Vaccination of turkeys against Chlamydophila psittaci through optimised DNA formulation and administration

We have demonstrated that vaccination of turkeys with an unformulated DNA vaccine induces significant protection against Chlamydophila (Cp.) psittaci infections. Nevertheless, the immunogenicity of the DNA vaccine can still be improved by increasing translation and transfection efficiency. Therefore, the ompA codon was adapted to the codon usage in birds, resulting in pcDNA1/MOMP_opt. To increase gene transfer, polyplexes of pcDNA1/MOMP_opt–EGFP with different cationic polymers, such as linear and branched polyethyleneimine (lPEI and brPEI) and starburst PAMAM dendrimers, and lipoplexes with cationic DOTAP/DOPE liposomes were created. Transfection of lPEI and brPEI polyplexes with an N/P ratio of 8 resulted in the highest transfection efficiencies, but lPEI polyplexes were completely destroyed following nebulisation. Secondly, we examined the capacity of nebulised or intramuscularly (IM) administered brPEI-pcDNA1/MOMP_opt to induce a significant protective immune response in SPF turkeys experimentally infected with 10⁸ TCID₅₀ of a virulent Cp. psittaci strain. Results were compared to IM administration of naked plasmid DNA and to results of non-vaccinated animals. Intramuscular administration of brPEI-pcDNA1/MOMP_opt increased the immunogenicity of the Cp. psittaci DNA vaccine as compared to IM administration of pcDNA1/MOMP_opt or aerosol delivery of brPEI-pcDNA1/MOMP_opt. Improved immunogenicity was correlated with increased protection. Vaccinated groups were significantly protected against Cp. psittaci challenge.     

Branches of the splenic artery and splenic arterial segments

In 200 adult autopsy specimens, the arterial supply to the pancreas and spleen was studied radiologically and by manual dissection. The splenic artery divided into two or three lobar arteries, which supplied its corresponding lobe; each lobar artery subsequently divided into two to four lobular branches. Six to twelve lobular branches were observed entering the splenic substance at the hilum. Lobar arteries did not anastomose with each other, hence, the lobes of the spleen are also termed segments. The lobules, however, were not found to be independent segments and the arteries of one lobule anastomosed with those of other lobules. The branching pattern of the splenic artery varied from one specimen to another, so much so that a prevailing pattern could not be identified. Polar arteries, particularly to the superior pole, arose quite proximal to the hilum in 51% of cases and were occasionally missed. In 45% of males and 40% of females, the posterior gastric artery arose from about the middle of the splenic artery. The splenic artery was not found to be tortuous in fetuses, newborns, and young children. Tortuosity was seen in only 10% of adults; thus, the characteristic tortuosity of the splenic artery appears to develop with age.     

Precursor IGF-II (proIGF-II) and mature IGF-II (mIGF-II) induce Bcl-2 And Bcl-X L expression through different signaling pathways in breast cancer cells

IGF-II plays a crucial role in fetal and cancer development by signaling through the IGF-I receptor. We have shown that inhibition of IGF-II by resveratrol (RSV) induced apoptosis and that proIGF-II (highly expressed in cancer) was more potent than mIGF-II in inhibiting this effect. Thus, we hypothesized that IGF-II differentially regulates the signaling cascade of the IGF-I receptor to stimulate the anti-apoptotic proteins Bcl-2 and Bcl-X(L) to prevent apoptosis. RSV treatment to breast cancer cells inhibited Bcl-2 and Bcl-X(L) expression and induced mitochondrial membrane depolarization. ProIGF-II was more potent than mIGF-II in: (1) activating the PI3/Akt pathway, (2) regulating Bcl-2 and Bcl-X(L) expression, and (3) inducing phosphorylation/nuclear translocation of Cyclic AMP-responsive element binding protein. Furthermore, IGF-II differentially regulated the intracellular translocation of Bcl-2 and Bcl-X(L), a critical process in breast cancer progression to hormone-independence. Our study provides a novel mechanism of how proIGF-II promotes progression and chemoresistance in breast cancer development.     

A randomized controlled trial examining the addition of folic acid to iron supplementation in the treatment of postpartum anemia

Objective

To evaluate the efficacy of adding folic acid to oral iron supplementation in postpartum women with anemia.

Methods

A randomized controlled trial was conducted in the Netherlands between April 8, 2008, and August 31, 2010. A total of 112 postpartum women with anemia (hemoglobin < 10.5 g/dL) were randomly allocated to receive 600 mg/day ferrous fumarate plus 1 mg/day folic acid (FFFA group) or 600/day ferrous fumarate alone (FF group) for 4 weeks. Primary outcome measures were hemoglobin and health status. Secondary outcome measures were fatigue, compliance, and adverse reactions.

Results

No between-group differences were observed in hemoglobin and health status after treatment, and no differences were found in fatigue scores. Approximately 75% of all women reported having at least one symptom resulting from ferrous fumarate use. Constipation caused by ferrous fumarate was significantly associated with non-compliance (P = 0.014).

Conclusion

The addition of folic acid to iron supplementation is not beneficial in women with postpartum anemia, as it has no effect on hematologic or health status parameters. Clinical Trial Registration: CCMO website NL21797.028.08 and Netherlands Trial Register NTR2232.     

