The demineralization resistance and mechanical assessments of different bioactive restorative materials for primary and permanent teeth: an in vitro study.

OBJECTIVES: This article examines the efficacy of two bioactive dental composites in preventing demineralization while preserving their mechanical and physical properties. MATERIALS AND METHODS: The study compares Beautifil Kids and Predicta® Bioactive Bulk-Fill (Predicta) composites with conventional dental composite. Flexural strength and elastic modulus were evaluated using a universal testing machine. A pH-cycling model assessed the composites' ability to prevent dentin demineralization. Color stability and surface roughness were measured using a spectrophotometer and non-contact profilometer, respectively, before and after pH-cycling, brushing simulation, and thermocycling aging. RESULTS: Beautifil Kids exhibited the highest flexural strength and elastic modulus among the materials (p < 0.05). Predicta demonstrated the highest increase in dentin surface microhardness following the pH-cycling model (p < 0.05). All groups showed clinically significant color changes after pH-cycling, with no significant differences between them (p > 0.05). Predicta exhibited greater color change after brushing and increased surface roughness after thermocycling aging (p < 0.05). While Beautifil Kids had higher surface roughness after pH-cycling (p < 0.05). DISCUSSION/CONCLUSION: Bioactive restorative materials with ion-releasing properties demonstrate excellent resistance to demineralization while maintaining mechanical and physical properties comparable to the control group.

Occurrence of salmonid alphavirus and piscine orthoreovirus-1 infections in migrating salmon (Salmo salar L.) post-smolt in western Norway.

Viral diseases are a serious problem in Atlantic salmon (Salmo salar L.) farming in Norway, often leading to reduced fish welfare and increased mortality. Disease outbreaks in salmon farms may lead to spread of viruses to the surrounding environment. There is a public concern that viral diseases may negatively affect the wild salmon populations. Pancreas disease (PD) caused by salmonid alphavirus (SAV) and heart and skeletal muscle inflammation (HSMI) caused by piscine orthoreovirus-1 (PRV-1) are common viral diseases in salmon farms in western Norway. In the current study, we investigated the occurrence of SAV and PRV-1 infections in 651 migrating salmon post-smolt collected from three fjord systems (Sognefjorden, Osterfjorden and Hardangerfjorden) located in western Norway in 2013 and 2014 by real-time RT-PCR. Of the collected post-smolts, 303 were of wild origin and 348 were hatchery-released. SAV was not detected in any of the tested post-smolt, but PRV-1 was detected in 4.6% of them. The Ct values of PRV-1 positive fish were usually high (mean 32.0; range: 20.1-36.8). PRV-1 prevalence in post-smolts from the three fjords was 6.1% in Sognefjorden followed by 4.8% in Osterfjorden and 2.3% in Hardangerfjorden. The prevalence PRV-1 was significantly higher in wild (6.9%) compared to hatchery-released post-smolt (2.6%). The occurrence of PRV-1 infection in the fish was lowest in the Hardangerfjorden which has the highest fish farming intensity. Our results suggest that SAV infection are uncommon in migrating smolt while PRV-1 infection can be detected at low level. These findings suggest that migrating smolts were at low risk from SAV or PRV-1 released from salmon farms located in their migration routes in 2013 and 2014.

Benefits and challenges of fostering research-focused communities of practice at a specialised health sciences university: An exploratory study.

Introduction: Structured undergraduate research, whether mandatory or elective, provides undergraduate students with a unique opportunity to develop their research skills. However, the majority of the students undertake individual research projects rather than working in a group. This study explores the perceived benefits and challenges of fostering research focused communities of practice at a specialised health sciences university in Riyadh, Saudi Arabia. Methods: This cross-sectional study was conducted at the College of Medicine, King Saud bin Abdulaziz University for Health Sciences (KSAU-HS) Riyadh, Saudi Arabia. The study was approved by the Ethics Committee at the King Abdullah International Medical Research Center (KAIMRC). A self-administered questionnaire was developed that assessed the perceived benefits and challenges of doing research in groups. Data were collected using a mixture of a dichotomous and a 5-point Likert scale and were analysed using Statistical Program for Social Scientists (SPSS). Results: Of the 380 medical students invited to participate in this study, 307 completed the questionnaire, with a response rate of 80.7%. The majority of the medical students (87%) agreed on the importance of teamwork in conducting medical research. Almost all medical students (96%) believed patience and tolerance were required to make the team successful. Significant differences were found between junior and senior medical students regarding their perceived benefits (P-value = 0.0001) and challenges (P-value = 0.0007). Conclusion: Although most of the students believed that doing research in groups is essential and that working within such groups enhances their research knowledge, forming these research groups was not without problems. The need for patience and tolerance to keep the group together, the issue of free-riders and the difficulties related to which research group to join were some of the challenges students encountered.

