Ultraviolet Irradiation Induces the Accumulation of Chondroitin Sulfate, but Not Other Glycosaminoglycans, in Human Skin

Ultraviolet (UV) light alters cutaneous structure and function. Prior work has shown loss of dermal hyaluronan after UV-irradiation of human skin, yet UV exposure increases total glycosaminoglycan (GAG) content in mouse models. To more fully describe UV-induced alterations to cutaneous GAG content, we subjected human volunteers to intermediate-term (5 doses/week for 4 weeks) or single-dose UV exposure. Total dermal uronyl-containing GAGs increased substantially with each of these regimens. We found that UV exposure substantially increased dermal content of chondroitin sulfate (CS), but not hyaluronan, heparan sulfate, or dermatan sulfate. UV induced the accumulation of both the 4-sulfated (C4S) and 6-sulfated (C6S) isoforms of CS, but in distinct distributions. Next, we examined several CS proteoglycan core proteins and found a significant accumulation of dermal and endothelial serglycin, but not of decorin or versican, after UV exposure. To examine regulation in vitro, we found that UVB in combination with IL-1α, a cytokine upregulated by UV radiation, induced serglycin mRNA in cultured dermal fibroblasts, but did not induce the chondroitin sulfate synthases. Overall, our data indicate that intermediate-term and single-dose UVB exposure induces specific GAGs and proteoglycan core proteins in human skin in vivo. These molecules have important biologic functions and contribute to the cutaneous response to UV

Background risk of breast cancer and the association between physical activity and mammographic density

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Misinformation increases symptom reporting: a test – retest study

OBJECTIVES: We examined whether misleading information (i.e. misinformation) may promote symptom reporting in non-clinical participants. DESIGN: A test-retest study in which we collected baseline data about participants' psychological symptoms and then misinformed them that they had rated two target symptoms relatively highly. During an interview, we determined whether participants would notice this misinformation and at direct and one-week follow-up, we evaluated whether the misinformation would exacerbate retest measures of the same symptoms. SETTING: A psychological laboratory. PARTICIPANTS: A total of 78 undergraduate students. MAIN OUTCOME MEASURES: Participants' scores on a widely used self-report measure of psychological symptoms. RESULTS: We found that most participants (63%) were blind to the discrepancies between their original symptom ratings and the upgraded scores they were misinformed with. Furthermore, at the one-week follow-up retest, blind participants revised their symptom ratings in the direction of the misinformation (i.e. they increased their ratings of these symptoms). CONCLUSION: Introspective monitoring of common psychological symptoms is poor and this creates an opportunity for misinformation and symptom escalation. Our finding bears relevance to theories about the iatrogenic amplification of medically unexplained symptoms

The attitudes of brain cancer patients and their caregivers towards death and dying: a qualitative study

<p>Abstract</p> <p>Background</p> <p>Much money and energy has been spent on the study of the molecular biology of malignant brain tumours. However, little attention has been paid to the wishes of patients afflicted with these incurable tumours, and how this might influence treatment considerations.</p> <p>Methods</p> <p>We interviewed 29 individuals – 7 patients dying of a malignant brain tumor and 22 loved ones. One-on-one interviews were conducted according to a pre-designed interview guide. A combination of open-ended questions, as well as clinical scenarios was presented to participants in order to understand what is meaningful and valuable to them when determining treatment options and management approaches. The results were analyzed, coded, and interpreted using qualitative analytic techniques in order to arrive at several common overarching themes.</p> <p>Results</p> <p>Seven major themes were identified. In general, respondents were united in viewing brain cancer as unique amongst malignancies, due in large part to the premium placed on mental competence and cognitive functioning. Importantly, participants found their experiences, however difficult, led to the discovery of inner strength and resilience. Responses were usually framed within an interpersonal context, and participants were generally grateful for the opportunity to speak about their experiences. Attitudes towards religion, spirituality, and euthanasia were also probed.</p> <p>Conclusion</p> <p>Several important themes underlie the experiences of brain cancer patients and their caregivers. It is important to consider these when managing these patients and to respect not only their autonomy but also the complex interpersonal toll that a malignant diagnosis can have.</p

Dietary preference, physical activity, and cancer risk in men: national health insurance corporation study

