An analytical model to design circumferential clasps for laser-sintered removable partial dentures

Objective

Clasps of removable partial dentures (RPDs) often suffer from plastic deformation and failure by fatigue; a common complication of RPDs. A new technology for processing metal frameworks for dental prostheses based on laser-sintering, which allows for precise fabrication of clasp geometry, has been recently developed. This study sought to propose a novel method for designing circumferential clasps for laser-sintered RPDs to avoid plastic deformation or fatigue failure.

Insulin resistance, lipodystrophy and cardiometabolic syndrome in HIV/AIDS

HIV associated insulin resistance, lipodistrophy and cardiometabolic syndrome have been extensively studied and continue to be the scope of much research. There is compelling evidence that both the HIV itself and the therapeutical regimes are major contributors to all of these associated comorbidities. HIV has increasingly been recognized as a disease of accelerated aging, manifested by increased progression of vascular disease and cellular markers of aging. The antiretroviral medication can increase insulin resistance and cause lipotoxocity and HIV-associated lipodystrophy leading to cardiovascular pathology. In this article we review the pathogenesis, management, and prevention of the long-term complications of HIV and its therapies, including cardiovascular disease, lipodystrophy, and insulin resistance along with the growing focus on biomarkers to predict development of end-organ disease. Through a focused literature search we review the established evidence, the developing research about the treatment strategies in treated HIV infection as well as identify potential areas for future research.     

Characteristic motifs for families of allergenic proteins

The identification of potential allergenic proteins is usually done by scanning a database of allergenic proteins and locating known allergens with a high sequence similarity. However, there is no universally accepted cut-off value for sequence similarity to indicate potential IgE cross-reactivity. Further, overall sequence similarity may be less important than discrete areas of similarity in proteins with homologous structure. To identify such areas, we first classified all allergens and their subdomains in the Structural Database of Allergenic Proteins (SDAP, http://fermi.utmb.edu/SDAP/) to their closest protein families as defined in Pfam, and identified conserved physicochemical property motifs characteristic of each group of sequences. Allergens populate only a small subset of all known Pfam families, as all allergenic proteins in SDAP could be grouped to only 130 (of 9318 total) Pfams, and 31 families contain more than four allergens. Conserved physicochemical property motifs for the aligned sequences of the most populated Pfam families were identified with the PCPMer program suite and catalogued in the webserver MotifMate (http://born.utmb.edu/motifmate/summary.php). We also determined specific motifs for allergenic members of a family that could distinguish them from non-allergenic ones. These allergen specific motifs should be most useful in database searches for potential allergens. We found that sequence motifs unique to the allergens in three families (seed storage proteins, Bet v 1, and tropomyosin) overlap with known IgE epitopes, thus providing evidence that our motif based approach can be used to assess the potential allergenicity of novel proteins.     

Baroreflex control of heart rate and renal sympathetic nerve activity in rats with low brain angiotensinogen

The main objective of the present study was to evaluate baroreceptor control of heart rate (HR) and renal sympathetic nerve activity (RSNA) in transgenic rats (TG) with low angiotensinogen production in glial cells, TGR(ASrAogen)-680. In addition, the sympathetic and vagal autonomic tonus to the heart was investigated. As previously shown, TG rats presented a lower arterial pressure (AP) and HR. However, TG rats had decreased AP variability during the night (8.9+/-0.4 mmHg vs 9.8+/-0.3 mmHg, in SD) accompanied by an increase in HR variability (39+/-1 beats/min vs 35+/-1 beats/min, in SD) and augmented locomotor activity during the night (3.5+/-0.3 counts/min vs 2.5+/-0.2 counts/min, in SD). In addition, TG rats presented increased baroreflex sensitivity for the RSNA (slope of line that correlates decreases in RSNA and increases in AP=1.36+/-0.18 vs 0.77+/-0.1, in SD) and an increased sensitivity for both the baroreflex bradycardia (0.79+/-0.04 ms/mmHg vs 0.52+/-0.04 ms/mmHg, in SD) and tachycardia (1.46+/-0.1 ms/mmHg vs 0.93+/-0.01 ms/mmHg, in SD). Further, TG rats had increased vagal tonus (25+/-3 beats/min vs 11+/-4 beats/min in SD) without significant change in the sympathetic tonus to the heart. These results confirm and extend previous observations showing that glial angiotensinogen, the main source of brain RAS peptides, importantly modulates sympathetic tonus, at least to the renal nerve, and vagal tonus to the heart.     

Pegylated-interferon alpha 2a treatment for chronic hepatitis C in patients on chronic haemodialysis

AIM: To evaluate the response to pegylated-interferon alpha 2a in chronic hepatitis C patients on chronic haemodialysis. METHODS: Ten patients with chronic C hepatitis were enrolled in this study. All had increased aminotransferases for more than 6 mo, positive antiHCV antibodies and positive PCR HCV-RNA. We administrated Peg-Interferon alpha 2a 180μg/wk for 48 wk. After 12 wk of treatment we evaluated the biochemical and early virological response (EVR). At the end of the treatment we evaluated the biochemical response and 24 wk after the end of the treatment we evaluated the sustained virological response (SVR). We monitored the side-effects during the treatment. RESULTS: Two patients dropped out in the first 12 wk of treatment and 2 after the first 12 wk of treatment. After 12 wk of treatment, 7 out of 8 patients had biochemical response and EVR and 1 had biochemical response but persistent viremia. We had to reduce the dose of pegylated-interferon to 135μg/wk in 2 cases. Three out of 6 (50%) patients had SVR 24 wk after the end of the treatment. Intention-to-treat analysis showed that 3 out of 10 patients (30%) had SVR. Side-effects occurred in most of the patients (flu-like syndrome, thrombocytopenia or leucopoenia), but they did not impose the discontinuation of treatment. CONCLUSION: After 12 wk of treatment with Peg-Interferon alpha 2a (40 ku) in patients on chronic haemodialysis with chronic C hepatitis, EVR was obtained in 87.5% (7/8) of the cases. SVR was achieved in 50% of the cases (3/6 patients) that finished the 48 wk of treatment.     

Using property based sequence motifs and 3D modeling to determine structure and functional regions of proteins

Homology modeling has become an essential tool for studying proteins that are targets for medical drug design. This paper describes the approach we developed that combines sequence decomposition techniques with distance geometry algorithms for homology modeling to determine functionally important regions of proteins. We show here the application of these techniques to targets of medical interest chosen from those included in the CASP5 (Critical Assessment of Techniques for Protein Structure Prediction) competition, including the dihydroneopterin aldolase from Mycobacterium tuberculosis, RNase III of Thermobacteria maritima, and the NO-transporter nitrophorin from saliva of the bedbug Cimex lectularius. Physical chemical property (PCP) motifs, identified in aligned sequences with our MASIA program, can be used to select among different alignments returned by fold recognition servers. They can also be used to suggest functions for hypothetical proteins, as we illustrate for target T188. Once a suitable alignment has been made with the template, our modeling suite MPACK generates a series of possible models. The models can then be selected according to their match in areas known to be conserved in protein families. Alignments based on motifs can improve the structural matching of residues in the active site. The quality of the local structure of our 3D models near active sites or epitopes makes them useful aids for drug and vaccine design. Further, the PCP motif approach, when combined with a structural filter, can be a potent way to detect areas involved in activity and to suggest function for novel genome sequences.