A Chitosan-PLGA based catechin hydrate nanoparticles used in targeting of lungs and cancer treatment.

OBJECTIVE: To prepare a novel Chitosan (CS)-coated-PLGA-NPs of catechin hydrate (CTH) and to improve lungs bioavailability via direct nose to lungs-delivery for the comparative assessment of a pulmokinetics study by the first-time UHPLC-MS/MS developed method in the treatment of lungs cancer via anticancer activities on H1299 lung cancer cells. MATERIAL AND METHODS: PLGA-NPs was prepared by solvent evaporation (double emulsion) method followed by coated with chitosan (CS) and evaluated based on release and permeation of drug, a comparative pulmokinetics study with their anticancer activities on H1299 lung cancer cells. RESULTS: The particle size, PDI and ZP of the optimized CAT-PLGA-NPs and CS-CAT-PLGA-NPs were determined 124.64 ±â€¯12.09 nm and 150.81 ±â€¯15.91 nm, 0.163 ±â€¯0.03 and 0.306 ±â€¯0.03, -3.94 ±â€¯0.19 mV and 26.01 ±â€¯1.19 mV respectively. Furthermore, higher entrapment efficiency was observed for CS-CAT PLGA NPs. The release pattern of the CS-CAT-PLGA NPs was found to favor the release of entrapped CAT within the cancer microenvironment. CS-CAT-PLGA-NPs exposed on H1299 cancer cells upto 24.0 h was found to be higher cytotoxic as compared to CAT-solution (CAT-S). CS-CAT-PLGA-NPs showed higher apoptosis of cancer cells after their exposure as compared to CAT-S. CS-CTH-PLGA-NPs showed tremendous mucoadhesive-nature as compared to CTH-S and CS-CTH-PLGA NPs by retention time (RT) of 0.589 min, and m/z of 289.21/109.21 for CTH alongwith RT of 0.613 min and m/z of 301.21/151.21 was found out for IS (internal standard), i.e. Quercetin). Likewise, for 1-1000 ng mL-1 (linear range) of % accuracy (92.01-99.31%) and %CV (inter & intra-day, i.e. 2.14-3.33%) was determined. The improved Cmax with AUC0-24 was observed extremely significant (p < 0.001) via i.n. as compared oral and i.v. in the wistar rat's lungs. The CS-approach was successfully designed and safely delivered CAT to the lungs without causing any risk. CONCLUSION: CS-CTH-PLGA-NPs were showed a significant role (p < 0.001) for the enhancement of lungs-bioavailability and potentially promising approach to treat lung cancers. CS-CTH-PLGA-NPs did not cause any toxicity, it showed safety and have no obvious toxic-effects on the rat's lungs and does not produce any mortality followed by no abnormal findings in the treated-rats.

Quantification and Evaluations of Catechin Hydrate Polymeric Nanoparticles Used in Brain Targeting for the Treatment of Epilepsy.

To formulate novel chitosan (CS)-coated-PLGA-nanoparticles (NPs) using a central composite design approach and use them in order to improve brain bioavailability for catechin hydrate (CH) through direct nose-to-central nervous system (CNS) delivery for the evaluation of a comparative biodistribution study of CH by the newly developed ultra high performance liquid chromatography mass spectroscopy and mass spectroscopy (UHPLC-MS/MS) method in the treatment of epilepsy. For PLGA-NPs' preparation, a double emulsion-solvent evaporation method was used, where a four-factor, three-level central composite design was used to obtain the best nanoformulation. For the optimization, four independent variables were chosen, that is, PLGA, polyvinyl alcohol (PVA), sonication time, and temperature. The optimized PLGA-NPs were further coated with chitosan and assessed for drug release, nasal permeation study, as well as a comparative pharmacokinetic and pharmacodynamic study. Independent and dependent variables helped to optimize the best nanoformulation based on the composition of PLGA (50.0 mg), PVA (1.10%), sonication time (90.0 s), and temperature (25.0 °C). The values of dependent variables were observed, such as polydispersity index (PDI), particle size, and zeta potential (ZP)-that is, 0.106 ± 0.01, 93.46 ± 3.94 nm, and -12.63 ± 0.08 mV, respectively. The ZPs of CS-coated PLGA-NPs were changed from negative to positive value with some alteration in the distribution of particle size. Excellent mucoadhesive-nature of CS-CH-PLGA-NPs as compared with CH-S and CH-PLGA-NPs was seen, with a retention time of 0.856 min and m/z of 289.23/245.20 for CH, together with a retention time of 1.04 min and m/z of 301.21/151.21 for Quercetin as an internal standard (IS). For a linear range (1-1000 ng mL-1), % accuracy (93.07-99.41%) and inter- and intraday % precision (0.39-4.90%) were determined. The improved Cmax with area under curve (AUC)0-24 was found to be highly significant (p < 0.001) in Wistar rats' brain as compared with the i.n. and i.v. treated group based on the pharmacokinetics (PK) results. Furthermore, CS-CH-PLGA-NPs were found to be more significant (p < 0.001) for the treatment of seizure threshold rodent models, that is, increasing current electroshock and pentylenetetrazole-induced seizures. A significant role of CS-CH-PLGA-NPs was observed, that is, p < 0.001, for the enhancement of brain bioavailability and the treatment of epilepsy.

