Tolerability and safety of novel half milliliter formulation of glatiramer acetate for subcutaneous injection: an open-label, multicenter, randomized comparative study

Daily glatiramer acetate (GA) 20 mg/1.0 mL is a first-line treatment for relapsing-remitting multiple sclerosis (RRMS). To reduce the occurrence of injection pain and local injection site reactions (LISRs), a reduced volume formulation of GA was developed. This study compared pain and LISRs after injecting the marketed and the novel formulations. RRMS patients currently injecting GA participated in this multicenter, randomized, crossover comparative study. All patients administered once-daily subcutaneous injections of GA 20 mg/1.0 mL (marketed formulation) or GA 20 mg/0.5 mL (reduced volume formulation) for 14 days. Patients were crossed-over to the alternate treatment for an additional 14 days. Using a Visual Analog Scale (VAS), patients recorded in daily diaries the severity of injection pain immediately and 5 min post-injection, and the presence and severity of LISRs (swelling, redness, itching, lump) within 5 min and 24 h post-injection. VAS pain scores were ranked significantly lower immediately and 5 min after GA 20 mg/0.5 mL injections (p < 0.0001). Although LISRs were rare for both preparations, the severity of reactions ranked significantly lower and fewer symptoms occurred within 5 min and 24 h of using the reduced volume formulation (p < 0.0001). GA injected subcutaneously in a reduced volume formulation is a more tolerable option

Oral health related behaviors among adult Tanzanians: a national pathfinder survey

<p>Abstract</p> <p>Background</p> <p>The oral health education programs which have been organised and delivered in Tanzania were not based on a thorough understanding of behaviours which influence oral health. Therefore, evaluation of these programs became difficult. This study aimed at investigating the oral health related behaviours and their determinants among Tanzanian adults.</p> <p>Methods</p> <p>A national pathfinder cross sectional survey was conducted in 2006 involving 1759 respondents from the six geographic zones of mainland Tanzania. Frequency distributions, Chi square and multiple logistic regression analyses were performed using SPSS version 13.0.</p> <p>Results</p> <p>The rates of abstinence from alcohol for the past 30 days and life time smoking were 61.6% and 16.7% respectively, with males being more likely to smoke (OR 9.2, CI 6.3 -12.9, p < 0.001) and drink alcohol (OR 1.5, CI 1.2 -1.8, p < 0.001). Multiple regression analysis revealed that; having dental pain (OR 0.7, CI 0.5-0.8; p < 0.001) and being minimally educated (OR 0.48, CI 0.4-0.6; p < 0.001) reduced the likelihood of having a high sugar score. Whereas being male (OR 1.5, CI 1.2- 1.8; p < 0.001), urban (OR 1.9, CI 1.5 -2.3; p < 0.001), and young (OR 1.5, CI 1.2 -1.8; p < 0.001) increased the likelihood of having a high sugar score. Urban residents were less likely to take alcohol (OR 0.7, CI 0.6-0.9; p < 0.01), or smoke cigarette (OR = 0.7, CI = 0.6-0.9); less likely to be those who do not use fruits (OR 0.3, CI 0.2-0.4; p < 0.001); dental clinic (OR 0.5, CI 0.4-0.7; p < 0.001); factory made tooth brushes (OR 0.1, CI 0.08-0.17; p < 0.001) and toothpaste (OR 0.1, CI 0.1-0.2; p < 0.001) than their rural counterparts. More rural (13.2%) than urban (4.6%) residents used charcoal.</p> <p>Conclusion</p> <p>The findings of this study demonstrated social demographic disparities in relation to oral health related behaviors, while dental pain was associated with low consumption of sugar and high likelihood to take alcohol.</p

Rejuvenation of metallic glasses by non-affine thermal strain.

When a spatially uniform temperature change is imposed on a solid with more than one phase, or on a polycrystal of a single, non-cubic phase (showing anisotropic expansion-contraction), the resulting thermal strain is inhomogeneous (non-affine). Thermal cycling induces internal stresses, leading to structural and property changes that are usually deleterious. Glasses are the solids that form on cooling a liquid if crystallization is avoided--they might be considered the ultimate, uniform solids, without the microstructural features and defects associated with polycrystals. Here we explore the effects of cryogenic thermal cycling on glasses, specifically metallic glasses. We show that, contrary to the null effect expected from uniformity, thermal cycling induces rejuvenation, reaching less relaxed states of higher energy. We interpret these findings in the context that the dynamics in liquids become heterogeneous on cooling towards the glass transition, and that there may be consequent heterogeneities in the resulting glasses. For example, the vibrational dynamics of glassy silica at long wavelengths are those of an elastic continuum, but at wavelengths less than approximately three nanometres the vibrational dynamics are similar to those of a polycrystal with anisotropic grains. Thermal cycling of metallic glasses is easily applied, and gives improvements in compressive plasticity. The fact that such effects can be achieved is attributed to intrinsic non-uniformity of the glass structure, giving a non-uniform coefficient of thermal expansion. While metallic glasses may be particularly suitable for thermal cycling, the non-affine nature of strains in glasses in general deserves further study, whether they are induced by applied stresses or by temperature change.This research was supported by the World Premier International Research Center Initiative (WPI), MEXT, Japan, by NSF China and MOST 973 China, and by the Engineering and the Engineering and Physical Sciences Research Council, UK (Materials World Network project). Y.H.S. acknowledges support from a China Scholarship Council (CSC) scholarship.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/nature1467

Functional Interactions between Retinoblastoma and c-MYC in a Mouse Model of Hepatocellular Carcinoma

