Genetic studies in autism have pinpointed a heterogeneous group of loci and genes. Further, environment may be an additional factor conferring susceptibility to autism. Transcriptome studies investigate quantitative differences in gene expression between patient-derived tissues and control. These studies may pinpoint genes relevant to pathophysiology yet circumvent the need to understand genetic architecture or gene-by-environment interactions leading to disease.We conducted alternate gene set enrichment analyses using differentially expressed genes from a previously published RNA-seq study of post-mortem autism cerebral cortex. We used three previously published microarray datasets for validation and one of the microarray datasets for additional differential expression analysis. The RNA-seq study used 26 autism and 33 control brains in differential gene expression analysis, and the largest microarray dataset contained 15 autism and 16 control post-mortem brains.While performing a gene set enrichment analysis of genes differentially expressed in the RNA-seq study, we discovered that genes associated with mitochondrial function were downregulated in autism cerebral cortex, as compared to control. These genes were correlated with genes related to synaptic function. We validated these findings across the multiple microarray datasets. We also did separate differential expression and gene set enrichment analyses to confirm the importance of the mitochondrial pathway among downregulated genes in post-mortem autism cerebral cortex.We found that genes related to mitochondrial function were differentially expressed in autism cerebral cortex and correlated with genes related to synaptic transmission. Our principal findings replicate across all datasets investigated. Further, these findings may potentially replicate in other diseases, such as in schizophrenia.The online version of this article (10.1186/s11689-018-9237-x) contains supplementary material, which is available to authorized users. Autism spectrum disorders (ASDs) constitute a heterogeneous group of neurodevelopmental disorders characterized by impaired social interaction, disrupted development of communication skills, and repetitive behaviors . Over anTranscriptome studies in autism have investigated quantitative differences in gene expression between the mRNA samples extracted from post-mortem tissue from patient brains as compared to control brains –19. One We have conducted an alternative analysis of the transcriptome data using differentially expressed genes from an RNA-seq dataset  and thren = 29 control samples, n = 27 autism samples). The Voineagu et al. dataset also contained samples from the cerebellum, which were not used in our study. The two other microarray datasets were from Chow et al.  [n = 6 control samples, n = 6 autism samples) [We analyzed gene expression in autism and control cerebral cortex using genes from Parikshak et al., an RNA-seq study , and micsamples) . We downThe Parikshak et al. dataset samples came from the National Institute of Child Health and Human Development-funded University of Maryland Brain and Tissue Bank and the Autism Tissue Program . The Voip < 0.05) in at least half of the autism or control samples, rather than half of the samples overall. All three studies for the microarray datasets used log2 transformation and quantile normalization. Voineagu et al. showed that all samples met quality control parameters, specifically, if the interarray Pearson correlation was not greater than 0.85 and if the array was an outlier in hierarchical clustering [Each microarray dataset was downloaded or received in its normalized form, except that we renormalized the Voineagu et al. dataset to include more probes. Our renormalized version of the Voineagu et al. dataset was the same except that we eliminated probes that did not have significant expression   using alg method . For DAV package , with EuWe set out to discover other biological processes that were not previously reported to be differentially regulated in the Parikshak et al.  or VoineWe performed separate DAVID functional annotation clustering analyses for the up- and downregulated genes from Parikshak et al. For the upregulated genes, few gene sets were significantly enriched after Benjamini-Hochberg adjustment  (Additiot test p = 0.001), Chow et al. dataset (p = 0.039), and Garbett et al. dataset (p = 0.076) . It was also downregulated in a similar multivariate analysis after limiting the dataset only to frontal cortex (p = 0.041) or temporal cortex (p = 0.057). While the mitochondria pathway was associated with autism, it was not associated with seizures, speech delay, motor delay, or global functioning in the Voineagu et al. dataset (p > 0.3 for each comparison).To exclude the possibility that the mitochondria pathway’s downregulation was unique to the Parikshak et al. study, we next validated this downregulation in other genomic datasets. We used three microarray studies for validation  Fig. . To ensup values were not significant , likely because of reduced sample sizes .Because these studies’ subjects overlapped, we did a separate validation analysis of the Chow et al. and Garbett et al. datasets after removing all but the subjects unique to these studies. The mitochondria pathway was still downregulated in these analyses, although the GABRA1, which codes for a gamma-aminobutyric acid (GABA) receptor subunit, and ATP5A1, which codes for an ATP synthase subunit, were strongly correlated (correlation = 0.876).In our reanalysis of the Parikshak et al. genes, the synapse-related gene sets were the most strongly enriched in those downregulated in autism, so we next determined the relationship between those synapse-related gene sets and the mitochondria pathway. Across all three microarray datasets, these two pathways had strong Pearson correlation Fig. . To exclGiven that the mitochondria pathway was among the most enriched in the Parikshak et al. downregulated genes, we did a separate analysis to confirm the importance of this pathway in autism cerebral cortex. Using the Voineagu et al. dataset, we performed a differential gene expression analysis using limma  between We next performed DAVID functional annotation clustering of the original up- and downregulated genes. The upregulated genes were enriched in only one gene set Additional file 2:Table S1. Properties of the Parikshak, Voineagu, Chow, and Garbett datasets. Table depicting the properties of the datasets analyzed in this study. Properties listed include sample size, number of features in the dataset, brain region, age range, gender, PMI range, RIN cutoff, and the source of the cases. (XLSX 12 kb)Additional file 3:Table S2. DAVID functional annotation clustering analysis of Parikshak et al. upregulated genes. Using the genes upregulated in autism cerebral cortex from Parikshak et al., DAVID functional annotation clustering was performed to generate groups of enriched gene sets. (XLSX 118 kb)Additional file 4:Table S3. DAVID functional annotation clustering analysis of Parikshak et al. downregulated genes. Using the genes downregulated in autism cerebral cortex from Parikshak et al., DAVID functional annotation clustering was performed to generate groups of enriched gene sets. (XLSX 134 kb)Additional file 5:Table S4. Synapse pathway and mitochondria pathway genes. The mitochondria pathway genes were downregulated in autism cerebral cortex in Parikshak et al. and were members of the GO “Mitochondrion” term. The synapse pathway genes were also downregulated in Parikshak et al. and were members of the UniProt “Synapse” term. All genes in the synapse pathway and in the related “M12” module from Voineagu et al. [u et al.  were excAdditional file 6:Figure S2. Heatmaps of mitochondrial genes in the Chow et al. and Garbett et al. microarray datasets. The rows are genes and the columns are subjects; the top vertical bar shows whether a subject was from autism (blue) or control (red). Generally, lower gene expression (blue in heatmap) maps onto the autism participants . Intensity of color is determined by a Z-score normalized by gene. Shown below the heatmap is the overlap of each sample with other study datasets, using the first letter of each study. (PDF 577 kb)Additional file 7:Table S5. Differential expression analysis between autism and control cerebral cortex in the Voineagu et al. dataset. Table of differential expression analysis between autism and control cerebral cortex in the Voineagu et al. dataset, adjusted for RIN, PMI, age, sex, and cortical location . The analysis was performed using the Bioconductor package limma and adjusted for multiple testing using the Benjamini-Hochberg method. Because several individuals were included twice  in this analysis, the analysis was also redone limiting samples only to frontal or temporal cortex. Note that the p values in the cortex-specific analyses are not adjusted for multiple testing. (XLSX 265 kb)Additional file 8:Table S6. DAVID functional annotation clustering analysis of Voineagu et al. upregulated genes. Using the genes upregulated in autism cerebral cortex from Voineagu et al., DAVID functional annotation clustering was performed to generate groups of enriched gene sets. (XLSX 48 kb)Additional file 9:Table S7. DAVID functional annotation clustering analysis of Voineagu et al. downregulated genes. Using the genes downregulated in autism cerebral cortex from Voineagu et al., DAVID functional annotation clustering was performed to generate groups of enriched gene sets. The top 5 clusters had several gene sets related to mitochondrial function. (XLSX 49 kb)


The replication crisis addresses a fundamental problem in psychological research. Reported associations are systematically inflated and many published results do not replicate, suggesting that the scientific psychological literature is replete with false-positive findings . On the individual study-level, some researchers use selective outcome reporting to illegitimately present findings in an opportunistic way. Outcome reporting bias is very prevalent in clinical science and indicates that authors omit or change primary outcomes on basis of the results in order to avoid undesired findings . According to the authors this finding cannot be explained by heterogeneity, publication bias or allegiance effects . Using a continuous measure of study quality ranging from 0 to 8 points in a meta-regression showed that each additional point increase in study quality reduced the average effect size by −0.07 points . The impact of low-quality study bias was very recently replicated by Cristea et al. (Study quality is an important determinant of treatment efficacy in clinical science, but unfortunately, most published psychotherapy trials use poor methods such as small sample sizes, inadequate concealment of allocation, no intent-to-treat analyses, and unblinded outcome assessors (e.g., Newby et al., a et al.  in a meta et al. , evidenca et al. . Due to a et al. . Furthera et al.  or even a et al.  in real-a et al. . That isa et al. . ReplicaAs in other psychological specialties (see Bakker et al., The author confirms being the sole contributor of this work and approved it for publication.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


In the article titled “Incorporating Family Function into Chronic Pain Disability: The Role of Catastrophizing” , an acknThe authors would like to acknowledge Dr. Majtaba Habibi, a co-adviser of Dr. Akbari's thesis, for his role in the project and revising an earlier version of the manuscript.This follows a decision by Shahid Beheshti University about an authorship claim by Dr. Habibi.


