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1.
Eur J Paediatr Dent ; 18(1): 15-18, 2017 Mar.
Article in English | MEDLINE | ID: mdl-28494596

ABSTRACT

AIM: The aim of this study was to verify whether socioeconomic determinants, such as parents' educational level, family income and dental service attendance by children, are associated with the presence of caries among an Italian population of children. MATERIALS AND METHODS: An observational retrospective study was carried out in a population of children aged 4-14 years who visited the Paediatric Dentistry Department of the University of Perugia, Italy. Children were stratified according to familial socioeconomic level (father's and mother's educational level, family income) and dental service attendance of children. Age- and sex- adjusted odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated by means of multivariate logistic regression models. RESULTS: A sample of 231 children (mean age 8.1 yrs, SD 2.6; 127 males, 104 females) was recruited. One hundred and sixty three (70.46%) children in the study had caries. Caries presence in children was higher in children where the mothers' educational level was lower (OR =6.1; 95% CI = 3.1 to 12.7), in children where the fathers' educational level was lower (OR =2.9; 95% CI =1.6 to 5.5) and in children with lower family income (OR = 9.9; 95% 95% CI = 5.1 to 20.1). No statistically significant difference were observed in terms of caries presence between the children who were visited at least once by a dentist and children who were not previously seen by a dental practitioner (OR = 0.8; 95% CI = 0.4 to 1.6). CONCLUSION: Socioeconomic level was an important predictor of caries presence among children. Both low income and low parental educational level were related to an increased presence of caries, whereas previous dental visits experience did not affect caries presence in children.


Subject(s)
Dental Care for Children/statistics & numerical data , Dental Caries/epidemiology , Educational Status , Income/statistics & numerical data , Parents , Child , Female , Humans , Male , Prevalence , Retrospective Studies , Risk Factors
2.
Eur J Paediatr Dent ; 18(4): 305-312, 2017 Dec.
Article in English | MEDLINE | ID: mdl-29380617

ABSTRACT

AIM: Children's dental fear and anxiety (DFA) causes significant problems in clinical practice. The 15-item Children's Fear Survey Schedule - Dental Subscale (CFSS-DS) and the 8-item Modified Child Dental Anxiety Scale (MCDAS) are the most widely used measures of dental fear in children. The aim of this study is to examine the reliability and validity of the Italian versions of the CFSS-DS and MCDAS, also in comparison with a simple visual analogue scale (VAS). MATERIALS AND METHODS: The CFSS-DS and MCDAS were translated into Italian by a consensus panel of experts and administered to 210 dental patients aged 4-11 years from three Italian Institutions. Internal reliability was assessed using the Cronbach's alpha correlation. A sub-sample of 60 children was selected for test-retest analysis. CFSS-DS and MCDAS, plus a VAS scale, rated both by children and parents, were validated using as gold standard the 4-item Frankl scale for behaviours assessed by dentists. RESULTS: Mean CFSS-DS score was 30.8 (SD: 11.1) and mean MCDAS score was 17.9 (SD: 7.2), significantly higher among children aged 4-7 years and among children at their first dental visit. The alpha value for internal reliability was 0.90 (95%, CI= 0.88-0.92) for CFSS-DS and 0.87 (95% CI=0.85-0.90) for MCDAS. Both CFSS-DS and MCDAS showed good test-retest reliability (rsp= 0.80; p<0.001 for both scales). CFSS-DS and MCDAS predicted a Frankl score ≤2 (i.e., indicating children with an uncooperative behaviour) with a fair accuracy (AUC=0.69 and AUC=0.68, respectively). The VAS scale was more effective in predicting a negative behaviour (AUC=0.78). The scales self-reported by children were only slightly more accurate than those reported by parents. CONCLUSION: The Italian versions of the CFSS-DS and MCDAS are valid and reliable tools for the assessment of dental fear in Italian children aged 4-11 years. A simple, one-item VAS, and dental fear and anxiety evaluation by parents may be valid and quick alternatives to multi-item indices to predict an uncooperative children behaviour.


