Achieving global mortality reduction targets and universal health coverage: The impact of COVID-19.

Wenhui Mao and coauthors discuss possible implications of the COVID-19 pandemic for health aspirations in low- and middle-income countries.

A novel locus for exertional dyspnoea in childhood asthma.

Most children diagnosed with asthma have respiratory symptoms such as cough, dyspnoea and wheezing, which are also important markers of overall respiratory function. A decade of genome-wide association studies (GWAS) have investigated genetic susceptibility to asthma itself, but few have focused on important respiratory symptoms that characterise childhood asthma.Using whole-genome sequencing (WGS) data for 894 asthmatic trios from a Costa Rican cohort, we performed family-based association tests (FBATs) to assess the association between genetic variants and multiple asthma-relevant respiratory phenotypes: cough, phlegm, wheezing, exertional dyspnoea and exertional chest tightness. We tested whether genome-wide significant associations were replicated in two additional studies: 1) 286 asthmatic trios from the Childhood Asthma Management Program (CAMP), and 2) 2691 African American current or former smokers from the COPDGene study.In the 894 Costa Rican trios, we identified a genome-wide significant association (p=2.16×10-9) between exertional dyspnoea and the single nucleotide polymorphism (SNP) rs10165869, located on chromosome 2q37.3, that was replicated in the CAMP cohort (p=0.023) with the same direction of association (combined p=3.28×10-10). This association was not found in the African American participants from COPDGene. We also found suggestive evidence for an association between SNP rs10165869 and the atypical chemokine receptor 3 (ACKR3).Our finding encourages the secondary association analysis of a wider range of phenotypes that characterise respiratory symptoms in other airway diseases/studies.

Did the poor gain from India's health policy interventions? Evidence from benefit-incidence analysis, 2004-2018.

BACKGROUND: Health policy interventions were expected to improve access to health care delivery, provide financial risk protection, besides reducing inequities that underlie geographic and socio-economic variation in population access to health care. This article examines whether health policy interventions and accelerated health investments in India during 2004-2018 could close the gap in inequity in health care utilization and access to public subsidy by different population groups. Did the poor and socio-economically vulnerable population gain from such government initiatives, compared to the rich and affluent sections of society? And whether the intended objective of improving equity between different regions of the country been achieved during the policy initiatives? This article attempts to assess and provide robust evidence in the Indian context. METHODS: Employing Benefit-Incidence Analysis (BIA) framework, this paper advances earlier evidence by highlighting estimates of health care utilization, concentration and government subsidy by broader provider categories (public versus private) and across service levels (outpatient, inpatient, maternal, pre-and post-natal services). We used 2 waves of household surveys conducted by the National Sample Survey Organisation (NSSO) on health and morbidity. The period of analysis was chosen to represent policy interventions spanning 2004 (pre-policy) and 2018 (post-policy era). We present this evidence across three categories of Indian states, namely, high-focus states, high-focus north eastern states and non-focus states. Such categorization facilitates quantification of reform impact of policy level interventions across the three groups. RESULTS: Utilisation of healthcare services, except outpatient care visits, accelerated significantly in 2018 from 2004. The difference in utilisation rates between poor and rich (between poorest 20% and richest 20%) had significantly declined during the same period. As far as concentration of healthcare is concerned, the Concentrate Index (CI) underlying inpatient care in public sector fell from 0.07 in 2004 to 0.05 in 2018, implying less pro-rich distribution. The CI in relation to pre-natal, institutional delivery and postnatal services in government facilities were pro-poor both in 2004 and 2018 in all 3 groups of states. The distribution of public subsidy underscoring curative services (inpatient and outpatient) remained pro-rich in 2004 but turned less pro-rich in 2018, measured by CIs which declined sharply across all groups of states for both outpatient (from 0.21 in 2004 to 0.16 in 2018) and inpatient (from 0.24 in 2004 to 0.14 in 2018) respectively. The CI for subsidy on prenatal services declined from approximately 0.01 in 2004 to 0.12 in 2018. In respect to post-natal care, similar results were observed, implying the subsidy on prenatal and post-natal services was overwhelmingly received by poor. The CI underscoring subsidy for institutional delivery although remained positive both in 2018 and 2004, but slightly increased from 0.17 in 2004 to 0.28 in 2018. CONCLUSIONS: Improvement in infrastructure and service provisioning through NHM route in the public facilities appears to have relatively benefited the poor. Yet they received a relatively smaller health subsidy than the rich when utilising inpatient and outpatient health services. Inequality continues to persist across all healthcare services in private health sector. Although the NHM remained committed to broader expansion of health care services, a singular focus on maternal and child health conditions especially in backward regions of the country has yielded desired results.