Judo competition is characterized structurally by weight category, which raises the importance of physiological control training in judo. The aim of the present review was to examine scientific papers on the physiological profile of the judokas, maintenance or loss of weight, framing issues, such as anthropometric parameters (body fat percentage), heart rate responses to training and combat, maximal oxygen uptake, hematological, biological and hormones indicators. The values shown in this review should be used as a reference for the evaluation of physical fitness and the effectiveness of training programs. Hence, this information is expected to contribute to the development of optimal training interventions aiming to achieve maximum athletic performance and to maintain the health of judokas. Judo became an official sport event in the Olympic Games of Munich in 1972 for men and in the 1992 Games (Barcelona) for women . In the 1964 Games, judo was invited in Tokyo for men, whereas the same happened for women in the 1988 Games (Seoul). In 1961, there were world championships in Paris. The first competition with weight categories took place in the 1964 Games (Tokyo), including three categories and an open, while in 1965 (Rio de Janeiro), five categories and an open were included in the program.Competitive judo demands high-intensity intermittent actions, in which optimal physical attributes are necessary in order to achieve technical-tactical development and success in combat ,2. ActuaJudo trainers and judokas should have a solid knowledge about physiological responses to competitions and physiological adaptations to training in order to design an adequate training session and season . A combiThere are many authors who have written about the variation of physical and physiological profile of judokas during the training season ,15, as wJudo is a combat sport with strict competitive weight categories. In 1964, when judo became an official Olympic event, a competitive weight class system was adopted. Judokas should optimally select the weight class that is appropriate to their height and physique. However, many of them often undergo severe weight reduction through calorie restriction in order to select a lower-weight class and, in this way, to gain an advantage over other judokas in a particular weight class. In order to achieve the weight that would allow them to participate in a specific class, many contestants undergo drastic food restriction, especially during the week preceding the competition. The amount of weight loss is subsequently regained as the athletes compensate for the sustained energy drain by excess food intake during the post-competition period . This raBody mass and body fat percentage are essential measurements that could change largely according to sex, age, weight category and training. With regards to sex, it has been established that body fat percentage for elite female judokas is about 10% higher than for male judokas . A studyet al.  has been extensively studied in judo, both in real competition, simulations of competition and training. [La−] values have ranged 7–10 mmol·L−1 after combat simulations [−] have not been found, either between competition levels [et al. [−] of 9.1 ± 1.1 mmol·L−1 after a specific training judo . In addition, Franchini et al. [−] after combats, at least in simulated combat. In these studies, it was found that peak [La−] was higher after the first combat compared to the second, third and fourth combat, about 2 mmol·L−1 [et al. [−] during competition in regional-level male judokas.The concentration of lactate in blood [Laulations ,55,58,60n levels  or sexes [et al.  reportedi et al.  found sii et al. , there wmmol·L−1 ,62. Takemmol·L−1 . Serranoet al. [12 L−1 and 5.8 × 109 L−1, respectively. These authors reported values of Hb of 15.5 g·L−1 and Hct of 43% for the same group of judokas. In female high level judokas, Hb was 12.5 g·dL−1 and 38% for Hct [−1 and 42%, respectively) than in adult judokas [Hematological evaluation in judokas has focused on concentrations of total erythrocytes and leukocytes, as well as quantification of hemoglobin (Hb) and hematocrit (Hct). Malczewska et al.  reported for Hct . In the  judokas .et al. [−1) and Htc (from 42% down to 39%) after a five-week training period in young judokas (16 years old). This finding was in agreement with that of Umeda et al. [2). This study concluded that energy restriction seemed to exacerbate alterations in immune markers, such as immunoglobulin, and complements induced by vigorous exercise at seven days after a competition. Although the changed values were still within normal limits, the authors hypothesized that the potential cumulative effect of these changes over many competitions in one year might well induce abnormal levels with a possibly harmful clinical effect on judokas. In contrast, the study of Kowatari et al. [Hb and Hct did not change significantly during a 20-day rapid weight loss period before competition ,29. A stet al.  found a a et al. , who shoi et al.  failed t3/µL and 2.98 ± 0.82–7.95 ±1.8 × 103/µL, respectively, in 18 male judokas [On the other hand, white blood cells and neutrophils in the blood values showed a significant increase after training judo, ±1.2–10.7 ± 1.8 × 10 judokas . Another judokas .et al. [et al. [et al. [et al. [Ohta et al.  and Umed [et al.  controll [et al.  showed a [et al.  only was [et al. ,29.et al. [Kim et al.  pointed Among sports where athletes are categorized by weight, judo is characterized by relatively short duration, high intensity and intermittent exercise with a combat lasting ~7.18 min in males. It has been shown that a single judo combat is able to induce mobilization of both protein and lipid metabolism .et al. [Finaud et al.  observedet al. ,30.et al. [−1).On the contrary, Filaire et al.  observed−1). Therefore, the authors hypothesize that since the judoka study was carried out with the misleading use of lipid metabolism (lipolysis), bringing with it the increase in free fatty acids and glycerol after the effort, characterized by an intake of a carbohydrate diet rather than that recommended, this can be the case. A study  about thet al. [Stress management before a competition for athletes is very important, especially for those who reduce their weight, such as judokas. In general, adrenocortical hormone is well known as a stress marker, and cortisol (C) is representative of it. Nowadays, the ratio of testosterone (T) to C (T/C) is a good marker of overtraining diagnosis . In a stet al.  and Obmiet al. , suggestet al. [Salvador et al.  comparedvs. interregional) by comparing physiological responses  and psychological responses prior to judo competitions [The relationships between psychophysiological variables have been investigated at two levels (regional etitions . C levelCorrelations between T levels and fighting in male participants in judo contests have been studied . A positet al. [Toda et al.  investiget al. [et al. [Degoutte et al.  examinedet al. , in line [et al. , showed This study has a something’s limitations. It discussed a compendium of studies related to the functional and physiological characteristics judo athlete. However, it is not a systematic review of these aspects. Coaches can consider directions and guidelines; and can serve as support for their workouts. Therefore, data must be taken with caution.The values shown in this review are vital for training control. It collaborates with the planning of training and maintaining the health of judokas.


In Da Cunha et al. , we provhttp://ecogenomics.github.io/CheckM/)) and Anvi’o  also revealed a high contamination index (between 45% and 57%), necessarily underestimated because quality analyses are limited to defined sets of markers [On top of the very high heterogeneity detected in Loki’s genome 78.21%), our quality analyses with CheckM  . No otheWe suspected that patches of contamination could also be present in Heimdall LC3 RpoA since this subunit is encoded by a single gene in LC3 (like in Thaumarchaeota and the related Bathyarchaea and Aigarchaea), whereas all other Asgards have a dimeric version . Unlike Spang et al. , we neveMethanopyrus kandleri in the 2D tree of Spang et al. [Spang et al.  argued tg et al. –8. This g et al. .Spang et al.  argued tWe never claimed that the Asgard/Eukarya affiliation could not be obtained without EF2. We ourselves obtained it when we removed EF2 from the concatenation of the eocyte proteins . ZarembFinally, the confirmed presence of many Eukaryotic Signature Proteins (ESPs) in the genomes of the additional Asgards  cannot bSpang et al.  stated t


Inflammatory bowel disease (IBD) is an autoimmune disease of unknown etiology and can lead to inflammation and cancer. Whey proteins contain many bioactive peptides with potential health benefits against IBD. We investigated the effect of low-temperature-processed whey protein concentrate (LWPC) on the suppression of IBD by using a dextran sodium sulfate (DSS)-induced colitis model in BALB/c mice. Oral intake of LWPC resulted in improved recovery of body weight in mice. Histological analysis showed that the epithelium cells of LWPC-treated mice were healthier and that lymphocyte infiltration was reduced. The increase in mucin due to the LWPC also reflected reduced inflammation in the colon. Transcriptome analysis of the colon by DNA microarrays revealed marked downregulation of genes related to immune responses in LWPC-fed mice. In particular, the expression of interferon gamma receptor 2 (Ifngr2) and guanylate-binding proteins (GBPs) was increased by DSS treatment and decreased in LWPC-fed mice. These findings suggest that LWPCs suppress DSS-induced inflammation in the colon by suppressing the signaling of these cytokines. Our findings suggest that LWPCs would be an effective food resource for suppressing IBD symptoms. Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic autoimmune disease condition, the pathogenesis of which is unknown . IBD is et al. [Crassostrea gigas) has been shown to reduce inflammation through immunomodulation [Recent research reveals that food-derived peptides from various sources, including seafood, milk and plants, contain bioactive functional properties, especially in the suppression of colitis. Young et al.  showed tdulation . Milk isdulation . Bioactidulation , or indidulation , improvedulation ,12. Bothdulation ,14,15. Wdulation , showingdulation . These set al. [et al. [The functional properties of cheese whey protein are known to differ from the properties of raw milk based on the sterilization method applied during processing. The milk pasteurization process is known to cause a low degree of protein denaturation; thus, whey generated by pasteurized milk processing has been reported to have more bioactive functions when compared to whey processed at higher temperatures. Li et al.  showed t [et al.  found thTherefore, the present study was conducted to evaluate the effects of low-temperature-treated whey proteins in relation to their suppression of colon inflammation in the dextran sulfate sodium (DSS) mouse model of experimental colitis. The possible mechanisms by which whey protein may exert its action were studied via DNA microarrays followed by a comparison of the gene expression levels.The low-temperature-processed whey concentrate (LWPC) powder was a commercial product kindly gifted by Asama Chemical Co. Ltd.  The LWPC was dissolved in distilled water and heated at 70 °C for 2 h, and this solution was concentrated by freeze-drying. The resulting powder is named high-temperature-processed whey protein concentrate (HWPC). The protein profiles of HWPC and LWPC were analyzed by SDS-polyacrylamide gel electrophoresis  with 5%–The two treatment diets were prepared based on the AIN-76 diet . Colitis was induced in Groups 1 to 3 through the administration of 2.5% dextran sulfate sodium (DSS) in the drinking water [Female BALB/c mice (4 weeks old) were obtained from CREA Japan Inc.  and housed in isolated cages at 20 °C under a 12 h light/dark cycle. After 10 days of acclimatization with the AIN-76 diet and water provided ng water , and eacet al. [Five colon tissue samples were obtained from each treatment group representing all 5 mice. Each tissue sample was taken from a different site so as to represent the whole column within a treatment group. The colon tissues were fixed overnight in 4% paraformaldehyde in phosphate-buffered saline, embedded in paraffin wax and sectioned (10 μm) using a microtome, followed by staining with hematoxylin and eosin (HE). Twenty-five slide spots from each treatment group were used for microscopical examination with 5 spots representing each tissue section. The slides were viewed under a light microscope. The slides were further evaluated with regard to histological damage to the colon using a semi-quantitative scoring system  with minet al. , with a The mouse colon was homogenized, and proteins were extracted with general SDS-PAGE sample buffer. The protein concentration was assessed using the Bio-Rad protein assay method. Equal amounts of each extract were then subjected to protein separation on SDS-PAGE (15% gel) and then electro-transferred onto a nitrocellulose membrane. The membrane was blocked with Tris-buffered saline and 6% milk protein and then incubated overnight at 4 °C with primary rabbit antibodies for mucin 2 , followed by incubation with a secondary antibody for rabbit IgG labeled with horse radish peroxidase. Detection was performed using the ECL system . Colon tissues were ground in liquid nitrogen, followed by RNA extraction using the SV Total RNA isolation system  according to the manufacturer’s protocol. The extracted RNA was checked by spectrophotometer analysis and electrophoresis and then stored at −80 °C for further use.RNA samples from each treatment replicate were pooled, and 500 ng of RNA from each treatment condition were used for transcriptome analysis of the mouse colon using a GeneChip 430A 2.0 mouse array . Experiments were performed according to the manufacturer’s technical manual (Affymetrix). Data obtained from scanning the arrays were normalized  and analyzed using Arraystar software . Genes that were up- or down-regulated by ≥2-fold in comparison with the DSS treatment were categorized using the Database for Annotation, Visualization and Integrated Database (DAVID) version 6.7 ,26 and tt-test.To validate the changes in the expression of the selected genes, we performed quantitative real time RT-PCR (QPCR). We selected guanylate binding protein 1 (Gbp1:NM_010259), Gbp2 (NM_010260) and interferon gamma receptor 2 (IFNgr2: NM_008338) for QPCR analysis. cDNA was synthesized using Superscript II reverse transcriptase  and oligo-dT primers. Primers for the genes were selected from PrimerBank ,29 as deet al. [et al. [et al. [et al. [The protein profiles of LWPC and HWPC were compared by SDS-PAGE . LWPC shet al.  and Mori [et al. . In the  [et al. . It is c [et al.  obtained [et al.  also obt [et al. .et al. [DSS-induced intestinal injury serves as an experimental model for human ulcerative colitis and is a well-established method for the chemical induction of intestinal injury . The chaet al.  found thUnder inflammatory conditions, excess infiltration of neutrophils can be observed clearly. Microscopic images of colon sections from mice subjected to different treatments are shown in et al. [et al. [et al. [in vivo and in vitro.In the colon, mucins are produced by goblet cells for lubrication . The avaet al.  reported [et al.  and Hong [et al.  also fouTo investigate the mechanism underlying the effect of LWPC, we evaluated the transcriptome of the mouse colon by DNA microarray analysis. Compared with the control group, 677 out of 22,626 probed genes were up- or down-regulated by over two-fold in the DSS treatment group , Table 3The 110 genes regulated by both DSS and LWPC were further classified into functional groups using the DAVID functional annotation program according to the GO biological process in the GO ontology, as shown in et al. [Quantitative real-time RT-PCR was performed to confirm the expression levels of Gbp1 and Gbp2 A,B. Bothet al.  found thet al. . Thus, tet al. . Accordiet al. . Accordiet al. , both Ilet al. . LWPC diet al. [et al. [et al. [Whey protein isolates subjected to high hydrostatic pressure have been shown to affect the suppression of tumor necrosis factor-alpha, interleukin 8 and interleukin 18 in Caco-2 colon cancer cells . Rusu etet al.  showed t [et al.  reported [et al. . Lactofe [et al.  reported [et al. . HoweverDSS-induced colitis was prevented by oral intake of LWPC, which also enhanced the recovery from colitis. Comprehensive analysis of gene expression in the colon by DNA microarray analysis showed that GBPs were downregulated by LWPC intake. Expression of GBPs is known to be regulated by interferon gamma. IFNgr2, a receptor for interferon gamma, was also downregulated by LWPC, which suggests that oral intake of LWPC results in the suppression of IFN gamma-mediated pathways and leads to the suppression of inflammation.