Subject(s)
Dental Anxiety/classification , Child , Child, Preschool , Humans , Italy , Reproducibility of Results , Surveys and Questionnaires
3.
Eur J Paediatr Dent ; 18(2): 121-130, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28598183

ABSTRACT

AIM: The aim of this paper was to review the published scientific literature to quantify the prevalence and mean score of dental fear/anxiety (DFA) in children/adolescents and its variation according to several variables. MATERIALS AND METHODS: Cross- sectional and cohort studies published from 2000 to 2014, that measured DFA in children /adolescents (aged 0-19 years), in the general population, or visiting private or public dental services (general or pediatric) or attending school and kindergarten, were searched, with specific terms, in 3 electronic databases (Medline, Embase, Web Of Science). Primary data, collected with specific questionnaires of demonstrated reliability and/or validity, were extracted. RESULTS: After screening 743 abstracts and evaluating 164 full-text publications, 36 articles were selected. Dental fear/anxiety prevalence rates were 12.2%, 10.0%, 12.2%,11.0% and 20.0% for the CFSS-DS, DAS, MDAS, DFS, and DFSS-SF scores, respectively. In the studies that used MCDAS Dental fear/prevalence rates varied from 13.3% to 29.3%. In the studies that used CFSS-DS ratings, the prevalence and the mean score of dental fear/anxiety was lower in Northern Europe than the remaining countries, the prevalence decreased with increasing age and the frequency was higher in females than males. CONCLUSIONS: Dental fear/anxiety is a common problem in children/adolescents worldwide, therefore, new strategies to overcome this relevant children/adolescent condition should be encouraged.


Subject(s)
Dental Anxiety/epidemiology , Adolescent , Child , Child, Preschool , Humans , Infant , Prevalence , Young Adult
4.
Eur J Paediatr Dent ; 17(3): 193-196, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27759407

ABSTRACT

AIM: The aim of the study was to establish whether caries prevalence on the buccal surfaces of first lower permanent molars (FLPMs) can be compared to those on the occlusal surfaces in order to justify the utility of extending pit and fissure sealing also to the extra-occlusal surfaces. MATERIALS AND METHODS: Design: an observational study was carried out in the children population (n=779) aged ≤14 years (mean age 7.68, SD 3.53) that presented at the Paediatric Dentistry Department of the University of Perugia. In the study were included 460 patients, and absolute frequency (number) of FLMP occlusal and buccal caries, together with their ratio and their difference in percentage, were recorded and analysed. Moreover, FLMP buccal caries variation related to age, sex and parent's nationality were calculated. RESULTS: Among the 460 children included (243 males) aged 5-14 years, 103 erupted FLPMs were analysed. Of their decayed surfaces (n=115), the occlusal surfaces were 62 (53.9%) and the buccal surfaces 53 (46.1%); the absolute frequency ratio was 1.17 and the percentage difference was 7.8%. The female gender was significantly related to buccal caries of FLPMs [OR = 2.66 (95% CI; 1.27-5.59; p=0.0096)] as was the age ranging between 10-14 years [OR = 2.73 (95% CI; 1.36-5.50; p =0.004)]. The parents nationality was not significantly related to buccal caries [Odds Ratio =1.47 (95% CI; 0.70-3.06; p = 09040)]. CONCLUSIONS: The similar caries susceptibility of buccal and occlusal surfaces of FLPMs stimulates further comparative studies about the usefulness of extending pit and fissure sealing to the buccal surfaces in addition to the occlusal prophylactic intervention, particularly with regard to the female sex and during the early eruption stages of these teeth.


Subject(s)
Dental Caries/prevention & control , Dental Enamel/drug effects , Molar/drug effects , Pit and Fissure Sealants/therapeutic use , Tooth Crown/drug effects , Adolescent , Age Factors , Child , Child, Preschool , DMF Index , Dental Caries/epidemiology , Dental Caries Susceptibility , Female , Humans , Incidence , Italy/epidemiology , Male , Sex Factors
5.
Eur J Paediatr Dent ; 25(1): 27-31, 2024 03 01.
Article in English | MEDLINE | ID: mdl-38323516

ABSTRACT

AIM: Public and private health services, which provide both preventive and health promotion interventions, were forced to suddenly stop their activities to limit the risk of infections during the pandemic emergency. Oral health administration, including that of children, was affected by these planned medical service closures, from both therapeutic and preventive perspectives. This study aims to analyse the consequences, at the oral cavity level, of failures to treat patients of childhood age, considering the impact of carious pathology on quality of life and incorrect eating and oral hygiene habits, which may occur in this age group. METHODS: This is a cross-sectional, single-center, observational study. One hundred patients from the Odontostomatological University Center (C.O.U.) of Perugia were randomly enrolled. CONCLUSION: Oral health status of the examined sample is satisfactory overall, considering the clinic's interruption of treatments with the resulting long period of no follow-up and the emotional and economic stress generated by the pandemic condition for both the young patients and their caregivers.


