ABSTRACT
Dental caries constitutes one of the most ubiquitous diseases in Australia, with Indigenous children presenting a notably higher prevalence than their non-Indigenous peers. This literature review aims to update the knowledge base developed by Christian and Blinkhorn in 2012, with a particular focus on the contemporary disparities in dental caries between Indigenous and non-Indigenous children. Our research strategy involved a thorough exploration of the Medline, PubMed, and Scopus databases to identify pertinent studies published between 2009 and 2022. Supplementary resources included various government websites and citation searches. We prioritised studies that focused on children aged 5-6 or 12 years-reflecting the World Health Organization's index ages for oral health-and that reported dental caries prevalence and experience indicators. Our review methodology was guided by the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. The updated search, spanning 2009 to 2023, retrieved studies that reported caries estimates exclusively from 2009 to 2014. Within this period, the prevalence of dental caries in Indigenous children's primary teeth ranged between 52% and 77%, while the prevalence in permanent teeth varied from 36% to 60%. This updated review indicated that Indigenous children continue to experience caries at an approximately twice higher rate than non-Indigenous children, sustaining the persisting disparity in caries estimates. The findings from this review show that no discernible improvement in dental caries rates among Australian Indigenous children has been observed in comparison to the previous review; and that Indigenous children continue to experience both higher prevalence and severity of dental caries compared to non-Indigenous children.
Subject(s)
Dental Caries , Child , Child, Preschool , Humans , Australia/epidemiology , Dental Caries/epidemiology , Dental Caries/ethnology , Health Status Disparities , PrevalenceABSTRACT
INTRODUCTION: Public service provision is one of the keys to reducing inequalities in the utilization of dental services. Given the increase in the aging population, there should be a focus on older adults' oral health. However, this is often overlooked. OBJECTIVES: This study investigates the effectiveness of public services in reducing income-related inequalities in dental service utilization among older South Australians. METHODS: A multiple counterfactual mediation analysis using the ratio of mediator probability weighting approach was used to explore the proposed mediation mechanism using a South Australian population of older adults (≥65 y). The exposure variable in the analysis was income, and the mediators were concession cards and the last dental sector (public or private). The outcome variable was the time of last dental visit. RESULTS: Half of the older adults with high income (≥$40,000) owned a concession card, and 10% of those who attended public dental services belonged to this group. Interestingly, only 16.3% of the study participants had visited the public dental sector at their last dental appointment. Results showed a negligible indirect effect (odds ratio [OR], 0.99; 95% confidence interval [CI], 0.85-1.05) and a significant direct effect (OR, 3.09; 95% CI, 2.24-4.87). By changing the potential outcome distributions to the counterfactual exposure distributions and taking the mediators' distribution as a counterfactual exposure distribution, the odds of dental visits occurring before the past 12 mo approximately tripled for low-income compared to high-income individuals. CONCLUSION: Income inequalities were associated with relatively delayed dental visits in older South Australians, and provision of public services could not improve this pattern. This might happen due to inequitable access to concession cards and public services. A review of policies is required, including addressing income inequalities and implementing short-term approaches to improve service utilization patterns in older South Australians. KNOWLEDGE TRANSFER STATEMENT: The findings of this study can enable policymakers for informed decision-making about the provision of public dental services for older Australians. This study emphasizes the importance of reviewing the current public dental services and subsidies and implementing short-term approaches to reduce income inequalities for older Australians.
ABSTRACT
BACKGROUND: Socioeconomically disadvantaged children are disproportionately affected by oral disease. Mobile dental services help underserved communities overcome barriers to accessing health care, including time, geography, and trust. The NSW Health Primary School Mobile Dental Program (PSMDP) is designed to provide diagnostic and preventive dental services to children at their schools. The PSMDP is mainly targeted toward high-risk children and priority populations. This study aims to evaluate the program's performance across five local health districts (LHDs) where the program is being implemented. METHODS: The evaluation will use routinely collected administrative data, along with other program-specific data sources, from the district public oral health services to conduct a statistical analysis that determines the reach and uptake of the program, its effectiveness, and the associated costs and cost-consequences. The PSMDP evaluation program utilises data from Electronic Dental Records (EDRs) and other data sources, including patient demographics, service mix, general health, oral health clinical data and risk factor information. The overall design includes cross-sectional and longitudinal components. The design combines comprehensive output monitoring across the five participating LHDs and investigates the associations between socio-demographic factors, service patterns and health outcomes. Time series analysis using difference-in-difference estimation will be conducted across the four years of the program, involving services, risk factors, and health outcomes. Comparison groups will be identified via propensity matching across the five participating LHDs. An economic analysis will estimate the costs and cost-consequences for children who participate in the program versus the comparison group. DISCUSSION: The use of EDRs for oral health services evaluation research is a relatively new approach, and the evaluation works within the limitations and strengths of utilising administrative datasets. The study will also provide avenues to improve the quality of data collected and system-level improvements to better enable future services to be aligned with disease prevalence and population needs.