Polycyclic aromatic hydrocarbons (PAHs) are widespread in marine ecosystems and originate from natural sources and anthropogenic activities. PAHs enter the marine environment in two main ways, corresponding to chronic pollution or acute pollution by oil spills. The global PAH fluxes in marine environments are controlled by the microbial degradation and the biological pump, which plays a role in particle settling and in sequestration through bioaccumulation. Due to their low water solubility and hydrophobic nature, PAHs tightly adhere to sediments leading to accumulation in coastal and deep sediments. Microbial assemblages play an important role in determining the fate of PAHs in water and sediments, supporting the functioning of biogeochemical cycles and the microbial loop. This review summarises the knowledge recently acquired in terms of both chronic and acute PAH pollution. The importance of the microbial ecology in PAH-polluted marine ecosystems is highlighted as well as the importance of gaining further in-depth knowledge of the environmental services provided by microorganisms. This review highlights the sources and fate of polycyclic aromatic hydrocarbons (PAHs) in the marine environment with particular emphasis on the microbial ecology and the biological pump controlling global PAH fluxes. Polycyclic aromatic hydrocarbons (PAHs) have attracted the interest of many scientists from different disciplines beyond biology, physics and chemistry. They are fascinating compounds due to their universality, their presence in interstellar space Tielens  and theiet al.et al.et al.PAHs are natural compounds synthesised by organisms, produced by combustion, and derived from fossil fuels and transformation processes Neff . In the et al.et al.et al.et al.et al.  by indigenous oil-degrading bacteria  and Gram-positive groups (Bacillus and Microbacterium) as sentinels for PAH biodegradation in Gulf beach sands. In coastal wetlands, polluted by weathered oil containing complex PAHs . They enter the marine environment by deposition on surface waters. Atmospheric PAH depositions have toxic effects on the oceanic phytoplankton communities thus perturbing the first level of marine food webs  organisms, ensuring the microbial loop through top-down regulation and ecosystem services by metabolic networks. These interactions, characterized by the coexistence of different species involved in positive and/or negative interactions, are an integral part of the functioning of ecosystems and govern microbial processes involved in the hydrocarbons biodegradation , genes involved in the first step of aerobic PAH biodegradation (Bordenave et al.et al.et al.et al.et al.et al.et al. (rhd genes was correlated with bioavailable PAH contents. The diversity of rhd genes was higher in deposited sediments than in suspended sediments and overlaying water (Xia et al.rhd genes in environmental studies has been further demonstrated by targeting their transcripts, which were shown to be induced just after the addition of fresh bioavailable PAHs contained in heavy crude oil (Paissé et al.l.et al.  demonstret al.et al.et al.et al.In the absence of functional evidence, the contribution of PAHs to structuring microbial communities could be difficult to evaluate because of the presence of multicontaminants. To overcome these difficulties, the high-throughput sequencing technology associated with appropriate statistical analyses, such as co-occurrence network analyses, offers the possibility of identifying pollutant–degrader interactions (Yergeau Because of the sediment complexity, the environmental observations alone are insufficient to fully understand the mechanisms controlling the microbial assemblages in the presence of PAHs. Laboratory studies, including single-cell physiology as well as appropriate microcosm and mesocosm experiments, are methods that facilitate understanding complex microbial assemblages (Cravo-Laureau and Duran et al.et al.et al.et al.et al.et al.et al.et al.et al. (Oxygen and redox oscillations are major fluctuations in estuarine and tidal sediments (Cravo-Laureau and Duran l.et al. .et al.et al.et al. (et al.The influence of PAHs on the interactions between microbial communities and meiofauna has been revealed by microcosms for studies into bioremediation strategies (Louati l.et al.  demonstrl. et al., highliget al.Although the issues related to oil pollution, particularly the concerns regarding to PAHs, are increasingly taken into consideration with the introduction of specific countermeasures, PAHs are still threatening environmental health. The marine environment is the major sink and receptacle of PAHs, which enter through different forms whose bioavailability varies according to their origin and their weathering processes. Microorganisms are the main actors in controlling and determining their fate in all marine ecosystems. The biological pump plays a pivotal role in the surface water and water-column trapping of PAHs, originating from both oil spills and atmospheric deposition, and then transporting them to the bottom. The utilisation of this spectacular phenomenon, by promoting it with fertilisers, for cleaning the open oceans and for carbon sequestration is currently under debate (De La Rocha The exploitation of oil reservoirs in more and more extreme conditions, such as deep sea and cold areas, in the context of climate change complicates the challenge. The study of oil reservoirs in more extreme conditions is required because these colder environments present different environmental parameters, including hydrostatic pressure, low temperature and water acidification, that may shape microbial processes. Further knowledge of the ecology of the adapted bacterial populations described in deep-sea sediments and of the PAH degraders found in cold Arctic Ocean sediments, both responsible for low PAH-degradation rates, is required to complete the global model of the fate of PAHs in the marine environment.Additionally, it is of paramount importance to gain information on how the modification of the resulting environmental parameters may affect the microbial assemblages, the biological pump and the global carbon cycle in a climate change scenario.


The aim of this study was to evaluate the effect of intra-canal calcium hydroxide (CH) remnants after ultrasonic irrigation and hand file removal on the push out bond strength of AH-26 and EndoSequence Bioceramic sealer . n=34) based on the CH removal technique; i.e. either with ultrasonic or with #35 hand file. Then specimens were divided into two subgroups according to the sealer used for root canal obturation: AH-26 or BC Sealer. After 7 days, 1 mm-thick disks were prepared from the middle portion of the specimens. The push out bond strength and failure mode were evaluated. Data were analyzed by the two-way ANOVA and Tukey’s post hoc tests. A total of 102 single-rooted extracted human teeth were used in this study. After root canal preparation up to 35/0.04 Mtwo rotary file, all the specimens received CH dressing except for 34 specimens in the control group. After 1 week, the specimens with CH were divided into 2 groups (P<0.05). The dominant mode of failure in all subgroups was of mixed type except for the BC Sealer specimens undergoing CH removal with hand file which dominantly exhibited adhesive mode of failure. The push out bond strength of both sealers was lower in specimens receiving CH. These values were significantly higher when CH was removed by ultrasonic (CH remnants had a negative effect on the push out bond strength of AH-26 and BC Sealer. Ultrasonic irrigation was more effective in removing CH. Amin et al. [These findings were consistent with the results of the studies of Guiotti et al. . Howeveret al. , 28-30. et al. [et al. [When comparing the control specimens, the push out bond strength of AH-26 was higher than BC Sealer but the difference was not statistically significant. However, in specimens receiving CH, the push out bond strength of AH-26 was significantly higher than BC Sealer regardless of the CH removal technique. Al-Haddad et al.  confirmeet al. , 11. Sho [et al.  attributIt should be noted that the clinical significance of this decrease in push out bond values and its effect on the outcome of endodontic treatments are not clear yet.et al. [et al. [et al. [The dominant mode of failure in all experimental groups was mixed with an exception of BC Sealer specimens which undergone CH removal by hand files. In the latter, the dominant mode of failure was adhesive indicating that higher levels of residual CH in BC Sealer specimens affectively reduced the bond strength. Mixed mode of failure may also be due to uninform CH removal from root canal walls that must be determined with further research. Akcay et al.  and Gokt [et al.  reported [et al.  used gut [et al. . FurtherResidual CH on dentinal walls of the root canal negatively affects the push out bond strength of AH-26 and Endosequence BC Sealer.