Heme metabolism genes Downregulated in COPD Cachexia.

INTRODUCTION: Cachexia contributes to increased mortality and reduced quality of life in Chronic Obstructive Pulmonary Disease (COPD) and may be associated with underlying gene expression changes. Our goal was to identify differential gene expression signatures associated with COPD cachexia in current and former smokers. METHODS: We analyzed whole-blood gene expression data from participants with COPD in a discovery cohort (COPDGene, N = 400) and assessed replication (ECLIPSE, N = 114). To approximate the consensus definition using available criteria, cachexia was defined as weight-loss > 5% in the past 12 months or low body mass index (BMI) (< 20 kg/m2) and 1/3 criteria: decreased muscle strength (six-minute walk distance < 350 m), anemia (hemoglobin < 12 g/dl), and low fat-free mass index (FFMI) (< 15 kg/m2 among women and < 17 kg/m2 among men) in COPDGene. In ECLIPSE, cachexia was defined as weight-loss > 5% in the past 12 months or low BMI and 3/5 criteria: decreased muscle strength, anorexia, abnormal biochemistry (anemia or high c-reactive protein (> 5 mg/l)), fatigue, and low FFMI. Differential gene expression was assessed between cachectic and non-cachectic subjects, adjusting for age, sex, white blood cell counts, and technical covariates. Gene set enrichment analysis was performed using MSigDB. RESULTS: The prevalence of COPD cachexia was 13.7% in COPDGene and 7.9% in ECLIPSE. Fourteen genes were differentially downregulated in cachectic versus non-cachectic COPD patients in COPDGene (FDR < 0.05) and ECLIPSE (FDR < 0.05). DISCUSSION: Several replicated genes regulating heme metabolism were downregulated among participants with COPD cachexia. Impaired heme biosynthesis may contribute to cachexia development through free-iron buildup and oxidative tissue damage.

The influence of Azadirachta indica, Melaleuca alternifolia, and Cocos nucifera on Candida albicans strain in tissue conditioner at varying time intervals.

AIM: The search for alternative therapies for oral candidiasis is a necessity and the use of medicinal plants seems to be one such promising solutions. Incorporation of phytotherapeutic agents, Azadirachta indica (neem oil), Melaleuca alternifolia oil (tea tree oil), and Cocos nucifera oil (coconut oil), were tested for their efficacy as antifungal agents against Candida albicans. Next, the efficacy of these three antifungal agents when incorporated in a soft relining material at minimum inhibitory concentration (MIC) was evaluated. SETTINGS AND DESIGN: Evaluative - In-vitro study design. MATERIALS AND METHODS: The MIC against C. albicans ATCC 24433 was calculated for M. alternifolia oil, A. indica oil, and C. nucifera oil using the broth microdilution method. Based on the preliminary screening results for MIC, tissue conditioner samples were prepared to evaluate the zone of inhibition (ZOI) and MIC. Antifungal activity of the MIC of the three oils was assessed and compared by measuring the mean ZOI. Antifungal activity of the three oils was assessed using one-way analysis of variance (ANOVA) and post hoc test. STATISTICAL ANALYSIS USED: Oneway ANOVA and post hoc Tukey honestly significant difference test. RESULTS: Inhibition against C. albicans was exhibited when 20% v/v, 25% v/v, and 15% v/v of C. nucifera oil, M. alternifolia oil, and A. indica oil were used, respectively. The results of ANOVA and post hoc test at the end of 48 h and 7 days suggested that all three oils were significantly different from each other (P = 0.000) and A. indica/neem oil with 15% concentration had the best antifungal activity at the end of 48 h and 7 days. CONCLUSION: The antimycotic activity of M. alternifolia, C. nucifera, and A. indica mixed with the Visco-gel tissue conditioner can be used as an alternative therapy for denture stomatitis.

