new insights gained from studying mouse models of Down syndrome, specific genes and pathways are being shown to be involved in the pathogenesis of the disorder. This is opening the way for exciting new studies of potential therapeutics for aspects of Down syndrome, particularly the learning and memory deficits.Chromosome copy number aberrations, anueploidies, are common in the human population but generally lethal. However, trisomy of human chromosome 21 is compatible with life and people born with this form of aneuploidy manifest the features of Down syndrome, named after Langdon Down who was a 19 Down Syndrome (DS) is the consequence of trisomy of human chromosome 21 (Hsa21) and is the most common genetic form of intellectual disability, occurring in approximately 1 in 700 live birthsThe additional copy of Hsa21 results in elevated expression of many of the genes encoded on this chromosome, with varying expression levels in different tissuesMouse models of DS are instrumental in identifying which genes contribute to DS phenotypes, and unraveling the mechanisms by which these phenotypes ariseIn this review, we highlight recent developments in understanding how overexpression of Hsa21 genes leads to many of the features of DS. We focus on key areas including brain, heart and cancer, as these are currently the most developed in our understanding of the molecular pathogenesis of DS.People with DS have learning and memory problems and exhibit differences in brain structure compared to the euploid populationdual-specificity tyrosine- (Y)-phosphorylation-regulated kinase 1A (Dyrk1A), potassium inwardly-rectifying channel, subfamily J, member 6 Gene (Girk2) and single-minded homologue 2 (Sim2), cause alterations in dendritic spine morphology and deficits in some behavioural testsAbcg1-U2af1) found on the Hsa21 sub-telomeric region in Ts1Yah mice  and SIM2dopey family member 2 (DOPEY2)Down syndrome cell adhesion molecule (DSCAM)The over-expression of a number of Hsa21 genes has been implicated in learning and memory deficits in single gene transgenic mouse models, suggesting that trisomy of these genes may contribute to learning disability in DS individuals. These genes include Fig.1), suggesting that this trisomic segment contains the causal dosage-sensitive genes for these detrimental developmental phenotypesNeurodevelopment is known to be altered in people with DS. Already by mid-gestation the brains of fetuses with DS are smaller than those which do not have the condition. Cerebellar granule cells in Ts65Dn mice have reduced proliferation rates and elongation of the cell cycle length which could potentially result in a decrease in brain massElevated rates of neuronal apoptosis related to oxidative stress have been reported in DSRecently, it was proposed that DYRK1A contributes to DS neural phenotypes, such as impaired dendritic growth, by disturbing neuron-restrictive silencer factor (REST/NRSF) levelsThis is a relatively new area of research in DS that is rapidly gaining momentum, and which arises from experiments carried out in mouse models in which behavioural, neurophysiological and cellular biology changes can be quantitatively assessed during development and ageing, and then modified through pharmacological intervention.Several pharmacological interventions to enhance cognition in people with DS have been suggested, based upon efficacy in the Ts65Dn mouse  occurs in people with DS, with 30-70% of DS individuals developing dementia by the age of 60APPAPP expression is also linked to enlargement of early endosomesdap160/ITSN1 (intersectin1), synj/SYNJ1 and nla/RCAN1 (runt-related tremscripthon factor 1), results in abnormal synaptic morphology and impaired vesicle recyclingNeurodegenerative phenotypes have also been observed in animal models of DSOther Hsa21 trisomic genes may also contribute to AD through different mechanisms. DYRK1A, an Hsa21 encoded kinase, phosphorylates Tau at a key priming site which may mediate its AD-related hyperphosphorylation in people with DSSix percent of children and adolescents with DS have epileptic seizuresPeople with DS have been reported to experience disturbed sleeping patterns. Studies of circadian activity in the Ts65Dn mouse model have reported conflicting results of both intactGATA binding protein 1 (GATA1) gene resulting in the synthesis of a truncated GATA1 protein termed GATA1sv-ets erythroblastosis virus E26 oncogene homolog (ERG), is required for development of the myeloproliferation defect in the Ts65Dn modelrunt-related transcription factor 1 (RUNX1) has also been proposed to regulate hematopoiesis via the phosphoinositide 3 (PI3)-kinase/AKT pathwayChildren with DS have a greatly elevated risk of developing the otherwise very rare transient myeloproliferative disorder (TMD), as well as acute megakaryocytic leukemia (AMKL) and acute lymphoblastic leukemia (ALL)Despite perturbations of hematopoietic development in the Ts1Cje, Ts65Dn and Tc1 models of DS, these mice do not develop leukaemia, even when the trisomic models also express disease-associated GATA1 mutationsmin, with mouse models of DS resulted in reduced formation of tumors, dependent on the trisomy of the Hsa21-encoded ETS2 generegulator of calcineurin (RCAN1), was shown to be sufficient to suppress tumour growth by attenuating angiogenesis via the regulation of vascular endothelial growth factor (VEGF) signalingRcan1 did not completely abrogate the effect of trisomy on tumour formation, suggesting that other Hsa21 genes also contribute to this phenotypeAlthough DS is associated with a predisposition to leukemia, people with DS have a reduced risk of developing most solid tumourscysteine-rich with EGF-like domains 1(CRELD1), a non-Hsa21 gene, contribute to the occurrence of AVSD in DSDSCAM- ZNF295 (zinc finger protein 295)] of Hsa21 may be sufficient for the development of CHDCongenital heart defects (CHD) are prevalent in 40% of children with DS and over 50% of all atrioventricular septal heart defects (AVSDs) in infancy are attributed to trisomy Hsa21DS is complex disorder and dissecting the genetic and molecular processes underlying the syndrome requires many different complementary approaches, including the study of human data and mouse and other model organisms. However, several recent breakthroughs have increased our understanding of the effects of Hsa21 trisomy. Combining information from studies of people with DS with the power of mouse models of trisomy has enabled genetic associations to be tested and continues to lead to the identification of genes that cause DS-associated pathology. Significant advances in basic research have been instrumental in determining the molecular mechanisms underlying these phenotypes leading to useful therapeutic interventions. However, many aspects of DS crucial to the health and well-being of people with the condition remain to be investigated and require study at all levels.


