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Paraphilia is a condition in which the sexual excitement relies on fantasizing and/or participating in unusual sexual behaviors although the line between "normal" and "abnormal" has been disputed. The project aimed to explore which sexual fantasies and behaviors are common and uncommon in the general population. Furthermore, the relationship between sexual fantasies, sexual behaviors, and problematic pornography consumption was examined. Finally, the impact of gender was assessed. Analyses were conducted on a sample of 139 participants. Correlations were found between fantasies, behaviors, and problematic pornography consumption. Furthermore, gender differences were found for both sexual fantasies and problematic pornography consumption. Finally, multiple regression revealed that age, gender [Men], fantasies, and behaviors were significant predictor of problematic pornography consumption. Those findings are in-line with previous studies which highlighted that the threshold to consider a sexual practice as being abnormal needs to be reconsidered on the basis of self-reported fantasies and behaviors in the general population., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Stalking is a significant social issue. The inconsistency as to what defines stalking has resulted in the creation of different methods to measure the crime. However, there has been minimal work done that assesses the severity of individual stalking behaviors. The aim of the present study was to assess the level of stalking behavior in terms of severity within a randomly selected sample of 924 cases from the database of the National Stalking Helpline. Item response theory analyses were used to assist in developing a scale that displays the ranking order of each stalking behavior. These analyses were also used to examine whether the stalking behavioral items created a single continuum of severity of stalking. Results indicated that 16 stalking behavioral items of the 28 items present in the National Stalking Helpline, best represented the severity of stalking. Unwanted communication behaviors such as text messages and phone calls were located at the lower end of the severity scale, whereas criminal damage and death threats were mapped on the higher end of the continuum. The findings also revealed that the 16 items categorized under 6 factors. The findings of the present study provide many implications for stalking agency professionals and criminal justice responses.

Stalking can be defined as a pattern of repeated, unwanted behaviors by one person to another. These behaviors may take the form of communicative intrusion, third-party contact, and physical or sexual assault. The individual stalking behaviors experienced by victims have been found to differ in every case, specifically dependent on their stalker-victim relationship. Recent tragedies have shown that the police force generally underestimates the risk of ex-intimate stalking and harassment behaviors. This study aims to identify patterns of stalking behaviors from a victim's perspective, specifically, whether there are any patterns of behavior among the ex-intimate stalkers, in comparison with acquaintance or stranger stalkers. Information from the accounts of individuals who had reported unwanted experiences as a result of one of three stalker-victim relationships (ex-intimate, acquaintance, or stranger) was extracted from the National Stalking Helpline database. Analyses were conducted on a sample of 1,626 victims' reports. One-way analysis of variance (ANOVA) and multiple logistic regressions were conducted to establish any common patterns of behavior among the subgroups of stalkers and to ascertain which behaviors increased the odds of being categorized as an ex-intimate stalker. Results indicated that ex-intimate stalkers presented considerably more behaviors than acquaintance or stranger stalkers; some of which included third-party contact, criminal damage, physical assault, and sexual assault. Results also indicated that ex-intimate stalkers presented more severe behaviors than the other subgroups. The majority of stalking behaviors were found to produce a statistically significant predictive contribution to being classed as an ex-intimate stalker. The findings in this study highlight that common misconception surrounding ex-intimate stalking still exists at every level of the Criminal Justice System. Results and implications for future research are discussed.

Degree of injury, as measured by the Homicide Injury Scale (HIS), was examined to advance understanding of the dynamics of sexual killing. A total of 350 nonserial, male sexual killers were included, and the different ways that the sexual element of their offenses and the act of killing were connected was accounted for by determining that cases were either directly sexual (the sexual element and killing were closely bound), or indirectly sexual (killing was not a source of sexual stimulation). The two groups, direct and indirect sexual killers, were each subjected to multiple linear regression analyses to examine the group-specific relationship between level of injury and predictor variables previously found to be associated with increased severity of attack. No differences in the mean total HIS scores between the indirect and the direct cases were found, suggesting a comparable emotional intensity between the groups. However, given that the groups differed in terms of the functional role of fatal violence, severity of attack could not be sufficiently explained as driven by anger. In line with this hypothesis, different predictors appeared to be associated with increased degree of injury sustained by victims of indirect compared with direct sexual killers. As such, situational components appear to play a role in the behavior of indirect sexual killers, whereas the behavior of direct perpetrators tends to be linked with the enactment of existing deviant fantasies. The role of anger in sexual homicide is discussed further, and overall, it is argued that irrespective of whether violence was initially driven by anger, evidence of sexual arousal to severe violence must be scrutinized within sexual homicide research as well as in psycholegal contexts.

Phylogenetic analyses based on mitochondrial 16S rDNA, nuclear 28S rDNA, and morphological and ecological traits of Aulactinia, Urticina and Cribrinopsis sea anemones inhabiting the Arctic-boreal region indicate discordances between trees derived from molecular sequences and those based on morphological traits. Nuclear genes were more informative than mitochondrial and morphological datasets. Our findings indicate that 16S rDNA has limited applicability for phylogenetic analyses at lower taxonomic levels and can only be used for distinction of families. Although 28S rDNA allowed for the classification of distinct genera, it could not confirm that species of Urticina and Cribrinopsis , which appeared to be closely related, were correctly separated into two different genera. The nuclear tree revealed inconsistencies between specimens belonging to European Urticina crassicornis and Pacific U. crassicornis ; the latter seems to be a different species. In contrast to Pacific U. crassicornis , the specimens collected from different localities in the Barents Sea are on the same tree branch. The same was observed for specimens of Aulactinia stella . Both species brood their young internally. The dispersal of sea anemones with brooding juveniles seems to be less limited than expected and might be sufficient to settle habitats more than a thousand kilometers away.

The study investigated whether different types of sexual homicide perpetrators are more or less skilled at delaying detection. A newly proposed direct/indirect typology was used alongside information about the time of arrest, the frequency of specific precautions as well as the impact of forensic strategies used by the perpetrators to examine skill at delaying detection. The results indicated that the time from the killing to the arrest, as measured in days, was longer for the direct than the indirect sexual killers. Despite the fact that the direct aggressors were better at delaying detection, overall the indirect and the direct offenders did not differ in the frequency of use of most of the precautions. However, different forensic awareness strategies were more efficacious for the direct and the indirect offenders. These results are discussed in relation to the crime scripts for the two perpetrator groups.