Barotrauma: Tooth under Pressure.

With the growing number of air passengers, flight attendants, leisure pilots, as well as military and airline pilots, dentists may encounter physiological and pathological phenomena precipitated by high altitude. With the introduction of the self-contained breathing apparatus (SCUBA), many of these manifestations caused by changes in atmospheric pressure were reported in association with diving as well. Limited literature exists on this subject. Hence, this article aims to review literature concerning the classification, etiology and manifestations of barodontalgia, as well as important clinical considerations for its management.

Barotrauma: Tooth Under Pressure.

With the growing number of air passengers, flight attendants, leisure pilots, as well as military and airline pilots, dentists may encounter physiological and pathological phenomena precipitated by high altitude. With the introduction of the self-contained breathing apparatus (SCUBA), many of these manifestations caused by changes in atmospheric pressure were reported in association with diving as well. Limited literature exists on this subject. Hence, this article aims to review literature concerning the classification, etiology and manifestations of barodontalgia, as well as important clinical considerations for its management.

Bilateral implant-retained auricular prosthesis for a patient with congenitally missing ears. A clinical report.

Microtia is a major congenital anomaly of the external ear. It includes a spectrum of deformities from a grossly normal but small ear to the absence of the entire external ear. These deformities account for three in every 10,000 births, with bilaterally missing ears seen in fewer than 10% of all cases. Congenital abnormalities of the ear are unlikely to result in the complete absence of the ears, but the patient presented in this article had bilateral congenitally missing ears. There was loss of anatomic landmarks and alteration of normal bony architecture. Minimal tissue was available for retention; therefore, conventional techniques could not be used for achieving retention. A two-implant-supported auricular prosthesis was planned, but the patient was found to have deficient bone in the implant site. Hence the implants were placed posterior to these sites, and the superstructure was modified to accommodate for this change in position of the implant to ensure the esthetic positioning of the prosthesis.

A finite element analysis of stress distribution in the bone, around the implant supporting a mandibular overdenture with ball/o ring and magnetic attachment.

Today implant dentistry has made great inroads into the treatment modalities that are available in treating an edentulous patient. Popularity of a two implant retained overdenture has created a necessity to examine the various attachment systems being used and the stresses that are transmitted to the alveolar bone. Hence a Three dimensional Finite Element Analysis was done to analyze the stress distribution in the mandibular bone with implant-supported overdenture having Ball/O-ring and Magnet attachments of different diameters. A segment of the anterior region of the mandible was modeled with implant and the overdenture. Four different models were generated having Ball/O-Ring and Magnet Attachments. Forces of 10 N, 35 N and 70 N were applied from the horizontal, vertical and oblique directions respectively and the stress distribution studied. It was concluded that the greatest stress concentrations were seen at the crest of the cortical bone and could be reduced by using smaller sized attachments for implant supported-overdenture.

Integrated bioinformatics analysis identifies established and novel TGFß1-regulated genes modulated by anti-fibrotic drugs.

