Showing papers by "University of Peradeniya published in 2016"

The global burden of injury: incidence, mortality, disability-adjusted life years and time trends from the Global Burden of Disease study 2013

Abstract: Background The Global Burden of Diseases (GBD), Injuries, and Risk Factors study used the disability-adjusted life year (DALY) to quantify the burden of diseases, injuries, and risk factors. This paper provides an overview of injury estimates from the 2013 update of GBD, with detailed information on incidence, mortality, DALYs and rates of change from 1990 to 2013 for 26 causes of injury, globally, by region and by country. Methods Injury mortality was estimated using the extensive GBD mortality database, corrections for ill-defined cause of death and the cause of death ensemble modelling tool. Morbidity estimation was based on inpatient and outpatient data sets, 26 cause-of-injury and 47 nature-of-injury categories, and seven follow-up studies with patient-reported long-term outcome measures. Results In 2013, 973 million (uncertainty interval (UI) 942 to 993) people sustained injuries that warranted some type of healthcare and 4.8 million (UI 4.5 to 5.1) people died from injuries. Between 1990 and 2013 the global age-standardised injury DALY rate decreased by 31% (UI 26% to 35%). The rate of decline in DALY rates was significant for 22 cause-of-injury categories, including all the major injuries. Conclusions Injuries continue to be an important cause of morbidity and mortality in the developed and developing world. The decline in rates for almost all injuries is so prominent that it warrants a general statement that the world is becoming a safer place to live in. However, the patterns vary widely by cause, age, sex, region and time and there are still large improvements that need to be made.

Global and national burden of diseases and injuries among children and adolescents between 1990 and 2013: findings from the global burden of disease 2013 study.

Abstract: Importance The literature focuses on mortality among children younger than 5 years. Comparable information on nonfatal health outcomes among these children and the fatal and nonfatal burden of diseases and injuries among older children and adolescents is scarce. Objective To determine levels and trends in the fatal and nonfatal burden of diseases and injuries among younger children (aged Evidence Review Data from vital registration, verbal autopsy studies, maternal and child death surveillance, and other sources covering 14 244 site-years (ie, years of cause of death data by geography) from 1980 through 2013 were used to estimate cause-specific mortality. Data from 35 620 epidemiological sources were used to estimate the prevalence of the diseases and sequelae in the GBD 2013 study. Cause-specific mortality for most causes was estimated using the Cause of Death Ensemble Model strategy. For some infectious diseases (eg, HIV infection/AIDS, measles, hepatitis B) where the disease process is complex or the cause of death data were insufficient or unavailable, we used natural history models. For most nonfatal health outcomes, DisMod-MR 2.0, a Bayesian metaregression tool, was used to meta-analyze the epidemiological data to generate prevalence estimates. Findings Of the 7.7 (95% uncertainty interval [UI], 7.4-8.1) million deaths among children and adolescents globally in 2013, 6.28 million occurred among younger children, 0.48 million among older children, and 0.97 million among adolescents. In 2013, the leading causes of death were lower respiratory tract infections among younger children (905 059 deaths; 95% UI, 810 304-998 125), diarrheal diseases among older children (38 325 deaths; 95% UI, 30 365-47 678), and road injuries among adolescents (115 186 deaths; 95% UI, 105 185-124 870). Iron deficiency anemia was the leading cause of years lived with disability among children and adolescents, affecting 619 (95% UI, 618-621) million in 2013. Large between-country variations exist in mortality from leading causes among children and adolescents. Countries with rapid declines in all-cause mortality between 1990 and 2013 also experienced large declines in most leading causes of death, whereas countries with the slowest declines had stagnant or increasing trends in the leading causes of death. In 2013, Nigeria had a 12% global share of deaths from lower respiratory tract infections and a 38% global share of deaths from malaria. India had 33% of the world’s deaths from neonatal encephalopathy. Half of the world’s diarrheal deaths among children and adolescents occurred in just 5 countries: India, Democratic Republic of the Congo, Pakistan, Nigeria, and Ethiopia. Conclusions and Relevance Understanding the levels and trends of the leading causes of death and disability among children and adolescents is critical to guide investment and inform policies. Monitoring these trends over time is also key to understanding where interventions are having an impact. Proven interventions exist to prevent or treat the leading causes of unnecessary death and disability among children and adolescents. The findings presented here show that these are underused and give guidance to policy makers in countries where more attention is needed.