Interactions between ecological communities of herbivores and microbes are commonly mediated by a shared plant. A tripartite interaction between a pathogenic fungus-host plant-herbivorous insect is an example of such mutual influences. In such a system a fungal pathogen commonly has a negative influence on the morphology and biochemistry of the host plant, with consequences for insect herbivore performance. Here we studied whether the biotrophic fungus Podosphaera ferruginea, attacking the great burnet Sanguisorba officinalis, affects caterpillar performance of the endangered scarce large blue butterfly Phengaris teleius. Our results showed that the pathogenic fungus affected the number and size of inflorescences produced by food-plants and, more importantly, had indirect, plant-mediated effects on the abundance, body mass and immune response of caterpillars. Specifically, we found the relationship between caterpillar abundance and variability in inflorescence size on a plant to be positive among healthy food-plants, and negative among infected food-plants. Caterpillars that fed on healthy food-plants were smaller than those that fed on infected food-plants in one studied season, while there was no such difference in the other season. We observed the relationship between caterpillar immune response and the proportion of infected great burnets within a habitat patch to be positive when caterpillars fed on healthy food-plants, and negative when caterpillars fed on infected food-plants. Our results suggest that this biotrophic fungal infection of the great burnet may impose a significant indirect influence on P. teleius caterpillar performance with potential consequences for the population dynamics and structure of this endangered butterfly., (© 2017 Institute of Zoology, Chinese Academy of Sciences.)

Prostate Cancer is the most common cancer and the second leading cause of cancer-related death in males. When prostate cancer acquires castration resistance, incurable metastases, primarily in the bone, occur. The aim of this study is to test the applicability of targeting melanoma cell adhesion molecule (MCAM; CD146) with a mAb for the treatment of lytic prostate cancer bone metastasis. We evaluated the effect of targeting MCAM using in vivo preclinical bone metastasis models and an in vitro bone niche coculture system. We utilized FACS, cell proliferation assays, and gene expression profiling to study the phenotype and function of MCAM knockdown in vitro and in vivo . To demonstrate the impact of MCAM targeting and therapeutic applicability, we employed an anti-MCAM mAb in vivo . MCAM is elevated in prostate cancer metastases resistant to androgen ablation. Treatment with DHT showed MCAM upregulation upon castration. We investigated the function of MCAM in a direct coculture model of human prostate cancer cells with human osteoblasts and found that there is a reduced influence of human osteoblasts on human prostate cancer cells in which MCAM has been knocked down. Furthermore, we observed a strongly reduced formation of osteolytic lesions upon bone inoculation of MCAM-depleted human prostate cancer cells in animal model of prostate cancer bone metastasis. This phenotype is supported by RNA sequencing (RNA-seq) analysis. Importantly, in vivo administration of an anti-MCAM human mAb reduced the tumor growth and lytic lesions. These results highlight the functional role for MCAM in the development of lytic bone metastasis and suggest that MCAM is a potential therapeutic target in prostate cancer bone metastasis. IMPLICATIONS: This study highlights the functional application of an anti-MCAM mAb to target prostate cancer bone metastasis., (©2019 American Association for Cancer Research.)

Despite the increasing number of studies on deadwood, we still have limited knowledge of its dynamics. The aim of this study was to examine the effect of deadwood on the biochemical properties of soil and stabilisation of soil organic matter (SOM). The investigation was carried out in the Czarna Rózga Reserve in Central Poland. The logs of four tree species at different stages of decomposition (III, IV and V) were selected for the analysis. Three replicate logs were sampled for each combination of decay classes, and the soil samples were collected from directly under the logs and from 1 m away from the logs. In this way, changes to the chemical and biochemical properties of the wood were determined. The SOM was physically fractioned. As the rate of deadwood decomposition increases, its biochemical activity increases and its chemical properties change. The biochemical activity, especially the soil's enzyme activity, was stimulated under highly decayed deadwood. The effects of deadwood are visible in SOM fractions, particularly in the content of the light fraction of SOM., (© FEMS 2019.)

Sexual sadism is assumed to be a crucial factor in sexual homicide. Prevalence estimates vary greatly due to differences in the definition of sexual sadism. A nationwide sample of 350 male perpetrators who had committed a sexual homicide offense against a female 14 years of age or above in England or Wales was assessed based on archival records. Sexual sadism was assessed using the Sexual Sadism Scale (SeSaS). Item response theory (IRT) analyses were conducted focusing on the 2-parameter logistic model. The single-factor structure of the SeSaS Part 1 was tested using confirmatory factor analysis. Estimates of both internal consistency and interrater agreement were satisfactory to substantial. IRT analysis showed that the Part 1 items captured moderate to severe levels of the latent construct (i.e., theta levels >0). Based on the Posterior Probability of Diagnosis index, the prevalence of the disorder was estimated at 37% in the sample. The substantial correlation between the SeSaS Part 1 total score and original clinical diagnoses of sadism confirms the criterion validity of the scale. Exertion of control and infliction of torture were among the more informative items. In sum, the results support the usefulness of the SeSaS instrument for assessing forensically relevant forms of sadism. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Despite increasing treatment options for this disease, prognosis remains poor. CRIPTO (TDGF1) protein is expressed at high levels in several human tumours and promotes oncogenic phenotype. Its expression has been correlated to poor prognosis in HCC. In this study, we aimed to elucidate the basis for the effects of CRIPTO in HCC. We investigated CRIPTO expression levels in three cohorts of clinical cirrhotic and HCC specimens. We addressed the role of CRIPTO in hepatic tumourigenesis using Cre-loxP-controlled lentiviral vectors expressing CRIPTO in cell line-derived xenografts. Responses to standard treatments (sorafenib, doxorubicin) were assessed directly on xenograft-derived ex vivo tumour slices. CRIPTO-overexpressing patient-derived xenografts were established and used for ex vivo drug response assays. The effects of sorafenib and doxorubicin treatment in combination with a CRIPTO pathway inhibitor were tested in ex vivo cultures of xenograft models and 3D cultures. CRIPTO protein was found highly expressed in human cirrhosis and hepatocellular carcinoma specimens but not in those of healthy participants. Stable overexpression of CRIPTO in human HepG2 cells caused epithelial-to-mesenchymal transition, increased expression of cancer stem cell markers, and enhanced cell proliferation and migration. HepG2-CRIPTO cells formed tumours when injected into immune-compromised mice, whereas HepG2 cells lacking stable CRIPTO overexpression did not. High-level CRIPTO expression in xenograft models was associated with resistance to sorafenib, which could be modulated using a CRIPTO pathway inhibitor in ex vivo tumour slices. Our data suggest that a subgroup of CRIPTO-expressing HCC patients may benefit from a combinatorial treatment scheme and that sorafenib resistance may be circumvented by inhibition of the CRIPTO pathway. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd., (Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)