Fibrosis is a leading cause of morbidity and mortality worldwide. Although fibrosis may involve different organ systems, transforming growth factor-ß (TGFß) has been established as a master regulator of fibrosis across organs. Pirfenidone and Nintedanib are the only currently-approved drugs to treat fibrosis, specifically idiopathic pulmonary fibrosis, but their mechanisms of action remain poorly understood. To identify novel drug targets and uncover potential mechanisms by which these drugs attenuate fibrosis, we performed an integrative 'omics analysis of transcriptomic and proteomic responses to TGFß1-stimulated lung fibroblasts. Significant findings were annotated as associated with pirfenidone and nintedanib treatment in silico via Coremine. Integrative 'omics identified a co-expressed transcriptomic and proteomic module significantly correlated with TGFß1 treatment that was enriched (FDR-p = 0.04) with genes associated with pirfenidone and nintedanib treatment. While a subset of genes in this module have been implicated in fibrogenesis, several novel TGFß1 signaling targets were identified. Specifically, four genes (BASP1, HSD17B6, CDH11, and TNS1) have been associated with pirfenidone, while five genes (CLINT1, CADM1, MTDH, SYDE1, and MCTS1) have been associated with nintedanib, and MYDGF has been implicated with treatment using both drugs. Using the Clue Drug Repurposing Hub, succinic acid was highlighted as a metabolite regulated by the protein encoded by HSD17B6. This study provides new insights into the anti-fibrotic actions of pirfenidone and nintedanib and identifies novel targets for future mechanistic studies.

Novel genetic loci associated with osteoarthritis in multi-ancestry analyses in the Million Veteran Program and UK Biobank.

Osteoarthritis is a common progressive joint disease. As no effective medical interventions are available, osteoarthritis often progresses to the end stage, in which only surgical options such as total joint replacement are available. A more thorough understanding of genetic influences of osteoarthritis is essential to develop targeted personalized approaches to treatment, ideally long before the end stage is reached. To date, there have been no large multiancestry genetic studies of osteoarthritis. Here, we leveraged the unique resources of 484,374 participants in the Million Veteran Program and UK Biobank to address this gap. Analyses included participants of European, African, Asian and Hispanic descent. We discovered osteoarthritis-associated genetic variation at 10 loci and replicated findings from previous osteoarthritis studies. We also present evidence that some osteoarthritis-associated regions are robust to population ancestry. Drug repurposing analyses revealed enrichment of targets of several medication classes and provide potential insight into the etiology of beneficial effects of antiepileptics on osteoarthritis pain.

Genetic variation in genes regulating skeletal muscle regeneration and tissue remodelling associated with weight loss in chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death globally. COPD patients with cachexia or weight loss have increased risk of death independent of body mass index (BMI) and lung function. We tested the hypothesis genetic variation is associated with weight loss in COPD using a genome-wide association study approach. METHODS: Participants with COPD (N = 4308) from three studies (COPDGene, ECLIPSE, and SPIROMICS) were analysed. Discovery analyses were performed in COPDGene with replication in SPIROMICS and ECLIPSE. In COPDGene, weight loss was defined as self-reported unintentional weight loss > 5% in the past year or low BMI (BMI < 20 kg/m2 ). In ECLIPSE and SPIROMICS, weight loss was calculated using available longitudinal visits. Stratified analyses were performed among African American (AA) and Non-Hispanic White (NHW) participants with COPD. Single variant and gene-based analyses were performed adjusting for confounders. Fine mapping was performed using a Bayesian approach integrating genetic association results with linkage disequilibrium and functional annotation. Significant gene networks were identified by integrating genetic regions associated with weight loss with skeletal muscle protein-protein interaction (PPI) data. RESULTS: At the single variant level, only the rs35368512 variant, intergenic to GRXCR1 and LINC02383, was associated with weight loss (odds ratio = 3.6, 95% confidence interval = 2.3-5.6, P = 3.2 × 10-8 ) among AA COPD participants in COPDGene. At the gene level in COPDGene, EFNA2 and BAIAP2 were significantly associated with weight loss in AA and NHW COPD participants, respectively. The EFNA2 association replicated among AA from SPIROMICS (P = 0.0014), whereas the BAIAP2 association replicated in NHW from ECLIPSE (P = 0.025). The EFNA2 gene encodes the membrane-bound protein ephrin-A2 involved in the regulation of developmental processes and adult tissue homeostasis such as skeletal muscle. The BAIAP2 gene encodes the insulin-responsive protein of mass 53 kD (IRSp53), a negative regulator of myogenic differentiation. Integration of the gene-based findings participants with PPI data revealed networks of genes involved in pathways such as Rho and synapse signalling. CONCLUSIONS: The EFNA2 and BAIAP2 genes were significantly associated with weight loss in COPD participants. Collectively, the integrative network analyses indicated genetic variation associated with weight loss in COPD may influence skeletal muscle regeneration and tissue remodelling.

