Fine structural analyses of pancreatic acinar cell nuclei from mice fed on genetically modified soybean

We carried out ultrastructural morphometrical and immunocytochemical analyses on pancreatic acinar cell nuclei from mice fed on genetically modified (GM) soybean, in order to investigate possible structural and molecular modifications of nucleoplasmic and nucleolar constituents.We found a significant lowering of nucleoplasmic and nucleolar splicing factors as well as a perichromatin granule accumulation in GM-fed mice, suggestive of reduced post-transcriptional hnRNA processing and/or nuclear export. This is in accordance to already described zymogen synthesis and processing modifications in the same animals

Rituximab for eosinophilic granulomatosis with polyangiitis: a systematic review of observational studies

Objective To analyse the available evidence about the use of rituximab (RTX) and other biologic agents in eosinophilic granulomatosis with polyangiitis (EGPA) patients and to provide useful findings to inform the design of future, reliable clinical trials. Methods A systematic review was performed. A systematic search was conducted in PubMed/MEDLINE, Scopus, Web of Science and the Cochrane library databases on RTX, and an extensive literature search was conducted on other biologic agents. Results Forty-five papers pertinent to our questions were found: 16 retrospective cohort studies, 8 case series, 3 prospective cohort studies and 18 single case reports, for a total of 368 EGPA patients. More than 80% of evaluable patients achieved complete or partial remission with a tendency towards a higher rate of complete response in the pANCA-positive subgroup. Conclusion Although the majority of the evaluable EGPA patients treated with RTX appears to achieve complete remission, we strongly believe that a number of sources of heterogeneity impair a clear interpretation of results and limit their transferability in clinical practice. Differences in design, enrolment criteria, outcome definition and measurement make a comparison among data obtained from studies on RTX and other biologic agents unreliable

Suicide Seasonality: Complex Demodulation as a Novel Approach in Epidemiologic Analysis

Seasonality of suicides is well-known and nearly ubiquitous, but recent evidence showed inconsistent patterns of decreasing or increasing seasonality in different countries. Furthermore, strength of seasonality was hypothesized to be associated with suicide prevalence. This study aimed at pointing out methodological difficulties in examining changes in suicide seasonality. METHODODOLOGY/PRINCIPAL FINDINGS: The present study examines the hypothesis of decreasing seasonality with a superior method that allows continuous modeling of seasonality. Suicides in Austria (1970-2008, N = 67,741) were analyzed with complex demodulation, a local (point-in-time specific) version of harmonic analysis. This avoids the need to arbitrarily split the time series, as is common practice in the field of suicide seasonality research, and facilitates incorporating the association with suicide prevalence. Regression models were used to assess time trends and association of amplitude and absolute suicide numbers. Results showed that strength of seasonality was associated with absolute suicide numbers, and that strength of seasonality was stable during the study period when this association was taken into account.Continuous modeling of suicide seasonality with complex demodulation avoids spurious findings that can result when time series are segmented and analyzed piecewise or when the association with suicide prevalence is disregarded

Testosterone, cortisol, hGH, and IGF‐1 levels in an Italian female elite volleyball team

Purpose To assess the transferability of the reference intervals (RI) of testosterone (T), cortisol (C), human growth hormone (hGH), and insulin‐like growth factor (IGF)‐1, calculated on a normal healthy population, to a population of female elite volleyball players. Secondary aim of this study is the evaluation of the T/C ratio as predictive tool of overtraining during the annual regular season. Methods A retrospective, longitudinal, observational study was performed, enrolling 58 professional female volleyball players periodically evaluated during the regular sportive season, which lasts from September to May. Results Statistically significant differences between the volleyball players and reference populations for T (P = .010), C (P < .001), and IGF‐1 (P < .001) were found. Three different statistical approaches to calculate the RI in the athlete group showed a high degree of concordance and pointed out a shift upwards of both lower and upper reference limits. The T/C ratio significantly changed among visits (P = .009). In particular, an overall decrease of about 30% was observed for this ratio during the season, suggesting a state of overtraining. Conclusion T, C, hGH, and IGF‐1 reference values calculated on elite volleyball female players are higher than those of the reference population used in normal clinical practice, suggesting that the health status of highly trained subjects needs the definition of tailored RI for these variables. Moreover, the utility of T/C ratio in the evaluation of overtraining is confirmed

Capecitabine and mitomycin C is an effective combination for anthracycline- and taxane-resistant metastatic breast cancer

Capecitabine is converted to 5-fluorouracil by thymidine phosphorylase, and mitomycin C is capable of upregulating the expression of thymidine phosphorylase suggesting a synergistic effect. Fifty- three patients ( median age 62 years) with anthracycline- and taxane- resistant, metastatic breast cancer received mitomycin C 6 mg/ m(2) on day 1, and capecitabine ( Xeloda) 2,000 mg/ m(2) / day from day 1 to day 14 with cycles repeated every 4 weeks. Overall, 77.4% had visceral metastases and 33 were pretreated with &gt;= 3 chemotherapy lines. A median of 6 cycles were given ( range 1 - 19) with a complete response observed in 2 patients ( 3.9%), partial response in 17 ( 33.3%) and stable disease in 19 ( 37.2%). Overall response rate was 37.2% ( 95% CI, 24.0 - 50.5%), with a median duration of 10.4 months. Median time to progression was 8.1 months and median survival was 17.4 months ( 1- and 2- year survival rates of 60 and 28%, respectively). Toxicity was mild. The most frequent grade 3/ 4 events were neutropenia ( 5.7% of patients), diarrhea ( 3.8%), and deep venous thrombosis ( 3.8%). Capecitabine plus mitomycin C may represent an effective and manageable treatment option for advanced breast cancer patients resistant to anthracyclines and taxanes. This approach provides an alternative for pretreated patients with advanced breast cancer. Copyright (c) 2006 S. Karger AG, Base