<p>Abstract</p> <p>Background</p> <p>The effects of vegetable preference and leisure-time physical activity (LPA) on cancer have been inconsistent. We examined the effects of dietary preference and physical activity, as well as their combined effect on cancer risk.</p> <p>Methods</p> <p>This prospective cohort study included 444,963 men, older than 40 years, who participated in a national health examination program begun in 1996. Based on the answer to the question "What kind of dietary preference do you have?" we categorized dietary preference as (1) vegetables, (2) mixture of vegetables and meat, and (3) meats. We categorized LPA as low (< 4 times/wk, < 30 min/session), moderate (2–4 times/wk, ≥ 30 min/session or ≥ 5 times/wk, < 30 min/session), or high (≥ 5 times/wk, ≥ 30 min/session). We obtained cancer incidence data for 1996 through 2002 from the Korean Central Cancer Registry. We used a standard Poisson regression model with a log link function and person-time offset to estimate incidence and relative risk..</p> <p>Results</p> <p>During the 6-year follow-up period, we identified 14,109 cancer cases. Multivariate analysis revealed that a preference for vegetables or a mixture of vegetables and meat as opposed to a preference for meat played a significant protective role against lung cancer incidence (aRR, 0.81; 95% confidence interval [CI], 0.68–0.98). Compared with the low LPA group, subjects with moderate-high LPA had a significantly lower risk for stomach (aRR, 0.91; 95%CI, 0.86–0.98), lung (aRR, 0.83; 95%CI, 0.75–0.92), and liver (aRR, 0.88; 95%CI, 0.81–0.95) cancer. Among current smokers, the combined moderate-high LPA and vegetable or mixture of vegetables and meat preference group showed a 40% reduced risk of lung cancer (aRR, 0.60; 95%CI, 0.47–0.76) compared with the combined low LPA and meat preference group. Among never/former smokers, subjects with moderate-high LPA and a preference for vegetables or a mixture of vegetables and meat showed reduced stomach cancer risk (aRR, 0.72; 95%CI, 0.54–0.95).</p> <p>Conclusion</p> <p>Our findings add to the evidence of the beneficial effects of vegetable preference on lung cancer risk and of physical activity on lung, stomach, and liver cancer risk. Additionally, vegetable preference combined with LPA might significantly reduce lung and stomach cancer risk.</p

Replication and Active Demethylation Represent Partially Overlapping Mechanisms for Erasure of H3K4me3 in Budding Yeast

Histone modifications affect DNA–templated processes ranging from transcription to genomic replication. In this study, we examine the cell cycle dynamics of the trimethylated form of histone H3 lysine 4 (H3K4me3), a mark of active chromatin that is viewed as “long-lived” and that is involved in memory during cell state inheritance in metazoans. We synchronized yeast using two different protocols, then followed H3K4me3 patterns as yeast passed through subsequent cell cycles. While most H3K4me3 patterns were conserved from one generation to the next, we found that methylation patterns induced by alpha factor or high temperature were erased within one cell cycle, during S phase. Early-replicating regions were erased before late-replicating regions, implicating replication in H3K4me3 loss. However, nearly complete H3K4me3 erasure occurred at the majority of loci even when replication was prevented, suggesting that most erasure results from an active process. Indeed, deletion of the demethylase Jhd2 slowed erasure at most loci. Together, these results indicate overlapping roles for passive dilution and active enzymatic demethylation in erasing ancestral histone methylation states in yeast

Dietary preference, physical activity, and cancer risk in men: national health insurance corporation study

<p>Abstract</p> <p>Background</p> <p>The effects of vegetable preference and leisure-time physical activity (LPA) on cancer have been inconsistent. We examined the effects of dietary preference and physical activity, as well as their combined effect on cancer risk.</p> <p>Methods</p> <p>This prospective cohort study included 444,963 men, older than 40 years, who participated in a national health examination program begun in 1996. Based on the answer to the question "What kind of dietary preference do you have?" we categorized dietary preference as (1) vegetables, (2) mixture of vegetables and meat, and (3) meats. We categorized LPA as low (< 4 times/wk, < 30 min/session), moderate (2–4 times/wk, ≥ 30 min/session or ≥ 5 times/wk, < 30 min/session), or high (≥ 5 times/wk, ≥ 30 min/session). We obtained cancer incidence data for 1996 through 2002 from the Korean Central Cancer Registry. We used a standard Poisson regression model with a log link function and person-time offset to estimate incidence and relative risk..</p> <p>Results</p> <p>During the 6-year follow-up period, we identified 14,109 cancer cases. Multivariate analysis revealed that a preference for vegetables or a mixture of vegetables and meat as opposed to a preference for meat played a significant protective role against lung cancer incidence (aRR, 0.81; 95% confidence interval [CI], 0.68–0.98). Compared with the low LPA group, subjects with moderate-high LPA had a significantly lower risk for stomach (aRR, 0.91; 95%CI, 0.86–0.98), lung (aRR, 0.83; 95%CI, 0.75–0.92), and liver (aRR, 0.88; 95%CI, 0.81–0.95) cancer. Among current smokers, the combined moderate-high LPA and vegetable or mixture of vegetables and meat preference group showed a 40% reduced risk of lung cancer (aRR, 0.60; 95%CI, 0.47–0.76) compared with the combined low LPA and meat preference group. Among never/former smokers, subjects with moderate-high LPA and a preference for vegetables or a mixture of vegetables and meat showed reduced stomach cancer risk (aRR, 0.72; 95%CI, 0.54–0.95).</p> <p>Conclusion</p> <p>Our findings add to the evidence of the beneficial effects of vegetable preference on lung cancer risk and of physical activity on lung, stomach, and liver cancer risk. Additionally, vegetable preference combined with LPA might significantly reduce lung and stomach cancer risk.</p