Rehabilitative Impact of Exercise Training on Human Skeletal Muscle Transcriptional Programs in Parkinson's Disease.

Parkinson's disease (PD) is the most common motor neurodegenerative disease, and neuromuscular function deficits associated with PD contribute to disability. Targeting these symptoms, our laboratory has previously evaluated 16-week high-intensity resistance exercise as rehabilitative training (RT) in individuals with PD. We reported significant improvements in muscle mass, neuromuscular function (strength, power, and motor unit activation), indices of neuromuscular junction integrity, total and motor scores on the unified Parkinson's disease rating scale (UPDRS), and total and sub-scores on the 39-item PD Quality of Life Questionnaire (PDQ-39), supporting the use of RT to reverse symptoms. Our objective was to identify transcriptional networks that may contribute to RT-induced neuromuscular remodeling in PD. We generated transcriptome-wide skeletal muscle RNA-sequencing in 5 participants with PD [4M/1F, 67 ± 2 years, Hoehn and Yahr stages 2 (n = 3) and 3 (n = 2)] before and after 16-week high intensity RT to identify transcriptional networks that may in part underpin RT-induced neuromuscular remodeling in PD. Following RT, 304 genes were significantly upregulated, notably related to remodeling and nervous system/muscle development. Additionally, 402 genes, primarily negative regulators of muscle adaptation, were downregulated. We applied the recently developed Pathway-Level Information ExtractoR (PLIER) method to reveal coordinated gene programs (as latent variables, LVs) that differed in skeletal muscle among young (YA) and old (OA) healthy adults and PD (n = 12 per cohort) at baseline and in PD pre- vs. post-RT. Notably, one LV associated with angiogenesis, axon guidance, and muscle remodeling was significantly lower in PD than YA at baseline and was significantly increased by exercise. A different LV annotated to denervation, autophagy, and apoptosis was increased in both PD and OA relative to YA and was also reduced by 16-week RT in PD. Thus, this analysis identified two novel skeletal muscle transcriptional programs that are dysregulated by PD and aging, respectively. Notably, RT has a normalizing effect on both programs in individuals with PD. These results identify potential molecular transducers of the RT-induced improvements in neuromuscular remodeling and motor function that may aid in optimizing exercise rehabilitation strategies for individuals with PD.

Skeletal muscle transcriptional networks linked to type I myofiber grouping in Parkinson's disease.

Parkinson's disease (PD) is a common neurodegenerative disorder impacting cognition, movement, and quality of life in >10 million individuals worldwide. We recently characterized and quantified a skeletal muscle pathology in PD represented by exaggerated type I myofiber grouping presumed to result from denervation-reinnervation processes. Our previous findings indicated that impaired neuromuscular junction integrity may be involved in type I grouping, which is associated with excessive motor unit activation during weight-bearing tasks. In this study, we performed transcriptional profiling to test the hypothesis that type I grouping severity would link to distinct gene expression networks. We generated transcriptome-wide poly(A) RNA-Seq data from skeletal muscle of individuals with PD [n = 12 (9 men, 3 women); 67 ± 2 yr], age- and sex-matched older adults (n = 12; 68 ± 2 yr), and sex-matched young adults (n = 12; 30 ± 1 yr). Differentially expressed genes were evaluated across cohorts. Weighted gene correlation network analysis (WGCNA) was performed to identify gene networks most correlated with indicators of abnormal type I grouping. Among coexpression networks mapping to phenotypes pathologically increased in PD muscle, one network was highly significantly correlated to type I myofiber group size and another to percentage of type I myofibers found in groups. Annotation of coexpressed networks revealed that type I grouping is associated with altered expression of genes involved in neural development, postsynaptic signaling, cell cycle regulation and cell survival, protein and energy metabolism, inflammation/immunity, and posttranscriptional regulation (microRNAs). These transcriptomic findings suggest that skeletal muscle may play an active role in signaling to promote myofiber survival, reinnervation, and remodeling, perhaps to an extreme in PD.NEW & NOTEWORTHY Despite our awareness of the impact of Parkinson's disease (PD) on motor function for over two centuries, limited attention has focused on skeletal muscle. We previously identified type I myofiber grouping, a novel indicator of muscle dysfunction in PD, presumably a result of heightened rates of denervation/reinnervation. Using transcriptional profiling to identify networks associated with this phenotype, we provide insight into potential mechanistic roles of skeletal muscle in signaling to promote its survival in PD.