Subject(s)
COVID-19 , Dental Caries , Child , Humans , Oral Health , Pandemics , Dental Caries/epidemiology , Cross-Sectional Studies , Quality of Life
6.
Sci Rep ; 13(1): 10646, 2023 06 30.
Article in English | MEDLINE | ID: mdl-37391501

ABSTRACT

Several glycoconjugate-based vaccines against bacterial infections have been developed and licensed for human use. Polysaccharide (PS) analysis and characterization is therefore critical to profile the composition of polysaccharide-based vaccines. For PS content quantification, the majority of Ultra High Performance Liquid Chromatography (UHPLC) methods rely on the detection of selective monosaccharides constituting the PS repeating unit, therefore requiring chemical cleavage and tailored development: only a few methods directly quantify the intact PS. The introduction of charged aerosol detector (CAD) technology has improved the response of polysaccharide analytes, offering greater sensitivity than other detector sources (e.g., ELSD). Herein, we report the development of a universal UHPLC-CAD method (UniQS) for the quantification and quality evaluation of polysaccharide antigens (e.g., Streptococcus Pneumoniae, Neisseria meningitidis and Staphylococcus aureus). This work laid the foundation for a universal UHPLC-CAD format that could play an important role in future vaccine research and development helping to reduce time, efforts, and costs.


Subject(s)
Monosaccharides , Neisseria meningitidis , Humans , Chromatography, High Pressure Liquid , Aerosols , Polysaccharides
7.
Eur J Paediatr Dent ; 24(2): 104-111, 2023 06 09.
Article in English | MEDLINE | ID: mdl-37140171

ABSTRACT

AIM: Parents and caregivers, particularly in Italy, often have limited knowledge about their children's oral health. The primary objective of the study is to evaluate the educational effectiveness of a book on nutrition and prevention of oral diseases entitled "Oral health of mother and child in the first 1000 days of life". MATERIALS: The sample for this study was composed of 103 adult Italian women who were potential caregivers of one or more children (e.g., mothers, grandmothers, babysitters, and educators). The enrolled women completed a preliminary online survey which included questions about their socio-demographic characteristics and their knowledge on oral health in the first 1000 days of life of newborns (30 questions). Following the survey, they received the educational book. After reading it, the participants completed a second online survey with the same 30 questions, to measure any improvement in their knowledge. CONCLUSION: It appears that our educational book about nutrition and prevention of oral diseases was effective in enhancing knowledge among the participants in our study. These findings suggest that this educational resource has the potential to be a valuable tool in preventing oral diseases in paediatric populations. However, further confirmation of these results should be obtained through randomised controlled trials.


Subject(s)
Oral Health , Parents , Adult , Child , Humans , Infant, Newborn , Female , Educational Status , Mothers , Books
8.
Eur J Paediatr Dent ; 23(1): 54-60, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35274543

ABSTRACT

AIM: When treating patients with Autism Spectrum Disorder (ASD) the doctor-patient relationship can be very challenging. The dentist is often forced to work under general anaesthesia or conscious sedation. Children with ASD are patients with an increased risk of caries due to poor oral hygiene, a cariogenic diet and the use of xerostomal drugs. In this work therapeutic strategies used to treat this kind of patients are evaluated and a new method to treat children with ASD is presented in order to increase awareness about this condition in the dental field. METHODS: The Atlas Center (a non-profit organisation in Peurgia, Italy) has developed a software, called paINTeraction, that allows these special children to immerse themselves in a virtual reality with the help of an operator. Through this system the child can explore the dental office (and all its sounds and noises) before the real dental visit, thus connecting to the dental professional, achieving greater compliance and reducing anxiety. CONCLUSION: paINTeraction, with the use of digital technology tools, may be particularly well suited to introduce patients to the therapeutic environment, particularly in the dental setting.


