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1.
Microbiol Spectr ; 10(3): e0254821, 2022 06 29.
Article in English | MEDLINE | ID: mdl-35670599

ABSTRACT

Quick and accurate detection of neutralizing antibodies (nAbs) against yellow fever is essential in serodiagnosis during outbreaks for surveillance and to evaluate vaccine efficacy in population-wide studies. All of this requires serological assays that can process a large number of samples in a highly standardized format. Albeit being laborious, time-consuming, and limited in throughput, the classical plaque reduction neutralization test (PRNT) is still considered the gold standard for the detection and quantification of nAbs due to its sensitivity and specificity. Here, we report the development of an alternative fluorescence-based serological assay (SNTFLUO) with an equally high sensitivity and specificity that is fit for high-throughput testing with the potential for automation. Finally, our novel SNTFLUO was cross-validated in several reference laboratories and against international WHO standards, showing its potential to be implemented in clinical use. SNTFLUO assays with similar performance are available for the Japanese encephalitis, Zika, and dengue viruses amenable to differential diagnostics. IMPORTANCE Fast and accurate detection of neutralizing antibodies (nAbs) against yellow fever virus (YFV) is key in yellow fever serodiagnosis, outbreak surveillance, and monitoring of vaccine efficacy. Although classical PRNT remains the gold standard for measuring YFV nAbs, this methodology suffers from inherent limitations such as low throughput and overall high labor intensity. We present a novel fluorescence-based serum neutralization test (SNTFLUO) with equally high sensitivity and specificity that is fit for processing a large number of samples in a highly standardized manner and has the potential to be implemented for clinical use. In addition, we present SNTFLUO assays with similar performance for Japanese encephalitis, Zika, and dengue viruses, opening new avenues for differential diagnostics.


Subject(s)
Encephalitis, Japanese , Yellow Fever , Zika Virus Infection , Zika Virus , Antibodies, Neutralizing , Antibodies, Viral , Humans , Neutralization Tests/methods , Yellow Fever/diagnosis , Yellow Fever/epidemiology , Yellow Fever/prevention & control , Yellow fever virus
2.
J Prosthet Dent ; 128(2): 167-173, 2022 Aug.
Article in English | MEDLINE | ID: mdl-33551142

ABSTRACT

STATEMENT OF PROBLEM: Flapless implant placement with immediate functional loading has been reported in anterior locations. However, data on posterior locations are lacking. PURPOSE: The purpose of this randomized controlled trial was to determine and compare clinical outcomes of flap versus flapless surgically placed single posterior mandibular dental implants subjected to immediate functional loading. MATERIAL AND METHODS: Participants with missing mandibular first molar teeth were recruited and randomized into 2 groups (n=51): flapped and flapless. Dental implants were surgically placed and loaded immediately with interim restorations following implant protective occlusion. Outcome measures were implant failure, crestal bone loss, and periodontal parameters: modified plaque index, modified sulcus bleeding index, and pocket depths. Outcome data were recorded at baseline, 6-month, and 12-month follow-up visits. Cone beam computed tomography scans were used to calculate crestal bone loss, and periodontal outcomes were recorded by using a resin covered periodontal probe (α=.05). RESULTS: After 12 months, similar implant failure rates (P>.05) were found between the groups. Crestal bone loss in the flapped group was statistically higher than in the flapless group at 6 months (0.83 ±0.21 mm versus 0.75 ±0.23 mm) and at 12 months (1.04 ±0.27 mm versus 0.90 ±0.24 mm) from the baseline. The modified plaque index, modified sulcus bleeding index, and peri-implant probing depths (PDs) in both groups increased from the baseline to 6-month follow-ups (Baseline modified plaque index: 0.82 ±0.54 versus 0.79 ±0.21; Baseline modified sulcus bleeding index: 0.74 ±0.21 versus 0.70 ±0.43; Baseline PD: 1.25 ±0.37 mm versus 1.20 ±0.22 mm; 6 months modified plaque index: 1.54 ±0.70 versus 1.21 ±0.45; 6 months modified sulcus bleeding index: 1.93 ±0.54 versus 1.51 ±0.61; 6 months PD: 3.20 ±0.73 mm versus 2.80 ±0.43 mm). At 12-month follow-ups after repeated oral hygiene reinforcements, periodontal parameters had improved (decreased) significantly. CONCLUSIONS: Flapless implant insertion with immediate functional loading could be considered as an appropriate treatment option for providing functional restorations on the day of implant placement with minimal surgical intervention, reducing crestal bone loss, and periodontal complications.


