Background: Dengue is the most important human viral disease transmitted by arthropod vectors. The availability of random peptide libraries (RPL) displayed on phage has provided a powerful tool for selecting sequences that mimic epitopes from microorganisms that are useful for diagnostic and vaccine development purposes. In this paper, we describe peptides that resemble the antigenic structure of B-cell epitopes of dengue virus identified from a phage-peptide library using human sera containing polyclonal antibodies against dengue virus. Materials and Methods: Eighteen phage clones were isolated from the phage-display peptide library, J404, by affinity selection using human antisera against dengue virus type 3. These clones were tested for reactivity by ELISA with a panel of hyperimmune ascitic fluids (HAFs) containing antibodies either against all four dengue serotypes, West Nile virus (WNV) or Eastern equine encephalitis virus (EEEV) with control ascitic fluid (NAF) used as a negative control. Results: Eight clones were recognized by HAFs against the four dengue serotypes, of which four significantly inhibited binding of anti-dengue antibodies to the virus. Two peptides with similar sequences to regions of NS3 and NS4B non-structural dengue virus proteins were identified. Conclusion: Our results suggest that these peptides could be used for the development of diagnostic tools for the detection of dengue virus infection and for a potential vaccine against this pathogen.

PURPOSE: While dental implants have displayed high success rates, poor mechanical fixation is a common complication, and their biomechanical response to occlusal loading remains poorly understood. This study aimed to develop and validate a computational model of a natural first premolar and a dental implant with matching crown morphology, and quantify their mechanical response to loading at the occlusal surface. MATERIALS AND METHODS: A finite-element model of the stomatognathic system comprising the mandible, first premolar and periodontal ligament (PDL) was developed based on a natural human tooth, and a model of a dental implant of identical occlusal geometry was also created. Occlusal loading was simulated using point forces applied at seven landmarks on each crown. Model predictions were validated using strain gauge measurements acquired during loading of matched physical models of the tooth and implant assemblies. RESULTS: For the natural tooth, the maximum vonMises stress (6.4 MPa) and maximal principal strains at the mandible (1.8 mε, −1.7 mε) were lower than those observed at the prosthetic tooth (12.5 MPa, 3.2 mε, and −4.4 mε, respectively). As occlusal load was applied more bucally relative to the tooth central axis, stress and strain magnitudes increased. CONCLUSION: Occlusal loading of the natural tooth results in lower stress-strain magnitudes in the underlying alveolar bone than those associated with a dental implant of matched occlusal anatomy. The PDL may function to mitigate axial and bending stress intensities resulting from off-centered occlusal loads. The findings may be useful in dental implant design, restoration material selection, and surgical planning.
Bicuspid ; Crowns ; Dental Implants ; Dental Occlusion ; Finite Element Analysis ; Humans ; Mandible ; Periodontal Ligament ; Stomatognathic System ; Tooth

BACKGROUND/OBJECTIVES: The main objective of this study was to evaluate the effects of a high cholesterol (HC) dietary challenge on cholesterol tissue accumulation, inflammation, adipocyte differentiation, and macrophage infiltration in guinea pigs. A second objective was to assess whether macronutrient manipulation would reverse these metabolic alterations. MATERIALS/METHODS: Male Hartley guinea pigs (10/group) were assigned to either low cholesterol (LC) (0.04g/100g) or high cholesterol (HC) (0.25g/100g) diets for six weeks. For the second experiment, 20 guinea pigs were fed the HC diet for six weeks and then assigned to either a low carbohydrate (CHO) diet (L-CHO) (10% energy from CHO) or a high CHO diet (H-CHO) (54% CHO) for an additional six weeks. RESULTS: Higher concentrations of total (P < 0.005) and free (P < 0.05) cholesterol were observed in both adipose tissue and aortas of guinea pigs fed the HC compared to those in the LC group. In addition, higher concentrations of pro-inflammatory cytokines in the adipose tissue (P < 0.005) and lower concentrations of anti-inflammatory interleukin (IL)-10 were observed in the HC group (P < 0.05) compared to the LC group. Of particular interest, adipocytes in the HC group were smaller in size (P < 0.05) and showed increased macrophage infiltration compared to the LC group. When compared to the H-CHO group, lower concentrations of cholesterol in both adipose and aortas as well as lower concentrations of inflammatory cytokines in adipose tissue were observed in the L-CHO group (P < 0.05). In addition, guinea pigs fed the L-CHO exhibited larger adipose cells and lower macrophage infiltration compared to the H-CHO group. CONCLUSIONS: The results of this study strongly suggest that HC induces metabolic dysregulation associated with inflammation in adipose tissue and that L-CHO is more effective than H-CHO in attenuating these detrimental effects.
Adipocytes ; Adipose Tissue* ; Animals ; Aorta ; Cholesterol ; Cholesterol, Dietary ; Cytokines ; Diet ; Diet, Carbohydrate-Restricted* ; Guinea Pigs* ; Humans ; Inflammation* ; Interleukins ; Macrophages* ; Male

BACKGROUND: Warm autoimmune hemolytic anemia (w-AIHA) is an uncommon disease with heterogeneous response to treatment. Steroids are the standard treatment at diagnosis, whereas rituximab has recently been recommended as the second-line therapy of choice. Our main objective was to document the response to treatment in patients with newly diagnosed w-AIHA, including the effectiveness of low-dose rituximab as frontline treatment and for refractory disease. METHODS: Patients with w-AIHA from 2002 to 2017 were included. Relapse-free survival (RFS), probability of maintained response (MR), and time-to-response were analyzed using the Kaplan–Meier method. Response was classified as complete, partial, and no response. RESULTS: We included 64 adults with w-AIHA (39 women and 25 men). The median age was 37 (16–77) years. Response rates to steroids alone were 76.7%, rituximab plus steroids, 100%; and cyclophosphamide, 80%. RFS with steroids at 6, 36, and 72 months was 86.3%, 65.1%, and 59.7%, respectively. Eighteen patients received rituximab at 100 mg/wk for 4 weeks plus high-dose dexamethasone as first-line therapy, with RFS at 6, 36, and 72 months of 92.3%, 58.7% and 44.1%, respectively. Eight patients refractory to several lines of therapy were treated with low-dose rituximab, and all achieved a response (three complete response and five partial response) at a median 16 days (95% confidence interval, 14.1–17.8), with a 75% probability of MR at 103 months; the mean MR was 81.93±18 months. CONCLUSION: Outcomes of w-AIHA treatment were considerably heterogeneous. Low rituximab doses plus high dexamethasone doses were effective for refractory disease.
Adult ; Anemia, Hemolytic, Autoimmune ; Cyclophosphamide ; Dexamethasone ; Diagnosis ; Female ; Humans ; Methods ; Mexico ; Rituximab ; Splenectomy ; Steroids