Subject(s)
Autism Spectrum Disorder , Dental Caries , Autism Spectrum Disorder/therapy , Child , Dental Caries/prevention & control , Humans , Oral Hygiene , Pediatric Dentistry , Physician-Patient Relations
9.
Eur J Paediatr Dent ; 22(4): 303-308, 2021 Dec.
Article in English | MEDLINE | ID: mdl-35034466

ABSTRACT

AIM: Malocclusions are widespread all over the world with high prevalence values and represent a social vulnerability and health problem because of the important burden of orthodontic treatment for both families and the public health service. The Italian Ministry of Health identified the principles for priority setting in dental care, i.e. patients with IOTN (Index of Orthodontic Treatment Need) 4-5 and those in particular conditions of health or social vulnerability. METHODS: A retrospective study was carried out to assess the IOTN and malocclusion in a population attending the public Orthodontic Health Service of Perugia (Italy) from September 2018 to February 2020. Medical charts, social income information, study models, photos and lateral cephalograms were examined to assess the orthodontic treatment need. CONCLUSION: Orthodontic health service in Italy tends to have many patients on the waiting list, while the 72% of subject under orthodontic treatment are not part of the orthodontic priority (IOTN grade 4-5). This study suggests the heath system to guarantee a priority of need for orthodontic treatment for patients with health vulnerabilities.


Subject(s)
Index of Orthodontic Treatment Need , Malocclusion , Dental Care , Esthetics, Dental , Health Services Needs and Demand , Humans , Italy/epidemiology , Malocclusion/epidemiology , Malocclusion/therapy , Orthodontics, Corrective , Retrospective Studies , Social Vulnerability
10.
Xenobiotica ; 40(12): 826-39, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20925584

ABSTRACT

Compound A ((1aR,5S,8S,10R,22aR)-5-tert-butyl-N-{(1R,2S)-1-[(cyclopropylsulfonyl)carbamoyl]-2-ethenylcyclopropyl}-14-methoxy-3,6-dioxo-1,1a,3,4,5,6,9,10,18,19,20,21,22,22a-tetradecahydro-8H-7,10-methanocyclopropa[18,19][1,10,3,6]dioxadiazacyclononadecino[12,11-b]quinoline-8-carboxamide) is a prototype of a series of subnanomolar inhibitors of genotypes 1, 2, and 3 hepatitis C virus (HCV) NS3/4A proteases. HCV NS3/4A protease inhibitors have demonstrated high antiviral effects in patients with chronic HCV infection and are likely to form a key component of future HCV therapy. Compound A showed excellent liver exposure in rats, which is essential for compounds intended to treat HCV. The compound was mainly eliminated intact in bile and showed greater than dose proportional systemic exposure in rats. Compound A demonstrated time- and temperature-dependent uptake into rat and human hepatocytes and proved to be a substrate for rat hepatic uptake transporter Oatp1b2 and for human hepatic uptake transporters OATP1B1 and OATP1B3. The liver selectivity observed for this compound is likely to be due to transporter-mediated hepatic uptake together with moderate passive permeability. Metabolism was mainly CYP3A-mediated and generated a reactive epoxide on the vinylcyclopropyl sulfonamide moiety that could be quenched by glutathione. Similar metabolic profiles of Compound A were obtained in liver microsomes of rats and humans. The oral bioavailability at 5 mg/kg was low due to extensive hepatic first-pass effect but clearly the intestinal absorption was enough to deliver a high amount of the compound to the liver. The metabolism and disposition properties of Compound A are particularly attractive to support its evaluation as a drug candidate for the treatment of hepatitis C.


