Stability, delivery and functions of human sperm RNAs at fertilization

Increasing attention has focused on the significance of RNA in sperm, in light of its contribution to the birth and long-term health of a child, role in sperm function and diagnostic potential. As the composition of sperm RNA is in flux, assigning specific roles to individual RNAs presents a significant challenge. For the first time RNA-seq was used to characterize the population of coding and non-coding transcripts in human sperm. Examining RNA representation as a function of multiple methods of library preparation revealed unique features indicative of very specific and stage-dependent maturation and regulation of sperm RNA, illuminating their various transitional roles. Correlation of sperm transcript abundance with epigenetic marks suggested roles for these elements in the pre- and post-fertilization genome. Several classes of non-coding RNAs including lncRNAs, CARs, pri-miRNAs, novel elements and mRNAs have been identified which, based on factors including relative abundance, integrity in sperm, available knockout data of embryonic effect and presence or absence in the unfertilized human oocyte, are likely to be essential male factors critical to early post-fertilization development. The diverse and unique attributes of sperm transcripts that were revealed provides the first detailed analysis of the biology and anticipated clinical significance of spermatozoal RNAs

Characterization of stochastic orders by L-functionals

Random variables may be compared with respect to their location by comparing certain functionals ad hoc, such as the mean or median, or by means of stochastic ordering based directly on the properties of the corresponding distribution functions. These alternative approaches are brought together in this paper. We focus on the class of L-functionals discussed by Bickel and Lehmann (1975) and characterize the comparison of random variables in terms of these measures by means of several stochastic orders based on iterated integrals, including the increasing convex orde

In vivo imaging of pancreatic tumours and liver metastases using 7 Tesla MRI in a murine orthotopic pancreatic cancer model and a liver metastases model

<p>Abstract</p> <p>Background</p> <p>Pancreatic cancer is the fourth leading cause of tumour death in the western world. However, appropriate tumour models are scarce. Here we present a syngeneic murine pancreatic cancer model using 7 Tesla MRI and evaluate its clinical relevance and applicability.</p> <p>Methods</p> <p>6606PDA murine pancreatic cancer cells were orthotopically injected into the pancreatic head. Liver metastases were induced through splenic injection. Animals were analyzed by MRI three and five weeks following injection. Tumours were detected using T2-weighted high resolution sequences. Tumour volumes were determined by callipers and MRI. Liver metastases were analyzed using gadolinium-EOB-DTPA and T1-weighted 3D-Flash sequences. Tumour blood flow was measured using low molecular gadobutrol and high molecular gadolinium-DTPA.</p> <p>Results</p> <p>MRI handling and applicability was similar to human systems, resolution as low as 0.1 mm. After 5 weeks tumour volumes differed significantly (p < 0.01) when comparing calliper measurments (n = 5, mean 1065 mm³+/-243 mm³) with MRI (mean 918 mm³+/-193 mm³) with MRI being more precise. Histology (n = 5) confirmed MRI tumour measurements (mean size MRI 38.5 mm²+/-22.8 mm²versus 32.6 mm²+/-22.6 mm²(histology), p < 0,0004) with differences due to fixation and processing of specimens. After splenic injection all mice developed liver metastases with a mean of 8 metastases and a mean volume of 173.8 mm³+/-56.7 mm³after 5 weeks. Lymphnodes were also easily identified. Tumour accumulation of gadobutrol was significantly (p < 0.05) higher than gadolinium-DTPA. All imaging experiments could be done repeatedly to comply with the 3R-principle thus reducing the number of experimental animals.</p> <p>Conclusions</p> <p>This model permits monitoring of tumour growth and metastasis formation in longitudinal non-invasive high-resolution MR studies including using contrast agents comparable to human pancreatic cancer. This multidisciplinary environment enables radiologists, surgeons and physicians to further improve translational research and therapies of pancreatic cancer.</p

Oncogenic Pathway Combinations Predict Clinical Prognosis in Gastric Cancer

Many solid cancers are known to exhibit a high degree of heterogeneity in their deregulation of different oncogenic pathways. We sought to identify major oncogenic pathways in gastric cancer (GC) with significant relationships to patient survival. Using gene expression signatures, we devised an in silico strategy to map patterns of oncogenic pathway activation in 301 primary gastric cancers, the second highest cause of global cancer mortality. We identified three oncogenic pathways (proliferation/stem cell, NF-κB, and Wnt/β-catenin) deregulated in the majority (>70%) of gastric cancers. We functionally validated these pathway predictions in a panel of gastric cancer cell lines. Patient stratification by oncogenic pathway combinations showed reproducible and significant survival differences in multiple cohorts, suggesting that pathway interactions may play an important role in influencing disease behavior. Individual GCs can be successfully taxonomized by oncogenic pathway activity into biologically and clinically relevant subgroups. Predicting pathway activity by expression signatures thus permits the study of multiple cancer-related pathways interacting simultaneously in primary cancers, at a scale not currently achievable by other platforms

Suicidal ideation expressed in online video diaries: New form of sharing intention to die