Subject(s)
Oral Health , Schools , Child , Humans , New South Wales , Cross-Sectional Studies , State Government , AustraliaABSTRACT
BACKGROUND: Oral health service utilization contributes to positive oral health and indicates realised access to services. The study aimed to describe patterns of oral health service use among overseas-born and Australian-born populations and assess equity in access to services. METHODS: The study used data from Australia's National Study of Adult Oral Health 2017-2018 and was guided by the Aday and Andersen framework of access to health and Australia's National Oral Health Plan. Descriptive analyses of service use by perceived need, enabling and predisposing factors were compared between four groups: Australian-born and overseas-born who mainly speak English and Australian-born and overseas-born who mainly speak a language other than English. RESULTS: Overseas-born who mainly speak a language other than English experienced greater oral health care inequity, largely driven by financial difficulty (avoided care due to cost: 42% vs 27%-28%; avoided/delayed visiting due to cost: 48% vs. 37%-38%; cost prevented treatment: 32% vs. 18%-24%). The most favourable visiting patterns were among the Australian-born population who speak a language other than English. CONCLUSIONS: The study shows clear inequity experienced among immigrants in accessibility as measured through indicators of oral health care utilization and factors related to inequity, such as the ability to pay for services.
Subject(s)
Emigrants and Immigrants , Oral Health , Humans , Adult , Australia/epidemiology , Patient Acceptance of Health Care , Health Services AccessibilityABSTRACT
OBJECTIVE: To examine the patterns and predictors of dental utilisation in culturally and linguistically diverse (CALD) and non-CALD groups in New South Wales. DESIGN: Secondary analysis of the 2013 and 2015 NSW Adult Population Health Survey (n=24,707). MAIN OUTCOME: Dental utilisation, defined as a dental visit within the last 12 months. CALD groups were defined using country of birth and language. Andersen's theoretical model was used. Chi-square test and multivariate logistic regression analysis adjusted for potential confounding. Sample weights adjusted for sampling design. RESULTS: Most (69%) of the population were Australian born; 20% spoke a language other than English at home. Dental utilisation was 58.9% and 63.9% for CALD and non-CALD groups respectively. The foreign-born non-English speaking group had the highest level of education (60%) but lower levels of dental utilisation (OR:0.81, CI 0.69-0.94) than all groups. Australian born non-English speakers had similar levels of dental utilisation to the reference group (OR:1.27, CI 0.99-1.63). CONCLUSION: There are significant disparities in dental care utilisation among CALD populations. Foreign born, non-English speaking CALD migrants, and people experiencing socioeconomic disadvantage, are at greatest risk of inadequate dental utilisation. Furthermore, the combination of predisposing factors, language and cultural barriers compound disparities in oral health care utilisation. This data highlights the need for oral healthcare services that are sensitive to population needs, to reduce disparities among CALD communities residing in NSW.
Subject(s)
Cultural Diversity , Transients and Migrants , Adult , Australia/epidemiology , Humans , Linguistics , New South WalesABSTRACT
BACKGROUND: In recent years, the consumption of sugar sweetened beverages has been declining, while low calorie sweetener and diet beverage consumption is increasing. Evidence about the effect of diet drinks on dental caries is insufficient, and has not accounted for the complexity of beverage consumption patterns. Therefore, the aim of this study is to examine the association between consuming diet drinks and dental caries among US adults. METHODS: We analyzed 2011-2014 NHANES dietary data of adults using cluster analysis, with individuals grouped based on their beverage consumption. Clusters were identified based on the R-square statistic and the local peak of the pseudo F statistic. Survey procedure and sample weights were used to account for the complex NHANES sampling design. RESULTS: Four beverage consumption patterns were identified: "high soda", "high diet drinks", "high coffee/tea" and "high water". The "High soda" cluster was the only one associated with higher DMFT after controlling for confounders (ß=1.02, 95% CI=0.42 - 1.63), whereas DT was associated with "high soda" (ß=0.45, 95% CI=0.25 - 0.64) and "high coffee/tea" (ß=0.24, 95% CI=0.01 - 0.47). On the other hand, the "high diet drinks" cluster was neither associated with DMFT (ß=0.69, 95% CI=0.51 - -0.35) nor DT (ß=0.07, 95% CI=-0.21 - 0.35). CONCLUSION: Diet drinks consumption may not be associated with increased risk of dental caries. However, more studies should be conducted in order to confirm this finding.
