Survival from cancer in young people: An overview of late effects focusing on reproductive health

This paper provides a summary of the areas of survival from childhood, teenage and young adult cancers and the significant late effects that can arise from treatment; with particular focus on the area of reproductive health and the impact on both fertility and pregnancy. To complete this review, Web of Science and MEDLINE were used. Search terms included: “"survival AND childhood OR teenage OR young adult cancer", "late effects", "childhood cancer", "teenage AND/OR young adult cancer", AND "fertility after cancer" OR "pregnancy AND cancer" OR "fertility preservation”. Additionally, the clinical expertise of the authors was drawn upon. Childhood cancer is a thankfully rare occurrence; however, the incidence is increasing. Survival rates remain high and this means that a growing population of childhood and young adult cancer survivors are reaching adulthood. For some of these adults, although cured of their cancer, they are now facing a future with lasting effects on their health from their treatments. These effects, commonly referred to as late effects, are defined as health problems related either directly to the underlying cancer or to its treatment and which occur months or years after treatment has finished. Reproductive health is an important consideration for these patients, and although many will be able to conceive naturally, some will exhibit impaired fertility after their treatments. This can include difficulties at all points along the path from conception to delivery of a live, healthy offspring. High‐quality, large‐population evidence is sparse in many areas relating to fertility risk from treatment and the maternal and fetal health of childhood cancer survivors. Yet given the potential for complications, the authors advocate consideration of fertility at the time of diagnosis and before potentially gonadotoxic treatment

The owl spreads its wings: global and international education within the local from critical perspectives

Within an era of a New Knowledge Society, assumptions abound regarding the ‘goodness' and justice of global interconnections and distributions of knowledge through international educational organizations and structures worldwide. Just as George Bush Jr. in attempting to justify the invasion of Iraq made claim to the democratic goodness of the US ‘spreading their freedoms' in the interests of an all-encompassing democratization of the world, so the assumption that sharing educational knowledge, especially an ‘all-knowing North' with a ‘helpless South' is without question for the greater good of all humanity

Does publication bias inflate the apparent efficacy of psychological treatment for major depressive disorder? A systematic review and meta-analysis of US national institutes of health-funded trials

Background The efficacy of antidepressant medication has been shown empirically to be overestimated due to publication bias, but this has only been inferred statistically with regard to psychological treatment for depression. We assessed directly the extent of study publication bias in trials examining the efficacy of psychological treatment for depression. Methods and Findings We identified US National Institutes of Health grants awarded to fund randomized clinical trials comparing psychological treatment to control conditions or other treatments in patients diagnosed with major depressive disorder for the period 1972–2008, and we determined whether those grants led to publications. For studies that were not published, data were requested from investigators and included in the meta-analyses. Thirteen (23.6%) of the 55 funded grants that began trials did not result in publications, and two others never started. Among comparisons to control conditions, adding unpublished studies (Hedges’ g = 0.20; CI95% -0.11~0.51; k = 6) to published studies (g = 0.52; 0.37~0.68; k = 20) reduced the psychotherapy effect size point estimate (g = 0.39; 0.08~0.70) by 25%. Moreover, these findings may overestimate the "true" effect of psychological treatment for depression as outcome reporting bias could not be examined quantitatively. Conclusion The efficacy of psychological interventions for depression has been overestimated in the published literature, just as it has been for pharmacotherapy. Both are efficacious but not to the extent that the published literature would suggest. Funding agencies and journals should archive both original protocols and raw data from treatment trials to allow the detection and correction of outcome reporting bias. Clinicians, guidelines developers, and decision makers should be aware that the published literature overestimates the effects of the predominant treatments for depression

An experimental model of rhinovirus induced chronic obstructive pulmonary disease exacerbations: a pilot study

BACKGROUND: Acute exacerbations of COPD are a major cause of morbidity, mortality and hospitalisation. Respiratory viruses are associated with the majority of exacerbations but a causal relationship has not been demonstrated and the mechanisms of virus-induced exacerbations are poorly understood. Development of a human experimental model would provide evidence of causation and would greatly facilitate understanding mechanisms, but no such model exists. METHODS: We aimed to evaluate the feasibility of developing an experimental model of rhinovirus induced COPD exacerbations and to assess safety of rhinovirus infection in COPD patients. We carried out a pilot virus dose escalating study to assess the minimum dose of rhinovirus 16 required to induce experimental rhinovirus infection in subjects with COPD (GOLD stage II). Outcomes were assessed by monitoring of upper and lower respiratory tract symptoms, lung function, and virus replication and inflammatory responses in nasal lavage. RESULTS: All 4 subjects developed symptomatic colds with the lowest dose of virus tested, associated with evidence of viral replication and increased pro-inflammatory cytokines in nasal lavage. These were accompanied by significant increases in lower respiratory tract symptoms and reductions in PEF and FEV(1). There were no severe exacerbations or other adverse events. CONCLUSION: Low dose experimental rhinovirus infection in patients with COPD induces symptoms and lung function changes typical of an acute exacerbation of COPD, appears safe, and provides preliminary evidence of causation

