Reduction of the Lamina Cribrosa Curvature After Trabeculectomy in Glaucoma

PURPOSE. To investigate whether the lamina cribrosa (LC) curvature is decreased after trabeculectomy. METHODS. Thirty-nine eyes of 39 patients with primary open-angle glaucoma who underwent trabeculectomy were included. Optic nerves were scanned by using enhanced-depth-imaging spectral-domain optical coherence tomography before and after trabeculectomy. The LC curvature was assessed by measuring the LC curvature index (LCCI) in seven horizontal Bscan images in each eye. RESULTS. The LCCI was significantly smaller at postoperative 6 months than at the preoperative level in all seven planes (all P < 0.001). Preoperative LCCI was associated with younger age at superior midperiphery, midhorizontal plane, inferior midperiphery (all P 0.005) and higher preoperative intraocular pressure (IOP) at superior and inferior midperiphery (both P ¼ 0.039). Younger age and larger preoperative LCCI were associated with a larger reduction of the LCCI at all three locations (P ¼ 0.003 and 0.031 at superior midperiphery, P ¼ 0.011 and 0.001 at midhorizontal plane, and P ¼ 0.014 and 0.005 at inferior midperiphery, respectively), whereas the percentage IOP lowering was associated at superior and inferior midperiphery (P ¼ 0.017 and 0.047, respectively). CONCLUSIONS. Lamina cribrosa curvature was reduced after trabeculectomy. This finding suggests that LC curvature may have value as a parameter relevant to optic nerve head biomechanics

Availability and Affordability of Medicines for the Treatment of Cardiovascular Diseases in Pharmacies in Six Regions of the Russian Federation

Aim. To evaluate the availability and affordability of medicines used to treat of cardiovascular diseases (CVD) in several regions of the Russian Federation with different climatic, geographic, economic and demographic characteristics. Material and methods. The study was conducted in 6 regional capitals, chosen to differ in geographically, economically, and demographically. In each city, 5 pharmacies providing free medicines to certain categories of citizens (beneficiaries) and 5 private pharmacies serving anyone were selected at random. Medicine availability was assessed in all pharmacies, along with price only in the private pharmacies. Data were obtained for both original drug and appropriate generics. A list of 25 of the most frequently prescribed medicines for cardiovascular diseases was compiled. Results. Some general findings emerged. With the existence of a generic drug, the original drug was not available in the pharmacy supplying beneficiaries. Diuretics, as well as some ACE inhibitors, are not available in a number of pharmacies for beneficiaries. Enalapril in most licensed pharmacies is represented by generics, lisinopril in a number of cities is represented by both the original drug and generics. The presence of sartans was much lower than ACE inhibitors. Bisoprolol was most common beta-blocker. Calcium antagonists: if amlodipine was present in all licensed pharmacies, at list as generic, then nifedipine was not available in many licensed pharmacies. Among antiplatelet agents, aspirin was available in most pharmacies, and clopidogrel was mostly represented by generics. As for statins, only simvastatin could be found in almost all pharmacies. When analyzing the cost of drugs in licensed pharmacies, it was found that drugs containing furosemide are the cheapest among generics – about 17 rubles. The most expensive treatment with generics of rosuvastatin – about 4,374 rubles a month. The most expensive original medicine was also rosuvastatin – about 4,500 rubles for 30 tablets, the cheapest – the original drug of furosemide – about 35 rubles. On average, the cost of CVD treatment with major classes of drugs, including ACE inhibitor, beta-blocker, antiplatelet drug and statin, is 1,921.9 rubles per month. Conclusion. The basic cardiovascular medicines were characterized by a relatively high availability in 6 regions of the Russian Federation included in the analysis both by the criterion of the availability of drugs and by the criterion of the minimum price.</jats:p

