Testicular cancer and cryptorchidism

The failure of testicular descent or cryptorchidism is the most common defect in newborn boys. The descent of the testes during development is controlled by insulin-like 3 peptide and steroid hormones produced in testicular Leydig cells, as well as by various genetic and developmental factors. While in some cases the association with genetic abnormalities and environmental causes has been shown, the etiology of cryptorchidism remains uncertain. Cryptorchidism is an established risk factor for infertility and testicular germ cell tumors (TGCT). Experimental animal models suggest a causative role for an abnormal testicular position on the disruption of spermatogenesis however the link between cryptorchidism and TGCT is less clear. The most common type of TGCT in cryptorchid testes is seminoma, believed to be derived from pluripotent prenatal germ cells. Recent studies have shown that seminoma cells and their precursor carcinoma in situ cells express a number of spermatogonial stem cell (SSC) markers suggesting that TGCTs might originate from adult stem cells. We review here the data on changes in the SSC somatic cell niche observed in cryptorchid testes of mouse models and in human patients. We propose that the misregulation of growth factors' expression may alter the balance between SSC self-renewal and differentiation and shift stem cells towards neoplastic transformation

Artemisia Gentileschi : inspiration and influence in early modern Italy

1 online resource (88 pages) : illustrations (chiefly colour), mapsIncludes abstract.Includes bibliographical references (pages 83-88).This thesis analyses the life and work of the early modern Italian painter Artemisia Gentileschi (1593-ca. 1654) to understand her sources of inspiration and influence. Artemisia rose to prominence during the 20th century when feminist art historians began to research women artists. Artemisia’s body of artwork, however, is often overshadowed by the work of her father Orazio or her ordeal of rape and the trial of her attacker in Rome. This thesis will look at the context of Artemisia’s life in Rome and Florence to draw connections between what she experienced and what she created. By comparing the art and ideologies Artemisia encountered against her own paintings, this thesis develops a deeper understanding of her unique female perspective and choice of subjects in a male-dominated era of artistic production. Through the examination of her work, the thesis aims to understand Artemisia’s talent and resilience

Bidirectional transcription of a novel chimeric gene mapping to mouse chromosome Yq

<p>Abstract</p> <p>Background</p> <p>The male-specific region of the mouse Y chromosome long arm (MSYq) contains three known highly multi-copy X-Y homologous gene families, <it>Ssty1/2</it>, <it>Sly </it>and <it>Asty</it>. Deletions on MSYq lead to teratozoospermia and subfertility or infertility, with a sex ratio skew in the offspring of subfertile MSYqdel males</p> <p>Results</p> <p>We report the highly unusual genomic structure of a novel MSYq locus, <it>Orly</it>, and a diverse set of spermatid-specific transcripts arising from copies of this locus. <it>Orly </it>is composed of partial copies of <it>Ssty1</it>, <it>Asty </it>and <it>Sly </it>arranged in sequence. The <it>Ssty1- </it>and <it>Sly-</it>derived segments are in antisense orientation relative to each other, leading to bi-directional transcription of <it>Orly</it>. Genome search and phylogenetic tree analysis is used to determine the order of events in mouse Yq evolution. We find that <it>Orly </it>is the most recent gene to arise on Yq, and that subsequently there was massive expansion in copy number of all Yq-linked genes.</p> <p>Conclusion</p> <p><it>Orly </it>has an unprecedented chimeric structure, and generates both "forward" (<it>Orly</it>) and "reverse" (<it>Orlyos</it>) transcripts arising from the promoters at each end of the locus. The region of overlap of known <it>Orly </it>and <it>Orlyos </it>transcripts is homologous to <it>Sly </it>intron 2. We propose that <it>Orly </it>may be involved in an intragenomic conflict between mouse X and Y chromosomes, and that this process underlies the massive expansion in copy number of the genes on MSYq and their X homologues.</p

Early Adolescent Predictors of Young Adults’ Distress and Adaptive Coping During the COVID-19 Pandemic: Findings From a Longitudinal Cohort Study