Epidemiological studies have probed the correlation between telomere length and the risk of lung cancer, but their findings are inconsistent in this regard. The present meta-analysis study has been carried out to demonstrate the association between relative telomere length in peripheral blood leukocytes and the risk of lung cancer using an established Q-PCR technique.A systematic search was carried out using PubMed, EMBASE, and ISI before 2015. A total of 2925 cases of lung cancer and 2931 controls from 9 studies were employed to probe the relationship between lung cancer and telomere length. ORs were used at 95% CI. Random-effects models were used to investigate this relationship based on the heterogeneity test. Heterogeneity among studies was analyzed employing subgroup analysis based on type studies and the year of publication.2=93%) compared to patients with squamous cell lung cancer, which was 1.78 . The meta-regression revealed that the effect of telomere length shortening, decreased and increased with the year of publication and the age of risks to lung cancer, was clearly related to short telomeres lengths.Random-effects meta-analysis revealed that patients with lung cancer were expected to have shorter telomere length than the control . The summary of the pooled ORs of telomere length in adenocarcinoma lung cancer patients was 1 (95%CI=0.68-1.47, ILung cancer risks clearly related with short telomeres lengths. In patients with breathing problems, lung cancer risk can be predicted by telomere length adjustment with age, sex, and smoking. Lung cancer is a leading cause of death worldwide. In 2008, more than 1.6 million new cases of lung cancer were diagnosed, which accounts for 13% of all new cancer cases. About 1.4 million people have lost their lives due to lung cancer that is estimated to be responsible for 18% of all deaths from lung cancer compared to 1.78  for SCC lung cancer. The pooled ORs showed that patients with SCC lung cancer were expected to have shorter telomere length than the control; however, it was found that there was no relationship between telomere length and the risk of lung cancer in patients with adenocarcinoma lung cancer. Overall, pooled ORs for both subtype was 1.40 , which indicated shorter telomere length in both lung cancer subtype.A subgroup analyses were performed in order to discover the source of heterogeneity and further explore the effects of the histologic subtype of lung cancer on telomere length as well as evaluate any differences between trials by ruling out the confounding effect of the histologic subtype of lung cancer. The pooled summary of ORs of telomere length in adenocarcinoma lung cancer patients was 1  , I2 87 %, P=0.1], and females  and age 1.32    .2 of sensitivity and specificity were 84.9% (P=0.001), 71.7% (P=0.001), 67.9% (P=0.001), 59.1% (P=0.008), and 81.1% (P=0.001), respectively. There was also little difference in the sensitivity analysis due to inaccuracies in the data presented or incorrect information in the articles.Sensitivity of these nine studies was demonstrated by forest plots as shown in et al.[To investigate the relationship between lung cancer and telomere length shortening in this meta-analysis, 2925 lung cancer cases and 2931 controls of 9 different articles were used (OR=1.13). The measurement method for the telomere length in all included studies, except Sun et al. was realet al.[et al.[et al.[P=0.003)[The greater number of studies showed significant associations between shorter telomere lengths in peripheral blood leukocytes and the risks of different subtype of lung carcinomas. Wu et al. and Jangl.[et al. found sil.[et al. indicate[P=0.003). Longer [P=0.003). The res[P=0.003),7. In ad[P=0.003). Both an[P=0.003). Consequ[P=0.003). When th[P=0.003).et al.[et al.[Various case control studies have reported shorter telomeres to be associated with the risk of lung cancer, whereas results from Seow et al. showed tet al.. They deet al.. Sanchezl.[et al. found a l.[et al.. Adenocaet al.[et al.[et al.[Telomere shortening has also been associated with smoking status. Our metet al. demonstret al.. Smokinget al.,34. The et al.. Jang etl.[et al. reportedl.[et al.. Shen etl.[et al. observedl.[et al..In conclusion, a positive association was found between short telomere length and the risk of lung cancer. In patients with breathing problems, the risk of lung cancer can be predicted by telomere length adjusted with age, sex, and smoking. The molecular mechanisms that induce a decrease in telomere length may be implicated in the expansion of histologic subtypes of lung cancer. The several remarkable advantages of the current study include the fact that search strategy was employed extensively with reviewing of titles and abstracts manually. The search period spanned for a long time so that studies are not excluded based on the years of publication. Finally, further large studies will be required to authenticate these results and evaluate the effect of genetic and environmental risk factors before and after cancer diagnosis.


L. monocytogenes, together with the severity of human listeriosis infections, make L. monocytogenes of particular concern for manufacturers of cold-stored “ready to eat” (RTE) foods. L. monocytogenes has been isolated from a wide variety of RTE foods and is responsible for several outbreaks associated with the consumption of RTE meat, poultry, dairy, fish and vegetable products. Although L. monocytogenes is among the most frequently-detected pathogens in dry fermented sausages, these products could be included in the category of RTE products in which the growth of L. monocytogenes is not favored and have rarely been implicated in listeriosis outbreaks. However, L. monocytogenes is highly difficult to control in fermented sausage processing environments due to its high tolerance to low pH and high salt concentration. In many Mediterranean-style dry fermented sausages, an empirical application of the hurdle technology often occurs and the frequent detection of L. monocytogenes in these products at the end of ripening highlights the need for food business operators to properly apply hurdle technology and to control the contamination routes of L. monocytogenes in the processing plants. In the following, through an up-to-date review of  published data, the main aspects of the presence of L. monocytogenes in Mediterranean-style dry fermented sausages will be discussed.The morphological, physiological and epidemiological features of  Peritrichous flagella give them a typical tumbling motility, occurring at 20–25 °C. Based on somatic (O) and flagellar (H) antigens, 13 serotypes of L. monocytogenes have been recognized. These are identified alphanumerically: 1/2a, 1/2b, 1/2c, 3a, 3b, 3c, 4a, 4ab, 4b, 4c, 4d, 4e and 7  and is able to multiply in food matrices at water activity (aw) values of 0.92 and in NaCl concentrations of 12%, generally lethal to other microorganisms. L. monocytogenes is a ubiquitous organism, widely distributed in the environment: the principal reservoirs are soil, forage and water . In thel., 2002 ).L. monocytogenes is the etiologic agent of listeriosis. Human cases of listeriosis are almost exclusively caused by L. monocytogenes. Very rare cases of infections are attributed to L. ivanovii and L. seeligeri. The difference in the pathogenic potential of L. monocytogenes strains has been demonstrated by means of in vivo bioassay and in vitro cell assay ; Lineage II, strains isolated from sporadic cases of listeriosis ; Lineage III, strains rarely associated with cases of listeriosis (serotypes 4a and 4c) . The dil., 2008 ; Robertsl., 2009 ). Rasmusnn, 2002 ). The linn, 2002 ). The mal., 2005 ), to lifl., 2007 ).L. monocytogenes, together with the severity of human listeriosis infections, make L. monocytogenes of particular concern for manufacturers of cold-stored “ready to eat” (RTE) foods , L. monocytogenes must not be present at levels exceeding 100 CFU/g during the shelf-life. In RTE foods able to support its growth, L. monocytogenes must be absent in 25 g at the time of leaving the production plant. However, if the producer can demonstrate that the product will not exceed the limit of 100 CFU/g throughout its shelf-life, this criterion does not apply  and in l., 2002 ; Van Coil., 2004 ; Shen etl., 2006 ). L. monl., 2000 ; Gillespl., 2006 ; Public l., 2006 ; U.S. Del., 2006 ; Todd anl., 2006 ). The EUl., 2006 ) lays doon, 2005 ). In 201L. monocytogenes has been previously found in every stage along the pork processing industry , includl., 1997 ; Korsak l., 1998 ). The sol., 2002 ). L. monl., 2000 ).et al., 2003 [et al., 2002 [et al., 1994 [et al., 1995 [et al., 1996 [et al., 1995 [et al., 2005 [et al., 2008 [et al., 2002 [et al., 2013 [et al., 1991 [et al., 2002 [et al., 2002 [et al., 2003 [et al., 2005 [The prevalence in feces is generally comprised between 0% and 50% . This wl., 2002 ). The rol., 2002 ; Nesbakkl., 1994 ; Saide-Al., 1995 ; Borch el., 1996 ). Contaml., 1995 ), and rel., 2005 ; López el., 2008 ), highlil., 2002 ; Meloni l., 2013 ). Several., 1991 ; Ripamonl., 2002 ; Autio el., 2003 ; Fabbi el., 2005 ) correlaet al., 2005 [et al., 2013 [The most frequent serotypes found in carcasses and slaughterhouse environments are 1/2a, 1/2c , while L. monocytogenes contamination tends to increase along the pork supply chain . Raw mel., 2002 ).L. monocytogenes  compared to the muscles of freshly slaughtered pigs (0%–2%). Raw meat represents the primary source of contamination of final products by l., 1999 ; Katharil., 1999 ; Kanuganl., 2002 ; Thévenol., 2005 ). In turay, 1996 ; Chasseil., 2002 ). The lel., 1996 ; Thévenol., 2005 ). Pork ml., 2005 ; Mureddul., 2014 ).L. monocytogenes can persist over time in the processing environment  capacity and weak or moderate ability to form biofilm after 24 to 40 h of incubation. Isolates from serotypes 1/2a, 1/2b and 4b presented higher adherence when compared to isolates from serotype 1/2c  showed a reduction of L. monocytogenes growth after 24, 48 and 72 h of incubation in isolates from processing environments and finished products.Once introduced into the plants, l., 2008 ), forminl., 1990 ; Gandhi l., 2012 ). In recl., 2012 ; Meloni l., 2014 ; Mureddul., 2014 ), the evl., 2014 ). Harborl., 2014 ). This cl., 2011 ). Decontl., 2004 ). Withouos, 1999 ; Meloni l., 2014 ). Previol., 2012 ). In a rl., 2014 ), the inL. monocytogenes isolated from meat-processing environments belong mainly to serotypes 1/2c and 1/2a .Mediterranean-style dry fermented sausages are characterized by their relatively longer shelf-life and the exceptional hygienic background, which is brought about by the production of lactic acid in the fermentation process (pH < 4.5–5) and low water activity (<0.90) of the final product . In genet al., 2005 [The meat used depends on eating habits, customs and the preferences prevailing in the geographical region where the fermented sausage is produced . This isl., 2005 ; Ordóñezl., 2005 ). The saet al., 2005 [et al., 2009 [After filling and the first warming up at 20–22 °C for 4–6 h, the fermentation stage for the manufacture of a standard dry fermented sausage can be summarized as follows: one to two days at 18–24 °C and 60% relative humidity (RH) and five days at 15 °C and 70% RH . After l., 2005 ; Ordóñezl., 2005 ). Howevel., 2005 ; Jofré el., 2009 ). At thel., 2009 ).L. monocytogenes is inhibited in fermented sausages by sequential steps: the “hurdle technology” concept includes several sequential hurdles, essential at different stages of the fermentation or ripening process . Due tori, 2002 ). These ri, 2002 ). In theri, 2002 ). Other l., 1994 ; Greco el., 1999 ; Mazzettl., 1999 ). This, l., 1999 ). This cl., 1993 ; Torrianl., 1994 ; Grazia l., 1998 ; Leroy al., 1998 ; Hebert l., 2000 ; Lucke, l., 2000 ). These l., 2005 ). This il., 2005 ). Only tl., 2005 ). This sl., 2005 ).L. monocytogenes at several stages. The raw materials may be contaminated from the slaughterhouse environment, during the production process or by contact with contaminated unprocessed raw materials, unclean surfaces or people  in the l., 2007 ). L. monsausages , reachinl., 1989 ; Cordanol., 1989 ; Levine l., 2001 ; Thévenol., 2005 ; De Cesal., 2007 ; Meloni l., 2009 ; Meloni l., 2012 ; Mureddul., 2014 ; Meloni l., 2014 ; Doménecl., 2015 ).L. monocytogenes have rarely been implicated in critical listeriosis outbreaks , and the global number of annual cases per 100,000 people is only 0.0000055 , representing a major public health concern . Many Ml., 2012 ). Mostlyl., 2012 ). Insuffl., 2014 ), and L.in, 1991 ), becausl., 2004 ; Thévenol., 2006 ).et al., 2006 [et al., 2014 [et al., 2014 [et al., 1991 [et al., 1991 [et al., 2009 [et al., 2012 [et al., 2007 [et al., 2009 [As already noted for raw meat and meat-processing environments, also in the Mediterranean-style sausages at the end of ripening, serotypes 1/2c, 1/2a and 1/2b are more often detected , while l., 1991 ). In Ital., 2009 ; Pontelll., 2012 ). Despitl., 2007 ) were rel., 2009 ).L. monocytogenes from various sources, including raw meat, slaughterhouse environments, production processes and post-processing conditions. In order to prevent these contamination sources, good manufacturing practices, correct sampling schemes, adequate cleaning and disinfection procedures and HACCP principles have to be applied. The use of starter cultures and the correct drying to lower the water activity can minimize the potential for growth of L. monocytogenes in Mediterranean-style fermented sausages. However, the frequent detection of L. monocytogenes at the end of ripening of these products highlights the need for food business operators to apply hurdle technology properly and to control the contamination routes of L. monocytogenes in meat processing plants.The outcome of the previous paragraphs can be summarized from a safety standpoint as follows: Mediterranean-style fermented sausages may be contaminated with