Subject(s)
Artificially Sweetened Beverages , Dental Caries , Adult , Beverages/adverse effects , Carbonated Beverages/adverse effects , Cluster Analysis , Dental Caries/epidemiology , Dental Caries/etiology , Diet/adverse effects , Humans , Nutrition SurveysABSTRACT
OBJECTIVE: The aim of this study is to examine the effect of diet drinks on dental erosion among a representative sample of US adults. METHODS: Adult dietary and dental data were analyzed from the 2003-2004 cycle of the National Health and Nutrition Examination Survey. Erosion was measured with a modified tooth wear index and was analyzed as a dichotomous variable. Cluster analysis was performed, and the cluster number was based on having a separate diet drink cluster and the R2 values. Survey procedure and sample weights were used. RESULTS: Most of the population (80%) had some form of dental erosive lesions. When compared with the total sample, people with erosion were more likely to be male (52.5%) and older. People with no erosive lesions were younger (42.3%) and non-Hispanic Black (21.2%). Cluster analysis resulted in 4 distinct clusters: high water, high diet drinks, high coffee/tea, and high soda. The respective percentage of individuals in each cluster who had erosion was 78.9%, 85%, 83.9%, and 76.2%, where the "high diet drinks" cluster showed the highest erosion (P = 0.28). Logistic regression modeling showed that the "high diet drinks" cluster had increased odds of erosion (odds ratio = 1.27; 95% CI = 0.58 to 2.77) when compared with the "high water" cluster, but the relationship was not statistically significant. CONCLUSION: High diet drinks consumption slightly increased the odds of dental erosion among US adults, although this relationship was not statistically significant. It is thus not yet clear that dentists should recommend diet drinks, as they might be linked to systemic diseases. Further research is needed to explore more about risk factors of erosion. KNOWLEDGE TRANSFER STATEMENT: The findings of this study are suggestive, though not significantly, that diet drinks may increase risk for dental erosion. While further research is needed, it is not clear that dentists should recommend these drinks as healthy substitutes for sugary drinks.
Subject(s)
Artificially Sweetened Beverages , Beverages , Adult , Beverages/adverse effects , Coffee , Dentition, Permanent , Female , Humans , Male , Nutrition Surveys , Tea , WaterABSTRACT
The prophylactic removal of asymptomatic third molars is a common but controversial procedure often rationalized as necessary to prevent future disease on adjacent teeth. Our objective in this retrospective cohort study of adult men was to examine whether second-molar loss differed by baseline status of the adjacent third molar, taking into account the individual's overall state of oral hygiene, caries, and periodontitis. We analyzed data from participants of the VA Dental Longitudinal Study who had at least 1 second molar present at baseline and 2 or more triennial dental examinations between 1969 and 2007. We classified second molars by third-molar status in the same quadrant: unerupted, erupted, or absent. Tooth loss and alveolar bone loss were confirmed radiographically. Caries and restorations, calculus, and probing depth were assessed on each tooth. We estimated the hazards of second-molar loss with proportional hazards regression models for correlated data, controlling for age, smoking, education, absence of the first molar, and whole-mouth indices of calculus, caries, and periodontitis. The analysis included 966 men and 3024 second molar/first molar pairs. Follow-up was 22 ± 11 y (median 24, range 3-38 y). At baseline, 163 third molars were unerupted, 990 were erupted, and 1871 were absent. The prevalence of periodontitis on the second molars did not differ by third-molar status. The prevalence of distal caries was highest on the second molars adjacent to the erupted third molars and lowest on the second molars adjacent to the unerupted third molars. Relative to the absent third molars, adjusted hazards of loss of second molars were not significantly increased for those adjacent to erupted (hazard ratio [HR] = 0.96, 95% confidence interval [CI] = 0.79-1.16) or unerupted (HR = 1.25, 95% CI = 0.91-1.73) third molars. We found similar results when using alveolar bone loss as the periodontitis indicator. Our findings suggest that retained third molars are not associated with an increased risk of second-molar loss in adult men.
