Non-reducible knee dislocation with interposition of the vastus medialis muscle

Irreducibility of the knee following complete dislocation is a rare event determined by the interposition of various capsulo-ligamentous structures in the joint space. Such cases often require urgent surgical treatment. We report the case of a healthy 70-year-old man with a sprain of the left knee that occurred after a sports trauma. The patient showed knee dislocation with multiple ligamentous injuries and articular block due to interposition of a portion of the vastus medialis muscle. After arthroscopic evaluation, we performed surgical treatment to free the muscle, regularize the medial meniscus and suture the posterior and medial capsule and ligaments; the cruciate ligaments were not treated. The most interesting aspect of the articular damage in this case was a wide detachment of the vastus medialis muscle with intra-articular dislocation. The decision to treat only the posterior lesions and allow the healing of the front ones by rehabilitation treatment was supported by full functional recovery and return to sports activity

Gravitational physics with antimatter

The production of low-energy antimatter provides unique opportunities to search for new physics in an unexplored regime. Testing gravitational interactions with antimatter is one such opportunity. Here a scenario based on Lorentz and CPT violation in the Standard- Model Extension is considered in which anomalous gravitational effects in antimatter could arise.Comment: 5 pages, presented at the International Conference on Exotic Atoms (EXA 2008) and the 9th International Conference on Low Energy Antiproton Physics (LEAP 2008), Vienna, Austria, September 200

Short-Term Withdrawal of Mitogens Prior to Plating Increases Neuronal Differentiation of Human Neural Precursor Cells

Background: Human neural precursor cells (hNPC) are candidates for neural transplantation in a wide range of neurological disorders. Recently, much work has been done to determine how the environment for NPC culture in vitro may alter their plasticity. Epidermal growth factor (EGF) and fibroblast growth factor-2 (FGF-2) are used to expand NPC; however, it is not clear if continuous exposure to mitogens may abrogate their subsequent differentiation. Here we evaluated if short-term removal of FGF-2 and EGF prior to plating may improve hNPC differentiation into neurons.Principal Findings: We demonstrate that culture of neurospheres in suspension for 2 weeks without EGF-FGF-2 significantly increases neuronal differentiation and neurite extension when compared to cells cultured using standard protocols. in this condition, neurons were preferentially located in the core of the neurospheres instead of the shell. Moreover, after plating, neurons presented radial rather than randomly oriented and longer processes than controls, comprised mostly by neurons with short processes. These changes were followed by alterations in the expression of genes related to cell survival.Conclusions: These results show that EGF and FGF-2 removal affects NPC fate and plasticity. Taking into account that a three dimensional structure is essential for NPC differentiation, here we evaluated, for the first time, the effects of growth factors removal in whole neurospheres rather than in plated cell culture.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Institutos do Milenio de Bioengenharia TecidualUniversidade Federal de São Paulo, Dept Physiol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biophys, São Paulo, BrazilUniv Fed Rio de Janeiro, Inst Ciencias Biomed, BR-21941 Rio de Janeiro, BrazilUniversidade Federal de São Paulo, Dept Physiol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biophys, São Paulo, BrazilFAPESP: fellowCNPq: fellowWeb of Scienc

Vaccinomics and Personalized Vaccinology: Is Science Leading Us Toward a New Path of Directed Vaccine Development and Discovery?

As is apparent in many fields of science and medicine, the new biology, and particularly new high-throughput genetic sequencing and transcriptomic and epigenetic technologies, are radically altering our understanding and views of science. In this article, we make the case that while mostly ignored thus far in the vaccine field, these changes will revolutionize vaccinology from development to manufacture to administration. Such advances will address a current major barrier in vaccinology—that of empiric vaccine discovery and development, and the subsequent low yield of viable vaccine candidates, particularly for hyper-variable viruses. While our laboratory's data and thinking (and hence also for this paper) has been directed toward viruses and viral vaccines, generalization to other pathogens and disease entities (i.e., anti-cancer vaccines) may be appropriate

BayesPI - a new model to study protein-DNA interactions: a case study of condition-specific protein binding parameters for Yeast transcription factors

<p>Abstract</p> <p>Background</p> <p>We have incorporated Bayesian model regularization with biophysical modeling of protein-DNA interactions, and of genome-wide nucleosome positioning to study protein-DNA interactions, using a high-throughput dataset. The newly developed method (BayesPI) includes the estimation of a transcription factor (TF) binding energy matrices, the computation of binding affinity of a TF target site and the corresponding chemical potential.</p> <p>Results</p> <p>The method was successfully tested on synthetic ChIP-chip datasets, real yeast ChIP-chip experiments. Subsequently, it was used to estimate condition-specific and species-specific protein-DNA interaction for several yeast TFs.</p> <p>Conclusion</p> <p>The results revealed that the modification of the protein binding parameters and the variation of the individual nucleotide affinity in either recognition or flanking sequences occurred under different stresses and in different species. The findings suggest that such modifications may be adaptive and play roles in the formation of the environment-specific binding patterns of yeast TFs and in the divergence of TF binding sites across the related yeast species.</p