Subject(s)
Alveolar Bone Loss , Dental Implants , Immediate Dental Implant Loading , Dental Implantation, Endosseous , Dental Prosthesis, Implant-Supported , Follow-Up Studies , Humans , Mandible , Surgical Flaps , Treatment Outcome
3.
Vaccines (Basel) ; 9(12)2021 Dec 16.
Article in English | MEDLINE | ID: mdl-34960238

ABSTRACT

The tremendous global impact of the current SARS-CoV-2 pandemic, as well as other current and recent outbreaks of (re)emerging viruses, emphasize the need for fast-track development of effective vaccines. Yellow fever virus 17D (YF17D) is a live-attenuated virus vaccine with an impressive efficacy record in humans, and therefore, it is a very attractive platform for the development of novel chimeric vaccines against various pathogens. In the present study, we generated a YF17D-based replicon vaccine platform by replacing the prM and E surface proteins of YF17D with antigenic subdomains from the spike (S) proteins of three different betacoronaviruses: MERS-CoV, SARS-CoV and MHV. The prM and E proteins were provided in trans for the packaging of these RNA replicons into single-round infectious particles capable of expressing coronavirus antigens in infected cells. YF17D replicon particles expressing the S1 regions of the MERS-CoV and SARS-CoV spike proteins were immunogenic in mice and elicited (neutralizing) antibody responses against both the YF17D vector and the coronavirus inserts. Thus, YF17D replicon-based vaccines, and their potential DNA- or mRNA-based derivatives, may constitute a promising and particularly safe vaccine platform for current and future emerging coronaviruses.

4.
Emerg Microbes Infect ; 10(1): 2279-2290, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34792431

ABSTRACT

The live-attenuated yellow fever 17D (YF17D) vaccine is one of the most efficacious human vaccines and also employed as a vector for novel vaccines. However, in the lack of appropriate immunocompetent small animal models, mechanistic insight in YF17D-induced protective immunity remains limited. To better understand YF17D vaccination and to identify a suitable mouse model, we evaluated the immunogenicity and protective efficacy of YF17D in five complementary mouse models, i.e. wild-type (WT) BALB/c, C57BL/6, IFN-α/ß receptor (IFNAR-/-) deficient mice, and in WT mice in which type I IFN signalling was temporally ablated by an IFNAR blocking (MAR-1) antibody. Alike in IFNAR-/- mice, YF17D induced in either WT mice strong humoral immune responses dominated by IgG2a/c isotype (Th1 type) antibodies, yet only when IFNAR was blocked. Vigorous cellular immunity characterized by CD4+ T-cells producing IFN-γ and TNF-α were mounted in MAR-1 treated C57BL/6 and in IFNAR-/- mice. Surprisingly, vaccine-induced protection was largely mouse model dependent. Full protection against lethal intracranial challenge and a massive reduction of virus loads was conferred already by a minimal dose of 2 PFU YF17D in BALB/c and IFNAR-/- mice, but not in C57BL/6 mice. Correlation analysis of infection outcome with pre-challenge immunological markers indicates that YFV-specific IgG might suffice for protection, even in the absence of detectable levels of neutralizing antibodies. Finally, we propose that, in addition to IFNAR-/- mice, C57BL/6 mice with temporally blocked IFN-α/ß receptors represent a promising immunocompetent mouse model for the study of YF17D-induced immunity and evaluation of YF17D-derived vaccines.


Subject(s)
Yellow Fever Vaccine/administration & dosage , Yellow Fever Vaccine/immunology , Yellow Fever/prevention & control , Yellow fever virus/immunology , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Disease Models, Animal , Female , Humans , Immunity, Cellular , Immunity, Humoral , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , T-Lymphocytes/immunology , Vaccines, Attenuated/administration & dosage , Vaccines, Attenuated/genetics , Vaccines, Attenuated/immunology , Yellow Fever/immunology , Yellow Fever/virology , Yellow Fever Vaccine/genetics , Yellow fever virus/genetics
5.
J Indian Prosthodont Soc ; 21(3): 249-255, 2021.
Article in English | MEDLINE | ID: mdl-34380811

