Social relationships among adolescents as described in an electronic diary: a mixed methods study

Social relationships among adolescents with mental disorders are demanding. Adolescents with depressive symptoms may have few relationships and have difficulties sharing their problems. Internet may offer reliable and easy to use tool to collect real-time information from adolescents. The aim of this study is to explore how adolescents describe their social relationships with an electronic diary. Mixed methods were used to obtain a broad picture of adolescents' social relationships with the data gathered from network maps and reflective texts written in an electronic diary. Adolescents who visited an outpatient clinic and used an intervention (N=70) designed for adolescents with signs of depression were invited to use the electronic diary; 29 did so. The quantitative data gathered in the electronic diary were summarized with descriptive statistics, and the qualitative data were categorized using a thematic analysis with an inductive approach. We found that social relationships among adolescents with signs of depression can vary greatly in regards to the number of existing relationships (from lacking to 21) and the quality of the relationships (from trustful to difficult). However, the relationships may change, and the adolescents are also willing to build up their social relationships. Professionals need to be aware of the diversity of adolescents' social relationships and their need for personalized support

Tissue hyaluronan expression, as reflected in the sputum of lung cancer patients, is an indicator of malignancy

Hyaluronan (HA) shows promise for detecting cancerous change in pleural effusion and urine. However, there is uncertainty about the localization of HA in tumor tissue and its relationship with different histological types and other components of the extracellular matrix, such as angiogenesis. We evaluated the association between HA and degree of malignancy through expression in lung tumor tissue and sputum. Tumoral tissue had significantly increased HA compared to normal tissue. Strong HA staining intensity associated with cancer cells was significant in squamous cell carcinoma compared to adenocarcinoma and large cell carcinoma. A significant direct association was found between tumors with a high percentage of HA and MVD (microvessel density) in tumoral stroma. Similarly significant was the direct association between N1 tumors and high levels of HA in cancer cells. Cox multivariate analysis showed significant association between better survival and low HA. HA increased in sputum from lung cancer patients compared to cancer-free and healthy volunteers and a significant correlation was found between HA in sputum and HA in cancer tissue. Localization of HA in tumor tissue was related to malignancy and reflected in sputum, making this an emerging factor for an important diagnostic procedure in patients suspected to have lung cancer. Further study in additional patients in a randomized prospective trial is required to finalize these results and to validate our quantitative assessment of HA, as well as to couple it to gold standard sputum cytology.Research supported by FAPESP (2010/11005-5 and 2010/04462) and CNPq (#471939/2010-2 and 483005/2012-6

Genotype–phenotype correlation in migraine without aura focusing on the rs1835740 variant on 8q22.1

A large two-stage GWAS by Antilla et al. reported the minor allele of rs1835740 on 8q22.1 to be associated with common types of migraine. The objective of the present study was to determine the clinical correlate of the variant in migraine without aura (MO). Clinical data on 339 successfully genotyped MO patients (patients with attacks of migraine without aura and no attacks of migraine with aura) were obtained by an extensive validated semi-structured telephone interview performed by a physician or a trained senior medical student. Reliable, systematic and extensive data on symptoms, age of onset, attack frequencies and duration, relevant comorbidity, specific provoking factors including different hormonal factors in females, and effect and use of medication, both abortive and prophylactic, were thereby obtained. A comparison of carriers and non-carriers were performed. Comparison of homozygotes with heterozygotes was not performed as the number of homozygotes was too small for statistical purposes. Data from other MO populations in the GWAS by Antilla et al. were not included as phenotype and clinical data were obtained differently. While thousands of patients are needed to detect a genetic variant like rs1835740, 339 are sufficient to detect meaningful clinical differences. 136 of 339 patients were carriers of the variant, 15 were homozygous. Comparison of carriers with non-carriers showed no significant difference in any of the parameters studied. In conclusion, the rs1835740 variant has no significant influence on the clinical expression of MO

Genetics of migraine in the age of genome-wide association studies

Genetic factors importantly contribute to migraine. However, unlike for rare monogenic forms of migraine, approaches to identify genes for common forms of migraine have been of limited success. Candidate gene association studies were often negative and positive results were often not replicated or replication failed. Further, the significance of positive results from linkage studies remains unclear owing to the inability to pinpoint the genes under the peaks that may be involved in migraine. Problems hampering these studies include limited sample sizes, methods of migraine ascertainment, and the heterogeneous clinical phenotype. Three genome-wide association studies are available now and have successfully identified four new genetic variants associated with migraine. One new variant (rs1835740) modulates glutamate homeostasis, thus integrates well with current concepts of neurotransmitter disturbances. This variant may be more specific for severe forms of migraine such as migraine with aura than migraine without aura. Another variant (rs11172113) implicates the lipoprotein receptor LRP1, which may interact with neuronal glutamate receptors, thus also providing a link to the glutamate pathway. In contrast, rs10166942 is in close proximity to TRPM8, which codes for a cold and pain sensor. For the first time this links a gene explicitly implicated in pain related pathways to migraine. The potential function of the fourth variant rs2651899 (PRDM16) in migraine is unclear. All these variants only confer a small to moderate change in risk for migraine, which concurs with migraine being a heterogeneous disorder. Ongoing large international collaborations will likely identify additional gene variants for migraine