Subject(s)
Dental Caries , Molar, Third , Adult , Dental Caries/epidemiology , Humans , Longitudinal Studies , Male , Molar/diagnostic imaging , Molar, Third/diagnostic imaging , Retrospective StudiesABSTRACT
BACKGROUND: There has been little examination of consumer attitudes towards the commercial advertising of healthcare services in Australia and how marketing is used by consumers in their health decision-making. In this research, we examined how consumers reported commercial advertising helped them to understand the health services available to them and the influence that marketing had upon their choices. METHODS: A survey instrument using a Likert scale to indicate agreement or disagreement with 21 questions was developed using qualitative interviews before being distributed online within Australia. Sampling of participants was stratified by age, gender and location. The results were subjected to statistical analysis with Spearman Rank Correlation test being used for bivariate analysis. RESULTS: One thousand five hundred sixty-four complete surveys were collected. The results revealed certain consumer beliefs, for example; the title of 'Dr' was believed to indicate skill and high levels of training (81.0%), with 80.3% agreeing incorrectly that use of the title was strictly regulated. Participants reported to have a higher confidence in their own abilities (71.2%) than the public (52.8%) in assessing health advertising. The level of self-confidence increased with higher education level and decreased by age (p < 0.05). Testimonials were reported to be lacking in reliability (67.7%) and that they should not be used in healthcare in the same manner as they are used in other industries. Only 44.8% of participants reported that they felt confident to spot a review that was not written by a genuine user of a service. CONCLUSIONS: The data demonstrated that many health consumers felt that while commercial health advertising was helpful, it was also confusing, with many participants also holding mistaken beliefs around other elements of commercial health advertising. While the advertising of healthcare services might have educational effects and be superficially empowering, advertising is primarily intended to sell, not educate. This research demonstrates that there is significant potential for healthcare advertising to mislead. Future developments in regulatory health advertising policy, and the related ethical frameworks developed by professional healthcare associations, need to consider how the consumers of healthcare services might be better protected from misleading and predatory advertising practices.
Subject(s)
Advertising , Health Services , Australia , Humans , Marketing , Reproducibility of ResultsABSTRACT
Early childhood caries (ECC) is a largely preventable condition that occurs when children develop caries in their primary teeth before the age of six. National trends of ECC indicate that prevalence is decreasing, but disparities between various sociodemographic groups may be increasing, despite intervention efforts. Dynamic mechanisms in caries development are hypothesized to be responsible for the observed population distributions of disease. Agent-based models (ABMs) have been utilized to explore similar hypotheses in many areas of health research. Therefore, we developed an ABM of ECC development mechanisms and examined population outcomes of hypothetical preventive intervention scenarios. We found that risk-based targeting had minimal impact on population averages or disparities and was largely due to the strength of the dynamic mechanisms among those considered to be at high caries risk. Universally increasing intervention access reduced population caries prevalence, but increased disparities between different groups of caries risk profiles. We show that population distributions of ECC can emerge as a result of dynamic mechanisms that have been shown to drive disease development. Understanding the effectiveness of a proposed intervention in relation to the hypothesized mechanism(s) that contributes to the outcome of interest is critical to future efforts to address population disparities in ECC.
Subject(s)
Dental Caries , Child , Child, Preschool , Dental Caries/epidemiology , Dental Caries/etiology , Humans , Nutrition Surveys , Prevalence , Tooth, DeciduousABSTRACT
OBJECTIVE: Improving the oral health of Aboriginal children is an Australian priority. Public policy recommends the development of evidence-based, culturally competent oral health promotion programs. Positive health outcomes are more likely for Aboriginal people when programs are co-designed with the community and tailored to local needs. This study aims to determine the impact of a community-led oral health promotion program for Aboriginal children in rural and remote communities. BASIC RESEARCH DESIGN: Consecutive surveys. Baseline data were collected on the oral health of Aboriginal children aged five-12 years in rural and remote communities in Central Northern New South Wales in 2014. Then, an evidence-based oral health promotion program was co-designed with local Aboriginal communities. It included daily toothbrushing, water bottle program, regular application of fluoride varnish, regular distribution of toothbrushes and fluoride toothpaste and dental health education and commenced in 2016 in three schools in the region. In 2018, oral health status and oral hygiene behaviours of participating children were compared against baseline data to evaluate the program. RESULTS: There was a significant reduction in tooth decay, plaque scores and gingivitis. The mean number of teeth affected by tooth decay was 4.13, compared to 5.31 in 2014. An increase was also seen in positive oral hygiene behaviour. CONCLUSIONS: The co-design elements of the program are critical to its success. Engaging local Aboriginal communities to co-design and deliver oral health promotion can reduce the burden of tooth decay experienced by Aboriginal children.