Convergence in the temperature response of leaf respiration across biomes and plant functional types

Abstract: Plant respiration constitutes a massive carbon flux to the atmosphere, and a major control on the evolution of the global carbon cycle. It therefore has the potential to modulate levels of climate change due to the human burning of fossil fuels. Neither current physiological nor terrestrial biosphere models adequately describe its short-term temperature response, and even minor differences in the shape of the response curve can significantly impact estimates of ecosystem carbon release and/or storage. Given this, it is critical to establish whether there are predictable patterns in the shape of the respiration–temperature response curve, and thus in the intrinsic temperature sensitivity of respiration across the globe. Analyzing measurements in a comprehensive database for 231 species spanning 7 biomes, we demonstrate that temperature-dependent increases in leaf respiration do not follow a commonly used exponential function. Instead, we find a decelerating function as leaves warm, reflecting a declining sensitivity to higher temperatures that is remarkably uniform across all biomes and plant functional types. Such convergence in the temperature sensitivity of leaf respiration suggests that there are universally applicable controls on the temperature response of plant energy metabolism, such that a single new function can predict the temperature dependence of leaf respiration for global vegetation. This simple function enables straightforward description of plant respiration in the land-surface components of coupled earth system models. Our cross-biome analyses shows significant implications for such fluxes in cold climates, generally projecting lower values compared with previous estimates.

Physical activity and obesity: what we know and what we need to know.

Abstract: Creating a negative energy balance by decreasing caloric consumption and increasing physical activity is a common strategy used to treat obesity. A large number of review and original research papers have considered the role of physical activity in weight loss and maintenance. However, their conclusions are at times conflicting. In this review, we have critically evaluated the findings of systematic reviews and meta-analyses and supplemented their conclusions with recently published, high-quality clinical trials. We have eliminated studies that were methodologically flawed in an attempt to reduce the ambiguity in the literature. We further sought, through selective review of these publications, to isolate the effects of various types of exercise, independent of dietary interventions, to further clarify their independent contributions. Thus, our review describes (i) combined calorie restriction with physical activity interventions, (ii) physical activity interventions without calorie restriction and (iii) the role of physical activity on maintenance of weight loss. Through this critical examination of the literature, we have provided conclusions to address certain ambiguities regarding the role of physical activity in obesity treatment that will inform clinical practice. We have also identified several long-standing gaps in knowledge that will inform future research.

Throughput Analysis and Optimization of Wireless-Powered Multiple Antenna Full-Duplex Relay Systems

Abstract: We consider a full-duplex (FD) decode-and-forward system in which the time-switching protocol is employed by the multiantenna relay to receive energy from the source and transmit information to the destination. The instantaneous throughput is maximized by optimizing receive and transmit beamformers at the relay and the time-split parameter. We study both optimum and suboptimum schemes. The reformulated problem in the optimum scheme achieves closed-form solutions in terms of transmit beamformer for some scenarios. In other scenarios, the optimization problem is formulated as a semidefinite relaxation problem and a rank-one optimum solution is always guaranteed. In the suboptimum schemes, the beamformers are obtained using maximum ratio combining, zero-forcing, and maximum ratio transmission. When beamformers have closed-form solutions, the achievable instantaneous and delay-constrained throughput are analytically characterized. Our results reveal that beamforming increases both the energy harvesting and loop interference suppression capabilities at the FD relay. Moreover, simulation results demonstrate that the choice of the linear processing scheme as well as the time-split plays a critical role in determining the FD gains.