We examined early adolescent predictors of later distress and adaptive coping in early adulthood, using data from a prospective longitudinal cohort study ( n = 786). In early adolescence (age 13), we assessed indicators of mental health (internalizing symptoms), stressor exposure (cumulative stressful life events), and family socialization (supportive parent–child interactions). In early adulthood (age 22), during the first COVID-19-related Swiss national lockdown, we assessed cumulative pandemic-related stressors, distress (poor well-being, hopelessness, and perceived disruptions to life) and adaptive coping. Early adolescent internalizing symptoms predicted lower well-being, more hopelessness, and perceived lifestyle disruptions in early adulthood, during the pandemic. Cumulative stressful life events during early adolescence moderated the association between cumulative pandemic-related stressors and perceived lifestyle disruptions. Supportive parent–child interactions fostered subsequent engagement in adaptive coping, which, in turn, predicted less hopelessness and better well-being. Findings reveal that early adolescent development is linked with distress and adaptive coping in later periods

Early adolescent predictors of young adults’ stress experiences and coping during the COVID-19 pandemic:Findings from a longitudinal cohort study

We examined early adolescent predictors of later distress and adaptive coping in early adulthood, using data from a prospective longitudinal cohort study (n = 786). In early adolescence (age 13), we assessed indicators of mental health (internalizing symptoms), stressor exposure (cumulative stressful life events), and family socialization (supportive parent–child interactions). In early adulthood (age 22), during the first COVID-19-related Swiss national lockdown, we assessed cumulative pandemic-related stressors, distress (poor well-being, hopelessness, and perceived disruptions to life) and adaptive coping. Early adolescent internalizing symptoms predicted lower well-being, more hopelessness, and perceived lifestyle disruptions in early adulthood, during the pandemic. Cumulative stressful life events during early adolescence moderated the association between cumulative pandemic-related stressors and perceived lifestyle disruptions. Supportive parent–child interactions fostered subsequent engagement in adaptive coping, which, in turn, predicted less hopelessness and better well-being. Findings reveal that early adolescent development is linked with distress and adaptive coping in later periods

The worst and the best:New insights into risk and resilience in young adults from the COVID-19 pandemic

Historic declines in young people’s mental health began to emerge before the COVID-19 pandemic. In the face of this youth mental health crisis, the pandemic constituted a naturalistic stressor paradigm that came with the potential to uncover new knowledge for the science of risk and resilience. Surprisingly, approximately 19-35% of people reported better well-being in the first few months of the COVID-19 pandemic than before. Therefore, in May and September 2020, we asked N=517 young adults from a cohort study to describe the best and the worst aspects of their pandemic lives (N=1,462 descriptions). Inductive thematic analysis revealed that the best aspects included the deceleration of life and a greater abundance of free time, which was used for hobbies, healthy activities, strengthening relationships, and for personal growth and building resilience skills. Positive aspects also included a reduction in educational pressures and work load and temporary relief from climate change concerns. The worst aspects included disruptions and changes to daily life; social distancing and restrictions of freedoms; negative emotions that arose in the pandemic situation, including uncertainty about the future; and the growing polarization of society. Science that aims to reverse the youth mental health crisis must pay increased attention to sources of young people’s distress that are not commonly measured (e.g., their educational, work, and time pressures; their fears and uncertainties about their personal, society’s, and the global future), and also to previously untapped sources of well-being – including those that young people identified for themselves while facing the COVID-19 pandemic

The worst and the best: new insights into risk and resilience in young adults from the COVID-19 pandemic

Historic declines in young people’s mental health began to emerge before the COVID-19 pandemic. In the face of this youth mental health crisis, the pandemic constituted a naturalistic stressor paradigm that came with the potential to uncover new knowledge for the science of risk and resilience. Surprisingly, approximately 19-35% of people reported better well-being in the first few months of the COVID-19 pandemic than before. Therefore, in May and September 2020, we asked N=517 young adults from a cohort study to describe the best and the worst aspects of their pandemic lives (N=1,462 descriptions). Inductive thematic analysis revealed that the best aspects included the deceleration of life and a greater abundance of free time, which was used for hobbies, healthy activities, strengthening relationships, and for personal growth and building resilience skills. Positive aspects also included a reduction in educational pressures and work load and temporary relief from climate change concerns. The worst aspects included disruptions and changes to daily life; social distancing and restrictions of freedoms; negative emotions that arose in the pandemic situation, including uncertainty about the future; and the growing polarization of society. Science that aims to reverse the youth mental health crisis must pay increased attention to sources of young people’s distress that are not commonly measured (e.g., their educational, work, and time pressures; their fears and uncertainties about their personal, society’s, and the global future), and also to previously untapped sources of well-being – including those that young people identified for themselves while facing the COVID-19 pandemic

Higher paracetamol levels are associated with elevated glucocorticoid concentrations in hair: findings from a large cohort of young adults