Mindfulness based interventions (MBIs) are increasingly used to help patients cope with physical and mental long-term conditions (LTCs). Epilepsy is associated with a range of mental and physical comorbidities that have a detrimental effect on quality of life (QOL), but it is not clear whether MBIs can help. We systematically reviewed the literature to determine the effectiveness of MBIs in people with epilepsy.Medline, Cochrane Central Register of Controlled Trials, EMBASE, CINAHL, Allied and Complimentary Medicine Database, and PsychInfo were searched in March 2016. These databases were searched using a combination of subject headings where available and keywords in the title and abstracts. We also searched the reference lists of related reviews. Study quality was assessed using the Cochrane Collaboration risk of bias tool.n = 171) and China (Hong Kong) (n = 60). Significant improvements were reported in depression symptoms, quality of life, anxiety, and depression knowledge and skills. Two of the included studies were assessed as being at unclear/high risk of bias - with randomisation and allocation procedures, as well as adverse events and reasons for drop-outs poorly reported. There was no reporting on intervention costs/benefits or how they affected health service utilisation.Three randomised controlled trials (RCTs) with a total of 231 participants were included. The interventions were tested in the USA  contains supplementary material, which is available to authorized users. The prevalence of stress, anxiety, and depression is higher among people with epilepsy when compared with the general population, and suicide rates are similarly elevated –5. The pStress is widely recognised as a risk factor for developing both anxiety and depression, and may also be a trigger for seizures in people with epilepsy . For exa…psychotherapy can improve depression and anxiety in patients with epilepsy”. In this context, Tang et al.  ). In tern et al.  found th1,106 = 0.35, p = 0.555). No significant difference was found between groups on the DCSES in Thompson et al. [1,37 = 2.14, p = 0.152) and Thompson et al. [equally effective regardless of anti-depressant medication or psychotherapy” (however study was not powered to detect this).The intervention group in Thompson et al.  were alsn et al.  . In addition, a greater decrease in depressive symptoms was found among the intervention group than the TAU group which approached significance for the PHQ-9 , and when the analysis was limited to those who provided both baseline and interim data the results were significant .Thompson et al.  reportedp = 0.125 both groups). This implies that the improvement in BDI-II scores was of no clinical significance.In Tang et al.  there wap < 0.001, hp2 = 0.288, 95% CI −6.44, −1.76). Using McNemar tests, it was shown that there was a clinically significant reduction in the MT group (p = 0.012) but not the SS group (p = 0.065) between pre-and post-intervention.Only Tang et al.  measured1,106 = 8.02, p = 0.006), associated with number of sessions attended, while the improvement in Thompson et al. [1,37 = 3.029, p = 0.090). In both studies physical and mental health QOL measures improved , with the improvement in the intervention group being clinically important in more participants and statistically significantly better (χ2 (1) = 4.356, p = 0.037, φ = 0.269). Other aspects of QOL were also found to have improved including energy, mood, medication effect and seizure worry.An epilepsy specific QOL measure was used in Tang et al.  - Qualitn et al.  approachn et al. ), but wen et al.  found stThompson et al.  also mea1,37 = 4.75, p = 0.036 [1,106 = 6.01, p = 0.016 [2,35 = 0.47, p = 0.63).Change in knowledge and skills relating to depression were assessed in Thompson et al.  and Thom = 0.036 ; F1,106  = 0.016 ) with im = 0.016  noted thsignificantly negatively correlated with change in BDI score ”. In addition, mBDI scores were found to be significantly associated with changes in knowledge and skills scores  in Thompson et al. [According to Thompson et al. , a changn et al. . This stCognitive functioning was assessed using a number of measures in Tang et al. . These ineither the participants nor the project staff were blinded to the group assignment”. The study was also judged as being at high risk of attrition bias because of missing data not being described and further due to the study’s repeated measures design, only participants who completed interim assessments were included in analyses. The Thompson et al. [Using the Cochrane Collaboration ‘Risk of Bias’ tool Table , studiesn et al.  study waThis review identified three studies which reported the findings of RCTs utilising MBIs in the treatment of people with epilepsy. The primary outcomes assessed in the three included papers were depression , 35 and “smaller differences seen in self-efficacy and self-compassion, or changes seen at follow-up”. In addition, all studies noted their results and generalisability were limited by taking place in just one site [This review included only three articles for final data extraction which limits the applicability of the findings. Despite positive findings, their generalisability and reliability are limited by several factors. As previously noted two of the studies were at unclear/high risk of bias - randomisation and allocation procedures, adverse events and reasons for drop-outs were poorly reported. Furthermore, two of the papers were described as being underpowered - Thompson et al.  highlighone site , 36, or one site . All stuDemographic and epilepsy characteristics of participants were poorly reported in Thompson et al.  and Thoma possible beneficial effect on seizure frequency” while “no reliable conclusions” could be reached on the effects of psychological treatments on psychological outcomes and QOL [To our knowledge no other systematic reviews have focused on the use of MBIs alone for people with epilepsy. However other systematic reviews have included a wider range of psychological treatments, some involving aspects of mindfulness. A review of psychological treatments for epilepsy  suggested there may be “ and QOL  (has bee and QOL  examined and QOL ) for peoAs the scope of this review was restricted to MBIs, interventions that included only some aspects of mindfulness were excluded. For example, Acceptance and Commitment Therapy (ACT) and Yoga for patients with drug-refractory epilepsy have been found to improve seizure frequency and QOL in RCTs , 43. YogThe findings of this review were limited due to the small number and poor quality of studies included. It was not possible to conduct a meta-analysis and results were therefore presented in a narrative format. In addition, we were unable to locate the full paper for one study at the full paper screening stage – the paper was therefore excluded. Furthermore, for pragmatic reasons our search strategy did not include an extensive grey literature search. However we did conduct a basic (as opposed to advanced) search of Google and searched electronic databases that index grey literature items. A strength is that as previously noted, we are not aware of another review focusing on the use of MBIs for people with epilepsy and it has therefore been valuable in determining the extent of existing research in this area.Further research is required before conclusions can be reached on the effectiveness of mindfulness as a therapeutic intervention for people with epilepsy. In order to establish longer-term outcomes of participation in MBIs, larger RCTs with longer follow-up periods and active control groups are required along with more detailed information relating to participants’ epilepsy.