A cross-sectional survey of the models in Bihar and Tamil Nadu, India for pooled procurement of medicines.

BACKGROUND: In India, access to medicine in the public sector is significantly affected by the efficiency of the drug procurement system and allied processes and policies. This study was conducted in two socioeconomically different states: Bihar and Tamil Nadu. Both have a pooled procurement system for drugs but follow different models. In Bihar, the volumes of medicines required are pooled at the state level and rate contracted (an open tender process invites bidders to quote for the lowest rate for the list of medicines), while actual invoicing and payment are done at district level. In Tamil Nadu, medicine quantities are also pooled at state level but payments are also processed at state level upon receipt of laboratory quality-assurance reports on the medicines. METHODS: In this cross-sectional survey, a range of financial and non-financial data related to procurement and distribution of medicine, such as budget documents, annual reports, tender documents, details of orders issued, passbook details and policy and guidelines for procurement were analysed. In addition, a so-called ABC analysis of the procurement data was done to to identify high-value medicines. RESULTS: It was observed that Tamil Nadu had suppliers for 100% of the drugs on their procurement list at the end of the procurement processes in 2006, 2007 and 2008, whereas Bihar's procurement agency was only able to get suppliers for 56%, 59% and 38% of drugs during the same period. Further, it was observed that Bihar's system was fuelling irrational procurement; for example, fluconazole (antifungal) alone was consuming 23.4% of the state's drug budget and was being procured by around 34% of the districts during 2008-2009. Also, the ratios of procurement prices for Bihar compared with Tamil Nadu were in the range of 1.01 to 22.50. For 50% of the analysed drugs, the price ratio was more than 2, that is, Bihar's procurement system was procuring the same medicines at more than twice the prices paid by Tamil Nadu. CONCLUSION: Centralized, automated pooled procurement models like that of Tamil Nadu are key to achieving the best procurement prices and highest possible access to medicines.

Influence of the Anx7 (+/-) knockout mutation and fasting stress on the genomics of the mouse adrenal gland.

The Anx7 gene codes for a Ca(2+)/GTPase with calcium channel and membrane fusion properties that has been proposed to regulate exocytotic secretion in chromaffin and other cell types. We have previously reported that the homozygous Anx7 (+/-) knockout mouse has an embryonically lethal phenotype. However, the viable heterozygous Anx7 (+/-) mouse displays a complex phenotype that includes adrenal gland hypertrophy, chromaffin cell hyperplasia, and defective IP(3) receptor (IP(3)R) expression. To search for a molecular basis for this phenotype, we have used cDNA microarray technology and have challenged control and mutant mice with fed or fasting conditions. We report that in the absence of the Anx7/IP(3)R signaling system, the cells in the adrenal gland are unable to discriminate between the fed and fasted states, in vivo. In control chromaffin cells, fasting is accompanied by an increased expression of structural genes for chromaffin cell contents, including chromogranin A and B, and DbetaH. There are also genes whose expression is specifically reduced. However, the Anx7 (+/-) mutation results in sustained expression of these nutritionally sensitive genes. We hypothesize that the calcium signaling defect due to the missing IP(3)R may be responsible for the global effects of the mutation on nutritionally sensitive genes. We further hypothesize that the tonically elevated expression of chromogranin A, a reportedly master control "switch" for dense core granule formation, may contribute to the process driving glandular hypertrophy and chromaffin cell hyperplasia in the Anx7 (+/-) mutant mouse.