Integrated Assessment of Genomic Correlates of Protein Evolutionary Rate

Rates of evolution differ widely among proteins, but the causes and consequences of such differences remain under debate. With the advent of high-throughput functional genomics, it is now possible to rigorously assess the genomic correlates of protein evolutionary rate. However, dissecting the correlations among evolutionary rate and these genomic features remains a major challenge. Here, we use an integrated probabilistic modeling approach to study genomic correlates of protein evolutionary rate in Saccharomyces cerevisiae. We measure and rank degrees of association between (i) an approximate measure of protein evolutionary rate with high genome coverage, and (ii) a diverse list of protein properties (sequence, structural, functional, network, and phenotypic). We observe, among many statistically significant correlations, that slowly evolving proteins tend to be regulated by more transcription factors, deficient in predicted structural disorder, involved in characteristic biological functions (such as translation), biased in amino acid composition, and are generally more abundant, more essential, and enriched for interaction partners. Many of these results are in agreement with recent studies. In addition, we assess information contribution of different subsets of these protein properties in the task of predicting slowly evolving proteins. We employ a logistic regression model on binned data that is able to account for intercorrelation, non-linearity, and heterogeneity within features. Our model considers features both individually and in natural ensembles (“meta-features”) in order to assess joint information contribution and degree of contribution independence. Meta-features based on protein abundance and amino acid composition make strong, partially independent contributions to the task of predicting slowly evolving proteins; other meta-features make additional minor contributions. The combination of all meta-features yields predictions comparable to those based on paired species comparisons, and approaching the predictive limit of optimal lineage-insensitive features. Our integrated assessment framework can be readily extended to other correlational analyses at the genome scale

GAPscreener: An automatic tool for screening human genetic association literature in PubMed using the support vector machine technique

<p>Abstract</p> <p>Background</p> <p>Synthesis of data from published human genetic association studies is a critical step in the translation of human genome discoveries into health applications. Although genetic association studies account for a substantial proportion of the abstracts in PubMed, identifying them with standard queries is not always accurate or efficient. Further automating the literature-screening process can reduce the burden of a labor-intensive and time-consuming traditional literature search. The Support Vector Machine (SVM), a well-established machine learning technique, has been successful in classifying text, including biomedical literature. The GAPscreener, a free SVM-based software tool, can be used to assist in screening PubMed abstracts for human genetic association studies.</p> <p>Results</p> <p>The data source for this research was the HuGE Navigator, formerly known as the HuGE Pub Lit database. Weighted SVM feature selection based on a keyword list obtained by the two-way z score method demonstrated the best screening performance, achieving 97.5% recall, 98.3% specificity and 31.9% precision in performance testing. Compared with the traditional screening process based on a complex PubMed query, the SVM tool reduced by about 90% the number of abstracts requiring individual review by the database curator. The tool also ascertained 47 articles that were missed by the traditional literature screening process during the 4-week test period. We examined the literature on genetic associations with preterm birth as an example. Compared with the traditional, manual process, the GAPscreener both reduced effort and improved accuracy.</p> <p>Conclusion</p> <p>GAPscreener is the first free SVM-based application available for screening the human genetic association literature in PubMed with high recall and specificity. The user-friendly graphical user interface makes this a practical, stand-alone application. The software can be downloaded at no charge.</p

A Straightforward but Not Piecewise Relationship between Age and Lymph Node Status in Chinese Breast Cancer Patients

PURPOSE: To investigate the relationship between age and axillary lymph node (LN) involvement in Chinese breast cancer patients, and to replicate a recently identified piecewise relationship between age and LN involvement. METHODS: A dataset, consisting of 3,715 patients (with complete information on study variables) with operable breast cancer consecutively surgically treated between 1996 and 2006, was derived from the database of Shanghai Cancer Hospital. Univariate and multivariate logistic regression were employed to analyze the relationship between age and LN. We subsequently performed a similar analysis on another dataset including 1,832 consecutive patients treated between 2007 and 2008 to replicate our findings in the first dataset. RESULTS: A U-shaped relationship (previously observed in two European populations) between age and LN status failed to be replicated in our dataset of Chinese patients. Instead, we observed a linear rather than piecewise relationship. After multivariate adjustment, the linear relationship was still present. Moreover, the interaction between age and LN involvement was not modified by tumor size. The odds of LN involvement decreased by 1.5% for each year increase in age (OR 0.985, 95% CI 0.979-0.991, P<0.001). Breast cancer subtypes were also associated with LN status. Proportions of basal-like and ERBB2+ subtypes decreased with increasing age. The observations in the first dataset were successfully replicated in a second independent dataset. CONCLUSION: We confirmed a straightforward but not piecewise relationship between age and LN status in Chinese patients. The different pattern between Chinese and European elderly patients should be considered when making clinical decisions