Background: Prenatal antibody transfer is an immune-mediated maternal effect by which females can shape postnatal offspring resistance to pathogens and parasites. Maternal antibodies passed on to offspring provide primary protection to neonates against diverse pathogenic antigens, but they may also affect offspring growth and influence the development of an offspring's own immune response. The effects of maternal antibodies on offspring performance commonly require that the disease environment experienced by a mother prior to breeding matches the environment encountered by her offspring after hatching/birth. However, other circumstances, like postnatal rearing conditions that affect offspring food availability, may also determine the effects of maternal antibodies on offspring growth and immunity. To date, knowledge about how prenatal immune-mediated maternal effects interact with various postnatal rearing conditions to affect offspring development and phenotype in wild bird population remains elusive. Here we experimentally studied the interactive effects of pre-laying maternal immunization with a bacterial antigen (lipopolysaccharide) and post-hatching rearing conditions, altered by brood size manipulation, on offspring growth and humoral immunity of wild great tits ( Parus major )., Results: We found that maternal immunization and brood size manipulation interactively affected the growth and specific humoral immune response of avian offspring. Among nestlings reared in enlarged broods, only those that originated from immunized mothers grew better and were heavier at fledging stage compared to those that originated from non-immunized mothers. In contrast, no such effects were observed among nestlings reared in non-manipulated (control) broods. Moreover, offspring of immunized females had a stronger humoral immune response to lipopolysaccharide during postnatal development than offspring of non-immunized females, but only when the nestling was reared in control broods., Conclusions: This study demonstrates that offspring development and their ability to cope with pathogens after hatching are driven by mutual influences of pathogen-induced prenatal maternal effects and post-hatching rearing conditions. Our findings suggest that immune-mediated maternal effects may have context-dependent influences on offspring growth and immune function, related to the postnatal environmental conditions experienced by the progeny., Competing Interests: The experiment and all procedures conducted on birds in the study were approved by the Poznań Local Ethics Committee for Animal Experimentation (permit number: 72/2012) and with permission from the Regional and General Directorate for Environmental Protection in Poland (permit numbers: OP-I.6401.394.2012.MMr and DOP-OZ.6401.03.18.2013.dł).Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

As with other sexual offenders, sexual homicide perpetrators can be reluctant to talk about their criminal behavior. Therefore, in homicide cases, forensic practitioners frequently rely on crime scene information to identify any sexual behavior associated with the offense. This study aims to identify objective and readily available crime scene information, alongside information about victims and perpetrators, based on 65 cases from England and Wales in the United Kingdom of men convicted of homicide who had committed a non-serial sexual homicide and 64 cases of men convicted of homicide where the available evidence indicated that it was a non-serial non-sexual homicide. Chi-square tests and logistic regression were used to analyze the data. There were few differences in terms of demographic information and criminal histories between the two perpetrator groups. There were crime scene indicators supporting the use of Ressler et al.'s definition of sexual homicide. The victims of sexual homicide were generally found in their home with the lower half of the body exposed and with evidence of vaginal sex. Furthermore, extreme injuries and strangulation were more frequent in sexual homicides. Use of weapon was associated with a non-sexual homicide. Victims of sexual homicide were as likely to know the perpetrator as not. Potential benefits of the characteristics reported to investigators and forensic practitioners tasked with identifying sexual homicides are discussed and areas for further research suggested.

Background: Parkinson's disease is a progressive neurodegenerative disorder, characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta. The causes of Parkinson's disease are not fully understood; however, increasing evidence implicates oxidative stress., Objectives: The study was aimed at assessing the nature of the changes in the oxidation-antioxidant balance in the cerebral cortex, striatum, hippocampus, thalamus, and cerebellum in a rat model of Parkinson's disease (PD)., Material and Methods: Sixteen male Wistar rats were divided into 2 groups: Icontrol, IIParkinson's disease. The 8-weeks-old animals were decapitated, their brains removed and the following structures dissected and then frozen for further biochemical assays: cerebral cortex, striatum, hippocampus, thalamus and cerebellum. The activities of: the catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx), glutathione S-transferase (GST), superoxide dismutase (SOD) and the isoenzymes: Cu/ZnSOD and MnSOD; together with the malondialdehyde (MDA) and the total oxidative status (TOS) concentrations were measured in each structure., Results: A significantly increased activities of SOD, Cu/ZnSOD, GST and reduced GR activity and an increase of MDA concentration were observed in the striatum of PD rats, comparing to the control group, combined with a significantly reduced activities of GR,SOD, Cu/ZnSOD and an increased GPX activity and MDA concentration in the hippocampus, a significantly lower GR, SOD, MnSOD, Cu/ZnSOD, and GST activities in the cerebral cortex. A significantly lower GR activity, higher CAT activity and MDA concentration in the thalamus and a significantly increased GR activity in the cerebellum were observed in PD rats compared to the corresponding control group., Conclusions: Oxidative stress in PD involves many brain structures and various antioxidant enzymes and oxidative status parameters become dysfunctional, depending on the area of the brain, which might reflect the complexity of the clinical symptoms of PD.