Effect of Anti-TGF-ß Treatment in a Mouse Model of Severe Osteogenesis Imperfecta.

Osteogenesis imperfecta (OI) is a heritable bone fragility disorder that is usually caused by mutations affecting collagen type I encoding genes. Recent studies in mouse models of recessive OI, Crtap-/- mice, and dominant OI, +/G610C mice, found that application of a transforming growth factor beta (TGF-ß) neutralizing antibody 1D11 rescues the bone phenotype. In the present study, we investigated TGF-ß signaling in a mouse model of severe dominant OI with a high incidence of spontaneous fractures, Col1a1Jrt/+ mice, and the effect of TGF-ß neutralizing antibody 1D11 on bone phenotype in 8-week-old mice. Col1a1Jrt/+ mice had elevated TGF-ß signaling in bone tissue. Treatment of Col1a1Jrt/+ mice with 1D11 was associated with increased bone length but had no significant effect on bone mass or bone mechanical properties, and no significant treatment-associated differences in serum markers of bone formation (alkaline phosphatase activity) or resorption (tartrate-resistant acid phosphatase) were found. Our data thus indicate that the TGF-ß neutralizing antibody 1D11 is not effective in a mouse model of dominant OI with a high incidence of spontaneous fractures. © 2018 American Society for Bone and Mineral Research.

Occurrence of salmonid alphavirus (SAV) and piscine orthoreovirus (PRV) infections in wild sea trout Salmo trutta in Norway.

Viral diseases represent a serious problem in Atlantic salmon (Salmo salar L.) farming in Norway. Pancreas disease (PD) caused by salmonid alphavirus (SAV) and heart and skeletal muscle inflammation (HSMI) caused by piscine orthoreovirus (PRV) are among the most frequently diagnosed viral diseases in recent years. The possible spread of viruses from salmon farms to wild fish is a major public concern. Sea trout S. trutta collected from the major farming areas along the Norwegian coast are likely to have been exposed to SAV and PRV from farms with disease outbreaks. We examined 843 sea trout from 4 counties in Norway for SAV and PRV infections. We did not detect SAV in any of the tested fish, although significant numbers of the trout were caught in areas with frequent PD outbreaks. Low levels of PRV were detected in 1.3% of the sea trout. PRV-infected sea trout were caught in both salmon farming and non-farming areas, so the occurrence of infections was not associated with farming intensity or HSMI cases. Our results suggest that SAV and PRV infections are uncommon in wild sea trout. Hence, we found no evidence that sea trout are at risk from SAV or PRV released from salmon farms.

The use of Quantiferon-TB gold in-tube test in screening latent tuberculosis among Saudi Arabia dialysis patients.

BACKGROUND AND AIM: Screening for tuberculosis (TB) is a key strategy for controlling infection. This study aimed to detect latent TB among dialysis patients. METHODS: This is a prospective study conducted in King Saud University, Riyadh involving hemodialysis (HD) and peritoneal dialysis (PD) patients aged ≥18 years. Patients were screened for latent TB infection (LTBI) using both TBskin test (TST) and QuantiFERONTB Gold In-Tube test (QFT-GIT). All participants were followed-up clinically and radiologically every 3 months for 2 years. RESULTS: A total of 243 (181 HD and 62 PD) patients were included and 112(46.1%) were males. 45.3% showed positive QFT in HD patients with sensitivity of 91.7%, specificity of 71.4%, positive predictive value (PPV) of 19.5%, and negative predictive value (NPV) of 91.1%. TST results in HD showed that positive TST was 17.4%, sensitivity was 63.2%, specificity was 95.5%, PPV was 51.5%, and NPV was 91.1%. Five (8.1%) showed positive QFT in PD patients with sensitivity of 7.7%, specificity of 91.8%, PPV of 6.6%, and NPV of 92.3%. TST results in PD showed that positive TST was 9.8%, sensitivity was 35.7%, specificity was 97.9%, PPV was 55.8%, and NPV was 93.3%. Previous TB infection was significantly correlated with QFT only in HD patients, but significantly associated with TST in both HD and PD patients. Also in HD, QFT was significantly associated with TST (P = 0.043). CONCLUSIONS: Due to high variability of QFT-GIT sensitivity, we recommend its use for its NPV and to use either TST or QFT in screening latent TB.