Skin cancer screening participation and impact on melanoma incidence in Germany – an observational study on incidence trends in regions with and without population-based screening

Background: The SCREEN (Skin Cancer Research to provide Evidence for Effectiveness of Screening in Northern Germany) project involved population-wide skin cancer screening with whole-body examination by general physicians and dermatologists. It was conducted in the German state of Schleswig-Holstein (July 2003–June 2004), but not in the German state of Saarland. Methods: The population-based registries of Schleswig-Holstein and Saarland provided data on melanoma incidence before, during, and after SCREEN to assess the association of skin cancer screening with incidence. Results: Approximately 19% of the Schleswig-Holstein population participated in SCREEN (women: 27%, men: 10%). A total of 52% of all melanomas diagnosed during SCREEN in Schleswig-Holstein were detected as part of the project. Melanoma incidence increased during SCREEN (invasive melanoma in women: +8.9 per 100 000 (95% confidence intervals (CI): 6.1; 11.7); men: +4.0 per 100 000 (95% CI: 1.6; 6.4)) and decreased afterwards (women: −10.6 per 100 000 (95% CI: −13.3; −7.9); men: −4.1 per 100 000 (95% CI: −6.5; −1.7)). Similar changes were not observed in Saarland that had no such project. The differences between the two states were greatest among women, the group with the greater SCREEN participation. Conclusion: The SCREEN project had a substantial impact on melanoma incidence. This is consistent with the impact of effective screening for other cancers

Different mechanisms are implicated in ERBB2 gene overexpression in breast and in other cancers

The ERBB2 gene is overexpressed in 30% of breast cancers and this has been correlated with poor prognosis. ERBB2 is upregulated in other cancers such as prostate, pancreas, colon and ovary. In breast cancer cells, the mechanisms leading to ERBB2 gene overexpression are increased transcription and gene amplification. In these cancers, AP-2 transcription factors are involved in ERBB2 overexpression, and AP-2 levels are correlated with p185(c-erbB-2) levels. In this work, we wanted to know if the same molecular mechanisms are responsible for the ERBB2 upregulation in non-breast cancers. We compared ERBB2 gene copy number, p185(c-erbB-2) and mRNA levels with AP-2 levels in several ovary, prostate, colon and pancreas cancer cells. A moderate expression of erbB-2 mRNA and protein were observed in some cells without gene amplification. In contrast to breast cancer cells, AP-2 factors were absent or low in some non-breast cells which did express ERBB2. It is thus likely that AP-2 is not a major player in the increased levels of erbB-2 transcripts in non-breast cancer cells. The transcriptional activity of the ERBB2 promoter in colon and ovary cancer cells was estimated using reporter vectors. The results showed that the promoter regions involved in ERBB2 gene overexpression in breast cancer cells are different from those that lead to the gene upregulation in colon and ovary cancers. In conclusion, our results indicate that different transcriptional and post-transcriptional mechanisms are responsible for the increased levels of erbB-2 transcript and protein in breast and non-breast cancer cells

A multi-targeted approach to suppress tumor-promoting inflammation

Cancers harbor significant genetic heterogeneity and patterns of relapse following many therapies are due to evolved resistance to treatment. While efforts have been made to combine targeted therapies, significant levels of toxicity have stymied efforts to effectively treat cancer with multi-drug combinations using currently approved therapeutics. We discuss the relationship between tumor-promoting inflammation and cancer as part of a larger effort to develop a broad-spectrum therapeutic approach aimed at a wide range of targets to address this heterogeneity. Specifically, macrophage migration inhibitory factor, cyclooxygenase-2, transcription factor nuclear factor-κB, tumor necrosis factor alpha, inducible nitric oxide synthase, protein kinase B, and CXC chemokines are reviewed as important antiinflammatory targets while curcumin, resveratrol, epigallocatechin gallate, genistein, lycopene, and anthocyanins are reviewed as low-cost, low toxicity means by which these targets might all be reached simultaneously. Future translational work will need to assess the resulting synergies of rationally designed antiinflammatory mixtures (employing low-toxicity constituents), and then combine this with similar approaches targeting the most important pathways across the range of cancer hallmark phenotypes

