Perceptions of stressful life events in Northern Irish school children: a longitudinal study.

Adults’ perceptions of stressful life events have been acknowledged as important moderators of the stress adjustment relationship. Until recently, however, there has been a lack of research on children's perceptions of negative life events. This study assesses children's own perceptions of the stressfulness of negative familial, academic and social events as well as events related to the political conflict in Northern Ireland. Method: Developmental changes in children's perceptions of events are traced over time. One hundred and sixty 8-year-old children completed a self-report measure of the perceived stressfulness of a range of negative life events. The sample was drawn from schools in the Greater Belfast area to include children of both genders, primary religious affiliations in Northern Ireland (i.e., Protestant and Roman Catholic) and of varying socio-economic status. Three years later, 113 of these children, then aged 11, were traced through the school system and completed the same measure. Results: Children's perceptions of stressful events are related to a host of social factors. Girls viewed many negative events as more stressful than their male counterparts. Roman Catholic and Protestant children differed in their perceptions of conflict-related events. Perceptions of various types of negative experiences were differentially related to socio-economic status and age. Conclusion: Personal, social and situational factors differentially determine children's perceptions of negative life experiences.

Kit-positive interstitial cells in the rabbit urethra: structural relationships with nerves and smooth muscle.

OBJECTIVE: To identify interstitial cells (ICs) in the wall of the rabbit urethra using antibodies to the Kit receptor, and to examine their location, morphology and relationship with nerves and smooth muscle cells (SMCs), as studies of enzymatically isolated cells from the rabbit urethra have established that there are specialized cells that show spontaneous electrical activity and have morphological properties of ICs. MATERIALS AND METHODS: Urethral tissues from rabbits were fixed, labelled with antibodies and examined with confocal microscopy. Some specimens were embedded in paraffin wax and processed for histology. Histological sections from the most proximal third and mid-third region of rabbit urethra were stained with Masson's Trichrome to show their cellular arrangement. RESULTS: Sections from both regions had outer longitudinal and inner circular layers of SM, and a lamina propria containing connective tissue and blood vessels; the lumen was lined with urothelial cells. The mid-third region had a more developed circular SM layer than the most-proximal samples, and had extensive inner longitudinal SM bundles in the lamina propria. Labelling with anti-Kit revealed immunopositive cells within the wall of the rabbit urethra, in the circular and longitudinal layers of the muscularis. Double-labelling with an antibody to SM myosin showed Kit-positive cells on the boundary of the SM bundles, orientated parallel to the axis of the bundles. Others were in spaces between the bundles and often made contact with each other. Kit-positive cells were either elongated, with several lateral branches, or stellate with branches coming from a central soma. Similar cells could be labelled with vimentin antibodies. Their relationship with intramural nerves was examined by double immunostaining with an anti-neurofilament antibody. There were frequent points of contact between Kit-positive cells and nerves, with similar findings in specimens double-immunostained with anti-neuronal nitric oxide synthase (nNOS). CONCLUSION: Kit-positive ICs were found within the SM layers of the rabbit urethra, in association with nerves, on the edge of SM bundles and in the interbundle spaces. The contact with nNOS-containing neurones might imply participation in the nitrergic inhibitory neurotransmission of the urethra. PMID: 17212607 [PubMed - indexed for MEDLINE]