Establishing a model of sexual assault reflecting psychosocial and behavioral characteristics of perpetrators of sexual killing and rape is necessary for development in risk assessment and intervention. Methodological variations in defining sexual killing have amalgamated serial and non-serial offenders and perpetrators with direct and indirect associations between killing and sexual arousal. This study defined sexual killing specifying that killing should be directly linked to sexual arousal, and sampled 48 sexual killers, operationalized to include only those engaging in post-mortem sexual interference, with one or two known female victims (non-serial), from prison service national (England and Wales) databases. These sexual killers were compared with 48 non-homicide, life or indeterminately sentenced sexual aggressors on psychological and crime scene characteristics. Contrary to previous research, fatal outcomes were associated with neither stranger victims nor weapon presence; sexual killing was characterized by severity of violence less so than non-fatal assault. Sexual killers more often reported problems with emotional loneliness, empathic concern, and sexual entitlement than the sexual aggressors. Theoretical and applied implications are discussed.

Investigations on the impact of chemicals on the environment and human health have led to the development of an exposome concept. The exposome refers to the totality of exposures received by a person during life, including exposures to life-style factors, from the prenatal period to death. The exposure to genotoxic chemicals and their reactive metabolites can induce chemical modifications of DNA, such as, for example, DNA adducts, which have been extensively studied and which play a key role in chemically induced carcinogenesis. Development of different methods for the identification of DNA adducts has led to adopting DNA adductomic approaches. The ability to simultaneously detect multiple PAH-derived DNA adducts may allow for the improved assessment of exposure, and offer a mechanistic insight into the carcinogenic process following exposure to PAH mixtures. The major advantage of measuring chemical-specific DNA adducts is the assessment of a biologically effective dose. This review provides information about the occurrence of the polycyclic aromatic hydrocarbons (PAHs) and their influence on human exposure and biological effects, including PAH-derived DNA adduct formation and repair processes. Selected methods used for determination of DNA adducts have been presented.

The aim of this study was to estimate the susceptibility of Staphylococcus hominis bacteria to the bacteriostatic agent in respiratory protective filters. Four types of filter media of different characteristics were tested. The number of bacteria was estimated by a culture-based method. It was proved that in treated filters the number of S. hominis was significantly reduced, even below the detection limit, while in untreated material bacteria were able to grow and multiply up to 100-fold within 8 hours. There was no correlation between filter structure and changes in the number of bacterial cells.

Background: Parkinson's disease is caused by the destruction of dopaminergic neurons in the substantia nigra of the midbrain. One of the possible factors involved in the pathogenesis of Parkinson's disease is impaired oxidativeantioxidative balance., Objectives: The present study aimed to evaluate selected parameters of the liver oxidative-antioxidative system in a Wistar rat model with Parkinson's disease treated with propofol., Material and Methods: Experiments were performed on 32 rats divided into 4 groups: 1 - control, 2 - Parkinson's disease, 3 - control with propofol, 4 - Parkinson's disease with propofol. The rats were decapitated at 8 weeks of age and their livers were collected. In the liver, the activities of catalase (CAT), glutathione peroxidase (GPx), glutathione transferase (GST), glutathione reductase (GR) and the concentrations of: Malondialdehyde (MDA), total antioxidant capacity (TAC), total oxidant status (TOS) were assessed., Results: The study demonstrated a decrease in CAT activity and an increase in MDA, TOS concentrations in group 2 compared to that of group 1. Administration of propofol in rats of group 4 caused an increase in CAT activity and a decrease in MDA concentration compared to that of group 2 and an increase in TAC, CAT, GR levels, decrease in MDA levels compared to that of group 1. There was also an increase in GR and TAC in group 3 compared to that of group 1., Conclusions: Propofol in Parkinson's disease stimulates the production of antioxidant enzymes in the liver, simultaneously decreasing oxidative stress, which has a beneficial effect on the oxidative-antioxidative balance.

The W/Y chromosome is unique among chromosomes as it does not recombine in its mature form. The main side effect of cessation of recombination is evolutionary instability and degeneration of the W/Y chromosome, or frequent W/Y chromosome turnovers. Another important feature of W/Y chromosome degeneration is transposable element (TEs) accumulation. Transposon accumulation has been confirmed for all W/Y chromosomes that have been sequenced so far. Models of W/Y chromosome instability include the assemblage of deleterious mutations in protein coding genes, but do not include the influence of transposable elements that are accumulated gradually in the non-recombining genome. The multiple roles of genomic TEs, and the interactions between retrotransposons and genome defense proteins are currently being studied intensively. Small RNAs originating from retrotransposon transcripts appear to be, in some cases, the only mediators of W/Y chromosome function. Based on the review of the most recent publications, we present knowledge on W/Y evolution in relation to retrotransposable element accumulation.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal form of cancer with few therapeutic options. We found that levels of the lysine methyltransferase SMYD2 (SET and MYND domain 2) are elevated in PDAC and that genetic and pharmacological inhibition of SMYD2 restricts PDAC growth. We further identified the stress response kinase MAPKAPK3 (MK3) as a new physiologic substrate of SMYD2 in PDAC cells. Inhibition of MAPKAPK3 impedes PDAC growth, identifying a potential new kinase target in PDAC. Finally, we show that inhibition of SMYD2 cooperates with standard chemotherapy to treat PDAC cells and tumors. These findings uncover a pivotal role for SMYD2 in promoting pancreatic cancer., (© 2016 Reynoird et al.; Published by Cold Spring Harbor Laboratory Press.)