Overview of diagnosis and management of paediatric headache. Part I: diagnosis

Headache is the most common somatic complaint in children and adolescents. The evaluation should include detailed history of children and adolescents completed by detailed general and neurological examinations. Moreover, the possible role of psychological factors, life events and excessively stressful lifestyle in influencing recurrent headache need to be checked. The choice of laboratory tests rests on the differential diagnosis suggested by the history, the character and temporal pattern of the headache, and the physical and neurological examinations. Subjects who have any signs or symptoms of focal/progressive neurological disturbances should be investigated by neuroimaging techniques. The electroencephalogram and other neurophysiological examinations are of limited value in the routine evaluation of headaches. In a primary headache disorder, headache itself is the illness and headache is not attributed to any other disorder (e.g. migraine, tension-type headache, cluster headache and other trigeminal autonomic cephalgias). In secondary headache disorders, headache is the symptom of identifiable structural, metabolic or other abnormality. Red flags include the first or worst headache ever in the life, recent headache onset, increasing severity or frequency, occipital location, awakening from sleep because of headache, headache occurring exclusively in the morning associated with severe vomiting and headache associated with straining. Thus, the differential diagnosis between primary and secondary headaches rests mainly on clinical criteria. A thorough evaluation of headache in children and adolescents is necessary to make the correct diagnosis and initiate treatment, bearing in mind that children with headache are more likely to experience psychosocial adversity and to grow up with an excess of both headache and other physical and psychiatric symptoms and this creates an important healthcare problem for their future life

Cyclin D1, cyclin E, and p21 have no apparent prognostic value in anal carcinomas treated by radiotherapy with or without chemotherapy

The purpose of this study was to assess the potential prognostic and/or predictive value of the expression of cyclin D1, cyclin E, and p21 protein in a series of 98 anal carcinomas (T1-4, N0-3) treated by radiotherapy with (51) or without (47) chemotherapy in one institution. Correlation with Mib1 index and p53 expression was also investigated. Median follow-up for surviving patients was 124 months (range: 30-266). Immunohistochemical staining was performed on pretreatment biopsies, applying a standard ABC technique for cyclin D1 (clone DSC6, DAKO, 1 : 300), cyclin E (clone 13A3, Novocastra, 1 : 100), p21(WAF/CIP1) (clone SX118, DAKO, 1 : 50), p53 (clone DO7, DAKO, 1 : 200), and Mib1 (Ki-67, Dianova, 1 : 20). Tumours were classified into low- or high-expression groups according to the expression level of the protein considered. High expression was found in 51% of tumours for cyclin E, in 33.7% for cyclin D1, and in 65% for p21. None of those factors were significantly associated with clinical variables such as advanced T or N categories. In a monovariate analysis, advanced T and N categories and longer overall treatment time were the only variables that correlated significantly with low rate of local control (LC) and disease-free survival. However, in a subgroup analysis, high p21 expression correlated with a trend for significantly higher 5-year LC (87 vs 68%, P=0.07) in the N0 patients. The results of this study suggest that the cell-cycle proteins investigated are unlikely to be clinically useful in predicting treatment response or prognosis in patients with anal carcinomas

Reduced Expression of Transcription Factor AP-2α Is Associated with Gastric Adenocarcinoma Prognosis

BACKGROUND: This study aims to investigate the expression and prognostic significance of activator protein 2α (AP-2α) in gastric adenocarcinoma. METHODOLOGY/PRINCIPAL FINDINGS: AP-2α expression was analyzed using real-time quantitative PCR (RT-qPCR), western blotting, and immunohistochemical staining methods on tissue samples from a consecutive series of 481 gastric adenocarcinoma patients who underwent resections between 2003 and 2006. The relationship between AP-2α expression, clinicopathological factors, and patient survival was investigated. RT- qPCR results showed that the expression of AP-2α mRNA was reduced in tumor tissue samples, compared with expression in matched adjacent non-tumor tissue samples (P = 0.009); this finding was confirmed by western blotting analysis (P = 0.012). Immunohistochemical staining data indicated that AP-2α expression was significantly decreased in 196 of 481 (40.7%) gastric adenocarcinoma cases; reduced AP-2α expression was also observed in patients with poorly differentiated tumors (P = 0.001) and total gastric carcinomas (P = 0.002), as well as in patients who underwent palliative tumor resection (P = 0.004). Additionally, reduced expression of AP-2α was more commonly observed in tumors that were staged as T4a/b (P = 0.018), N3 (P = 0.006), and M1 (P = 0.008). Kaplan-Meier survival curves revealed that reduced expression of AP-2α was associated with poor prognosis in gastric adenocarcinoma patients (P<0.001). Multivariate Cox analysis identified AP-2α expression as an independent prognostic factor for overall survival (HR = 1.512, 95% CI = 1.127-2.029, P = 0.006). CONCLUSIONS/SIGNIFICANCE: Our data suggest that AP-2α plays an important role in tumor progression and that reduced AP-2α expression independently predicts an unfavorable prognosis in gastric adenocarcinoma patients