Universal access to medicines: evidence from Rajasthan, India.

India has outlined its commitment to achieving universal health coverage and several states in India are rolling out strategies to support this aim. In 2011, Rajasthan implemented an ambitious universal access to medicines programme based on a centralized procurement and decentralized distribution model. In terms of the three dimensions of universal health coverage, the scheme has made significant positive strides within a short period of implementation. The key objectives of this paper are to assess the likely implications of providing universal access to essential medicines in Rajasthan, which has a population of 70 million. Primary field-level data were obtained from 112 public health-care facilities using multistage random sampling. National Sample Survey Organization data and health system data were also analysed. The per capita health expenditure during the pre-reform period was estimated to be ₹5.7 and is now close to ₹50. Availability of essential medicines was encouraging and utilization of public facilities had increased. With additional per capita annual investment of ₹43, the scheme has brought about several improvements in the delivery of essential services and increased utilization of public facilities in the state and, as a result, enhanced efficiency of the system. Although there was an attempt to convert the scheme into a targeted one with the change in government, strong resistance from the civil society resulted in such efforts being defeated and the universality of the scheme has been retained.

Force transfer and stress distribution in an implant-supported overdenture retained with a hader bar attachment: a finite element analysis.

Background and Objectives. A key factor for the long-term function of a dental implant is the manner in which stresses are transferred to the surrounding bone. The effect of adding a stiffener to the tissue side of the Hader bar helps to reduce the transmission of the stresses to the alveolar bone. But the ideal thickness of the stiffener to be attached to the bar is a subject of much debate. This study aims to analyze the force transfer and stress distribution of an implant-supported overdenture with a Hader bar attachment. The stiffener of the bar attachments was varied and the stress distribution to the bone around the implant was studied. Methods. A CT scan of edentulous mandible was used and three models with 1, 2, and 3 mm thick stiffeners were created and subjected to loads of emulating the masticatory forces. These different models were analyzed by the Finite Element Software (Ansys, Version 8.0) using von Mises stress analysis. Results. The results showed that the maximum stress concentration was seen in the neck of the implant for models A and B. In model C the maximum stress concentration was in the bar attachment making it the model with the best stress distribution, as far as implant failures are concerned. Conclusion. The implant with Hader bar attachment with a 3 mm stiffener is the best in terms of stress distribution, where the stress is concentrated at the bar and stiffener regions.

Crowns to create esthetics for mal-aligned central incisors: a case report.

This case report describes the smile design of crowded upper central anteriors in a female patient aged 25 years. The patient wanted the correction to be completed in a short period of time. A smile design schedule was drawn up involving root canal treatment of the central incisors and placing posts in both the teeth. All ceramic crowns were then fabricated to establish a very satisfactory and pleasing esthetics.

Nanodentistry: A Paradigm Shift-from Fiction to Reality.

Nanodentistry is an emerging field with significant potential to yield new generation of technologically advanced clinical tools and devices for oral healthcare. Nanoscale topology and quantitative biomechanical or biophysical analysis of dental surfaces are of significant interest. In particular, using Atomic force microscopy techniques-diseases such as dental caries, tooth hypersensitivity, and oral cancer can be quantified based on morphological, biophysical and biochemical nanoscale properties of tooth surface itself and dental materials or oral fluids such as saliva. An outlook on future "nanodentistry" developments such as saliva exosomes based diagnostics, designing biocompatible, antimicrobial dental implants and personalized dental healthcare is presented. This article examines current applications of nanotechnology alongside proposed applications in the future and aims to demonstrate that, as well as a good deal of science fiction, there is some tangible science fact emerging from this novel multidisciplinary science.