Behavioral signs of pain and functional impairment in a mouse model of osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is a congenital disorder caused most often by dominant mutations in the COL1A1 or COL1A2 genes that encode the alpha chains of type I collagen. Severe forms of OI are associated with skeletal deformities and frequent fractures. Skeletal pain can occur acutely after fracture, but also arises chronically without preceding fractures. In this study we assessed OI-associated pain in the Col1a1Jrt/+ mouse, a recently developed model of severe dominant OI. Similar to severe OI in humans, this mouse has significant skeletal abnormalities and develops spontaneous fractures, joint dislocations and vertebral deformities. In this model, we investigated behavioral measures of pain and functional impairment. Significant hypersensitivity to mechanical, heat and cold stimuli, assessed by von Frey filaments, radiant heat paw withdrawal and the acetone tests, respectively, were observed in OI compared to control wildtype littermates. OI mice also displayed reduced motor activity in the running wheel and open field assays. Immunocytochemical analysis revealed no changes between OI and WT mice in innervation of the glabrous skin of the hindpaw or in expression of the pain-related neuropeptide calcitonin gene-related protein in sensory neurons. In contrast, increased sensitivity to mechanical and cold stimulation strongly correlated with the extent of skeletal deformities in OI mice. Thus, we demonstrated that the Col1a1Jrt/+ mouse model of severe OI has hypersensitivity to mechanical and thermal stimuli, consistent with a state of chronic pain.

Effect of sclerostin antibody treatment in a mouse model of severe osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is a heritable bone fragility disorder that is usually caused by mutations affecting collagen type I production in osteoblasts. Stimulation of bone formation through sclerostin antibody treatment (Sost-ab) has shown promising results in mouse models of relatively mild OI. We assessed the effect of once-weekly intravenous Sost-ab injections for 4weeks in male Col1a1(Jrt)/+mice, a model of severe dominant OI, starting either at 4weeks (growing mice) or at 20weeks (adult mice) of age. Sost-ab had no effect on weight or femur length. In OI mice, no significant treatment-associated differences in serum markers of bone formation (alkaline phosphatase activity, procollagen type I N-propeptide) or resorption (C-telopeptide of collagen type I) were found. Micro-CT analyses at the femur showed that Sost-ab treatment was associated with higher trabecular bone volume and higher cortical thickness in wild type mice at both ages and in growing OI mice, but not in adult OI mice. Three-point bending tests of the femur showed that in wild type but not in OI mice, Sost-ab was associated with higher ultimate load and work to failure. Quantitative backscattered electron imaging of the femur did not show any effect of Sost-ab on CaPeak (the most frequently occurring calcium concentration in the bone mineral density distribution), regardless of genotype, age or measurement location. Thus, Sost-ab had a larger effect in wild type than in Col1a1(Jrt)/+mice. Previous studies had found marked improvements of Sost-ab on bone mass and strength in an OI mouse model with a milder phenotype. Our data therefore suggest that Sost-ab is less effective in a more severely affected OI mouse model.

The humoral and cellular responses induced locally and systemically after parenteral influenza vaccination in man.

Studies of the immune response after influenza vaccination in man, with focus on the immune activity occurring locally at mucosal surfaces and in associated lymphoid tissue, provide a valuable insight into immunity to influenza. The aim of influenza vaccination is to develop immunological memory resulting in enhanced rapid specific response upon subsequent influenza encounter. The tonsils are thought to play an important role as an activating, effector and memory site for immune responses against influenza. We have shown that normally high numbers of influenza-specific antibody secreting cells (ASC) are present in the nasal mucosa of healthy adults but upon parenteral vaccination the numbers remain stable. However, a rapid transient increase in influenza-specific ASC is observed in the tonsils and peripheral blood after vaccination. In the tonsils and blood, parenteral vaccination results in a significant decrease in CD4(+) cells upon vaccination, which are probably recruited to the draining lymph node.

The humoral immune response and protective efficacy of vaccination with inactivated split and whole influenza virus vaccines in BALB/c mice.

Recently the urgency of developing a pandemic influenza vaccine has lead to the re-evaluation of the use of whole virus vaccine. We have compared the humoral immune response and the protective efficacy of whole and split influenza virus vaccines in mice. Whole virus vaccine was more immunogenic particularly after the first dose of vaccine, generally eliciting higher numbers of systemic antibody secreting cells and an earlier and higher neutralising antibody response. Immunisation with one dose of whole virus vaccine more effectively reduced viral shedding upon non-lethal homologous viral challenge, but two doses of split virus vaccine was most effective at limiting viral replication and this was correlated with high influenza specific serum IgG concentrations. The two vaccine formulations induced different T helper profiles particularly after one dose of vaccine; split virus vaccine induced a type 2 bias response, whereas whole virus vaccine elicited a dominant type 1 response.