Neural correlates of sexual cue reactivity in individuals with and without compulsive sexual behaviours

Although compulsive sexual behaviour (CSB) has been conceptualized as a "behavioural" addiction and common or overlapping neural circuits may govern the processing of natural and drug rewards, little is known regarding the responses to sexually explicit materials in individuals with and without CSB. Here, the processing of cues of varying sexual content was assessed in individuals with and without CSB, focusing on neural regions identified in prior studies of drug-cue reactivity. 19 CSB subjects and 19 healthy volunteers were assessed using functional MRI comparing sexually explicit videos with non-sexual exciting videos. Ratings of sexual desire and liking were obtained. Relative to healthy volunteers, CSB subjects had greater desire but similar liking scores in response to the sexually explicit videos. Exposure to sexually explicit cues in CSB compared to non-CSB subjects was associated with activation of the dorsal anterior cingulate, ventral striatum and amygdala. Functional connectivity of the dorsal anterior cingulate-ventral striatum-amygdala network was associated with subjective sexual desire (but not liking) to a greater degree in CSB relative to non-CSB subjects. The dissociation between desire or wanting and liking is consistent with theories of incentive motivation underlying CSB as in drug addictions. Neural differences in the processing of sexual-cue reactivity were identified in CSB subjects in regions previously implicated in drug-cue reactivity studies. The greater engagement of corticostriatal limbic circuitry in CSB following exposure to sexual cues suggests neural mechanisms underlying CSB and potential biological targets for interventions

Turnip yellow mosaic virus in Chinese cabbage in Spain: Commercial seed transmission and molecular characterization