ABSTRACT

Aim: To compare speech intelligibility (SI), nasal resonance, and swallowing ability in maxillectomy patients with a customized obturator to the conventional obturator. Settings and Design: Non-randomized controlled study. Materials and Methods: Forty-eight maxillectomy patients were recruited and assessment of SI, nasal resonance, and swallowing ability was done at three situations: without obturator, with conventional obturator, and with customized obturator. Recordings of unrehearsed conversation, counting from number 1-20 and four sets of Chapel Hill Multilingual Intelligibility Test in the Hindi language were used to assess SI and nasal resonance. SI was evaluated by untrained listeners and graded according to a 6-point scale. Nasal resonance was evaluated by speech pathologists on a 7-point scale of severity. Swallowing ability was evaluated by water drinking test. Statistical Analysis Used: One-way ANOVA, Post hoc Bonferroni and Chi square test. Results: SI and nasal resonance showed a statistically significant difference between any two groups (P < 0.001). Water drinking time was significantly different between without obturator and with customized obturator (P < 0.001), but the difference was not statistically significant between without obturator and with obturator (P < 0.004). Conclusion: SI, nasal resonance, and swallowing ability improved with customized obturator in comparison to the conventional obturator.


Subject(s)
Deglutition , Speech Intelligibility , Drinking , Humans , Nose , Palatal Obturators
6.
Nature ; 590(7845): 320-325, 2021 02.
Article in English | MEDLINE | ID: mdl-33260195

ABSTRACT

The expanding pandemic of coronavirus disease 2019 (COVID-19) requires the development of safe, efficacious and fast-acting vaccines. Several vaccine platforms are being leveraged for a rapid emergency response1. Here we describe the development of a candidate vaccine (YF-S0) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that uses live-attenuated yellow fever 17D (YF17D) vaccine as a vector to express a noncleavable prefusion form of the SARS-CoV-2 spike antigen. We assess vaccine safety, immunogenicity and efficacy in several animal models. YF-S0 has an excellent safety profile and induces high levels of SARS-CoV-2 neutralizing antibodies in hamsters (Mesocricetus auratus), mice (Mus musculus) and cynomolgus macaques (Macaca fascicularis), and-concomitantly-protective immunity against yellow fever virus. Humoral immunity is complemented by a cellular immune response with favourable T helper 1 polarization, as profiled in mice. In a hamster model2 and in macaques, YF-S0 prevents infection with SARS-CoV-2. Moreover, a single dose conferred protection from lung disease in most of the vaccinated hamsters within as little as 10 days. Taken together, the quality of the immune responses triggered and the rapid kinetics by which protective immunity can be attained after a single dose warrant further development of this potent SARS-CoV-2 vaccine candidate.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/immunology , COVID-19/prevention & control , Genetic Vectors/genetics , SARS-CoV-2/immunology , Vaccines, Attenuated/immunology , Yellow Fever Vaccine/genetics , Animals , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/genetics , Cricetinae , Disease Models, Animal , Female , Glycosylation , Macaca fascicularis/genetics , Macaca fascicularis/immunology , Macaca fascicularis/virology , Male , Mesocricetus/genetics , Mesocricetus/immunology , Mesocricetus/virology , Mice , Safety , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/metabolism , Vaccines, Attenuated/administration & dosage , Vaccines, Attenuated/adverse effects , Vaccines, Attenuated/genetics
7.
mBio ; 11(2)2020 04 07.
Article in English | MEDLINE | ID: mdl-32265332

ABSTRACT

Recent outbreaks of yellow fever virus (YFV) in West Africa and Brazil resulted in rapid depletion of global vaccine emergency stockpiles and raised concerns about being unprepared against future YFV epidemics. Here we report that a live attenuated virus similar to the Japanese encephalitis virus (JEV) vaccine JE-CVax/Imojev that consists of YFV-17D vaccine from which the structural (prM/E) genes have been replaced with those of the JEV SA14-14-2 vaccine strain confers full protection in mice against lethal YFV challenge. In contrast to the YFV-17D-mediated protection against YFV, this protection is not mediated by neutralizing antibodies but correlates with YFV-specific nonneutralizing antibodies and T cell responses against cell-associated YFV NS1 and other YFV nonstructural (NS) proteins. Our findings reveal the potential of YFV NS proteins to mediate protection and demonstrate that chimeric flavivirus vaccines, such as Imojev, could confer protection against two flaviviruses. This dual protection may have implications for the possible off-label use of JE-CVax in case of emergency and vaccine shortage during YFV outbreaks. In addition, populations in Asia that have been vaccinated with Imojev may already be protected against YFV should outbreaks ever occur on that continent, as several countries/regions in the Asia-Pacific are vulnerable to international spread of the YFV.IMPORTANCE Efficient and safe vaccines against yellow fever (e.g., YFV-17D) that provide long-lasting protection by rapidly inducing neutralizing antibody responses exist. However, the vaccine supply cannot cope with an increasing demand posed by urban outbreaks in recent years. Here we report that JE-CVax/Imojev, a YFV-17D-based chimeric Japanese encephalitis vaccine, also efficiently protects against YFV infection in mice. In case of shortage of the YFV vaccine during yellow fever outbreaks, (off-label) use of JE-CVax/Imojev may be considered. Moreover, wider use of JE-CVax/Imojev in Asia may lower the risk of the much-feared YFV spillover to the continent. More generally, chimeric vaccines that combine surface antigens and replication machineries of two distinct flaviviruses may be considered dual vaccines for the latter pathogen without induction of surface-specific antibodies. Following this rationale, novel flavivirus vaccines that do not hold a risk for antibody-dependent enhancement (ADE) of infection (inherent to current dengue vaccines and dengue vaccine candidates) could be designed.