Using reports of forest losses caused directly by large scale windstorms  from the European forest institute database (comprising 276 PD reports from 1951–2010), total growing stock (TGS) statistics of European forests and the daily North Atlantic Oscillation (NAO) index, we identify a statistically significant change in storm intensity in Western, Central and Northern Europe (17 countries). Using the validated set of storms, we found that the year 1990 represents a change-point at which the average intensity of the most destructive storms indicated by PD/TGS > 0.08% increased by more than a factor of three. A likelihood ratio test provides strong evidence that the change-point represents a real shift in the statistical behaviour of the time series. All but one of the seven catastrophic storms (PD/TGS > 0.2%) occurred since 1990. Additionally, we detected a related decrease in September–November PD/TGS and an increase in December–February PD/TGS. Our analyses point to the possibility that the impact of climate change on the North Atlantic storms hitting Europe has started during the last two and half decades. As pointed out by Feser et al.Studies of historical large scale storms have mostly focused on the meteorological parameters 134et al.et al.et al.et al.20−1 or more. On the other hand, Seidl et al.Forests and forested area are growing quickly in Europe1213http://www.efiatlantic.efi.int/portal/databases/forestorms/). All of the storms included in the analysis have caused PD/TGS of at least 0.012%, and they were validated to be of large scale (>500 km in diameter) with the reanalysed weather datasets provided by Wetterzentrale and NCAR/NCEPIn this paper, we present a systematic approach for combining forest growth12et al. (2010) totals around 960 Mm3 PD in 60 years. Forest losses have been greatest in Central Europe, where they have totaled approximately 340 Mm3 in 1951–2010. In Northern and Western Europe, the losses have been around 260 Mm3 and 290 Mm3, respectively. The most heavily affected countries have been France (≈260 Mm3), Germany (≈240 Mm3) and Sweden (≈220 Mm3). Largest individual damages have resulted from the storms Vivian and Wiebke , Lothar and Martin , Gudrun , Kyrill ; and Klaus . The bias caused by increased TGS values was removed from our analyses by using PD/TGS, rather than PD, as the proxy variable that indicates storm intensity. Additionally, in our analyses, we only focused on a validated set of large scale storms indicated by PD/TGS ≥ 0.012%. The decadal PD/TGS in Europe from 1951 to 2010 for the validated set of storms is shown in TGS has increased in Western, Central and Northern Europe from 1951 to 2010  by nearlet al.−1 . It has recently been shown−1. Spruce trees that can be uprooted account roughly for 30–40% of the TGS in Europe. Thus, when the gust speeds exceed 42 ms−1, the potential for forest damages increases considerably. This can be seen from www.europeanwindstorms.org ((c) Copyright Met Office, University of Reading and University of Exeter. Licensed under Creative Commons CC BY 4.0 International Licence: http://creativecommons.org/licenses/by/4.0/deed.en_GB). The blue and red areas representing uprooting and tree breakage regimes, respectively, are meant to be illustrative rather than quantitative.Usbeck et al.et al.Hanna 2-value is, in fact, very close to zero). This is broadly in agreement with the findings of Allan et al.2 value of the correlation is 0.65; if the last decade is left out, the value is 0.75. While this could be a result of a sampling error in a data set of just six points, Hanna et al.et al.It is clear from To answer the question whether the apparent change around 1990 is real or not, we utilize the generalized likelihood ratio testIn addition to the aforementioned procedure, we also test the hypothesis of a change-point at 1990 in a model that explicitly takes into account the effects of NAO index on PD/TGS. The model in question has the form of a Generalized Linear Model (GLM), where the covariates are the yearly-averaged NAO indices and the dependent variables are the PD/TGS values. The shape parameter of GPD is modeled as We made a systematic climatological study of 56 large scale windstorms based on data of significant forest damages (PD/TGS ≥ 0.012%) from 1951 to 2010 in 17 countries representing Western, Central and Northern Europe. The value of the study arises from the fact that the data is independent of meteorological observations – which, of course, do not provide complete coverage of the area – and of meteorological models.et al.et al.et al.−1 (see www.europeanwindstorms.org)Our results confirm that in the past three decades (1981–2010), PD/TGS in European forests caused by severe extratropical storms have become 3–4 times as large, per decade, as they were in the 1950’s, 1960’s and 1970’s. During the past 60 years, also the TGS has almost doubled in Europe. Unlike Schelhaas et al.−1, that there has been a decline in European windstorms during the present century. At first sight, this appears contradictory to our finding of the change-point in 1990. However, one should note that Dawkins et al. only examined the period 1979 onward, and thus the decline is relative to the two last decades of the 20th century that were dominated by the catastrophic storms of 1990 and 1999. Our data, on the other hand, suggests that the storminess in the first decade of this century was still at a clearly higher level than it was prior to 1990.Dawkins et al.In accordance with earlier studies , the dates of occurrence of primary damages and the reanalysed weather datasets provided by Wetterzentrale and NCAR/NCEPStorm intensity was defined by PD/TGS/storm count. Storm intensity and storm count were investigated relative to the monthly NAO-index. Climatic variability of the severe large scale storms  was assessed for seasons DJF and SON. The climatic assessment was carried out using annual seasonal averages but the results are presented on decadal scale to concentrate on climatic variability and change.How to cite this article: Gregow, H. et al. Increasing large scale windstorm damage in Western, Central and Northern European forests, 1951-2010. Sci. Rep.7, 46397; doi: 10.1038/srep46397 (2017).Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.


As the root canal system considered to be complex and unpredictable, using root canal irrigants and medicaments are essential in order to enhance the disinfection of the canal. Sodium hypochlorite is the most common irrigant in endodontics. Despite its excellent antimicrobial activity and tissue solubility, sodium hypochlorite lacks some important properties such as substantivity and smear layer removing ability.The aim of this review was to address benefits and drawbacks of combining sodium hypochlorite with other root canal irrigants and medicaments.According to the reviewed articles, NaOCl is the most common irrigation solution in endodontics. However, it has some drawbacks such as inability to remove smear layer. One of the drawbacks of NaOCl is its inability to remove the smear layer and lack of substantivity.The adjunctive use of other materials has been suggested to improve NaOCl efficacy. Nevertheless, further studies are required in this field. However, due to the fact that 35 to 50% of the surface area of the canal system remains untouched by endodontic instruments using an appropriate root canal irrigantis necessary in order to improve disinfection of the root canal system [In ideal form, irrigants should have antimicrobial action, tissue-dissolution activity, demineralization, lubrication, and ability to removing smear layer and debris .2As NaOCl has excellent antimicrobial action and also tissue solubility, it has been used in endodontics as the most common irrigation solution. NaOCl is available as 1-15% aqueous solutions with alkaline pH (around 11) .One important drawback of NaOCl is its inability forsmear layer removal . Therefoi.e. dentin) and are released gradually. Chlorhexidine (CHX) is a cationic bis-guanide with residual antibacterial activity. Combination of NaOCl and CHX has been proposed to increase their antibacterial action [One of the other drawbacks of NaOCl is the lack of substantivity . Substanl action .The antibacterial effect of NaOCl can be achieved in two different ways. A high concentration of chloride ions produces high cytotoxicity, which explains the excellent antibacterial effect. But at a lower pH, the high proportion of hypo chloric acid is explanation of the antibacterial effect. The fact that the proportion of chloride ions decreases in the solution does not mean that the solution will lose its antibacterial effect -4.3Adding EDTA to NaOCl can decrease the pH of NaOCl in a time-dependent manner. This may affect free chlorines in solution and increase in chlorine gas and hypochlorous acid, subsequently decreases the hypochlorite ion , 10.Equal proportions of 1-2% NaOCl with 17% EDTA may result in pH of 8.0 from an initial value of 10 after 48 hours. However, when mixed in a 1:3 ratio, pH was stable during 48-hour time, possibly because of immediate interaction between solutions . Baumgaret al. [et al. [Zehnder et al.  conclude [et al.  are in aet al. [et al. [Girard et al.  evaluate [et al.  conclude [et al. .et al. [et al. [Saquy et al.  evaluateet al. , 15. Gra4The combination of CHX and NaOCl has the ability to increase their antibacterial characteristics. Furthermore, CHX has a unique property named substantivity  . The assOne study using electrospray ionization concluded that 2% CHX may rapidly produce orange-brown precipitate in combination with 1% and 5.25% NaOCl, and orange-white precipitate in combination with 0.16% NaOCl . On the et al. [Some studies have been done to show the chemical composition of the flocculate created by association of CHX with NaOCl -22. Marcet al.  combinedet al. [ex vivo. They showed a decrease in count of patent dentinal tubules in coronal and middle thirds of the canal between irrigation with irrigation with 5.25% NaOCl and 5.25% NaOCl/2% CHX [et al. [et al. [et al. [Using nuclear magnetic resonance, Krishnamurthy and Sudhakaran  detectedet al.  showed t [et al.  studied  [et al.  conclude [et al.  also sho [et al. .In conclusion, combination of CHX and NaOCl may cause some color changes and also the formation of an insoluble precipitate may interfere with canal seal. The canal system can be dried using sterile paper points before the final rinse by CHX.5et al. [et al. [ALX is a disinfectant with greater affinity for major virulence factors than CHX . Kim et et al.  showed t [et al.  in 2017  [et al.  showed g6It has been shown that good results may be obtained by the association of NaOCl to CA in permanent teeth -36. Thiset al. [Zehnder et al.  concludeet al.  showed t7MA is used as a conditioner in dental adhesives . For smeet al. [There is only one study on the interaction between NaOCl and MA. Chandak et al.  showed t8in vitro [High surface tension is one of the major drawbacks of NaOCl. Adding surfactants increase the ability of NaOCl to penetrate the main canal and canal irregularities in vitro , 46. Comet al. [et al. [Stojicic et al.  concludeet al. . William [et al.  revealedet al. [Another issue is the effect of surfactants on the stability of NaOCl. Adding surfactants modifies the stability of NaOCl , 50. Ethet al.  evaluateet al. [et al. [Cameron et al.  showed tet al. . Howeveret al. . In addi [et al.  showed t9Octenisept  is an antimicrobial/antibiofilm agent can be potentially combined with NaOCl during root canal treatment. A recent study showed that the whitish precipitate formed with the NaOCl-OCT mixture was identified as phenoxyethanol, a compound already present in OCT, and it may occlude dentinal tubules .Bukhary and Balto  showed g10et al. [Chlor-XTRA is a new NaOCl-based irrigation solution composed of 5.85% NaOCl and a detergent to reduce surface tension. Its appearance is clear light yellow green. It is completely soluble in water with a chlorine-like odour. It is 2.6 times more digestive than regular NaOCl. Furthermore, its wetting ability is 2.5 times greater than regular NaOCl . Recentlet al.  demonstret al. [et al. [Jungbluth et al.  showed t [et al.  showed t11et al. [A new modified NaOCl solution (Hypoclean) has been introduced by Giardino. This solution is a detergents-based irrigant composed of 5.25% NaOCl and 2 detergents . Recentlet al.  showed t122 are samples of such usage that utilize chemicals with the aim of facilitating the tissue remnant removal [Root canals cannot be cleaned by physical instruments alone. Chemicals can help to supplement this procedure. Irrigation with NaOCl and intracanal placement of Ca(OH) removal .2 and NaOCl. Hasselgren et al. [2 paste has the ability of tissue dissolving after 12 days. They also showed an increase in tissue dissolving of NaOCl after pretreatment with Ca(OH)2 for 30 minutes up to 7 days. In another study, Metzler and Montgomery [2 paste for 7 days followed by irrigation with NaOCl can clean canal isthmuses better than hand mechanical preparation alone. Yang et al. [2 partially dissolved pulp tissue. The anaerobic environment could not alter the tissue dissolving property. Wadachi et al. [2 for seven days or NaOCl for >30 seconds. Combination of NaOCl and Ca(OH)2 was more effective than separate protocols. On the other hand, some researches have shown that Ca(OH)2 may be ineffective for pulpal tissue dissolving. Morgan et al. [2 for tissue dissolving. In summary, it seems that pretreatment with Ca(OH)2 medicament may increase the tissue dissolving effect of NaOCl.Some controversies have been reported regarding the synergistic effects of Ca(OH)n et al.  showed tntgomery  concludeg et al.  showed ti et al.  also shon et al.  also sho13MTA has been produced as gray and white MTA; both with the base of Portland cement. Hydrophilic powder needs some moisture for optimal setting. Traditionally, MTA powder is mixed with supplied sterile water in a 3:1 powder/liquid ratio. Different liquids have been suggested for mixing with the MTA powder -66.et al. [Using differential scanning calorimetry, Zapf et al.  concludeet al. , immersiet al. [Ballester-Palacios et al.  showed tet al [et al. [Al-Anezi et al . showed  [et al.  assessedAccording to this study and other documents -77, it cDue to the excellent antimicrobial activity and tissue solubility, NaOCl is the most common irrigation solution in endodontics. However, it has some drawbacks such as inability to remove smear layer. One of the drawbacks of NaOCl is its inability to remove the smear layer and lack of substantivity. Therefore, the adjunctive use of other materials has been suggested to improve its efficacy.Combining NaOCl with EDTA decreases free available chlorine dramatically. However, using EDTA or CA was suggested removing the smear layer associated with mechanical instrumentation.Combination of CHX and NaOCl has been suggested to enhance their antibacterial activity and induce substantivity.Combining NaOCl with MA and CA reduces free available chlorine.Regarding adding surfactants to NaOCl, studies regarding the effect of surfactants on the tissue solubility of NaOCl are controversial. However, surfactants reduce free available chlorine in NaOCl solutions.2 may enhance the ability of tissue dissolving of NaOCl.Pretreatment with Ca(OH)NaOCl is detrimental to MTA reaction product formation. Furthermore, immersion of white MTA in NaOCl may result in the formation of brown discoloration. In addition, NaOCl significantly lowers the surface roughness of MTA, decreases its setting time, improves its handling properties and increases its cytotoxicity.Combining NaOCl with some other irrigating solutions such as MTAD, oxygen peroxide, and strong acids (like phosphoric acid and nitric acid) should be studied in the future.