[EN] Seed transmission of Turnip yellow mosaic virus (TYMV, genus Tymovirus) was evaluated in the whole seeds and seedlings that emerged from three commercial Chinese cabbage (Brassica pekinensis) seed batches. Seedlings in the cotyledon stage and adult plants were assayed for TYMV by DAS-ELISA and confirmed by RT-PCR. The proportion of whole seeds infected with TYMV was at least 0.15 %. The seeds of the three seed batches were grown in Petri dishes, and surveyed in the cotyledon stage in trays that contained a peat:sand mixture grown in greenhouses or growth chambers, which were analysed in the cotyledon and adult stages. The seed-to-seedling transmission rate ranged from 2.5 % to 2.9 % in two different seed batches (lot-08 and lot-09, respectively). Spanish isolates derived from turnip (Sp-03) and Chinese cabbage (Sp-09 and Sp-13), collected in 2003, 2009 and 2013 in two different Spanish regions, were molecularly characterised by analysing the partial nucleotide sequences of three TYMV genome regions: partial RNA-dependent RNA polymerase (RdRp), methyltransferase (MTR) and coat protein (CP) genes. Phylogenetic analyses showed that the CP gene represented two different groups: TYMV-1 and TYMV-2. The first was subdivided into three subclades: European, Australian and Japanese. Spanish isolate Sp-03 clustered together with European TYMV group, whereas Sp-09 and Sp-13 grouped with the Japanese TYMV group, and all differed from group TYMV-2. The sequences of the three different genomic regions examined clustered into the same groups. The results suggested that Spanish isolates grouped according to the original hosts from which they were isolated. The inoculation of the Spanish TYMV isolates to four crucifer plants species (turnip, broccoli, Brunswick cabbage and radish) revealed that all the isolates infected turnip with typical symptoms, although differences were observed in other hosts.Alfaro Fernández, AO.; Serrano, A.; Tornos, T.; Cebrian Mico, MC.; Córdoba-Sellés, MDC.; Jordá, C.; Font San Ambrosio, MI. (2016). Turnip yellow mosaic virus in Chinese cabbage in Spain: Commercial seed transmission and molecular characterization. EUROPEAN JOURNAL OF PLANT PATHOLOGY. 146(2):433-442. doi:10.1007/s10658-016-0929-3S4334421462Assis Filho, M., & Sherwood, J. L. (2000). Evaluation of seed transmission of Turnip yellow mosaic virus and Tobacco mosaic virus in Arabidopsis thaliana. Phytopathology, 90, 1233–1238.Benetti, M. P., & Kaswalder, F. (1983). Trasmisione per seme del virus del mosaico giallo rapa. Annali dell Istituto Sperimentale per la Patologia Vegetale, 8, 67–70.Blok, J., Mackenzie, A., Guy, P., & Gibbs, A. (1987). Nucleotide sequence comparisons of Turnip yellow mosaic virus isolates from Australia and Europe. Archives of Virology, 97, 283–295.Brunt, A., Crabtree, K., Dallwitz, M., Gibbs, A., Watson, L., & Zurcher, E.J. (1996). Plant Viruses Online: Descriptions and Lists from the VIDE Database. Version: 20th August 1996. URL http://biology.anu.edu.au/Groups/MES/vide/ .Campbell, R. N., Wipf-Scheibel, C., & Lecoq, H. (1996). Vector-assissted seed transmission of melon necrotic spot virus in melon. Phytopathology, 86, 1294–1298.Dreher, T. W., & Bransom, K. L. (1992). Genomic RNA sequence of Turnip yellow mosaic virus isolate TYMC, a cDNA-based clone with verified infectivity. Plant Molecular Biology, 18, 403–406.Fakhro, A., Von Bargen, S., Bandte, M., Büttner, C., Franken, P., & Schwarz, D. (2011). Susceptibility of different plant species and tomato cultivars to two isolates of Pepino mosaic virus. European Journal of Plant Pathology, 129, 579–590.Gibbs, A. J., & Gower, J. C. (1960). The use of a multiple-transfer method in plant virus transmission studies: some statistical points arising in the analysis of results. Annals of Applied Biology, 48, 75–83.Hayden, C. M., Mackenzie, A. M., & Gibbs, A. J. (1998a). Virion protein sequence variation among Australian isolates of turnip yellow mosaic tymovirus. Archives of Virology, 143, 191–201.Hayden, C. M., Mackenzie, A. M., Skotnicki, M. L., & Gibbs, A. (1998b). Turnip yellow mosaic virus isolates with experimentally produced recombinant virion proteins. Journal of General Virology, 79, 395–403.Hein, A. (1984). Transmission of Turnip yellow mosaic virus through seed of Camelina sativa gold of pleasure. Journal of Plant Diseases and Protection, 91, 549–551.Herrera-Vásquez, J. A., Córdoba-Sellés, M. C., Cebrián, M. C., Alfaro-Fernández, A., & Jordá, C. (2009). Seed transmission of Melon necrotic spot virus and efficacy of seed-disinfection treatments. Plant Pathology, 58, 436–452.Hull, R. (2002). Matthews’ plant virology (4a ed.1001 pp). San Diego: Academic Press.Johansen, E., Edwards, M. C., & Hampton, R. O. (1994). Seed transmission of viruses: current perspectives. Annual Review of Phytopathology, 32, 363–386.Kirino, N., Inoue, K., Tanina, K., Yamazaki, Y., & Ohki, S. T. (2008). Turnip yellow mosaic virus isolated from Chinese cabbage in Japan. Journal of General Plant Pathology, 74, 331–334.Markham, R., & Smith, K. S. (1949). Studies on the virus of turnip yellow mosaic. Parasitology, 39, 330–342.Mathews, R. E. F. (1980). Turnip yellow mosaic virus, CMI/AAB Descriptions of plant virus No. 230 (No. 2 revised). Kew: Commonwealth Mycology Institute/Association of Applied Biologists.Mitchell, E. J., & Bond, J. M. (2005). Variation in the coat protein sequence of British isolates of Turnip yellow mosaic virus and comparison with previously published isolates. Archives of Virology, 150, 2347–2355.Pagán, I., Fraile, A., Fernández-Fueyo, E., Montes, N., Alonso-Blanco, C., & García-Arenal, F. (2010). Arabidopsis thaliana as a model for the study of plant-virus co-evolution. Philosophical Transations of the Royal Society Biological Sciences, 365, 1983–1995.Paul, H. L., Gibbs, A., & Wittman-Liebold, B. (1980). The relationships of certain Tymoviruses assessed from the amino acid composition of their coat proteins. Intervirology, 13, 99–109.Pelikanova, J. (1990). Garlic mustard a spontaneous host of TYMV. Ochrana Rostlin, 26, 17–22.Procházková, Z. (1980). Host range and symptom differences between isolates of Turnip mosaic virus obtained from Sisymbrium loeselii. Biologia Plantarum, 22, 341–347.Rimmer, S. R., Shtattuck, V. I., & Buchwaldt, L. (2007). Compendium of brassica diseases (1ª Edición ed.p. 117). USA: APS press.Rot, M. E., & Jelkman, W. (2001). Characterization and detection of several filamentous viruses of cherry: Adaptation of an alternative cloning method (DOP-PCR), and modification of an RNA extraction protocol. European Journal of Plant Pathology, 107, 411–420.Sabanadzovic, S., Abou-Ghanem, N., Castellano, M. A., Digiaero, M., & Martelli, G. P. (2000). Grapevine fleck virus-like in Vitis. Archives of Virology, 145, 553–565.Špack, J., & Kubelková, D. (2000). Serological variability among European isolates of Radish mosaic virus. Plant Pathology, 49, 295–301.Špack, J., Kubelková, D., & Hnilicka, E. (1993). Seed transmission of Turnip yellow mosaic virus in winter turnip and winter oilseed rapes. Annals of Applied Biology, 123, 33–35.Stobbs, L. W., Cerkauskas, R. F., Lowery, T., & VanDriel, L. (1998). Occurrence of Turnip yellow mosaic virus on oriental cruciferours vegetables in Southern Ontario, Canada. Plant Disease, 82, 351.Tamura, K., Peterson, D., Peterson, N., Stecher, G., Nei, M., & Kumar, S. (2011). MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Molecular Biology and Evolution, 28, 2731–2739