Subject(s)
Antiviral Agents/metabolism , Antiviral Agents/pharmacokinetics , Hepacivirus/enzymology , Protease Inhibitors/metabolism , Protease Inhibitors/pharmacokinetics , Viral Nonstructural Proteins/antagonists & inhibitors , Animals , Antiviral Agents/administration & dosage , Antiviral Agents/blood , Biological Transport/drug effects , Dogs , Hepacivirus/drug effects , Humans , Injections, Intravenous , Liver/drug effects , Liver/metabolism , Membrane Transport Proteins/metabolism , Metabolic Networks and Pathways/drug effects , Microsomes, Liver/drug effects , Protease Inhibitors/administration & dosage , Protease Inhibitors/blood , Rats , Rats, Sprague-Dawley , Tandem Mass Spectrometry , Time Factors , Viral Nonstructural Proteins/metabolism
11.
Eur J Paediatr Dent ; 21(2): 115-122, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32567942

ABSTRACT

AIM: The aim of this review is to quantify the prevalence and type of malocclusion among children and adolescents during the different stages of dentition worldwide. MATERIALS AND METHODS: Recent studies (from 2009 to 2019), published in Medline, Web of Science and Embase and orthodontic text-books have been comprehensively reviewed herein. The methodological quality of the included studies was assessed using STROBE criteria. RESULTS: After screening 450 records and analysing 284 relevant full-text publications, 77 studies were included in this review. A good degree of evidence was obtained due to the medium-high methodological quality level of included studies. The worldwide prevalence of malocclusion was 56% (95% CI: 11-99), without differences in gender. The highest prevalence was in Africa (81%) and Europe (72%), followed by America (53%) and Asia (48%). The malocclusion prevalence score did not change from primary to permanent dentition with a common score of 54%. Malocclusion traits such as Angle's classes, overjet, overbite, and asymmetrical midline shift essentially did not change their prevalence during different dentitions. Conversely, traits such as cross-bite and diastema reduced their prevalence during permanent dentition, while scissor-bite and dental crowding increased their scores. CONCLUSION: The worldwide high prevalence of malocclusion and its early onset during childhood should induce policymakers as well as paediatric physicians and dentists to devise policies and adopt clinical strategies for preventing malocclusion since younger children's ages.


Subject(s)
Malocclusion , Overbite , Adolescent , Child , Dentition , Europe , Humans , Prevalence
12.
Eur J Paediatr Dent ; 20(3): 224-232, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31489823

ABSTRACT

AIM: Recently, the application of restorative materials containing metacrilate monomers in the conservative and paediatric dentistry has focused on the possible negative effects due to the use of these composites. In particular the release of monomers from reconstructions as a result of an insufficient polymerisation, can spread along the mucosal and dental tissues with potential immunological ed cytotoxic effects. Regarding to the importance of this issue, the aim of this study is to provide a descriptive review of the literature on potential local and systemic interactions of metacrylic and acrylic monomers with the immune system, both in vitro and in vivo. RESULTS: The most highly used monomers in composite materials applied in conservative dentistry include: 2-hydroessietil- methacrylate (HEMA), triethylene glycol-dimethacrylate (TEGDMA), bisphenol A glycidyl-methacrylate (BisGMA) and urethane- dimethacrylate (UDMA). Different investigations have been performed for better understanding of the potential side effects of metacrylic monomers on immune system cells. Different factors such as cell population, exposure time and parameters more strictly connected to these materials, such as molecular weight, chemical composition and mechanical characteristics, seem to be directly involved in these reactions.


Subject(s)
Composite Resins , Methacrylates , Bisphenol A-Glycidyl Methacrylate , Child , Dental Materials , Humans , Materials Testing
13.
Eur J Paediatr Dent ; 20(4): 295-301, 2019 12.
Article in English | MEDLINE | ID: mdl-31850772

ABSTRACT

AIM: Caries lesions begin with enamel acid demineralisation mediated by microorganisms. Lasers with sub-ablative energy might act as a prophylactic intervention to reinforce enamel against lesions caused by acid. MATERIALS AND METHODS: A systematic review of the literature was performed evaluating only in vitro studies published from 2010 to 2018. The research was performed using the following databases: Medline, Embase and the Web Of Science. A further search was performed consulting the list of references of the included studies as well as book chapters which dealt with this topic. RESULTS: A total of 347 records were retrieved and, after their evaluation, 36 studies were included. CO2 lasers were the most described and effective device in preventing acid demineralisation. This type of laser was unique in improving the already positive results obtained with fluoride-based interventions. Er,Cr:YSGG (with fluencies > 8.5J/cm2), diode and argon lasers also improved enamel acid resistance (p-values ranging from 0.05 to 0.001) producing similar effects with fluoride-based interventions. Regarding the sealant retention outcome, the Er:YAG laser was able to perform an enamel etching which was as effective as the traditional acid etching with the advantage of being easier and usually well accepted by low-compliant patients (i.e. younger children). Nd:YAG presented the worst results. The most common structural changes after the laser irradiation were water and carbonate reduction in the enamel combined with a phosphate and calcium enamel content increase. Moreover, the calcium/phosphate ratio was found to reach the 1.67 ideal ratio. CONCLUSION: The in vitro studies that examined the prophylactic use of lasers for increasing enamel acid resistance presented interesting results that are enough to support a further in vivo experiment. This would entail the use of a clinical laser as an alternative or in combination with fluoride-based interventions.


