白介素与溃疡性结肠炎

近年来对白介素(interleukin,IL)和溃疡性结肠炎(ulcerative colitis,UC)的研究取得了很大进展,我们通过总结整理以前有关IL和UC的文献,概括出IL的产生和在UC发病及病理变化中的作用机制:IL-1直接介导了UC初期阶段炎症的发生:IL-8、IL-6直接促进炎性细胞过度分泌和/或抑制了炎性细胞的凋亡,IL-2分泌减少导致免疫系统内细胞间网络调节失衡, 使局部炎症介质和自由基释放,引起细胞毒作用,IL主要通过影响机体整体和/或局部免疫系统的功能介导UC的产生,并与UC的迁延难愈和反复发作有关．     

Half blind superiority tests for clinical trials of anti-infective drugs

This paper introduces a test of superiority of new anti-infective drug B over comparator drug A based on a randomized clinical trial. This test can be used to demonstrate assay (trial) sensitivity for noninferiority trials and rigorously tailor drug choice for individual patients. Our approach uses specialized baseline covariates X_A,X_B, which should predict the benefits of drug A and drug B, respectively. Using a response surface model for the treatment effect, we test for superiority at the (X_A,X_B) point that is most likely to show superiority. We identify this point based on estimates from a novel half-blind pseudo likelihood, where we augment a blinded likelihood (mixed over the treatment indicator) with likelihoods for the overall success rates for drug A and drug B (mixed over X_A,X_B). The augmentation results in much better estimates than those based on the mixed blinded likelihood alone but, interestingly, the estimates almost behave as if they were based on fully blinded data. We also develop an analogous univariate method using X_A for settings where X_B has little variation. Permutation methods are used for testing. If the “half-blind” test rejects, pointwise confidence interval can be used to identify patients who would benefit from drug B. We compare the new tests to other methods with an example and via simulations.     

Non-opsonising aggregates of IgG and complement in haemoglobin C erythrocytes

Haemoglobin C (HbC) differs from normal HbA by a lysine for glutamate substitution at position 6 of beta-globin. Heterozygous AC and homozygous CC phenotypes are associated with shortened erythrocyte life spans and mild anaemia. AC and CC erythrocytes contain elevated amounts of membrane-associated haemichromes, band 3 clusters, and immunoglobulin G (IgG) in vivo. These findings led us to investigate whether AC and CC erythrocytes might expose elevated levels of IgG and complement, two opsonins that have been implicated in the phagocytic clearance of senescent and sickle erythrocytes. Surprisingly, we found IgG, complement, and other plasma proteins co-localised in aggregates beneath the membrane of circulating AC and CC erythrocytes. These observations, and our finding of similar aggregates in erythrocytes heterozygous or homozygous for haemoglobin S (sickle-cell haemoglobin), suggest that the vast majority of membrane-associated IgG and complement detected in these abnormal erythrocytes is intracellular and does not contribute to the eventual opsonic clearance of these cells. Phagocytosis studies with macrophages provide evidence in support of this suggestion. Studies of erythrocyte clearance that involve the detection of membrane-associated IgG and complement as putative opsonins should investigate the possibility that these plasma proteins reside in the erythrocyte interior, and not on the cell surface.     

Clinical correlates of low-risk variants in FGFR2, TNRC9, MAP3K1, LSP1 and 8q24 in a Dutch cohort of incident breast cancer cases

Introduction

Seven SNPs in five genomic loci were recently found to confer a mildly increased risk of breast cancer.

Methods

We have investigated the correlations between disease characteristics and the patient genotypes of these SNPs in an unselected prospective cohort of 1,267 consecutive patients with primary breast cancer.

Results

Heterozygote carriers and minor allele homozygote carriers for SNP rs889312 in the MAP3K1 gene were less likely to be lymph node positive at breast cancer diagnosis (P = 0.044) relative to major allele homozygote carriers. Heterozygote carriers and minor allele homozygote carriers for SNP rs3803662 near the TNCR9 gene were more likely to be diagnosed before the age of 60 years (P = 0.025) relative to major allele homozygote carriers. We also noted a correlation between the number of minor alleles of rs2981582 in FGFR2 and the average number of first-degree and second-degree relatives with breast cancer and/or ovarian cancer (P = 0.05). All other disease characteristics, including tumour size and grade, and oestrogen or progesterone receptor status, were not significantly associated with any of these variants.

Conclusion

Some recently discovered genomic variants associated with a mildly increased risk of breast cancer are also associated with breast cancer characteristics or family history of breast cancer and ovarian cancer. These findings provide interesting new clues for further research on these low-risk susceptibility alleles.     

Fluorescence studies of the dehydration of cefadroxil monohydrate

Although cefadroxil does not exhibit the phenomenon of photoluminescence when dissolved in a fluid medium, the compound has been found to exhibit fluorescence in its solid-state monohydrate crystal form. The monohydrate was found to exhibit complicated photoluminescence, where two different sets of emission spectra could be obtained upon irradiation with an appropriate excitation wavelength. One of these photophysical systems became strongly suppressed when the monohydrate was half-dehydrated, and only one of the photophysical systems could be observed in this hemihydrate. In the fully dehydrated state, both photophysical pathways became almost totally suppressed, so that the nonsolvated cefadroxil became effectively nonfluorescent.     

Sociodemographic and Lesbian-Specific Factors Associated with Physical Activity Among Adult Lesbians

BackgroundAlthough participation in moderate and vigorous physical activity (MVPA) results in health benefits, the majority of adult lesbians are not sufficiently active. The purpose of this study was to examine the relationships between sociodemographic factors (age, education level, body mass index [BMI], race, partner status, employment status, annual household income, general health status, diagnosis of chronic conditions, children under 18 years living at home) and lesbian-specific factors (connection with the lesbian community, public identification as a lesbian) to participation in MVPA.MethodsParticipants included 847 self-identified lesbians 18 to 74 years old (M_age = 40.5; SD = 11.6) who completed a 20-minute, web-based survey.FindingsThe binary logistic regression model that included the 10 demographic factors was significantly associated with MVPA, χ² (15, N = 847) = 105.62, p < .001. However, when the two lesbian-specific factors were added, the model did not improve significantly, χ² (2, N = 847) = 5.20, p = .07. BMI and general health status were significantly associated with MVPA (Wald χ² (2) = 19.5, p < .001) and (Wald χ² (4) = 41.2, p < .001). Obese participants had 54.5% lower odds than healthy weight participants to engage in sufficient amounts of MVPA. Participants who reported general health status as excellent compared with those who reported poor had 12.7 times greater odds of engaging in sufficient amounts of MVPA.ConclusionsFuture research should extend on this study by utilizing sampling methods that target the recruitment of lesbian women not actively involved in lesbian-related activities.     

Psychiatry takes to the streets: the New York City initiative for the homeless mentally ill

The authors describe New York City's program to remove seriously mentally ill homeless people from the streets to a public hospital. They report on the 298 patients hospitalized during the first year of this program. Most of the patients were male (66%), single (77%), and from outside of New York City (79%) and claimed a history of previous psychiatric hospitalization (92%) and that they had been homeless for more than 1 year (66%). Most of the patients suffered from schizophrenia (80%) and had additional medical diagnoses (73%). Follow-up contact with the patients 2 years after initiation of the program revealed that 55% of the patients either were living in a community setting or were under institutional care.