Objectives: The aim of the present study was to analyse the impact of education of patients with irritable bowel syndrome (IBS) on their quality of life., Methods: The study was carried out at the Gastroenterology Outpatient Clinic of the Independent Public Clinical Hospital No. 4 in Lublin and Gastroenterology Outpatient Clinic of the Cardinal Stefan Wyszyński Regional Specialist Hospital in Lublin in the years 2010-2011. The quality of life was analysed using the Quality of Life Questionnaire (QOL-Q R. Schalock, K. Keith). The group of 83 patients with the diagnosis of irritable bowel syndrome, who gave their consent for inclusion in the study, was provided with information about the essence of the disease, disease-related diet and lifestyle, course of the disease, medications, and check-ups., Results: Our patients educated by the physician, nurse and those provided with written information had substantially higher scores in multi-dimensional aspects of the quality of life after education. Six months after education patients with IBS showed a significantly higher quality of life in all aspects, i.e. Satisfaction, Competence/productivity, Empowerment/independence and Social inclusion/community integration. The understanding of the essence of their disease contributed to a decrease in anxiety associated with the neoplastic disease and worrying symptoms, which significantly reduced the incidence of complaints., Conclusions: 1. Quality of life of patients with irritable bowel syndrome is substantially reduced in all the examined spheres. 2. Education of patients with IBS resulted in enhanced quality of life and reduced disease-related complaints. 3. Education of patients with IBS plays a significant role in the entire therapeutic process.

Some Basidiomycota were chosen for studies of key ligninases synthesis (25°C, 30 days) in modified medium (shaken or not cultures) with added wheat straw. Liquid Czapek medium with straw yielded a higher amount of laccase than peroxidase, ground straw induced enzyme worse than chopped straw. With peroxidase the reverse dependencies were observed. Laccase of Lentinus edodes synthesized two enzyme isoforms (ca 30 and 16 kDa). In T. versicolor culture active laccase protein with highest molecular mass ca 65 kDa was found. P. sajor-caju yielded three different peroxidase isoforms. Ligninase biosynthesis depended on strain, straw fragmentation extent, culture method and growth medium.

T-cell and NK-cell lymphomas are uncommon lymphomas with an aggressive clinical course. The causes and precise cellular origins of most T-cell lymphomas are still not well defined. The WHO classification utilizes morphologic and immunophenotypic features in conjunction with clinical aspects and in some instances genetics to delineate a prognostically and therapeutically meaningful categorization. The anatomic localization of neoplastic T-cells and NK-cells parallels in part their proposed normal cellular counterparts and functions. T-cells of the adaptive immune system are mainly based in lymph nodes and peripheral blood, whereas lymphomas derived from T-cells and NK-cells of the innate immune system are mainly extranodal. This approach allows for better understanding of some of the manifestations of the T-cell and NK-cell lymphomas, including their cellular distribution, some aspects of morphology and even associated clinical findings., (Published by Elsevier Ltd.)

A case of metastatic mixed acinar-neuroendocrine carcinoma (MANEC) of the pancreas to the liver is reported. A diagnostic percutaneous US-guided FNA and core biopsy of a liver nodule was performed. The FNA smears were cellular and showed neoplastic cells in clusters with acinar formation, isolated single cells, and scattered naked nuclei. The cytoplasm was finely granular. The nuclei were relatively uniform, some with speckled chromatin and prominent nucleoli. The immunohistochemistry performed on the cell block showed strong positivity for cytokeratin AE1/AE3, chromogranin, and synaptophysin. Furthermore, the tumor cells were weakly positive for α1-antichymotrypsin. The Ki-67 mitotic index was up to 50%. Based on the morphology and supporting immunohistochemical stains, the final cytopathologic diagnosis rendered was "Positive for malignant cells. Carcinoma with mixed acinar and endocrine features." To our knowledge, this is the first report of a metastatic MANEC to the liver diagnosed based on cytology with confirmatory histology. The difficulties in the cytopathologic diagnosis and differential diagnosis of MANEC are discussed in this article., (Copyright © 2011 Wiley Periodicals, Inc.)

Background: Major histocompatibility complex (MHC) proteins constitute an essential component of the vertebrate immune response, and are coded by the most polymorphic of the vertebrate genes. Here, we investigated sequence variation and evolution of MHC class I and class II DRB, DQA and DQB genes in the brown bear Ursus arctos to characterise the level of polymorphism, estimate the strength of positive selection acting on them, and assess the extent of gene orthology and trans-species polymorphism in Ursidae., Results: We found 37 MHC class I, 16 MHC class II DRB, four DQB and two DQA alleles. We confirmed the expression of several loci: three MHC class I, two DRB, two DQB and one DQA. MHC class I also contained two clusters of non-expressed sequences. MHC class I and DRB allele frequencies differed between northern and southern populations of the Scandinavian brown bear. The rate of nonsynonymous substitutions (dN) exceeded the rate of synonymous substitutions (dS) at putative antigen binding sites of DRB and DQB loci and, marginally significantly, at MHC class I loci. Models of codon evolution supported positive selection at DRB and MHC class I loci. Both MHC class I and MHC class II sequences showed orthology to gene clusters found in the giant panda Ailuropoda melanoleuca., Conclusions: Historical positive selection has acted on MHC class I, class II DRB and DQB, but not on the DQA locus. The signal of historical positive selection on the DRB locus was particularly strong, which may be a general feature of caniforms. The presence of MHC class I pseudogenes may indicate faster gene turnover in this class through the birth-and-death process. South-north population structure at MHC loci probably reflects origin of the populations from separate glacial refugia.

Produced by Staphylococcus aureus, SplB belongs to the chymotrypsin-like serine protease family. Since the biological role of SplB protease is unknown, the design and application of its specific inhibitors may help to reveal the function of this enzyme. Until now no SplB inhibitors have been reported. Herein, we present the design and synthesis of novel α-aminophosphonic analogues of glutamine, as well as their peptidyl derivatives. The inhibitory effects of these compounds towards the newly discovered SplB serine protease from S. aureus are characterized. We have also investigated the influence of aromatic ester substituents on inhibitory potency towards SplB. One of the compounds-Cbz-Glu-Leu-Gln(P)(OC(6)H(4)-4-O-CH(3))(2)-displayed an apparent second-order inhibition rate value of 1400 M(-1)s(-1)., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objective: Squamous intraepithelial lesions (SILs) are classified as low-grade SIL (LGSIL) and high-grade SIL (HGSIL). 'LGSIL cannot exclude high grade' (LGSIL-H) interpretive category has been used in cases where findings exceed criteria for LGSIL, but do not fulfill the criteria for HGSIL. This study analyzed follow-up histology of LGSIL-H cases and compared the follow-up results of LGSIL-H with LGSIL to determine the utility of LGSIL-H category using a single institution's experience., Study Design: Pap smears with LGSIL-H interpretation from 2005 to 2008 were retrieved. Histological follow-up results for LGSIL-H cases were analyzed and compared to the follow-up results of LGSIL cases., Results: Cases with LGSIL-H interpretation (311) comprised 0.18% of all cases (170,307). Follow-up was available for 144 patients and 13.2% had benign findings, 51.4% had cervical intraepithelial neoplasia (CIN) 1, and 35.4% had CIN 2 or higher. In comparison, of 425 patients with LGSIL, 22.6% had benign findings, 71% had CIN 1 and 6.4% had CIN 2 or higher., Conclusion: A significantly greater number of patients with LGSIL-H interpretation had a CIN 2 or higher lesion on follow-up compared to patients with LGSIL. This suggests LGSIL-H may be a useful diagnostic category., (Copyright © 2012 S. Karger AG, Basel.)