Subject(s)
Antibodies, Viral/blood , Cross Protection , Japanese Encephalitis Vaccines/genetics , Japanese Encephalitis Vaccines/immunology , T-Lymphocytes/immunology , Yellow Fever/prevention & control , Animals , Antibodies, Neutralizing , HEK293 Cells , Humans , Male , Mice , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/immunology , Viral Nonstructural Proteins/immunology , Yellow Fever/immunology , Yellow fever virus
8.
Emerg Microbes Infect ; 9(1): 520-533, 2020.
Article in English | MEDLINE | ID: mdl-32116148

ABSTRACT

The recent Zika virus (ZIKV) epidemic in the Americas, followed by the yellow fever virus (YFV) outbreaks in Angola and Brazil highlight the urgent need for safe and efficient vaccines against the ZIKV as well as much greater production capacity for the YFV-17D vaccine. Given that the ZIKV and the YFV are largely prevalent in the same geographical areas, vaccines that would provide dual protection against both pathogens may obviously offer a significant benefit. We have recently engineered a chimeric vaccine candidate (YF-ZIKprM/E) by swapping the sequences encoding the YFV-17D surface glycoproteins prM/E by the corresponding sequences of the ZIKV. A single vaccine dose of YF-ZIKprM/E conferred complete protection against a lethal challenge with wild-type ZIKV strains. Surprisingly, this vaccine candidate also efficiently protected against lethal YFV challenge in various mouse models. We demonstrate that CD8+ but not CD4+ T cells, nor ZIKV neutralizing antibodies are required to confer protection against YFV. The chimeric YF-ZIKprM/E vaccine may thus be considered as a dual vaccine candidate efficiently protecting mice against both the ZIKV and the YFV, and this following a single dose immunization. Our finding may be particularly important in the rational design of vaccination strategies against flaviviruses, in particular in areas where YFV and ZIKV co-circulate.


Subject(s)
Yellow Fever Vaccine/immunology , Yellow Fever/prevention & control , Yellow fever virus/immunology , Zika Virus/immunology , Animals , Antibodies, Neutralizing/immunology , Chlorocebus aethiops , Mice , T-Lymphocytes/immunology , Vero Cells , Yellow Fever/immunology , Yellow Fever Vaccine/therapeutic use
9.
Emerg Microbes Infect ; 8(1): 1734-1746, 2019.
Article in English | MEDLINE | ID: mdl-31797751

ABSTRACT

By infecting mice with the yellow fever virus vaccine strain 17D (YFV-17D; Stamaril®), the dose dependence and evolutionary consequences of neurotropic yellow fever infection was assessed. Highly susceptible AG129 mice were used to allow for a maximal/unlimited expansion of the viral populations. Infected mice uniformly developed neurotropic disease; the virus was isolated from their brains, plaque purified and sequenced. Viral RNA populations were overall rather homogenous [Shannon entropies 0-0.15]. The remaining, yet limited intra-host population diversity (0-11 nucleotide exchanges per genome) appeared to be a consequence of pre-existing clonal heterogeneities (quasispecies) of Stamaril®. In parallel, mice were infected with a molecular clone of YFV-17D which was in vivo launched from a plasmid. Such plasmid-launched YFV-17D had a further reduced and almost clonal evolution. The limited intra-host evolution during unrestricted expansion in a highly susceptible host is relevant for vaccine and drug development against flaviviruses in general. Firstly, a propensity for limited evolution even upon infection with a (very) low inoculum suggests that fractional dosing as implemented in current YF-outbreak control may pose only a limited risk of reversion to pathogenic vaccine-derived virus variants. Secondly, it also largely lowers the chance of antigenic drift and development of resistance to antivirals.