Membrane diffusion- and capillary blood volume measurements are not useful as screening tools for pulmonary arterial hypertension in systemic sclerosis: a case control study

<p>Abstract</p> <p>Background</p> <p>There is no optimal screening tool for the assessment of pulmonary arterial hypertension (PAH) in patients with systemic sclerosis (SSc). A decreasing transfer factor of the lung for CO (TLCO) is associated with the development of PAH in SSc. TLCO can be partitioned into the diffusion of the alveolar capillary membrane (Dm) and the capillary blood volume (Vc). The use of the partitioned diffusion to detect PAH in SSc is not well established yet. This study evaluates whether Dm and Vc could be candidates for further study of the use for screening for PAH in SSc.</p> <p>Methods</p> <p>Eleven SSc patients with PAH (SScPAH+), 13 SSc patients without PAH (SScPAH-) and 10 healthy control subjects were included. Pulmonary function testing took place at diagnosis of PAH. TLCO was partitioned according to Roughton and Forster. As pulmonary fibrosis in SSc influences values of the (partitioned) TLCO, these were adjusted for fibrosis score as assessed on HRCT.</p> <p>Results</p> <p>TLCO as percentage of predicted (%) was lower in SScPAH+ than in SScPAH- (41 ± 7% <it>vs</it>. 63 ± 12%, p < 0.0001, respectively). Dm% in SScPAH+ was decreased as compared with SScPAH- (22 ± 6% <it>vs</it>. 39 ± 12%, p < 0.0001, respectively), also after adjustment for total fibrosis score (before adjustment: B = 17.5, 95% CI 9.0–25.9, p = < 0.0001; after adjustment: B = 14.3, 95% CI 6.0–21.7, p = 0.008). No difference was found in Vc%. There were no correlations between pulmonary hemodynamic parameters and Dm% in the PAH groups.</p> <p>Conclusion</p> <p>SScPAH+ patients have lower Dm% than SScPAH- patients. There are no correlations between Dm% and hemodynamic parameters of PAH in SScPAH+. These findings do not support further study of the role of partitioning TLCO in the diagnostic work- up for PAH in SSc.</p

Colonoscopic surveillance improves survival after colorectal cancer diagnosis in inflammatory bowel disease

Item does not contain fulltextBACKGROUND: Colonoscopic surveillance provides the best practical means for preventing colorectal cancer (CRC) in inflammatory bowel disease (IBD) patients. Strong evidence for improved survival from surveillance programmes is sparse. METHOD: The aim of this study was to compare tumour stage and survival of IBD patients with CRC who were a part of a surveillance programme with those who were not. A nationwide pathology database (PALGA (pathologisch anatomisch landelijk geautomatiseerd archief)) was consulted to identify IBD patients with CRC treated in all eight university hospitals in The Netherlands over a period of 15 years. Patients were assigned to the surveillance group when they had undergone one or more surveillance colonoscopies before a diagnosis of CRC. Patients who had not undergone surveillance served as controls. Tumour stage and survival were compared between the two groups. RESULTS: A total of 149 patients with IBD-associated CRC were identified. Twenty-three had had colonoscopic surveillance before CRC was discovered. The 5-year CRC-related survival rate of patients in the surveillance group was 100% compared with 74% in the non-surveillance group (P=0.042). In the surveillance group, only one patient died as a consequence of CRC compared with 29 patients in the control group (P=0.047). In addition, more early tumour stages were found in the surveillance group (P=0.004). CONCLUSIONS: These results provide evidence for improved survival from colonoscopic surveillance in IBD patients by detecting CRC at a more favourable tumour stage