Subject(s)
Health Promotion , Oral Health , Australia , Child , Child, Preschool , Humans , Native Hawaiian or Other Pacific Islander , New South WalesABSTRACT
KNOWLEDGE TRANSFER STATEMENT: Irrespective of country, socially disadvantaged children experience greater levels of preventable dental disease than their more socially advantaged peers. Motivational interviewing (MI) is recognized as a potential intervention tool for reducing prevalence of child dental disease. The challenges of implementing MI in 4 trials involving socially vulnerable children are highlighted in this commentary, with some potential solutions offered.
Subject(s)
Dental Caries , Motivational Interviewing , Child , Humans , Oral Health , Peer GroupABSTRACT
BACKGROUND: The Minamata treaty (2013) enacted a globally binding agreement to phase down amalgam use, which may significantly affect dental care for underserved populations. To comply with the Minamata treaty, strategic approaches need to be implemented to reduce amalgam use while imposing minimal risk on the dental care of the underserved. OBJECTIVES: To establish strategic approaches to reduce amalgam use, the aim of this study is to use a marketing research analysis to determine which patient-related factors influence pediatric dentists' choice of amalgam. METHODS: A survey containing questions regarding amalgam use, perception about the environmental impact of amalgam waste, and hypothetical clinical scenarios of a child with dental caries with varying levels of caries risk and types of dental insurance was developed and pretested. Emails linked to an electronic survey were sent via Qualtrics to all active American Academy of Pediatric Dentistry members (n = 5,101), followed by 3 reminders. Descriptive analysis and choice-based conjoint analysis were performed to investigate trade-offs between selected factors, using SAS version 9.3. RESULTS: Of 892 (17.6%) replies, 850 responses were eligible for analysis. Only 385 (45%) respondents indicated using amalgam, and their responses were analyzed in the conjoint model. Respondents' selection of amalgam varied between 8% and 28% across all the clinical scenarios, with most respondents choosing composite or stainless steel crowns. Conjoint analysis revealed that, while both caries risk and type of insurance affected respondents' decision about amalgam use, caries risk was the driving factor in decision-making for using amalgam. CONCLUSION: These results underscore the importance of prevention and management of risk factors to successfully phase down amalgam use. KNOWLEDGE TRANSFER STATEMENT: Our study applied the marketing research tool, choice-based conjoint analysis, to investigate the relative importance of different factors on dentists' decision-making regarding amalgam use. This study should be of great interest to policy makers when developing strategic approaches to comply with the 2013 United Nations Environment Programme (a.k.a. Minamata treaty) policy recommendations for phase-down of dental amalgam.
Subject(s)
Dental Caries , Dental Restoration, Permanent , Child , Dental Amalgam , Dental Materials , Dentists , Humans , United StatesABSTRACT
OBJECTIVE: This qualitative analysis explores how school staff interacted with a daily in-school toothbrushing program in three schools in rural areas in Central Northern New South Wales, Australia, with a high population of enrolled Aboriginal students. RESEARCH DESIGN: Three focus groups were conducted in the schools. Participants included school teachers and one Aboriginal Oral Health Aide who manage the daily program. Focus groups were conducted, and where permitted, audio-recorded and transcribed verbatim. Thematic analysis was used to analyse the transcripts. This study was granted ethics approval by the New South Wales Aboriginal Health and Medical Research Council (App 1281/17). RESULTS: Four themes were identified: 1) Belief of Program Need and Benefit; 2) Forming routine; 3) Children's responses and 4) Sustainability. School staff embraced the program and valued the need for and benefit of the program for children in their school, seeing it as part of the extended role of the school to promote students' health and well-being. Two important enablers for the program's sustainability emerged; promoting and supporting local school leadership and training existing school staff or local Aboriginal people to manage it. CONCLUSION: Training local Aboriginal people or existing school staff to implement a daily in-school toothbrushing program and facilitating school leadership is an important enabler for sustainable oral health promotion, including in-school toothbrushing programs, in Aboriginal communities.