Discovery of the First Insect Nidovirus, a Missing Evolutionary Link in the Emergence of the Largest RNA Virus Genomes

Nidoviruses with large genomes (26.3–31.7 kb; ‘large nidoviruses’), including Coronaviridae and Roniviridae, are the most complex positive-sense single-stranded RNA (ssRNA+) viruses. Based on genome size, they are far separated from all other ssRNA+ viruses (below 19.6 kb), including the distantly related Arteriviridae (12.7–15.7 kb; ‘small nidoviruses’). Exceptionally for ssRNA+ viruses, large nidoviruses encode a 3′-5′exoribonuclease (ExoN) that was implicated in controlling RNA replication fidelity. Its acquisition may have given rise to the ancestor of large nidoviruses, a hypothesis for which we here provide evolutionary support using comparative genomics involving the newly discovered first insect-borne nidovirus. This Nam Dinh virus (NDiV), named after a Vietnamese province, was isolated from mosquitoes and is yet to be linked to any pathology. The genome of this enveloped 60–80 nm virus is 20,192 nt and has a nidovirus-like polycistronic organization including two large, partially overlapping open reading frames (ORF) 1a and 1b followed by several smaller 3′-proximal ORFs. Peptide sequencing assigned three virion proteins to ORFs 2a, 2b, and 3, which are expressed from two 3′-coterminal subgenomic RNAs. The NDiV ORF1a/ORF1b frameshifting signal and various replicative proteins were tentatively mapped to canonical positions in the nidovirus genome. They include six nidovirus-wide conserved replicase domains, as well as the ExoN and 2′-O-methyltransferase that are specific to large nidoviruses. NDiV ORF1b also encodes a putative N7-methyltransferase, identified in a subset of large nidoviruses, but not the uridylate-specific endonuclease that – in deviation from the current paradigm - is present exclusively in the currently known vertebrate nidoviruses. Rooted phylogenetic inference by Bayesian and Maximum Likelihood methods indicates that NDiV clusters with roniviruses and that its branch diverged from large nidoviruses early after they split from small nidoviruses. Together these characteristics identify NDiV as the prototype of a new nidovirus family and a missing link in the transition from small to large nidoviruses

c-Jun N-terminal kinase activation has a prognostic implication and is negatively associated with FOXO1 activation in gastric cancer

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Abstract Background Since the biological function of c-Jun N-terminal kinase (JNK) in gastric cancer remains unclear, we investigated the clinical significance of JNK activation and its association with FOXO1 activation. Methods Immunohistochemical tissue array analysis of 483 human gastric cancer specimens was performed, and the results of the immunostaining were quantified. The correlation between JNK activation (nuclear staining for pJNK) and clinicopathological features, the proliferation index, prognosis or FOXO1 inactivation (cytoplasmic staining for pFOXO1) was analyzed. The SNU-638 gastric cancer cell line was used for in vitro analysis. Results Nuclear staining of pJNK was found in 38 % of the gastric carcinomas and was higher in the early stages of pTNM (P < 0.001). pJNK staining negatively correlated with lymphatic invasion (P = 0.034) and positively correlated with intestinal type by Laurens classification (P = 0.037), Ki-67-labeling index (P < 0.001), cyclin D1 (P = 0.045), cyclin E (P < 0.001) and pFOXO1 (P < 0.001). JNK activation correlated with a longer patients survival (P =0.008) and patients with a JNK-active and FOXO1-inactive tumor had a higher survival rate than the remainder of the population (P = 0.004). In vitro analysis showed that JNK inhibition by SP600125 in SNU-638 cells decreased cyclin D1 protein expression and increased FOXO1 activation. Further, JNK inhibition markedly suppressed colony formation, which was partially restored by FOXO1 shRNA expression. Conclusions Our results indicate that JNK activation may serve as a valuable prognostic factor in gastric cancer, and that it is implicated in gastric tumorigenesis, at least in part, through FOXO1 inhibition

Proteomic analysis of the Plasmodium male gamete reveals the key role for glycolysis in flagellar motility.