They concluded that the animals scratched ‘primarily because of an immune/stimulus itch, possibly triggered by ectoparasite bites/movements’ [acute if they have rapid onset and/or short course or chronic if they extend over a prolonged period of time. The response to different types of stressors  also reflects this difference [In their interesting article, Duboscq et al.  used behvements’ , pp. 1–2fference .et al. [et al. [The authors put forth different hypotheses on self-directed behaviours related to the effect that parasitological (presence of ectoparasites), environmental  and social factors  have in affecting the rates of self-directed behaviours, including scratching. Such hypotheses are presented as alternative in the first part of the Introduction , p. 2 anet al.  also expet al. , p. 2 oret al. , p. 11, et al. ,5 whereaet al. . In humaet al. . Whateve [et al. . In maca [et al. . In prim [et al. –15. Hencet al. [if but when a certain factor can be more effective than another in producing scratching. Stressors can be additive but they operate in the short- or long-term depending on whether they are transient (acute) or prolonged (chronic) [Once established that the different factors are not alternative and that their relationship with scratching has been demonstrated, it is worth focusing on the role that each factor can have in relation to the time scale. We will particularly focus on scratching. The framework of Duboscq et al.  could bechronic) . Thus, iet al. study group, the scratching due to long-lasting ectoparasite load  can be the primary component of the overall baseline scratching levels. However, this does not exclude the possibility that scratching can significantly increase—compared with baseline—in response to a transient stressor, such as a conflict. In the short period around the event, the aggression can be primarily responsible for scratching variation but only a sequential, temporal analysis can unveil this aspect [t0) and the tight time window (t0 − t1) immediately following the aggressive event in order to detect the variation of scratching levels [t0 and t1 cannot be linked to parasite load if the load is not significantly different between t0 and t1. There is no reason to believe that, in the absence of any other additional perturbing factor, the ectoparasite load varies significantly in the minutes immediately preceding and following the stressful event. Of course, an extra control measure can be taken in this respect if deemed necessary. It may be questioned that in the short term a change in the parasite activity , andow t0 − t immediatet al. [In conclusion, the relative weight of the different factors affecting scratching can change depending on the time scale and timing selected. The article by Duboscq et al.  is valua


The concept of mental toughness (MT) has garnered substantial interest over the past two decades. Scholars have published several narrative reviews of this literature (e.g., Connaughton et al., r = 0.67 at p < 0.05; Cowden et al., r = 0.171 at p < 0.05; Cowden et al., Well-executed systematic reviews offer many advantages for summarizing, synthesizing and integrating findings across studies when compared with non-systematic evaluations (e.g., clear and accountable methods; see Gough et al., Given the predominance of self-reported MT among the primary studies of Lin et al.'s  systematLin et al.'s  findingsAs the first systematic review of the quantitative literature on the associations between MT and key correlates, I commend Lin et al.  for theiThe author confirms being the sole contributor of this work and approved it for publication.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Selegiline is used to treat Parkinsonian patients. Other indications of its use have recently been discovered.Scouting special and beneficial side effects of selegiline treatment.Two-year old male Wistar rats were daily treated with 0.25 mg/kg of selegiline s.c. (subcutaneous injection). The rats were sacrificed following a four-weeks’ treatment.Mass of testes, number of sperms, progressive motility of sperms, and their viability definitely increased.Selegiline can successfully be used to stop/counterbalance certain symptoms of aging. Pharmacet al .Peculiar pharmacological characteristics of selegiline  were discovered by Knoll and Magyar , was proet al [The original indication of selegiline has had its renaissan. Gordon et al  carried et al , 9.et al [Knoll  and Knolet al  experimein vivo experiments on rats to show individual differences in sexual activity and also how it can be improved by treatments with selegiline [et al [tuberculum olfactorium, corpus striatum and substantia nigra in the state of resting [Preliminary pharmacological experiments aimed at the use of selegiline in the possible improvement of human reproduction power. The initial process of reproduction  in some mammalian organisms contain two steps. One of them is when a male approaches a female, they copulate so that the sperms of the male enters the sexual organ of the female. Dalló , Dalló alegiline -23. Dalle [et al  carried e [et al . Knoll ce [et al , 24 dedu resting . SelegilKnoll, Dalló and co. -24 classAnother essentially important factor of reproduction is the entire quality of sperms that is the number of sperms, their progressive motility and viability (ratio of live versus dead sperms).et al [et al [Clinical observations by Urry et al , 26 showl [et al  found thIn vitro effects of caffeine and theophylline on human semen quality were tested by Dougherty et al [-2 through 10-6 M concentrations without any change in sperm motility and viability of sperms.ty et al  from 10-et al [Recent publications by Mihalik et al -31 treatet al gave the first direct proof of penetration of selegiline into the testes of rats [Tekes  of rats . Followi of rats .Similar results were found when using a rabbit model . The selet al [Zieher et al  determinet al ,Contrary to the effect of selegiline on the physical/copulatory activity of rats and on the brain’s dopamine concentration, the concentration of deprenyl in the testes did not show any definite increase following a four-weeks’ treatment using selegiline in aged rats.This paper is meant to show how selegiline treatment influences the “quality” of sperms following chronic treatments with their usual therapeutic dose.22.11) was the kind gift of Chinoin Chemical and Pharmaceutical Works(Budapest); its present name is Sanofi-Aventis/Chinoin .Selegiline .2.32.3.1Ten rats (five treated and five controls) were o.c. treated with a 0.25 mg/kg daily dose of selegiline for four weeks. Treatments were performed according to the experimental protocol approved by ethical committee of ANTSZ , permission number: 1810/03/2004. The experimental conditions conformed to 86/509 EEC (European Economic Community) regulation. The control group received only the physiological salt solution.2.3.2The testes and epididymes were removed and the cauda epididymes were ligated at autopsy and kept in PBS  until semen evaluation. Following the separation of the complete epididymis, the testicles were weighed. The epididymes were placed in Petri dishes containing 0.5 mL PBS with 10 mg/mL of BSA (Bovine Serum Albumin). Cauda epididymes were minced with iridectomy scissors, by five deep cuts. The Petri dishes were covered and incubated at 37 °C for 10 minutes. Prior to the assessment of sperm motility, 10 µL of supernatant was dropped at the prewarmed slides and covered with a lid. The sample was held at 37 °C while the velocity parameters, including the progressive motility of minimum 100 sperms at 10 fields, were observed. Progressive sperm motility was evaluated using the standard method of Bearden and Fuquay . The meaThe total sperm number was determined by using a hemocytometer. Approximately, 10 µL of the diluted semen was added to 390 µL of Hank’s Balanced Formaldehyde Solution. Ten microliters of semen, fixed in formaldehyde were transferred to the counting chamber of the hemocytometer and the cells were counted with the help of a light microscope (200x). The sperm cell number of ten large squares multiplied by the dilution rate gave the original sperm cell count.Sperm cell morphology was evaluated by stain of Eosin-Nigrosine and Spermac Stain at a 400x magnification  as it is prescribed .2.3.3Small pieces of each testicle and adrenal gland were precisely weighed by analytical scales. The pieces were homogenized with PBS by a tissue homogenization (Janke&Kunkel Ika-Werk Ultra Turrax). The homogenates were centrifuged at 4000 rpm for 20 minutes. The supernatant was stored at - 20 °C. The stock-dilution of tissue was 1g/10ml at the homogenization which was 1:5 diluted individually for the determination of tissue hormone concentrations. Serum and tissue cortisol and testosterone concentrations were measured by ELISA . The intra-assay variability (CV) of cortisol ELISA was 3.3%; the inter-assay CV was 6.1%. The intra-assay CV of testosterone ELISA was 3.21%; the inter-assay CV was 4.74%.et al [et al [The testes were halved, homogenized in a solution of 0.1 M trifluoroacetic acid, centrifuged and their dopamine contents were measured by HPLC according to Rao et al . The anal [et al  containi31).Important characteristics of sperms show definite improvement in their progressive mobility (Table 2).The average mass of the testes, number of sperms and viability (live/dead sperms) were also increased relative to these characteristics of rats in the control group. Cortisol content in the serum increased, while that in the adrenal gland significantly decreased. Selegiline treatment definitely affected the testosterone level in the sera, the adrenal glands and testes, whose levels decreased (Table 4Hársing and Vizi  did not et al [et al [Zieher et al  raised tl [et al  suggesteet al [et al [et al [in vitro. Ramirez et al [Our results do not correspond to those of Urry et al , 26, andl [et al  as low tl [et al  and Bavil [et al  used catez et al  publishe