IntroductionSuicide risk is increasing among all population groups, and no effective prevention method has been established due to high variability of risk factors.ObjectivesTo (1) determine risk factors in people, who video-streamed unsuccessful suicide attempt, and (2) assess whether screening video blog websites is an effective suicide prevention.MethodsParticipants (n = 24, 14 M and 10F, age range = 19 to 53) with past history of suicidal attempts were recruited online to participate in encrypted video qualitative interview. Three scales assessed suicidal tendencies and Internet addiction: Columbia–suicide severity rating (C-SSRS), suicide assessment five-step evaluation and triage (SAFE-T), validated Internet addiction scale of own design. Reported data are mixed quantitative and qualitative measures.ResultsParticipants were stratified into two age categories (students vs. working professionals), and all were determined to be addicted to Internet. Each group engaged in minimum 15 suicides ideation-related postings, prior to attempting suicide. Young participants typically posted impulsive, quick massages capturing distress caused by peers and family conflicts; seeking short-time recognition was evidenced by eliciting more “likes” and “comments” for each post. Working professionals posted less, but each video was lengthier and messages were emotional, usually ending in tearful summary of life events leading up to suicidal thoughts. While students expressed anger with “the system” as motivation to die, working professionals had financial problems and trouble forming long-lasting friendships.ConclusionPeople of all age groups increasingly document intention to die via blog video posts. These messages can be captured by prevention professionals who can reach out to troubled students and working adults.Disclosure of interestThe author has not supplied his/her declaration of competing interest.</jats:sec

Digital communities of people with paraphilia: A study of zoophiles

IntroductionAccessibility of the Internet allows people to connect anonymously and without boundaries – features particularly important for people with relatively rare sexual preference such as paraphilia.ObjectivesTo (1) allow for conceptualization and improved management of zoophilic patients in clinical practice or forensic examinations, (2) analyze how zoophiles network using online discussion forums, and (3) describe main goals of digital networking.MethodsA qualitative observational study of user activity (n = 958) on discussion forums, combined with brief demographic survey. Data were analyzed according to principles of grounded theory. Next, surveys of own design (demographic, discreet + open ended questions) were answered by 350 participants. Presented data show aggregate conclusions from mixed methods qualitative and quantitative analysis.ResultsZoophiles (or, zoos) use Internet to connect with other zoophiles (26.6% to have casual sex, 17.7% for dating, and 17% to exchange pornography). Connections are easiest to be established in countryside, where zoophilia clusters. In fact, there are village communities of zoos where explicit sharing of animal sexual partner(s) (28%) and/or voyeurism (30%) serve as bonding ritual. Over 40% of zoophiles are reluctant to meet other zoos in person, since they view them as “weird”, pointing to phenomenon of internalized stigmatization due to having non-normative sexuality. Online forums are also used by zoophiles to exchange information about which districts are at risk of becoming a target of social ostracism.ConclusionsPeople with zoophilia use digital communities to network, meet for sex, find dating partners and for own safety reasons.Disclosure of interestThe authors have not supplied their declaration of competing interest.</jats:sec

Psychiatric treatment-associated stigmatization as viewed through eyes of rural health clinic patients

IntroductionHaving a mental disease is frequently a stigmatizing experience for patients. We know little about urban inhabitants who travel to rural health clinics to receive mental treatment.ObjectivesRecruit and interview urban-based psychiatric patients who, to avoid stigmatization; travel to rural community clinics with the intention of receiving treatment.MethodsStudy included participants (n = 32) who exchanged treatment in government subsidized city clinics for rural community centers. Qualitative interviews lasting thirty minutes were recorded and transcribed for content analysis. MAXQDA, version 12, was used to annotate transcripts with topic specific nodes, followed by cluster theme and trend analysis.ResultsTrend analysis yielded three areas of concern for subsidized urban psychiatry: cost/insurance, lack of staff professionalism, and family-driven ostracism. Seven respondents cited cost as the main factor, influencing the choice of rural-based care over city clinic. Patients with stable income, but without insurance (n = 14), felt unwelcome in city clinics as their ability to pay was frequently questioned by supporting staff. Lack of trained social workers caused additional distress, as participants could not receive access to additional resources. Only four patients said that their psychiatrists acknowledged poor clinic environment and encouraged remaining in treatment. For 18 respondents, family demanded that they receive treatment in rural clinic so that no one finds out about their mental disease.ConclusionIn large urban clinics, stigma in psychiatry comes in many flavors, especially projected by unprofessional clinic staff and ashamed family. Lack of support forces patients to travel to rural premises to receive unbiased, stress-free care.Disclosure of interestThe authors have not supplied their declaration of competing interest.</jats:sec

Rethinking classification of zoophilia

IntroductionIn 2011, Anil Aggrawal proposed ten-point classification system of zoophilia, based on forensic literature review.Objectives(1) Allow for conceptualization and improved management of zoophilic patients in clinical practice or forensic examinations, (2) describe identity of modern-day zoophiles, including demographics and psycho-social profile, and (3) determine normative and pathologic traits and behaviours.MethodsA qualitative observational study of user activity (n = 958) on discussion forums, combined with brief demographic survey. Data were analyzed according to principles of grounded theory. Surveys of own design (demographic, discreet + open ended questions) were answered by 350 participants. Presented data show aggregate conclusions from mixed methods qualitative and quantitative analysis.ResultsProposed classification system categorizes zoos as either classic, sexual, romantic, or platonic. Relationship goals of classic and romantic zoos are reminiscent of those typical of human partnership, differentiated by the commitment and psychological distress level (romantic zoos, affectionate relationship goals outweigh sexual pursuit; classic zoos, romantic and sexual urges cause distress rather than pleasure). Sexual zoos show high prevalence of hypersexuality traits. Platonic zoos are typically confused about the roots of their sexuality. Contrary to common perceptions, prevalence of sexual sadism is extremely low (&lt;1% in our study). Sociopathic traits determine propensity for animal cruelty, which is not synonymous with typical zoophilia. Half of respondents were in committed relationship with human partner, whom they frequently attempted to “convert” into practicing zoophile.ConclusionsWe can categorize zoophiles into four sub-types. Emotional attachment and sexual urges play equal role in bonding with animal partner.Disclosure of interestThe authors have not supplied their declaration of competing interest.</jats:sec