Subject(s)
Evolution, Molecular , Genetic Variation , Yellow Fever/virology , Yellow fever virus/genetics , Animals , Antibodies, Viral/blood , Brain/pathology , Brain/virology , Disease Models, Animal , Mice , Plasmids/genetics , Yellow Fever Vaccine
10.
NPJ Vaccines ; 3: 56, 2018.
Article in English | MEDLINE | ID: mdl-30564463

ABSTRACT

The recent Zika virus (ZIKV) epidemic in the Americas led to an intense search for therapeutics and vaccines. Here we report the engineering of a chimeric virus vaccine candidate (YF-ZIKprM/E) by replacing the antigenic surface glycoproteins and the capsid anchor of YFV-17D with those of a prototypic Asian lineage ZIKV isolate. By intracellular passaging, a variant with adaptive mutations in the E protein was obtained. Unlike YFV-17D, YF-ZIKprM/E replicates poorly in mosquito cells. Also, YF-ZIKprM/E does not cause disease nor mortality in interferon α/ß, and γ receptor KO AG129 mice nor following intracranial inoculation of BALB/c pups. A single dose as low as 1 × 102 PFU results, as early as 7 days post vaccination, in seroconversion to neutralizing antibodies and confers full protection in AG129 mice against stringent challenge with a lethal inoculum (105 LD50) of either homologous or heterologous ZIKV strains. Induction of multi-functional CD4+ and CD8+ T cell responses against ZIKV structural and YFV-17D non-structural proteins indicates that cellular immunity may also contribute to protection. Vaccine immunogenicity and protection was confirmed in other mouse strains, including after temporal blockade of interferon-receptors in wild-type mice to facilitate ZIKV replication. Vaccination of wild-type NMRI dams with YF-ZIKprM/E results in complete protection of foetuses against brain infections and malformations following a stringent intraplacental challenge with an epidemic ZIKV strain. The particular characteristic of YF-ZIKprM/E in terms of efficacy and its marked attenuation in mice warrants further exploration as a vaccine candidate.

11.
J Prosthodont ; 26(5): 376-380, 2017 Jul.
Article in English | MEDLINE | ID: mdl-26588357

ABSTRACT

PURPOSE: To determine whether a fixed partial denture (FPD) or an implant replacement of a single missing tooth leads to better masticatory efficiency and patient satisfaction. MATERIALS AND METHODS: One-hundred and twenty participants with missing mandibular right first molars were selected on the basis of predefined inclusion and exclusion criteria. After obtaining informed consent, 60 participants were randomized to the teeth-supported (FPD) group and 60 to the implant placement group (IMP). The study was divided into the following parts: (i) Completion of a Likert scale satisfaction questionnaire (postrehabilitation) by the participants. (ii) Evaluation of masticatory efficiency and performance 3 months after rehabilitation. Data were evaluated by applying t-test and z-test using statistical analysis (α ˂ 0.05). RESULTS: Masticatory efficiency of participants in the IMP and FPD groups was 74.95 ± 0.90% and 74.41 ± 3.35%, respectively (p = 0.607). Total satisfaction questionnaire scores for the two groups were also not significantly different; however, the mean scores of overall satisfaction and function categories in this questionnaire were significantly higher for the IMP group, while the mean score for the duration of treatment question was higher for the FPD group (p < 0.05). CONCLUSION: The results of this study suggested that although masticatory performance and efficiency were not statistically different for single teeth replaced with implants or FPDs, patients perceived higher satisfaction with implant restorations; they also preferred the shorter treatment times for rehabilitation in the FPD group.


Subject(s)
Dental Prosthesis, Implant-Supported , Denture, Partial, Fixed , Mastication , Molar , Patient Satisfaction , Tooth Loss/surgery , Adult , Dental Prosthesis, Implant-Supported/psychology , Denture, Partial, Fixed/psychology , Humans , Male , Mandible , Middle Aged , Surveys and Questionnaires , Treatment Outcome
12.
Natl J Maxillofac Surg ; 8(2): 125-129, 2017.
Article in English | MEDLINE | ID: mdl-29386815