Subject(s)
Health Services, Indigenous , School Health Services , Toothbrushing , Australia , Child , Humans , Native Hawaiian or Other Pacific Islander , New South WalesABSTRACT
OBJECTIVES: To determine the potential for immunodiagnostic application of two recombinant forms of Clonorchis sinensis omega-class glutathione transferases (rCsGSTo1 and rCsGSTo2) against human small liver-fluke C. sinensis and Opisthorchis viverrini infections. METHODS: Specific antibody levels against rCsGSTo1 and rCsGSTo2 in patients' sera of egg-positive opisthorchiasis (n = 87) and clonorchiasis (n = 120), as well as those in sera from patients with other helminthic infections (n = 252) and healthy controls (n = 40) were retrospectively analysed by ELISA. RESULTS: We observed highly positive correlation coefficients between specific antibody levels against rCsGSTo1 and rCsGSTo2 and egg counts per gramme of faeces (EPG) of patients with opisthorchiasis (n = 87; r = 0.88 for rCsGSTo1 and r = 0.90 for rCsGSTo2). Sera from opisthorchiasis patients whose EPG counts >100 (n = 43) revealed high antibody titres against both antigens. Patients' sera with low EPG counts (<100, n = 44) also exhibited reliable sensitivities of 93.2% and 97.7% for rCsGSTo1 and rCsGSTo2, respectively. Sera from clonorchiasis patients showed sensitivities of 90% (108/120 samples) and 89.2% (107/120 sera) for rCsGSTo1 and rCsGSTo2. Overall diagnostic sensitivities for liver-fluke infections were 92.3% for rCsGSTo1 (191/207 samples) and 93.2% for rCsGSTo2 (193/207 samples). Specificities were 89.7% (rCsGSTo1) and 97.6% (rCsGSTo2). CONCLUSIONS: Detection of specific antibody levels against rCsGSTo1 or rCsGSTo2 might be promising for the serodiagnosis of patients infected with these two phylogenetically close carcinogenic liver-flukes.
Subject(s)
Clonorchiasis/diagnosis , Clonorchis sinensis/enzymology , Glutathione Transferase/blood , Opisthorchiasis/diagnosis , Serologic Tests , Adolescent , Adult , Aged , Aged, 80 and over , Animals , Antibodies, Helminth/blood , Biomarkers/blood , Child , Clonorchiasis/blood , Enzyme-Linked Immunosorbent Assay/methods , Feces/parasitology , Female , Humans , Male , Middle Aged , Opisthorchiasis/blood , Parasite Egg Count , Retrospective Studies , Sensitivity and Specificity , Young AdultABSTRACT
Asparagine (Asn) is a powerful turn-inducer residue, with a large propensity to occupy the second position in the central region of ß-turns of proteins. The present work aims at investigating the role of a local anchoring between the Asn side chain and the main chain in this remarkable property. For this purpose, the H-bonding patterns of an asparagine residue in an isolated protein chain fragment forming a γ- or a ß-turn have been determined using IR/UV double resonance gas phase spectroscopy on laser-desorbed, jet-cooled short models in conjunction with relevant quantum chemistry calculations. These gas phase data provide evidence for an original double anchoring linking the Asn primary amide side chain (SC), which adopts a gauche+ rotameric form, to its main chain (MC) local environment. From both IR spectroscopic evidence (H-bond induced red shifts) and quantum chemistry, Asn SC is found to behave as a stronger H-bond acceptor than donor, resulting in stronger MCâSC H-bonds than SCâMC ones. These gas phase structural data, relevant to a hydrophobic environment, have been used as a reference to assess the anchoring taking place in high resolution crystallized proteins of the Protein Data Bank. This approach reveals that, when the SC adopts a gauche+ orientation, the stronger MCâSC bonds are preserved in many cases whereas the SCâMC bonds are always disrupted, in qualitative agreement with the gas phase ranking of these interactions. Most interestingly, when Asn occupies the second position of central part of a ß-turn (i.e., the very turn-inducer position), the MCâSC H-bonds are also disrupted and replaced by a water-mediated SC to MC anchoring. Owing to the specific features of the hydrated Asn side chain, we propose that it could be a turn precursor structure, able to facilitate turn formation in the early events of the folding process.