Multiple primary lung cancer may present in synchronous or metachronous form. Synchronous multiple primary lung cancer is defined as multiple lung lesions that develop at the same time, whereas metachronous multiple primary lung cancer describes multiple lung lesions that develop at different times, typically following treatment of the primary lung cancer. Patients with previously treated lung cancer are at risk for developing metachronous lung cancer, but with the success of computed tomography and positron emission tomography, the ability to detect both synchronous and metachronous lung cancer has increased.We present a case of a 63-year-old Hispanic man who came to our hospital for evaluation of chest pain, dry cough, and weight loss. He had recently been diagnosed with adenocarcinoma in the right upper lobe, with a poorly differentiated carcinoma favoring squamous cell cancer based on bronchoalveolar lavage of the right lower lobe for which treatment was started. Later, bronchoscopy incidentally revealed the patient to have an endobronchial lesion that turned out to be mixed small and large cell neuroendocrine lung cancer. Our patient had triple synchronous primary lung cancers that histologically were variant primary cancers.Triple synchronous primary lung cancer management continues to be a challenge. Our patient’s case suggests that multiple primary lung cancers may still occur at a greater rate than can be detected by high-resolution computed tomography. In both men and women, lung cancer is the leading cause of cancer-related death. Risk factors associated with lung cancer include environmental risk factors, genetic factors, and tobacco smoke exposure. Patients with lung cancer are at an increased risk of developing secondary lung cancers at the same time as the first (synchronous) or later in life (metachronous). In these cases, it is critical to determine whether the secondary tumor is an independent primary tumor or a recurrence or metastasis of the first primary tumor, because this determination influences how the disease is staged and managed as well as the patient prognosis.et al. [In 1924, the first case of two distinct primary lung cancers was published by Beyreuther et al. , whereaset al. .We identified a unique case of triple SLC, including adenocarcinoma, squamous cell carcinoma, and mixed small and large cell neuroendocrine carcinoma, which has poor prognostic implications. Biopsy of the other lesions helped us differentiate metastatic disease from primary lung cancer. The fact that our patient had three different primary cancers made treatment challenging.A 63-year-old homeless Hispanic man diagnosed with lung cancer 5 months previously in our hospital presented with ongoing sharp chest pain of 2 weeks’ duration, shortness of breath, chronic dry cough, and weight loss of 20 pounds within 2 months. The patient also had experienced physical activity limitations for the previous 2 months. He denied experiencing diarrhea, nausea, vomiting, or abdominal pain, and he did not have anorexia, fever, chills, or phlegm production.The patient’s past medical history included a cerebrovascular accident with residual left-sided weakness, bronchial asthma, lung adenocarcinoma (stage IIIB) diagnosed by computed tomography (CT)-guided right upper lobe biopsy 5 months previously. He was receiving adjuvant cisplatin-based chemotherapy. His social history included 55 pack-years of smoking and a family history of cancer; his mother had colon cancer, and his brother had an unknown type of cancer. He had no environmental exposures. He was taking aspirin and atorvastatin and was using an albuterol inhaler and a fluticasone inhaler.The patient was cachectic and afebrile on physical examination, with a blood pressure of 146/84 mmHg, and his oxygen saturation was 94% with administration of 2 L of oxygen by nasal cannula. He had bilateral grade 3 clubbing and a bronchial breath sound in the right upper lobe. Cardiovascular examination revealed normal heart sounds, and the patient’s abdomen was soft with no organomegaly. In addition, laboratory analyses of the patient’s peripheral blood and urine were normal, although his sodium levels were low.A chest x-ray showed a persistent right upper lobe mass Fig. . This wa1)/forced vital capacity ratio, moderately decreased FEV1, and moderate obstruction.In view of the patient’s new symptoms of acute chest pain and shortness of breath, repeat chest CT was done, which ruled out pulmonary embolism but showed a persistent right upper lobe mass with new mediastinal lymphadenopathy. Positron emission tomography (PET) was performed, which revealed hypermetabolic activity in the 6-cm mass in the right upper lobe , right hilar nodes (SUV 2.8), and 1.5-cm left hilar lymph nodes (SUV 4.9) Fig. . No hypeThe patient underwent bronchoscopy for further evaluation prior to the planned mediastinoscopy. An endobronchial lesion in the left main stem Fig.  was an iWe identified a rare case of triple SLC, including adenocarcinoma, squamous cell carcinoma, and mixed small and large cell neuroendocrine carcinoma.et al. [MPLC can be synchronous (occurring simultaneously) or metachronous (occurring at different times) . The criet al. , is a seet al. .et al. [Antakli et al.  made modet al. . They adet al. .field cancerization, suggests that carcinogenic exposure or genetic factors affect tissues or organs, potentiating many cells in the same area to become transformed [There are multiple challenges associated with diagnosing a second primary lung cancer. First, if the secondary tumor arises within 2 years of the primary tumor, it is challenging to determine whether that tumor is a new primary tumor or a result of a residual metastasis from the original primary tumor. Second, if the secondary tumor is of the same histological type, it complicates the diagnosis of a new cancer because it is plausible that a secondary tumor of the same histological type could be an extension of the original cancer. Third, if the secondary tumor arises in an area impacted by radiotherapy (given as a treatment for the primary tumor), there can be further uncertainty whether the secondary tumor is a result of metastasis from the original tumor rather than a new cancer. Additionally, a synchronous second primary cancer judged to have associated metastatic disease would classify the patient as stage IV, which would likely contraindicate a potentially curative resection. The erroneous designation of a metachronous second primary cancer as a local recurrence might have similar therapeutic implications. A steadily growing hypothesis, known as nsformed .p53 tumor suppressor gene (chromosome 17) occur frequently in lung carcinoma, with rates up to 70% in small cell lung cancer and 50% in non-small cell lung cancer. Studies have shown that p53 mutational analysis is good diagnostic tool for diagnosing multiple SLC in 35 to 66% of cases [Analysis of the clonal origin of tumors can help determine whether multiple lung tumors arise from the same clone and therefore the same tumor. Mutations in the of cases . In addiof cases . Analysiof cases . This anof cases .et al., who showed that surgical intervention is safe and effective for patients with resectable metachronous lung cancer and good pulmonary reserve [stereotactic ablative radiotherapy), or percutaneous image-guided tumor ablation [Multiple synchronous primary lung cancers should be treated as two separate and distinct tumors, including their staging and treatment . Managem reserve . Howeverablation , 17.et al. [et al. [et al. [et al. [et al. [Multiple retrospective analyses have illustrated the prognostic implications of MPLC. Lee et al.  demonstr [et al.  demonstr [et al.  reported [et al.  illustra [et al.  showed tet al. [et al. [et al. [There are four histological lung tumor types: adenocarcinoma, squamous cell, and mixed large and small cell carcinoma. Usually, lung cancers have a single histological type; however, there are reports of patients with MPLC with different histology, including our patient. Jung-Legg et al.  reported [et al.  describe [et al.  reportedMPLC can be defined as synchronous or metachronous, and the management of patients with MPLC continues to be a challenge. Although the use of high-resolution CT has increased the ability to diagnose MPLC, our patient’s case suggests that MPLCs may still occur at a greater rate than can be detected.


Böttiger et al.  present n = 49 to n = 95,072. Given that the total number of analysed cases is n = 126,829, the study by Yasunaga et al. -physicians typically provide more optimal post-return of spontaneous circulation treatments, including therapeutic hypothermia and percutaneous coronary intervention’ . While tn = 18,462). Hagihara et al. [The same limitations apply to the second largest study  is a retrospective analysis of two previous publications, independently describing survival after OHCA in the UK (paramedic-based EMS) and in Germany (physician-based EMS). While survival in Germany was significantly higher, ambulance response times were also shorter in Germany. No information is available on important prognostic factors such as age of patients or percentage of cases with shockable rhythm.The third-largest study by Fischer et al.  (n = 429n = 4144) is a conference abstract presenting limited information. The authors again used the national Japanese OHCA database and the period of data collection overlaps with both Japanese studies described earlier.The work by Kojima et al.   of patients suffering from OHCA. The pooled sample size with n = 126,829 was dominated by two Japanese studies [They correctly mention significant heterogeneity among the study sizes (ranging from  studies , making Second, von Vopelius-Feldt and Benger point out that the study by Fischer et al.  did not Third, it is correct that the cited publication by Kojima et al.  is a conA major limitation in this whole scientific field – and as discussed in our publication  – is tha