Atypical Odontalgia (AO) is a term applied to a continuous pain in the teeth or in the tooth socket after extraction in the absence of any identifiable dental cause, under the International Classification of Headache Disorders (ICHD) and somatosensory abnormalities are common features in these patients, where Quantitative Sensory Testing (QST) are helpful tools to evaluate these cases.The aim of the pilot study was to determine the effect of topical application of anesthetic cream in quantitative sensory testing (QST) findings of AO patients.Methods Ten (7 women and 3 men) consecutive AO patients  with mean pain duration of 2.7 years . QST was performed in all patients at baseline and 3 minutes after topical application of anesthetic cream . QST included tests of mechanical detection threshold (MDT) and mechanical pain threshold (MPT) with von Frey monofilaments, dynamic mechanical allodynia with cotton swab (DMA1) and with toothbrush (DMA2), heat pain thermal detection (HPD), cold pain thermal detection (CPD), temporal summation (WUR) and controlled pain modulation (CPM). The present pain intensity was also recorded with visual analogue scale (VAS). Results were analyzed with non-parametric Wilcoxon test with significance level of 5%.QST mean values showed no differences after topical application of anesthetic cream, except for DMA2 (p=0.02) and WUR (p=0.02). Moreover mean pain in visual analogue scale relieved from 6,03 to 2,12 .In this pilot study significant changes in intraoral somatosensory function were observed in AO after topical application of anesthetic cream for dynamic mechanical allodynia, associated to a reduction of pain intensity. These results may reflect peripheral and central sensitization of trigeminal pathways.There were no conficts of interest in the performance of this study.


A suitable approach to select cancer stem cells (CSC), the black seed of melanomas would enable their characterization and elimination.Cancerous tissues from primary and metastatic lesions of patients with malignant melanomas (n=150) were investigated by cell cultures and molecular genetics. Double labelled cells were sorted by BD FACSAvia Sorter. Gene expression analysis by Real Time PCR  and RNA microarray (Agilent) has been performed (n=48).90% of the cell cultures grew and cancer initiating cells could be IF FACS sorted . Colocalisation of unique GD3 sialilated glycosphingolipids and antiCD20 binding was proved. Characteristic growth pattern, spheroid forming, CSC markers  was observed Figure . We founUnique GD3 sialilated glycosphingolipids with colocalised CD20 proved to be selection markers for CSC in metastatic melanomas. Our strategy paves the way for detection and characterization of cancer stem cells and provides material for therapeutic developments to eliminate the black seeds of melanomas.


Journal of Studies on Alcohol and Drugs (4), Alcoholism: Clinical and Experimental Research (3), and Addictive Behaviors (3). The authors who published most frequently on BI efficacy were "Carey KB,” "Fleming MF,” "Floyd RL,” “Martens MP,” "Nilsen P,” "Saitz R," and "Shang G,” with two publications each. The quantitative approach was prevalent among studies, with randomized controlled trials the most frequent (35). The BIs were conducted mainly in clinical and health-services settings (18). However, interventions were also conducted via the Internet (5) and by telephone (4). Regarding the study population, 22 articles addressed BI for men and women, 14 addressed BI for women, and 9 addressed BI for pregnant women. The efficacy of BI in the reduction of alcohol consumption was confirmed in most research, but some studies showed a reduction only in men. Further specific research using a study population solely comprised of women is deemed necessary.The aim of this study was to systematically review the efficacy of brief intervention (BI) in reducing alcohol use in women. We performed an electronic search across all databases using Thomson Reuters (formerly ISI) Web of Knowledge to identify multidisciplinary content. The term "brief intervention" was associated with the words "alcohol" and "women." We selected studies published between 2006-2010. Of the 95 studies found, 52 were excluded because they were presented at meetings or did not focus specifically on the subject of interest. Forty-three articles with the central theme of realization and/or evaluation of BI efficacy were included in the analysis. Abstracts of these papers underwent content analysis. The year 2007 had the most publications (13) as did the following journals:


Cluster headache (CH) is an extremely severe and debilitating trigemino-autonomic pain syndrome.About 10% of patients with CH manifest a chronic form CH (CCH). Extracts of Boswellia serrata have been clinically studied for the treatment of many inflammatory conditions such as osteoarthritis and rheumatoid arthritis (3). The resin from Boswellia Serrata contains a number of biological actives called pentacyclic triterpene acids, which give the extract its anti-inflammatory and analgesic properties, with boswellic acid the major active ingredient (4). These acids have been demonstrated to interfere with the body’s natural inflammatory response by inhibiting cytokines and leukocyte activity. The present study aims to evaluate the long-term efficacy of Boswellia Serrata  on headaches and disturbed sleep in patients with CCH.In an open-label study, 4 patients with CCH and disturbed sleep received oral Boswellia Serrata.The effects were long-lasting in 3 patients (mean 15 months) and transient (6 months) in one patient. The rapid improvement of nocturnal pain within weeks is similar to the analgetic effect observed in recent trials using Boswellia Serrata in cancer pain The mechanisms of how Boswellia Serrata reduces pain in CCH remain unclear. Boswellic acids, constituents of Boswellia extract have subsequently been identified as selective redox independent noncompetitive inhibitors of both 5-lipoxygenase, the key enzyme in leukotriene biosynthesis and human leukocyte elastase. Proinflammatory cytokines, such as leukotrienes, are known to play a role in the pathophysiology of CH. This study provides Class IV evidence that oral Boswellia Serrata  reduces the intensity and frequency of headaches in patients with CCH.None


Reliable measurement of esophageal pressure is a prerequisite for analysis of respiratory system mechanics in spontaneous breathing patients. For that purpose, various types of balloon catheters exist that differ in material, size and shape. In physical models we studied the quality of pressure measurement via six different balloon catheters, three of them containing a second balloon for measurement of gastric pressure.2O) at different levels of superimposed pressure.Nine balloons of six esophageal catheters were investigated in three conditions: measurement of balloon pressure during initial inflations immediately after unpacking; measurement of static pressures at different filling volumes; and compliance estimation in physical models (27, 54, 90 ml/cmH2O if the balloon was filled appropriately. Overfilling of the balloon resulted in larger errors only in two catheters. Compliance estimations resulted in errors below 1 ml/ cmH2O. Superimposed pressure had no relevant effect on compliance estimation.During the initial inflation most catheters showed pressure artifacts resulting from material adhesion. Those artifacts disappeared during following inflations. Static pressure measurements could be performed with an error below 1 cmHThe reliability of pressure measurements and also of compliance estimation via the tested catheters is high. Only in two catheters was the filling volume a critical point for a precise measurement of pressure or for estimation of compliance. Immediately after unpacking, adhesion of the balloon material might prevent reliable pressure measurement, therefore before the first measurement overfilling of the balloon and retention of the excess gas seems strongly recommended.


Evaluate the effect of myocardial scar burden, scar location, and scar transmurality on response to cardiac resynchronization therapy (CRT)not respond to cardiac resynchronization therapy (CRT). Results from these studies have varied on the importance of scar location, transmurality, and burden on response to CRT. We analyzed cardiac MRI in patients undergoing CRT from 4 centers (two in Europe and two in the US), and hypothesized that the presence of transmural scar in the posterolateral wall (the most frequent site of left ventricular lead placement in CRT) would preclude positive response to CRT.Several recent single center studies have used late Gadolinium enhancement (LGE) MRI to predict which patients would likely Cardiac MRI was performed according to standard methods and included at a minimum, cine imaging and LGE imaging using a Gadolinium-based contrast agent. All patients met current criteria for CRT . Sixty (60) patients from 4 centers were analyzed, and any patient with infarct enhancement on LGE by visual inspection was processed into an LGE bullseye map following AHA guidelines. Total scar burden (as % of LV mass) as well as the presence of transmural scar in the posterolateral or septal segments were assessed. 48% of patients (29/60) patients had LGE and 59% of those (17/29) had transmural scar in at least one AHA segment. Positive response was assessed at 6 months both by clinical  and echocardiographic (reduction of LVESV by 15%) parameters.posterolateral scar responded by clinical criteria, and only one patient with posterolateral scar responded by echocardiographic criteria . The negative predictive value for the presence of transmural septal scar or total scar burden >15% were lower (NPV = 64-67%).None of the patients with transmural non-response to CRT.The presence of transmural posterolateral scar by LGE is predictive of