Paracetamol is one of the most commonly used over-the-counter medications. Experimental studies suggest a possible stress-suppressing effect of paracetamol in humans facing experimental stress-inducing paradigms. However, no study has investigated whether paracetamol and steroid hormones covary over longer time frames and under real-life conditions. This study addresses this gap by investigating associations between steroid hormones (cortisol, cortisone, and testosterone) and paracetamol concentrations measured in human hair, indexing a timeframe of approximately three months. The data came from a large community sample of young adults (N = 1002). Hair data were assayed using liquid chromatography–tandem mass spectrometry. Multiple regression models tested associations between paracetamol and  steroid hormones, while adjusting for a wide range of potential confounders, such as sex, stressful live events, psychoactive substance use, hair colour, and body mass index. Almost one in four young adults from the community had detectable paracetamol in their hair (23%). Higher paracetamol hair concentrations were robustly associated with more cortisol (β = 0.13, η$_{p}$ = 0.016, p < 0.001) and cortisone (β = 0.16, η$_{p}$ = 0.025, p < 0.001) in hair. Paracetamol and testosterone hair concentrations were not associated. Paracetamol use intensity positively correlated with corticosteroid functioning across several months. However, a potential corticosteroid-inducing effect of chronic paracetamol use has yet to be tested in future experimental designs

Controlled release of Dextrin-conjugated growth factors to support growth and differentation of neural stem cells

An essential aspect of stem cell in vitro culture and in vivo therapy is achieving sustained levels of growth factors to support stem cell survival and expansion, while maintaining their multipotency and differentiation potential. This study investigated the ability of dextrin (~74,000 g/mol; 27.8 mol% succinoylation) conjugated to epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF; or FGF-2) (3.9 and 6.7% w/w protein loading, respectively) to support the expansion and differentiation of stem cells in vitro via sustained, controllable growth factor release. Supplementation of mouse neural stem cells (mNSCs) with dextrin-growth factor conjugates led to greater and prolonged proliferation compared to unbound EGF/bFGF controls, with no detectable apoptosis after 7 days of treatment. Immunocytochemical detection of neural precursor (nestin) and differentiation (Olig2, MAP2, GFAP) markers verified that controlled release of dextrin-conjugated growth factors preserves stem cell properties of mNSCs for up to 7 days. These results show the potential of dextrin-growth factor conjugates for localized delivery of bioactive therapeutic agents to support stem cell expansion and differentiation, and as an adjunct to direct neuronal repair

Substance use in sexual minority youth: prevalence in an urban cohort

Background Little comparative data on substance use (SU) between sexual minority youth (SMY) and heterosexual youth (HET) is available. This study compares the prevalence of SU in an urban cohort between SMY and HET and evaluates demographic and psychosocial predictors of SU. Methods Data came from a prospective-longitudinal cohort study in an urban setting (N = 1297). SU and psychosocial variables such as internalizing symptoms, self-control, sensation-seeking, bullying-victimization, subjective stress, leisure activities, and peer influences were assessed with self-reports at age 17 and 20. SU was stratified by sex and sexual attraction, and the groups were compared using regression models, with demographic and psychosocial variables included as covariates. Results SMY- and HET-youth displayed differences in a number of psychosocial variables. Overall, SMY- and HET-youth differed in their 12-months prevalence of SU: At age 17, SMY-females had significantly higher rates of SU than HET-females for cannabis (aOR = 2.14, p = 0.04), ecstasy/MDMA (aOR = 4.29, p = 0.01), and hallucinogens (aOR = 5.59, p = 0.02). At age 20, SMY-females had significantly higher rates of SU than HET-females for tobacco (aOR = 2.06, p = 0.03), cannabis (aOR = 2.24, p = 0.004), ecstasy/MDMA (aOR = 3.93, p < 0.001), stimulants (aOR = 3.45, p = 0.002), and hallucinogens (aOR = 6.65, p < 0.001). SMY-males reported significantly lower rates for tobacco and cannabis than HET-males at age 17. At age 20, they reported significantly higher rates for the use of ecstasy/MDMA (aOR = 2.30, p = 0.04) and hallucinogens (aOR = 2.43, p = 0.03). Conclusions Given that psychosocial variables were significant covariates of SMY-status and SU, our results underline the importance of accounting for these when explaining differences in SU between adolescents. While differentiation by sex is established in most studies, such standardized comparisons are lacking with regards to sexual identities. But knowledge about SU of SMY is critical for designing effective interventions. This is especially true for SMY-females: Thus, SU in SMY-females early in life needs to be explored more thoroughly and addressed with adequate prevention measures