Epithelial Proinflammatory Response and Curcumin-Mediated Protection from Staphylococcal Toxic Shock Syndrome Toxin-1

Staphylococcus aureus initiates infections and produces virulence factors, including superantigens (SAgs), at mucosal surfaces. The SAg, Toxic Shock Syndrome Toxin-1 (TSST-1) induces cytokine secretion from epithelial cells, antigen presenting cells (APCs) and T lymphocytes, and causes toxic shock syndrome (TSS). This study investigated the mechanism of TSST-1-induced secretion of proinflammatory cytokines from human vaginal epithelial cells (HVECs) and determined if curcumin, an anti-inflammatory agent, could reduce TSST-1-mediated pathology in a rabbit vaginal model of TSS. TSST-1 caused a significant increase in NF-κB-dependent transcription in HVECs that was associated with increased expression of TNF- α, MIP-3α, IL-6 and IL-8. Curcumin, an antagonist of NF-κB-dependent transcription, inhibited IL-8 production from ex vivo porcine vaginal explants at nontoxic doses. In a rabbit model of TSS, co-administration of curcumin with TSST-1 intravaginally reduced lethality by 60% relative to 100% lethality in rabbits receiving TSST-1 alone. In addition, TNF-α was undetectable from serum or vaginal tissue of curcumin treated rabbits that survived. These data suggest that the inflammatory response induced at the mucosal surface by TSST-1 is NF-κB dependent. In addition, the ability of curcumin to prevent TSS in vivo by co-administration with TSST-1 intravaginally suggests that the vaginal mucosal proinflammatory response to TSST-1 is important in the progression of mTSS

Growth Factors Regulate Expression of Osteoblast‐Associated Genes

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141995/1/jper1345.pd

Localized microstimulation of primate pregenual cingulate cortex induces negative decision-making

The pregenual anterior cingulate cortex (pACC) has been implicated in human anxiety disorders and depression, but the circuit-level mechanisms underlying these disorders are unclear. In healthy individuals, the pACC is involved in cost-benefit evaluation. We developed a macaque version of an approach-avoidance decision task used to evaluate anxiety and depression in humans and, with multi-electrode recording and cortical microstimulation, we probed pACC function as monkeys performed this task. We found that the macaque pACC has an opponent process-like organization of neurons representing motivationally positive and negative subjective value. Spatial distribution of these two neuronal populations overlapped in the pACC, except in one subzone, where neurons with negative coding were more numerous. Notably, microstimulation in this subzone, but not elsewhere in the pACC, increased negative decision-making, and this negative biasing was blocked by anti-anxiety drug treatment. This cortical zone could be critical for regulating negative emotional valence and anxiety in decision-making.National Institutes of Health (U.S.) (Javits Merit Grant R01 NS025529)United States. Office of Naval Research (N000140710903)National Parkinson Foundation (U.S.) (Lynn Diamond Fellowship