ABSTRACT

STATEMENT OF PROBLEM: Because of the toxicity of vanadium in Ti-6Al-4V alloy, next generation of titanium alloys is proposed to focus on niobium-containing alloy, but for clinical applications, it is crucial for this alloy to bond with acrylic resins with or without the use of primers. However, literature was lacking about the effect of primers on bonding of autopolymerizing resins to Ti-6Al-7Nb. OBJECTIVES: To evaluate the effect of different metal primers on the shear bond strength of acrylic resin to Ti-6Al-7Nb. MATERIALS AND METHODS: A total of 30 dis-shaped wax patterns (10 mm in diameter and 2 mm thickness) were prepared and casted using Ti-6Al-7Nb. After casting, the disk surfaces were finished with abrasive paper under water. Specimens were equally divided into three groups on the basis of the use of primer: metal primer (GC II metal primer) (Group 1), Universal Tokuyama primer (Group 2), no primer (Group 3). Tape of 50 µm thickness was applied on each of the specimens. Then, self-cure acrylic resin was mixed and applied on the center part of the tape, on which Bernouilles tube was placed. The tensile bond strength was measured with a universal testing machine. The data were obtained for all the specimens and analyzed using Statistical Package for Social Sciences version 17.0 at a statistically significance level of <0.05. RESULTS: Mean tensile force was maximum for Group 2 (28.58 ± 39.40 N) and minimum for control Group 3 (6.24 ± 10.97 N), thereby showing a significant inter-group difference (P < 0.001). On applying post hoc test (Tukey HSD), both the Group 1 and Group 2 showed a statistically significant difference as compared to control Group 3; however, the difference between two experimental groups was not statistically significant (P > 0.05). CONCLUSIONS: Tokuyama primer and GC II metal primer had a significant effect on improving the bond strength between autopolymerizing denture base resin and Ti-6Al-7Nb.

13.
Dis Model Mech ; 9(10): 1203-1210, 2016 10 01.
Article in English | MEDLINE | ID: mdl-27483350

ABSTRACT

Hepatitis E virus (HEV) is one of the prime causes of acute viral hepatitis, and chronic hepatitis E is increasingly recognized as an important problem in the transplant setting. Nevertheless, the fundamental understanding of the biology of HEV replication is limited and there are few therapeutic options. The development of such therapies is partially hindered by the lack of a robust and convenient animal model. We propose the infection of athymic nude rats with the rat HEV strain LA-B350 as such a model. A cDNA clone, pLA-B350, was constructed and the infectivity of its capped RNA transcripts was confirmed in vitro and in vivo Furthermore, a subgenomic replicon, pLA-B350/luc, was constructed and validated for in vitro antiviral studies. Interestingly, rat HEV proved to be less sensitive to the antiviral activity of α-interferon, ribavirin and mycophenolic acid than genotype 3 HEV (a strain that infects humans). As a proof-of-concept, part of the C-terminal polymerase sequence of pLA-B350/luc was swapped with its genotype 3 HEV counterpart: the resulting chimeric replicon replicated with comparable efficiency as the wild-type construct, confirming that LA-B350 strain is amenable to humanization (replacement of certain sequences or motifs by their counterparts from human HEV strains). Finally, ribavirin effectively inhibited LA-B350 replication in athymic nude rats, confirming the suitability of the rat model for antiviral studies.


Subject(s)
Hepatitis E virus/physiology , Hepatitis E/virology , Animals , Antiviral Agents/pharmacology , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/virology , Cell Line, Tumor , Clone Cells , DNA, Complementary/genetics , Disease Models, Animal , Disease Susceptibility , Hepatitis E/pathology , Hepatitis E virus/drug effects , Humans , Liver/pathology , Liver/virology , Liver Neoplasms/pathology , Liver Neoplasms/virology , Mice , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA, Viral/administration & dosage , RNA-Dependent RNA Polymerase/metabolism , Rats, Nude , Replicon/genetics , Virus Replication/drug effects , Virus Shedding/drug effects
14.
J Cancer Res Ther ; 12(2): 1102-3, 2016.
Article in English | MEDLINE | ID: mdl-27461709

ABSTRACT

Buccal carcinoma is one of the most common oral malignant neoplasms, especially in the South Asian region. Radiotherapy, which plays a significant role in the treatment of this carcinoma, has severe adverse effects. Different types of prosthesis may be constructed to protect healthy tissues from the adverse effects of treatment and concentrate radiation in the region of the tumor mass. However, the technique for fabrication of shielding stent with Lipowitz's alloy (cerrobend/Wood's alloy) has not been well documented. This article describes detailed technique for fabrication of such a stent for unilateral buccal carcinoma patients to spare the unaffected oral cavity from potential harmful effects associated with radiotherapy.