Subject(s)
Asparagine/chemistry , Peptides/chemistry , Amides/chemistry , Gases/chemistry , Hydrogen Bonding , Protein Structure, Secondary , Quantum Theory , Spectrophotometry, InfraredABSTRACT
It is unclear whether the reactivation of hepatitis B virus (HBV) influences the prognosis of hepatocellular carcinoma (HCC) after resection in patients with chronic hepatitis B. The aim of this study was to identify the influence of HBV reactivation on the recurrence of hepatitis B-related HCC after curative resection in patients with low viral load (HBV DNA <2000 IU/mL). We retrospectively analysed a total of 130 patients who underwent curative resection for HBV-related early stage HCC (single nodule; <5 cm/two or three nodules; <3 cm) with pre-operative HBV DNA levels <2000 IU/mL with serial HBV DNA tests. The predictive factors including HBV reactivation for the recurrence of HBV-related HCC after curative resection were investigated. Fifty-three patients (41%) had HBV reactivation after resection among 130 patients. HBV reactivation was observed in 22 of 53 patients with undetectable baseline HBV DNA and in 31 of 77 patients with detectable baseline HBV DNA. Cumulative recurrence rates after resection at 1, 2 and 3 years were 17.0%, 23.3% and 31.4%, respectively. The multivariable analysis demonstrated that the risk factors for the recurrence were the presence of microvascular invasion (hazard ratio (HR) 2.62, P = 0.003), multinodularity (HR 4.61, P = 0.005), HBV reactivation after resection (HR 2.03, P = 0.032) and HBeAg positivity (HR 2.06, P = 0.044). HBV reactivation after curative resection is associated with the recurrence of HBV-related HCC in patients with low viral load.
Subject(s)
Carcinoma, Hepatocellular/etiology , Carcinoma, Hepatocellular/surgery , Hepatitis B virus/physiology , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/virology , Liver Neoplasms/etiology , Liver Neoplasms/surgery , Viral Load , Virus Activation , Adult , Aged , Carcinoma, Hepatocellular/pathology , Female , Hepatitis B, Chronic/drug therapy , Humans , Liver Cirrhosis/etiology , Liver Cirrhosis/pathology , Liver Neoplasms/pathology , Male , Middle Aged , Neoplasm Grading , Neoplasm Recurrence, Local , Neoplasm Staging , Postoperative Period , Preoperative Period , Risk Factors , Treatment Outcome , Tumor BurdenABSTRACT
Glutathione peroxidase (GPx; EC 1.11.1.9) is an important antioxidant enzyme that catalyses the reduction of organic and inorganic hydroperoxides to water in oxygen-consuming organisms, using glutathione as an electron donor. Here, we report the characterization of a GPx of Cryptosporidium parvum (CpGPx). CpGPx contained a standard UGU codon for cysteine instead of a UGA opal codon for seleno-cysteine (SeCys) at the active site, and no SeCys insertion sequence (SECIS) motif was identified within the 3'-untranslated region (UTR) of CpGPx, which suggested its selenium-independent nature. In silico and biochemical analyses indicated that CpGPx is a cytosolic protein with a monomeric structure. Recombinant CpGPx was active over a wide pH range and was stable under physiological conditions. It showed a substrate preference against organic hydroperoxides, such as cumene hydroperoxide and t-butyl hydroperoxide, but it also showed activity against inorganic hydroperoxide, hydrogen peroxide. Recombinant CpGPx was not inhibited by potassium cyanide or by sodium azide. The enzyme effectively protected DNA and protein from oxidative damage induced by hydrogen peroxide, and was functionally expressed in various developmental stages of C. parvum. These results collectively suggest the essential role of CpGPx for the parasite's antioxidant defence system.