Purpose: We investigated the role of genetic, physiological, environmental, and epigenetic factors in regulating CYP2A6 expression and nicotine metabolism., Methods: Human livers (n = 67) were genotyped for CYP2A6 alleles and assessed for nicotine metabolism and CYP2A6 expression (mRNA and protein). In addition, a subset of livers (n = 18), human cryopreserved hepatocytes (n = 2), and HepG2 cells were used for DNA methylation analyses., Results: Liver samples with variant CYP2A6 alleles had significantly lower CYP2A6 protein expression, nicotine C-oxidation activity, and affinity for nicotine. Female livers had significantly higher CYP2A6 protein and mRNA expression compared to male livers. Livers exposed to dexamethasone and phenobarbital had higher CYP2A6 expression and activity, however the difference was not statistically significant. Age and DNA methylation status of the CpG island and a regulatory site were not associated with altered CYP2A6., Conclusions: We identified genotype, gender, and exposure to inducers as sources of variation in CYP2A6 expression and activity, but much variation remains to be accounted for.

Objectives: This research was designed to analyze the presence of fetal female DNA, expressed in copy number, in the plasma of the pregnant woman with preeclampsia-complicated pregnancy., Study Design: Twenty-four pregnant women with female fetuses identified by means of ultrasound scanning were enrolled in this pilot study. The study group consisted of 12 pregnant women with symptoms of preeclampsia, with 12 healthy women, matched for gestational age, as controls., Results: Mean DNA number of genomic equivalents per reaction in the group was 201 geq/PCR (from 44.9 to 375) and increased over time after onset of PE, which was the reason for pregnancy termination. In the group of women with preeclampsia, a notably higher DNA copy number in comparison to the control group was noted (p=0.0003 U Mann-Whitney test)., Conclusions: The pilot study presented in this work confirms that also in the case of preeclampsia-complicated pregnancy with female fetuses it is possible to implement the method of fetal DNA quantification. Use of the presented methods confirms that in severe preeclampsia-complicated pregnancies an increase of the number of DNA genomic equivalents per reaction in comparison to the control group is observed. Due to the small study group further research on the described issue is vital, but this study proves that it is also feasible among women carrying female fetuses.

We studied dendritic, myeloid (mDCs) (BDCA1+/CD19-) and plasmacytoid cells (pDCs) (BDCA2+/CD123+) and B-cells (CD19+) at relapse, after short intravenous methyloprednisolone therapy and 30 days after treatment completion (remission period) and results were compared with a control group of healthy volunteers. We confirmed the decrease in BDCA2+/CD123+ after therapy (p=0.00006) and then an increase (p=0.0032) in comparison to the control group. The level of B CD19+ cells after GC therapy increased compared to the control group (p=0.00809) and had stabilised 30 days after therapy. The effect of methyloprednisolone on DC function and B-cell levels thus changes.

The widespread use of sonography as a screening tool for fetal anomalies has facilitated prenatal detection of several fetal conditions characterized by urinary tract dilatation. These conditions are more common in male fetuses and are generally a result of an anatomic defect causing obstruction along the urinary tract system. Although the prognosis of these conditions largely depends on the specific anomaly, several poor prognostic factors have been described. These factors include detection at an early gestational age, bilateral marked dilatation, a persistently obstructed bladder, oligohydramnios causing pulmonary hypoplasia, and the presence of associated fetal or chromosomal anomalies. We report a case in which a male fetus at 14 weeks' gestation had a diagnosis of rapidly progressing bilateral hydronephrosis, massive bladder dilatation, hydroureter, and a surprisingly normal amniotic fluid volume. Serial sonographic surveillance assisted us in obtaining the correct diagnosis, which was important for adequately consulting the patient regarding the fetal prognosis in the affected index pregnancy as well as the likelihood of recurrence in future gestations.

Cytochrome P450 2A6 (CYP2A6) is a human enzyme best known for metabolizing tobacco-related compounds, such as nicotine, cotinine (COT), and nitrosamine procarcinogens. CYP2A6 genetic variants have been associated with smoking status, cigarette consumption, and tobacco-related cancers. Our objective was to functionally characterize four nonsynonymous CYP2A6 sequence variants with respect to their haplotype, allele frequency, and association with in vivo CYP2A6 activity. In vivo, nicotine was administered orally to 281 volunteers of Black African descent. Blood samples were collected for kinetic phenotyping and CYP2A6 genotyping. In vitro, nicotine C-oxidation catalytic efficiencies of heterologously expressed variant enzymes were assessed. The four uncharacterized sequence variants were found in seven novel alleles CYP2A6(*)24A&B ; (*)25, (*)26, (*)27, and *28A&B, most were associated with impaired in vivo CYP2A6 activity. Nicotine metabolism groupings, based on the in vivo data of variant alleles, were created. Mean trans-3'-hydroxycotinine/cotinine (3HC/COT) differed (P<0.001) between normal (100%), intermediate (64%), and slow (40%) groups. Systemic exposure to nicotine following oral administration also differed (P<0.001) between normal (100%), intermediate (139%), and slow (162%) metabolism groups. In addition, alleles of individuals with unusual phenotype-genotype relationships were sequenced, resulting in the discovery of five novel uncharacterized alleles and at least one novel duplication allele. A total of 7% of this population of Black African descent had at least one of the eight novel characterized alleles and 29% had at least one previously established allele. These findings are important for increasing the accuracy of association studies between CYP2A6 genotype and behavioral, disease, or pharmacological phenotypes.