The PD-1/PD-L1 Axis: An Immune-Mediated Mechanism of Chemoresistance in Cancer

The ability of tumour cells to avoid immune destruction (immune escape) and their acquired resistance to anti-cancer drugs constitute important barriers to the successful management of cancer. The interaction between specific molecules on the surface of tumour cells with their corresponding receptors on immune effector cells can result in inhibition of these effector cells, consequently allowing tumour cells to evade the host’s anti-tumour immune response. The interaction of the Programmed Death Ligand 1 (PD-L1) on the surface of tumour cells with the Programmed Death-1 (PD-1) receptor on cytotoxic T lymphocytes leads to inactivation of these immune effectors, and is a specific example of an immune escape mechanism tumour cells use to avoid immune destruction. Clinically, antibodies capable of blocking the PD-1/PD-L1 interaction have demonstrated significant therapeutic benefit, and are currently being used to help bolster patients’ immune response against malignant cells in a variety of cancer types. Here we show that the PD-1/PD-L1 interaction also leads to tumour cell resistance to conventional chemotherapeutic agents. Incubation of PD-L1-expressing human and mouse tumour cells with PD-1-expressing Jurkat T cells or purified recombinant PD-1 resulted in tumour cell resistance to doxorubicin and docetaxel. Interference with the PD-1/PD-L1 interaction using blocking anti-PD-1 or anti-PD-L1 antibody or shRNA-mediated gene silencing resulted in attenuation of PD-1/PD-L1-mediated drug resistance. Moreover, inhibition of the PD-1/PD-L1 signalling axis using anti-PD-1 antibody enhanced the effect of doxorubicin chemotherapy to inhibit 4T1 tumour cell metastasis in an in vivo mouse model of mammary carcinoma. These findings indicate that blockade of the PD-1/PD-L1 axis may be a useful approach to immunosensitize and chemosensitize tumours in cancer patients and provide a rationale for the use of anti-PD-1/PD-L1 antibodies as adjuvants to chemotherapy.

Drug use amongst young people attending emotional and behavioural difficulty units during adolescence: A longitudinal anlaysis

This paper reports on the findings from a longitudinal survey of the drug use behaviours of young people who were attending Emotional and Behavioural Difficulty (EBD) units from the age of 11-16 years. It forms part of the Belfast Youth Development Study, a longitudinal study of adolescent drug use. This paper presents a follow-up report to a cross-sectional paper that reported on drug use behaviours of a sample of young people attending EBD units when aged 12/13 years at school year 9 (McCrystal et al 2005a). In the present paper reported drug use and behaviours associated with increased risk of its use between the ages of 11-16 years were examined. The findings show that those attending EBD Units consistently reported higher levels of licit and illicit drug use throughout adolescence. Compared with young people in mainstream school, higher levels of behaviours associated with drug use including antisocial behaviour, disaffection with school, and poor communication with their parents/guardians were noted. These findings have implications for the development and timing of targeted prevention initiatives for young people attending EBD units at all stages of adolescent development.

Substance Use Behaviours of Young People with A Moderate Learning Disability: A longitudinal analysis

Substance use behaviours of young people attending a special school are reported over a four year period from the age of 12-16 years. The paper investigated these behaviours by surveying a cohort of young people with a statement for moderate learning disabilities annually during the last four years of compulsory schooling. The findings show that these young people consistently reported lower levels of tobacco, alcohol and cannabis use compared with those attending mainstream school. No other illicit drug use was reported. The potential implications of these findings are discussed in relation to the context and timing of targeted substance education and prevention initiatives for young people with moderate learning disability attending a special school.

Plasma levels of the immunomodulatory cytokine interleukin-10 during normal human pregnancy: a longitudinal study.

Pregnancy is proposed to be a Th2 phenomenon, where Th2 cytokines inhibit Th1 responses to improve fetal survival. The importance of interleukin-10 (IL-10), an immunomodulatory cytokine produced by Th2 cells, in the maintenance of normal pregnancy is becoming increasingly apparent. In a longitudinal case-control study, the physiological effect of pregnancy on plasma IL-10 was investigated. The plasma concentration of IL-10 was determined using an ELISA technique in 99 pregnant women sampled at 12, 20 and 35 weeks of gestation, 38 non-pregnant control subjects sampled in parallel and in a subgroup of women sampled at 3 days post-partum (n, pregnant 21, non-pregnant 21). Plasma IL-10 was significantly higher in pregnant women at 12, 20 and 35 weeks of gestation (p