Subject(s)
Alloys , Carcinoma/radiotherapy , Mouth Mucosa , Mouth Neoplasms/radiotherapy , Organ Sparing Treatments/methods , Stents , Carcinoma/diagnosis , Humans , Mouth Mucosa/pathology , Mouth Neoplasms/diagnosis
15.
J Cancer Res Ther ; 12(1): 314-7, 2016.
Article in English | MEDLINE | ID: mdl-27072257

ABSTRACT

BACKGROUND: Radiation stents made of Lipowitz metal or cerrobend alloy are commonly used to shield uninvolved tissues from electron beams used in therapeutic radiation treatment of head and neck cancers. However, studies investigating the efficacy of cerrobend shielding stent in patients with unilateral buccal carcinoma remain rare. PURPOSE: To evaluate the efficacy of cerrobend shielding stents in minimizing the potential adverse effects of radiation on oral tissues in buccal carcinoma patients. MATERIALS AND METHODS: Twenty.eight participants were selected for the study based on predetermined inclusion criteria, out of which four participants were lost to follow-.up. Half of the remaining participants. (N = 12) were randomly given cerrobend shielding stent and the remaining 12 formed the control group. The effects of radiotherapy were evaluated by using Radiation Therapy Oncology Group. (RTOG) 0435 Head and Neck adverse effects grading tool. All participants were evaluated for xerostomia, mucositis, dysphagia, salivary changes, dysguesia, pain, trismus and radiation caries at baseline and 1 and 3. months post.radiotherapy. RESULTS: All adverse effects were higher in control compared to study group, with post therapy difference for pain in swallowing, salivary changes, mucositis, dysphagia, dry mouth and caries being statistically significant. CONCLUSIONS: Cerrobend alloy can be used effectively as shielding stent to reduce the adverse effects associated with external beam radiation therapy in unilateral buccal carcinoma patients.


Subject(s)
Alloys/therapeutic use , Carcinoma/radiotherapy , Head and Neck Neoplasms/radiotherapy , Mouth Mucosa/radiation effects , Carcinoma/pathology , Head and Neck Neoplasms/pathology , Humans , Mouth Mucosa/pathology , Radiation Injuries/pathology , Radiotherapy/adverse effects , Radiotherapy Dosage , Stents
16.
J Prosthet Dent ; 115(6): 712-7, 2016 Jun.
Article in English | MEDLINE | ID: mdl-26803180

ABSTRACT

STATEMENT OF PROBLEM: Few studies compare the radiographic changes in bone density associated with immediate implant loading protocols. PURPOSE: The purpose of this longitudinal study was to quantitatively assess radiographic changes in alveolar bone density around immediate functionally and nonfunctionally loaded implants. MATERIAL AND METHODS: A prospective longitudinal study was conducted in which 20 participants with partially edentulous mandibles received implants that were immediately loaded either functionally (IFL) or nonfunctionally (INFL). Standardized intraoral periapical radiographs were made at baseline, 3, and 6 months. These were digitized and analyzed using the histogram tool of the GNU Image Modulation Program for changes in alveolar bone density at crestal and lateral apical levels around the implant. RESULTS: An increase in the mean lateral apical pixel grayscale values of 4.68 ±0.80 at 3 months and 4.15 ±0.29 at 6 months was observed with IFL, while INFL demonstrated an increase of 5.66 ±0.53 at 3 months and 6.07 ±0.59 at 6 months. A decrease in the mean crestal pixel grayscale values of -24.40 ±7.41 with IFL and -16.86 ±5.14 with INFL was found from baseline to 3 months. CONCLUSIONS: On the basis of this longitudinal study, it was concluded that immediate loading stimulated alveolar bone formation at 6 months after implant placement. The immediate functional loading of implants resulted in a significantly greater degree of bone demineralization at the alveolar crest from implant placement up to 3 months compared with immediate nonfunctional loading.