A test of the ‘one‐point method’ for estimating maximum carboxylation capacity from field‐measured, light‐saturated photosynthesis

Abstract: Simulations of photosynthesis by terrestrial biosphere models typically need a specification of the maximum carboxylation rate (Vcmax ). Estimating this parameter using A-Ci curves (net photosynthesis, A, vs intercellular CO2 concentration, Ci ) is laborious, which limits availability of Vcmax data. However, many multispecies field datasets include net photosynthetic rate at saturating irradiance and at ambient atmospheric CO2 concentration (Asat ) measurements, from which Vcmax can be extracted using a 'one-point method'. We used a global dataset of A-Ci curves (564 species from 46 field sites, covering a range of plant functional types) to test the validity of an alternative approach to estimate Vcmax from Asat via this 'one-point method'. If leaf respiration during the day (Rday ) is known exactly, Vcmax can be estimated with an r(2) value of 0.98 and a root-mean-squared error (RMSE) of 8.19 μmol m(-2) s(-1) . However, Rday typically must be estimated. Estimating Rday as 1.5% of Vcmax, we found that Vcmax could be estimated with an r(2) of 0.95 and an RMSE of 17.1 μmol m(-2) s(-1) . The one-point method provides a robust means to expand current databases of field-measured Vcmax , giving new potential to improve vegetation models and quantify the environmental drivers of Vcmax variation.

Drinking water quality and chronic kidney disease of unknown etiology (CKDu): synergic effects of fluoride, cadmium and hardness of water.

Abstract: High prevalence of chronic kidney disease of unknown etiology (CKDu) in some regions of the world is suspected mainly due to a toxin-mediated renal failure We examined the incidence of CKDu and potable chemical water quality in a CKDu-affected region This region has been identified as a high-risk zone for CKDu (location: latitude: 83500°–90000°, longitude: 803833°–813000°, North Central Province, NCP, Sri Lanka) by the World Health Organization (WHO) However, within this macro-region, small pockets of CKDu non-prevalence zones do exist; notably, the residents in those pockets consume spring water Therefore, the drinking water quality of four areas, namely high-CKDu-prevalence areas (zone I), low-CKDu-prevalence area (zone II), the CKDu-free isolated pockets (zone III) and control areas (controls) were examined for F, Al, Cd, and As, and hardness and the statistical analysis were carried out to probe possible correlations among these parameters The fluoride and hardness concentrations of water in zone III and control areas are much lower compared to zones I and II, and the water hardness is ~61 mg/L CaCO3 In zones I and II, the harness of drinking water is ~121–180 mg/L CaCO3; however, Al, Cd and As concentrations are almost comparable and below WHO recommendations In most of the locations in zones I and II, the F concentration in drinking water is higher than the WHO recommendations The peculiar distribution patterns of CKDu point to a synergic effect of trace elements in water for etiology of the disease

In-vitro alpha amylase inhibitory activity of the leaf extracts of Adenanthera pavonina.