Gastrointestinal stromal tumors (GIST) are the example of very rare sarcoma of alimentary tract. In the presented material, 5 cases of GIST were diagnosed and treated in our Department. One tumor was localized in stomach, two in rectum and one in jejunum. Primal localization of the last tumor was not discovered. It was visualized between rectum and bladder, covered by the omentum. In each case confirmation of the diagnosis was done on the basis of the immunohistochemical staining--CD117(+). In four cases surgery was the primary treatment. Only in one case radical resection was performed. In other three cases radical resection was not possible due to the presence of liver metastases (in two cases) and the size of the tumor (20 x 10 cm). One patient was disqualified from the surgical treatment. Four patients were qualified for the chemotherapy with imatinib. In one case, patient did not undergo the treatment. In the group treated with imatinib the early reply was satisfactory. On the ground of our material we conclude that patients usually begin the treatment in the advanced stage of the disease. When the GIST diagnosis is probable, one has to broaden the histopathological examination with immunohistochemical staining for CD117 antigen. Making the right diagnosis is crucial for patients, since imatinib is effective even in the advanced stages of the disease. Nevertheless radical surgical treatment is still the primary choice for the patients with GIST.

The currently available microwave technology permits the development and implementation of a temperature-programmed microwave-assisted synthesis (TPMS) of ordered mesoporous silicas (OMSs). Unlike in previously reported syntheses of OMSs, in which only the final hydrothermal treatment was carried out under microwave irradiation, this work takes advantage of the existing capabilities of modern microwave systems to program the temperature and time for the entire synthesis of these materials. To demonstrate the flexibility of the proposed microwave-assisted synthesis, besides programming two consecutive steps involving initial stirring of the gel at a lower temperature and static hydrothermal treatment at a higher temperature, we explored the possibility of temperature programming of the latter step. A major advantage of microwave technology is the feasibility of temperature and time programming, which has been demonstrated by the synthesis of one of the most popular OMSs, SBA-15, over an unprecedented range of temperatures from 40 to 200 degrees C. Since the synthesis of OMSs has not yet been explored and reported at temperatures exceeding 150 degrees C, this work is focused on the SBA-15 samples prepared at higher temperatures (such as 160, 180, and even 200 degrees C). These SBA-15 samples show better thermal stability than those synthesized at commonly used temperatures either under conventional or microwave conditions. Moreover, a partial decomposition of the template during high-temperature microwave-assisted syntheses does not compromise the formation of well-ordered SBA-15 materials. This study shows that the simplicity and capability of temperature and time programming in TPMS allows one not only to tune the adsorption and structural properties of OMSs but also to easily screen a wide range of conditions in order to optimize and scale-up their preparation as well as to significantly reduce the time of synthesis from days to hours.

The presence of annual and biennial individuals within the same population has been recently demonstrated in the myrmecophilous butterflies Maculinea rebeli and Maculinea alcon, which present a cuckoo strategy inside Myrmica nests, and Maculinea arion which is a predatory species. Here, we present field and laboratory data on polymorphic larval growth in two other predatory species of Maculinea: M. teleius and M. nausithous. Body mass distributions of pre-pupation larvae were bimodal in both species. These results point to the existence of larvae that develop in 1 or 2 years. We also showed that the probability of pupation depended on larval body mass. In the case of M. teleius, the critical body mass at which larvae have a 50% probability of pupation is about 80 mg. We suggest that polymorphism in Maculinea may have evolved as an adaptation to life in ant nests, a habitat which protects them from predators and provides food. However, the quality of this resource is highly variable and unpredictable. According to the bet-hedging hypothesis, if the habitat is unpredictable, females should have an advantage by producing more variable offspring. In the case of Maculinea butterflies, this may involve maintaining larvae that develop in 1 or 2 years.

Mesoporous carbons were synthesized from polyacrylonitrile (PAN) using ordered and disordered mesoporous silica templates and were characterized using transmission electron microscopy (TEM), powder X-ray diffraction, nitrogen adsorption, and thermogravimetry. The pores of the silica templates were infiltrated with carbon precursor (PAN) via polymerization of acrylonitrile from initiation sites chemically bonded to the silica surface. This polymerization method is expected to allow for a uniform filling of the template with PAN and to minimize the introduction of nontemplated PAN, thus mitigating the formation of nontemplated carbon. PAN was stabilized by heating to 573 K under air and carbonized under N2 at 1073 K. The resulting carbons exhibited high total pore volumes (1.5-1.8 cm3 g(-1)), with a primary contribution of the mesopore volume and with relatively low microporosity. The carbons synthesized using mesoporous templates with a 2-dimensional hexagonal structure (SBA-15 silica) and a face-centered cubic structure (FDU-1 silica) exhibited narrow pore size distributions (PSDs), whereas the carbon synthesized using disordered silica gel template had broader PSD. TEM showed that the SBA-15-templated carbon was composed of arrays of long, straight, or curved nanorods aligned in 2-D hexagonal arrays. The carbon replica of FDU-1 silica appeared to be composed of ordered arrays of spheres. XRD provided evidence of some degree of ordering of graphene sheets in the carbon frameworks. Elemental analysis showed that the carbons contain an appreciable amount of nitrogen. The use of our novel infiltration method and PAN as a carbon precursor allowed us to obtain ordered mesoporous carbons (OMCs) with (i) very high mesopore volume, (ii) low microporosity, (iii) low secondary mesoporosity, (iv) large pore diameter (8-12 nm), and (v) semi-graphitic framework, which represent a desirable combination of features that has not been realized before for OMCs.