Migraine Treatment With Rizatriptan and Almotriptan: A Crossover Study

Background.— Rizatriptan and almotriptan are effective and well-tolerated triptans that have not been compared directly. Objective.— To evaluate the effectiveness of rizatriptan 10 mg and almotriptan for the acute treatment of migraine, in a real-world setting. Methods.— Of a large, multicenter, open-label, crossover study, we conducted a substudy to contrast the effectiveness of rizatriptan 10 mg and almotriptan 12.5 mg for the acute treatment of 2 migraine attacks in a sequential, crossover manner. Time to outcome was assessed using stopwatches. Mean and median times to onset of pain relief (PR) and pain freedom (PF) for rizatriptan and almotriptan were compared. The effect of rizatriptan on times to onset of PR and PF, adjusting for potential confounding factors (treatment sequence, treatment order, and use of rescue medication), was computed via a Cox proportional hazard model. Results.— Out of the 146 patients taking almotriptan as their usual care medication, 79 used stopwatch for both attacks. Significantly more patients taking rizatriptan achieved onset of PR within 2 hours after dosing than those taking almotriptan (88.6% vs 73.4%, P = .007). A higher proportion of patients taking rizatriptan achieved PF within 2 hours after dosing than those taking almotriptan (55.7% vs 45.6%, P = .10). Times to onset of PR and PF were significantly shorter with those patients taking rizatriptan than with those taking almotriptan (median time to PR: 45 vs 60 minutes, P = .002; median time to PF: 100 vs 135 minutes, P = .004). The adjusted proportional hazard ratios (rizatriptan vs almotriptan) for times to onset of PR and PF were 1.51 (95% confidence interval 1.20 to 1.88) and 1.42 (95% confidence interval 1.15 to 1.76), respectively. More patients were very satisfied when treating their attacks with rizatriptan than with almotriptan. Rizatriptan was preferred by most patients. Conclusions.— Times to achieve PR and PF were significantly shorter for patients using rizatriptan, as compared with those using almotriptan.     

Normalization of violence among inner-city youth: a formulation for research

A causal model is formulated for the thesis that in inner-city youth exposed to high levels of violence, cognitions that normalize violence mitigate affective effects of exposure while increasing risk for violent behavior, thus perpetuating violence in the very process of adapting to it psychologically. Gender differences in the cognitive normalization of violence may explain gender differences in affective and behavioral effects of exposure. Empirical studies are needed to directly test this model.     

Expansion of microsatellite in the thyroid hormone receptor-alpha1 gene linked to increased receptor expression and less aggressive thyroid cancer.

PURPOSE: The purpose of this study was to determine whether the length of the THRA1 microsatellite, which resides in a noncoding portion of the thyroid hormone receptor-alpha1 gene, affects receptor expression and is linked to clinicopathological parameters in thyroid cancer. EXPERIMENTAL DESIGN: In 30 cases of surgically resected sporadic thyroid cancer, the length of the THRA1 microsatellite was determined by DNA sequence analysis, and expression of thyroid hormone receptor-alpha1 was assessed immunohistochemically in thin sections cut from tumor blocks. The length of THRA1 and expression of thyroid hormone receptor-alpha1 were also assessed in seven cancer cell lines. Regression analysis was used to gauge the correlation between the size of THRA1 and receptor expression. Multivariate analysis was used to test for links to the clinical parameters of gender, age, histology, stage, nodal involvement, distant metastasis, extrathyroidal invasion and tumor-node-metastasis (TNM) classification. RESULTS: A statistically significant correlation between the length of THRA1 and thyroid hormone receptor-alpha1 expression was observed in both cell lines and primary thyroid cancers. Thyroid tumors that displayed higher than average thyroid hormone receptor-alpha1 expression had expanded THRA1 microsatellites and were less aggressive as judged by TNM ranking. A statistically significant correlation was also found between low thyroid hormone receptor-alpha1 expression and more aggressive thyroid cancer, as judged by extrathyroidal invasion and nodal involvement. CONCLUSIONS: Less aggressive thyroid cancer was found to be linked to increased thyroid hormone receptor-alpha1 expression and an expanded THRA1 microsatellite.     

Role of community risk factors and resources on breast carcinoma stage at diagnosis

BACKGROUND: The current study investigated the individual and community determinants of breast carcinoma stage at diagnosis (BCSAD) using multiple data sources merged with cancer registry data. The literature review yielded 5 studies that analyzed cancer registry data merged with community-level variables (1995-2004). METHODS: Community variables constructed for the current study reflected social and economic risk factors, physician supply, and health maintenance organization penetration. Multivariate logistic regression was used to identify the significant predictors of increasingly progressive BCSAD. RESULTS: Disparities remained for black and Hispanic females in California, who were least likely to be diagnosed early compared with their white counterparts. Younger (< 40 years) and middle-aged (40-64 years) females were less likely to be diagnosed with early BCSAD, compared with older females (> or = 65 years). Utilizing services at hospitals serving a lower volume of patients with breast carcinoma was associated with later BCSAD. After controlling for individual-level factors, community-level variables constructed at the census block group and county level were tested. If a woman resided in a neighborhood with greater percentages of female-headed households, persons living below the poverty level, less educated people, and more recent immigrants, then her chances of being diagnosed at an earlier stage were diminished. If, conversely, she resided in a neighborhood with greater percentages of females > or = 65 years (a proxy for Medicare coverage), her access to medical care and the probability of earlier BCSAD increased. County-level insurance rates and residing in counties where greater percentages of women ever had a mammogram were associated with in situ and early-stage diagnosis. Similarly, the supply of primary care physicians and radiologists was associated positively with earlier BCSAD. CONCLUSIONS: Results confirmed community-level predictors of socioeconomic and delivery system context matter, although the individual-level predictors showed a stronger effect. Nevertheless, analysis of community variables is promising for guiding and evaluating the effects of health policy and developing community and delivery system interventions for earlier detection and treatment of breast carcinoma.