Inactivation of the RB tumor suppressor and activation of the MYC family of oncogenes are frequent events in a large spectrum of human cancers. Loss of RB function and MYC activation are thought to control both overlapping and distinct cellular processes during cell cycle progression. However, how these two major cancer genes functionally interact during tumorigenesis is still unclear. Here, we sought to test whether loss of RB function would affect cancer development in a mouse model of c-MYC-induced hepatocellular carcinoma (HCC), a deadly cancer type in which RB is frequently inactivated and c-MYC often activated. We found that RB inactivation has minimal effects on the cell cycle, cell death, and differentiation features of liver tumors driven by increased levels of c-MYC. However, combined loss of RB and activation of c-MYC led to an increase in polyploidy in mature hepatocytes before the development of tumors. There was a trend for decreased survival in double mutant animals compared to mice developing c-MYC-induced tumors. Thus, loss of RB function does not provide a proliferative advantage to c-MYC-expressing HCC cells but the RB and c-MYC pathways may cooperate to control the polyploidy of mature hepatocytes

Toxicity and cellular uptake of gold nanoparticles: what we have learned so far?

Gold nanoparticles have attracted enormous scientific and technological interest due to their ease of synthesis, chemical stability, and unique optical properties. Proof-of-concept studies demonstrate their biomedical applications in chemical sensing, biological imaging, drug delivery, and cancer treatment. Knowledge about their potential toxicity and health impact is essential before these nanomaterials can be used in real clinical settings. Furthermore, the underlying interactions of these nanomaterials with physiological fluids is a key feature of understanding their biological impact, and these interactions can perhaps be exploited to mitigate unwanted toxic effects. In this Perspective we discuss recent results that address the toxicity of gold nanoparticles both in vitro and in vivo, and we provide some experimental recommendations for future research at the interface of nanotechnology and biological systems

Pleiotropy of genetic variants on obesity and smoking phenotypes: Results from the Oncoarray Project of The International Lung Cancer Consortium

Obesity and cigarette smoking are correlated through complex relationships. Common genetic causes may contribute to these correlations. In this study, we selected 241 loci potentially associated with body mass index (BMI) based on the Genetic Investigation of ANthropometric Traits (GIANT) consortium data and calculated a BMI genetic risk score (BMI-GRS) for 17,037 individuals of European descent from the Oncoarray Project of the International Lung Cancer Consortium (ILCCO). Smokers had a significantly higher BMI-GRS than never-smokers (p = 0.016 and 0.010 before and after adjustment for BMI, respectively). The BMI-GRS was also positively correlated with pack-years of smoking (p<0.001) in smokers. Based on causal network inference analyses, seven and five of 241 SNPs were classified to pleiotropic models for BMI/smoking status and BMI/pack-years, respectively. Among them, three and four SNPs associated with smoking status and pack-years (p<0.05), respectively, were followed up in the ever-smoking data of the Tobacco, Alcohol and Genetics (TAG) consortium. Among these seven candidate SNPs, one SNP (rs11030104, BDNF) achieved statistical significance after Bonferroni correction for multiple testing, and three suggestive SNPs (rs13021737, TMEM18; rs11583200, ELAVL4; and rs6990042, SGCZ) achieved a nominal statistical significance. Our results suggest that there is a common genetic component between BMI and smoking, and pleiotropy analysis can be useful to identify novel genetic loci of complex phenotypes

Alignment of the ALICE Inner Tracking System with cosmic-ray tracks

37 pages, 15 figures, revised version, accepted by JINSTALICE (A Large Ion Collider Experiment) is the LHC (Large Hadron Collider) experiment devoted to investigating the strongly interacting matter created in nucleus-nucleus collisions at the LHC energies. The ALICE ITS, Inner Tracking System, consists of six cylindrical layers of silicon detectors with three different technologies; in the outward direction: two layers of pixel detectors, two layers each of drift, and strip detectors. The number of parameters to be determined in the spatial alignment of the 2198 sensor modules of the ITS is about 13,000. The target alignment precision is well below 10 micron in some cases (pixels). The sources of alignment information include survey measurements, and the reconstructed tracks from cosmic rays and from proton-proton collisions. The main track-based alignment method uses the Millepede global approach. An iterative local method was developed and used as well. We present the results obtained for the ITS alignment using about 10^5 charged tracks from cosmic rays that have been collected during summer 2008, with the ALICE solenoidal magnet switched off.Peer reviewe

Delivering in‐school interventions to improve dietary behaviours amongst 11‐ to 16‐year‐olds: A systematic review

Childhood obesity is a global health concern, which has both short‐and long‐term health consequences for the individual, and is a potential burden on health care services and the wider economy. The school environment is a setting where changes can be applied to dietary behaviours, as schools have direct and intensive contact with children. This systematic review evaluated school‐based interventions designed to improve dietary behaviours among adolescents (11‐to 16‐year‐olds). The aims were to review types of interventions delivered, dietary behaviours targeted, and interventions' effectiveness in improving dietary behaviour and associated intervention components. Twenty‐nine school‐based interventional studies with this population were identified for review. The data were synthesized by identifying and comparing individual studies' results, intervention components, and characteristics.Interventions appeared more effective when they involved peers, used educational media to deliver health messages, increased availability of healthy foods in school,and incorporated computer‐based individualized feedback with normative information on eating behaviours. A limitation of the review was the lack of description in cer-tain reviewed studies and the nonfeasibility of conducting a meta‐analysis owing to study heterogeneity. Future interventions with this population could consider including the aforementioned components, gender‐specific feedback, and both short‐and long‐term follow‐ups as change may not be apparent immediately and to determine if changes are sustained