Ordered silicas with large (9-15 nm), uniform, cagelike mesopores were synthesized under acidic aqueous conditions from tetraethyl orthosilicate in the presence of sodium chloride using poly(ethylene oxide)-poly(butylene oxide)-poly(ethylene oxide) triblock copolymer B50-6600 (EO39BO47EO39, Dow Chemicals) as a supramolecular template. Except for the use of NaCl in our case, the synthesis mixture composition was the same as that originally reported by Zhao et al. for the synthesis of FDU-1 silica, which was later shown to exhibit a cubic close-packed (Fm3m) structure with stacking faults related to the occurrence of hexagonal close-packed stacking sequences. The copolymer-templated silicas were formed at room temperature and in most cases were subjected to the hydrothermal treatment at 373 or 393 K. The calcined materials were characterized using small-angle X-ray scattering (SAXS) and nitrogen and argon adsorption at 77 K. SAXS patterns were generally similar to those reported for FDU-1 silica, indicating the cubic close-packed (Fm3m) structure, but the presence of stacking faults characteristic of a hexagonal close-packed structure cannot be precluded. The addition of the salt was found to significantly narrow the pore size distributions and to improve the uniformity of entrances to the cagelike mesopores, whereas the pore diameter, specific surface area, and pore volume were similar (in most cases slightly lower) to those for FDU-1 silicas obtained in the absence of NaCl. The materials synthesized in the presence of NaCl also appeared to have better resolved SAXS patterns. The feasibility of tailoring the pore cage diameter (from approximately 9.5 to 14.5 nm) and pore entrance diameter (from below 4 to approximately 8 nm) simply by adjusting the hydrothermal treatment temperature and time was demonstrated, indicating that these simple and convenient ways of structural design of cagelike mesopores are operative in the case of syntheses in the presence of inorganic salts.

Purpose: To evaluate the role of ethosuximide, sodium valproate and lamotrigine in children and adolescents with typical absence seizures (AS)., Methods: A systematic review of randomized controlled trials that included children or adolescents with typical absence seizures who received treatment with ethosuximide, sodium valproate or lamotrigine., Results: Four RCTs fulfilled the inclusion criteria. Due to the heterogeneity of the studies the results could not be pooled in a meta-analysis., Conclusions: We found no reliable evidence to inform clinical practice. The design of further trials should be pragmatic and compare one drug with another.

We investigated the role of tumor suppressor p53 and Fas (CD95/APO-1), a member of the tumor necrosis factor receptor family, in neural progenitors response to gamma-irradiation exposure. Telencephalic cells were obtained from wild-type C57Bl/6, or p53-/- or fas-/-, 15-day-old mouse embryos. They were cultured in conditions allowing neural progenitors to form proliferating clusters (neurospheres). A 2 Gy gamma-irradiation induced a G1 cell cycle arrest and triggered apoptosis in wild-type neural progenitor cultures in correlation with an enhanced expression of p53 and of its downstream target p21(WAF1), both of them acquiring a nuclear localization. These effects did not occur in p53-/- neural progenitors demonstrating the central role played by p53 in their response to ionizing radiation. Furthermore, the monoclonal antibody Jo2 directed against Fas induced apoptosis of wild type but not of fas-/- neural progenitors, indicating the existence of a functional Fas signaling pathway in neural progenitors. Ionizing radiation induced an increase of Fas membrane expression related to a p53-dependent increase of fas mRNA expression in wild-type neural progenitors. Moreover, fas-/- neural progenitors exhibited delayed radiation-induced apoptosis compared to wild-type cells. Therefore, these findings establish a role for Fas/CD95 related to p53 in the response of neural progenitors to gamma-radiation exposure. Similar mechanisms could be triggered in neural progenitors in case of different stresses during brain development or in the course of various diseases affecting the adult brain.

Genetically variable CYP2A6 is the primary enzyme that inactivates nicotine to cotinine. Our objective was to investigate allele frequencies among five ethnic groups and to investigate the relationship between genetically slow nicotine metabolic inactivation and smoking status, cigarette consumption, age of first smoking and duration of smoking. Chinese, Japanese, Canadian Native Indian, African-North American and Caucasian DNA samples were assessed for CYP2A6 allelic frequencies (CYP2A6*1B-*12,*1x2). Adult Caucasian non-smokers (n = 224) (1-99 cigarettes/lifetime) and smokers (n = 375) (> or = 100 cigarettes/lifetime) were assessed for demographics, tobacco/drug use history and DSM-IV dependence and genotyped for CYP2A6 alleles associated with decreased nicotine metabolism (CYP2A6*2, CYP2A6*4, CYP2A6*9, CYP2A6*12). CYP2A6 allele frequencies varied substantially among the ethnic groups. The proportion of Caucasian slow nicotine inactivators was significantly lower in current, DSM-IV dependent smokers compared to non-smokers [7.0% and 12.5%, respectively, P = 0.03, odds ratio (OR) = 0.52; 95% confidence interval (CI) 0.29-0.95]; non-dependent smokers showed similar results. Daily cigarette consumption (cigarettes/day) was significantly (P = 0.003) lower for slow (21.3; 95% CI 17.4-25.2) compared to normal inactivators (28.2; 95% CI 26.4-29.9); this was observed only in DSM-IV dependent smokers. Slow inactivators had a significantly (P = 0.03) lower age of first smoking compared to normal inactivators (13.0 years of age; 95% CI 12.1-14.0 versus 14.2; 95% CI 13.8-14.6), and a trend towards smoking for a shorter duration. This study demonstrates that slow nicotine inactivators are less likely to be adult smokers (dependent or non-dependent). Slow inactivators also smoked fewer cigarettes per day and had an earlier age of first smoking (only dependent smokers).

A bacteriological study of 114 infertile patients in Northern Nigeria revealed a prevalence rate for genital tuberculosis of 16.7%. The low incidence of a past history of pulmonary tuberculosis may relate to a gastro-intestinal sources of the infective organisms, illiteracy and delay in seeking medical advice. The presenting features are indistinguishable from those of chronic pelvic inflammatory disease. Since 94.7% of the patients are young (20 to 35 years of age) and the mean duration of infertility long (8.1 years), despite marriage in childhood, infertile women in this environment should be investigated without delay at an earlier age so as to improve diagnosis and subsequent prognosis.