Subject(s)
Antibodies, Protozoan/immunology , Cryptosporidiosis/parasitology , Cryptosporidium parvum/enzymology , Glutathione Peroxidase/metabolism , Amino Acid Sequence , Animals , Antioxidants/metabolism , Cryptosporidium parvum/drug effects , Cryptosporidium parvum/genetics , Cryptosporidium parvum/immunology , Cytosol/enzymology , Glutathione/metabolism , Glutathione Peroxidase/genetics , Humans , Hydrogen Peroxide/pharmacology , Molecular Sequence Data , Oxidation-Reduction , Oxidative Stress , Phylogeny , Potassium Cyanide/pharmacology , Protein Structure, Tertiary , Protozoan Proteins/genetics , Protozoan Proteins/metabolism , Recombinant Proteins , Sequence Alignment , Sodium Azide/pharmacologyABSTRACT
In mouse tooth development, the roots of the first lower molar develop after crown formation to form 2 cylindrical roots by post-natal day 5. This study compared the morphogenesis and cellular events of the mesial-root-forming (MRF) and bifurcation-forming (BF) regions, located in the mesial and center of the first lower molar, to better define the developmental mechanisms involved in multi-rooted tooth formation. We found that the mesenchyme in the MRF showed relatively higher proliferation than the bifurcation region. This suggested that spatially regulated mesenchymal proliferation is required for creating cylindrical root structure. The mechanism may involve the mesenchyme forming a physical barrier to epithelial invagination of Hertwig's epithelial root sheath. To test these ideas, we cultured roots in the presence of pharmacological inhibitors of microtubule and actin polymerization, nocodazole and cytochalasin-D. Cytochalasin D also inhibits proliferation in epithelium and mesenchyme. Both drugs resulted in altered morphological changes in the tooth root structures. In particular, the nocodazole- and cytochalasin-D-treated specimens showed a loss of root diameter and formation of a single-root, respectively. Immunolocalization and three-dimensional reconstruction results confirmed these mesenchymal cellular events, with higher proliferation in MRF in multi-rooted tooth formation.
Subject(s)
Mesoderm/cytology , Molar/growth & development , Morphogenesis/physiology , Tooth Root/growth & development , Animals , Animals, Newborn , Cell Count , Cell Proliferation/drug effects , Cytochalasin D/pharmacology , Dental Sac/cytology , Dental Sac/growth & development , Enamel Organ/cytology , Enamel Organ/growth & development , Epithelium/drug effects , Epithelium/growth & development , Image Processing, Computer-Assisted/methods , Imaging, Three-Dimensional/methods , Ki-67 Antigen/analysis , Mesoderm/drug effects , Mice , Mice, Inbred ICR , Molar/cytology , Molar/drug effects , Morphogenesis/drug effects , Nocodazole/pharmacology , Nucleic Acid Synthesis Inhibitors/pharmacology , Odontogenesis/drug effects , Odontogenesis/physiology , Organ Culture Techniques , Tooth Root/cytology , Tooth Root/drug effects , Tubulin Modulators/pharmacologyABSTRACT
BACKGROUND: Tricyclic antidepressants have good efficacy in irritable bowel syndrome with diarrhea (IBS-D), but their clinical use is limited by considerations of tolerability. Tianeptine, another antidepressant, acts as a selective serotonin reuptake enhancer. We compared tianeptine with amitriptyline for the treatment of patients with IBS-D. METHODS: We undertook a multicenter, randomized, open-label, non-inferiority clinical study that compared tianeptine with amitriptyline, each in combination with probiotics, for the treatment of IBS-D. Subjects were randomized to receive tianeptine (37.5 mg)/probiotics (Bacillus subtilis + Streptococcus faecium) or amitriptyline (10 mg)/probiotics (Bacillus subtilis + Streptococcus faecium) for 4 weeks. A total of 228 patients were analyzed by the intention-to-treat approach. The primary efficacy endpoint was the proportion of patients who had global relief of IBS symptoms at week 4. The secondary efficacy endpoints were intensity of abdominal pain/discomfort, stool frequency/consistency, quality of life, and overall satisfaction with treatment. KEY RESULTS: At week 4, non-inferiority of the tianeptine group to the amitriptyline group (treatment difference -15.1%; 95% CI -26.6% to -3.8%) was shown, with 81.1% (99 of 122 patients) of the patients in the tianeptine group and 66.0% (70 of 106 patients) in the amitriptyline group reporting global relief of IBS symptoms. The secondary endpoints also demonstrated non-inferiority of the tianeptine group to the amitriptyline group. Adverse events such as dry mouth and constipation were significantly lower in the tianeptine group than the amitriptyline group (P<0.05). CONCLUSIONS & INFERENCES: Tianeptine is not inferior to amitriptyline for treating IBS-D in terms of both efficacy and tolerability.