Subject(s)
Dental Caries , Lasers, Solid-State , Child , Dental Enamel , Fluorides , Humans , Phosphates
14.
Immunology ; 89(1): 142-51, 1996 Sep.
Article in English | MEDLINE | ID: mdl-8911152

ABSTRACT

Recent evidence suggests that after repeated stimulations with inactivated C. albicans (CA) cells, CD2F1 mice respond with a cytokine pattern typical of T-helper 1 (ThI) subset development. The purpose of this study was to analyse the sequence of immunological events which, soon after priming mice with CA, lead to the development of primary and anamnestic response. A comprehensive kinetics analysis of cytokine mRNA expression was performed by Northern blot assay, in peritoneal exudate cells (PEC), at different phases of immune response to CA: after priming (one i.p. injection of 2 x 10(7) CA cells mouse), during development of the primary immune response (five progressive CA i.p. injections over a 2-week period) and in the anamnestic response (CA booster 30 days after the primary response). In vitro assays were performed 2 and 24 hr after every CA stimulation. The response to CA priming was characterized by an early and high expression of interleukin-2 (IL-2) and IL-1 beta mRNAs At 24hr. IL-2 mRNA was still at a high level, while IL-1 beta had greatly decreased. A weak expression of IL-10 was only induced at 2 hr. whereas IL-12 p40 subunit, interferon-7 (IFN-7) IL-4 and IL-5 mRNAs were undetectable. In this phase no in vitro proliferative response of PEC to CA was observed, whereas a significant natural killer (NK) activity was induced. From the second CA injection, the IFN-7 mRNA was already induced at 2 hr. Its expression level increased progressively with the number of CA injections persisting up to 24 hr after the fifth stimulation. A progressive increase of IL-2 mRNA expression was also induced whereas IL-1 beta and IL-10 mRNAs were always transiently expressed at 2 hr at levels similar to those observed after the priming. IL-12 p40 subunit. IL-4 and IL-5 mRNAs were never detectable. The expression of this selected cytokine pattern typical of Thl response was correlated with the development of CA-specific T lymphocytes as confirmed by the in vitro proliferative response of CA-5d-induced PEC to CA. NK activity also increased progressively with the number of CA injections and after the fifth stimulation lymphokine-activated killer (LAK) activity was also induced. The anamnestic response to CA was characterized by a very quick induction of high levels of IL-2, II N-gamma and IL-1 beta mRNAs. IL-2 and IFN-gamma mRNAs remained high up to 24 hr while IL-1 beta mRNA decreased strongly. A weak, transient expression of IL-10 mRNA was induced at 2 hr whereas the IL-12 p40 subunit, IL-4 and IL-5 mRNAs were not detectable. The presence of CA-specific memory lymphocytes was confirmed by the in vitro specific proliferative response of PEC to CA. CA booster caused also a very rapid and high level of NK/LAK activation. In conclusion, these results indicate that CA is able to progressively trigger differential on of the Th1 subset which develops in the absence of IL-12, and that Th memory cells retain the same selected Th1 cytokine profile developed in the primary immune response.


Subject(s)
Candida albicans/pathogenicity , Cytokines/genetics , Gene Expression Regulation , Lymphocyte Activation , Th1 Cells/immunology , Animals , Immunity, Cellular , Immunization , Immunization, Secondary , Immunologic Memory , Interferon-gamma/genetics , Interleukin-10/genetics , Interleukin-2/genetics , Killer Cells, Natural/immunology , Mice , Mice, Inbred Strains , Time Factors , Vaccines, Inactivated
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