BACKGROUND: Gametogenesis and fertilization play crucial roles in malaria transmission. While male gametes are thought to be amongst the simplest eukaryotic cells and are proven targets of transmission blocking immunity, little is known about their molecular organization. For example, the pathway of energy metabolism that power motility, a feature that facilitates gamete encounter and fertilization, is unknown. METHODS: Plasmodium berghei microgametes were purified and analysed by whole-cell proteomic analysis for the first time. Data are available via ProteomeXchange with identifier PXD001163. RESULTS: 615 proteins were recovered, they included all male gamete proteins described thus far. Amongst them were the 11 enzymes of the glycolytic pathway. The hexose transporter was localized to the gamete plasma membrane and it was shown that microgamete motility can be suppressed effectively by inhibitors of this transporter and of the glycolytic pathway. CONCLUSIONS: This study describes the first whole-cell proteomic analysis of the malaria male gamete. It identifies glycolysis as the likely exclusive source of energy for flagellar beat, and provides new insights in original features of Plasmodium flagellar organization

Functional Differences in the Backward Shifts of CA1 and CA3 Place Fields in Novel and Familiar Environments

Insight into the processing dynamics and other neurophysiological properties of different hippocampal subfields is critically important for understanding hippocampal function. In this study, we compared shifts in the center of mass (COM) of CA3 and CA1 place fields in a familiar and completely novel environment. Place fields in CA1 and CA3 were simultaneously recorded as rats ran along a closed loop track in a familiar room followed by a session in a completely novel room. This process was repeated each day over a 4-day period. CA3 place fields shifted backward (opposite to the direction of motion of the rat) only in novel environments. This backward shift gradually diminished across days, as the novel environment became more familiar with repeated exposures. Conversely, CA1 place fields shifted backward across all days in both familiar and novel environments. Prior studies demonstrated that CA1 place fields on average do not exhibit a backward shift during the first exposure to an environment in which the familiar cues are rearranged into a novel configuration, although CA3 place fields showed a strong backward shift. Under the completely novel conditions of the present study, no dissociation was observed between CA3 and CA1 during the first novel session (although a strong dissociation was observed in the familiar sessions and the later novel sessions). In summary, this is the first study to use simultaneous recordings in CA1 and CA3 to compare place field COM shift and other associated properties in truly novel and familiar environments. This study further demonstrates functional differentiation between CA1 and CA3 as the plasticity of CA1 place fields is affected differently by exposure to a completely novel environment in comparison to an altered, familiar environment, whereas the plasticity of CA3 place fields is affected similarly during both types of environmental novelty

Augmentation of osteochondral repair with hyperbaric oxygenation: a rabbit study

<p>Abstract</p> <p>Background</p> <p>Current treatments for osteochondral injuries often result in suboptimal healing. We hypothesized that the combination of hyperbaric oxygen (HBO) and fibrin would be superior to either method alone in treating full-thickness osteochondral defects.</p> <p>Methods</p> <p>Osteochondral repair was evaluated in 4 treatment groups (control, fibrin, HBO, and HBO+fibrin groups) at 2-12 weeks after surgical injury. Forty adult male New Zealand white rabbits underwent arthrotomy and osteochondral surgery on both knees. Two osteochondral defects were created in each femoral condyle, one in a weight-bearing area and the other in a non-weight-bearing area. An exogenous fibrin clot was placed in each defect in the right knee. Left knee defects were left empty. Half of the rabbits then underwent hyperbaric oxygen therapy. The defects in the 4 treatment groups were then examined histologically at 2, 4, 6, 8, and 12 weeks after surgery.</p> <p>Results</p> <p>The HBO+fibrin group showed more rapid and more uniform repair than the control and fibrin only groups, but was not significantly different from the group receiving HBO alone. In the 2 HBO groups, organized repair and good integration with adjacent cartilage were seen at 8 weeks; complete regeneration was observed at 12 weeks.</p> <p>Conclusions</p> <p>HBO significantly accelerated the repair of osteochondral defects in this rabbit model; however, the addition of fibrin produced no further improvement.</p