Subject(s)
Alveolar Bone Loss/diagnostic imaging , Dental Implantation, Endosseous/adverse effects , Immediate Dental Implant Loading/adverse effects , Alveolar Bone Loss/etiology , Bone Density , Dental Implantation, Endosseous/methods , Humans , Immediate Dental Implant Loading/methods , Prospective Studies , Radiography, Dental , Time Factors
17.
J Prosthodont ; 25(5): 371-4, 2016 Jul.
Article in English | MEDLINE | ID: mdl-26221967

ABSTRACT

PURPOSE: To analyze and compare crestal bone loss and pocket depth around platform-switched implants placed at two intraoral locations. MATERIALS AND METHODS: Eighty platform-switched implants, 40 in the maxillary anterior region (group - ANT) and 40 in the mandibular posterior region (group - POST), were placed in healthy men aged between 25 and 45 years, and restored following two-stage surgical and progressive loading protocols. Digital radiographs for crestal bone level assessment and pocket depths on facial, mesial, distal, and palatal/lingual sites around the implant were recorded at definitive restoration cementation (baseline) and 6-month follow-up. Difference in pre- and post-periodontal pocket depths and crestal bone loss levels were measured and analyzed statistically using SPSS v.16.0, applying the Mann-Whitney test (p < 0.05 considered significant). RESULTS: Mean bone loss was significantly higher in group ANT (1.2 ± 0.3 mm) than in group POST (0.7 ± 0.02 mm). Palatal pocket depth increase was significantly greater in the ANT group (p = 0.01), and distal pocket depth increase was significantly greater for the POST group (p = 0.002). CONCLUSION: The amount of bone loss noted in the maxillary anterior region compared to the mandibular posterior region was significantly more. This could possibly be because of greater vertical cantilever and offset loads in the anterior compared to the posterior region. Significantly greater pocket depth in mandibular posterior distal and maxillary anterior palatal regions could be related to oral hygiene maintenance issues.


Subject(s)
Alveolar Bone Loss , Dental Implantation, Endosseous , Periodontal Pocket , Adult , Cementation , Dental Implants , Dental Prosthesis Design , Follow-Up Studies , Humans , Male , Mandible , Maxilla , Middle Aged
18.
J Adv Prosthodont ; 7(1): 8-14, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25722831

ABSTRACT

PURPOSE: To assess function by identifying changes in swallowing and masticatory performance in maxillary obturator prosthesis wearers. MATERIALS AND METHODS: Sixty subjects were recruited for the study, of which 20 were obturator wearers, 20 were completely dentulous and 20 had removable partial/complete dentures with similar Eichner's Index. Swallowing ability was evaluated with and without obturator using the "Water Drinking Test"; Masticatory performance was evaluated with the Sieve test; and maximum occlusal force was recorded with the help of a digital bite sensor. The data was analyzed using the Statistical Package for Social Science version 15.0 with a confidence level at 95%. RESULTS: Profile, behavior of drinking and time taken to drink were significantly improved (P<.001) in subjects after wearing obturator. Masticatory performance was not significantly different (P=.252) in obturator wearer when compared with dentulous or removable partial/complete denture wearer, but significantly (P<.001) high inter group difference in maximum occlusal force existed. Correlation between masticatory performance and maximum occlusal force was not significant (P=.124). CONCLUSION: Swallowing ability was significantly improved after wearing obturator but masticatory performance was not significantly different from those having similar occlusal support zone in their dentition.

20.
Prosthet Orthot Int ; 38(6): 510-4, 2014 Dec.
Article in English | MEDLINE | ID: mdl-24311365

ABSTRACT

BACKGROUND AND AIM: Replacement of missing ear is a challenging task in which extensive array of materials and techniques have been employed. Materials such as silicones and methacrylate acrylic resins have been widely used for auricular prosthesis. This article describes a simplified procedure for fabricating resilient heat-cured acrylic resin auricular prosthesis, retained with a custom-made acrylic bar with ball attachments. CASE DESCRIPTION AND METHODS: A male patient was reported with right ear loss. A modified technique was preferred to fabricate ear prosthesis with resilient heat-cured acrylic resin in which heat-cured acrylic retentive bar was incorporated. FINDINGS AND OUTCOMES: Contrary to silicones, resilient heat-cured acrylic resin was more economical and compatible with acrylic retentive bar and resulted in a more long-lasting auricular prosthesis. CONCLUSION: Resilient heat-cured acrylic resin was proven to be a better alternative in terms of strength and durability. CLINICAL RELEVANCE: This article presents an economical and simplified approach for the fabrication of prosthesis for a missing ear.


Subject(s)
Ear Auricle/surgery , Ear Deformities, Acquired/rehabilitation , Ear Deformities, Acquired/surgery , Plastic Surgery Procedures/methods , Prostheses and Implants , Acrylic Resins/economics , Cost-Benefit Analysis , Humans , Male , Middle Aged , Prosthesis Design , Prosthesis Implantation/methods , Silicones/economics , Treatment Outcome
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