Modern tests of Lorentz invariance

Motivated by ideas about quantum gravity, a tremendous amount of effort over the past decade has gone into testing Lorentz invariance in various regimes. This review summarizes both the theoretical frameworks for tests of Lorentz invariance and experimental advances that have made new high precision tests possible. The current constraints on Lorentz violating effects from both terrestrial experiments and astrophysical observations are presented.Comment: Modified and expanded discussions of various points. Numerous references added. Version matches that accepted by Living Reviews in Relativit

Gender differences in patients with dizziness and unsteadiness regarding self-perceived disability, anxiety, depression, and its associations

BACKGROUND: It is known that anxiety and depression influence the level of disability experienced by persons with vertigo, dizziness or unsteadiness. Because higher prevalence rates of disabling dizziness have been found in women and some studies reported a higher level of psychiatric distress in female patients our primary aim was to explore whether women and men with vertigo, dizziness or unsteadiness differ regarding self-perceived disability, anxiety and depression. Secondly we planned to investigate the associations between disabling dizziness and anxiety and depression. METHOD: Patients were recruited from a tertiary centre for vertigo and balance disorders. Participants rated their global disability as mild, moderate or severe. They filled out the Dizziness Handicap Inventory and the two subscales of the Hospital Anxiety Depression Scale (HADS). The HADS was analysed 1) by calculating the median values, 2) by estimating the prevalence rates of abnormal anxiety/depression based on recommended cut-off criteria. Mann-Whitney U-tests, Chi-square statistics and odds ratios (OR) were calculated to compare the observations in both genders. Significance values were adjusted with respect to multiple comparisons. RESULTS: Two-hundred and two patients (124 women) mean age (standard deviation) of 49.7 (13.5) years participated. Both genders did not differ significantly in the mean level of self-perceived disability, anxiety, depression and symptom severity. There was a tendency of a higher prevalence of abnormal anxiety and depression in men (23.7%; 28.9%) compared to women (14.5%; 15.3%). Patients with abnormal depression felt themselves 2.75 (95% CI: 1.31-5.78) times more severely disabled by dizziness and unsteadiness than patients without depression. In men the OR was 8.2 (2.35-28.4). In women chi-square statistic was not significant. The ORs (95% CI) of abnormal anxiety and severe disability were 4.2 (1.9-8.9) in the whole sample, 8.7 (2.5-30.3) in men, and not significant in women. CONCLUSIONS: In men with vertigo, dizziness or unsteadiness emotional distress and its association with self-perceived disability should not be underestimated. Longitudinal surveys with specific pre-defined co-variables of self-perceived disability, anxiety and depression are needed to clarify the influence of gender on disability, anxiety and depression in patients with vertigo, dizziness or unsteadiness

Sensitivity of Global Translation to mTOR Inhibition in REN Cells Depends on the Equilibrium between eIF4E and 4E-BP1

Initiation is the rate-limiting phase of protein synthesis, controlled by signaling pathways regulating the phosphorylation of translation factors. Initiation has three steps, 43S, 48S and 80S formation. 43S formation is repressed by eIF2α phosphorylation. The subsequent steps, 48S and 80S formation are enabled by growth factors. 48S relies on eIF4E-mediated assembly of eIF4F complex; 4E-BPs competitively displace eIF4E from eIF4F. Two pathways control eIF4F: 1) mTORc1 phosphorylates and inactivates 4E-BPs, leading to eIF4F formation; 2) the Ras-Mnk cascade phosphorylates eIF4E. We show that REN and NCI-H28 mesothelioma cells have constitutive activation of both pathways and maximal translation rate, in the absence of exogenous growth factors. Translation is rapidly abrogated by phosphorylation of eIF2α. Surprisingly, pharmacological inhibition of mTORc1 leads to the complete dephosphorylation of downstream targets, without changes in methionine incorporation. In addition, the combined administration of mTORc1 and MAPK/Mnk inhibitors has no additive effect. The inhibition of both mTORc1 and mTORc2 does not affect the metabolic rate. In spite of this, mTORc1 inhibition reduces eIF4F complex formation, and depresses translocation of TOP mRNAs on polysomes. Downregulation of eIF4E and overexpression of 4E-BP1 induce rapamycin sensitivity, suggesting that disruption of eIF4F complex, due to eIF4E modulation, competes with its recycling to ribosomes. These data suggest the existence of a dynamic equilibrium in which eIF4F is not essential for all mRNAs and is not displaced from translated mRNAs, before recycling to the next