Abstract: Diabetes has caused a major burden to the health sector in the developing countries and has shown an increasing trend among the urban population. It is estimated that most patients are with type II diabetes which could be easily treated with dietary changes, exercise, and medication. Sri Lanka carries a long history ayurvedic medicine where it uses the plant for treating many diseases. Therefore it is important to screen medicinal plants scientifically so they could be used safely and effectively in the traditional medical system and also be used for further investigations. Adenanthera pavonina is a plant used in the Ayurvedic medical system in Sri Lanka for treating many diseases including diabetics. We evaluated the anti-diabetic properties and the antioxidant properties of Adenanthera pavonina leaves. The methanol extract of the leaves was sequentially extracted with petroleum ether and thereafter was partitioned between EtOAc, and water. The α-amylase inhibition assay was performed using the 3,5- dinitrosalicylic acid method. The antioxidant activities were measured using the DPPH free radical scavenging activity and the total phenolic content using Folin-Ciocalteu’s reagent. The cytotoxicity of the extract was evaluated using the Brine shrimp bioassay. The IC50 values of α amylase inhibitory activity of MeOH, EtOAc, petroleum ether, and water were 16.16 ± 2.23, 59.93 ± 0.25, 145.49 ± 4.86 and 214.85 ± 9.72 μg/ml respectively and was similar to that of Acarbose (18.63 ± 1.21 (μg/ml). Antioxidant activities were also determined and the EtOAc fraction showed the highest total phenolic content (34. 62 ± 1.14 mg/g extract) and the highest DPPH scavenging activity with an IC50 of 249.92 ± 3.35 μg/ml. The leaf extracts of Adenanthera pavonina exhibit remarkable α-amylase inhibitory activity in the crude methanolic extract. Hence leaves of Adenanthera pavonina has a potential to be used as a regular green vegetable and also be investigated further in isolating pure compounds with anti-diabetic activity.

Mapping the Risk of Snakebite in Sri Lanka - A National Survey with Geospatial Analysis.

Abstract: Background There is a paucity of robust epidemiological data on snakebite, and data available from hospitals and localized or time-limited surveys have major limitations. No study has investigated the incidence of snakebite across a whole country. We undertook a community-based national survey and model based geostatistics to determine incidence, envenoming, mortality and geographical pattern of snakebite in Sri Lanka. Methodology/Principal Findings The survey was designed to sample a population distributed equally among the nine provinces of the country. The number of data collection clusters was divided among districts in proportion to their population. Within districts clusters were randomly selected. Population based incidence of snakebite and significant envenoming were estimated. Model-based geostatistics was used to develop snakebite risk maps for Sri Lanka. 1118 of the total of 14022 GN divisions with a population of 165665 (0.8%of the country’s population) were surveyed. The crude overall community incidence of snakebite, envenoming and mortality were 398 (95% CI: 356–441), 151 (130–173) and 2.3 (0.2–4.4) per 100000 population, respectively. Risk maps showed wide variation in incidence within the country, and snakebite hotspots and cold spots were determined by considering the probability of exceeding the national incidence. Conclusions/Significance This study provides community based incidence rates of snakebite and envenoming for Sri Lanka. The within-country spatial variation of bites can inform healthcare decision making and highlights the limitations associated with estimates of incidence from hospital data or localized surveys. Our methods are replicable, and these models can be adapted to other geographic regions after re-estimating spatial covariance parameters for the particular region. Author Summary Snakebite is a neglected tropical disease which mainly affects the rural poor in tropical countries. There is little reliable data on snakebite, which makes it difficult to estimate the true disease burden. Hospital statistics underestimate numbers of snakebites because a significant proportion of victims in tropical countries seek traditional treatments. On the other hand, time limited or localized surveys may be inaccurate as they may underestimate or overestimate numbers depending on when and where they are performed. To get a truer picture of the situation in Sri Lanka, where snakebites are an important cause of hospital admission, we undertook an island-wide community survey to determine the number of bites, envenomings and deaths due to snakebite in the previous 12 months. We found that there were more than 80,000 bites, 30,000 envenomings and 400 deaths due to snakebite, much more than claimed by official statistics. There was variation in numbers of bites and envenomings in different parts of the country and, using the data from our survey, we were able develop snakebite risk maps to identify snakebite hotspots and cold spots in the country. These maps would be useful for healthcare decision makers to allocate resources to manage snakebite in the country. We used free and open source software and replicable methods, which we believe can be adopted to other regions where snakebite is a public health problem.

Oral submucous fibrosis: a historical perspective and a review on etiology and pathogenesis

Abstract: Oral submucous fibrosis (OSF) is a chronic, insidious disease characterized by progressive submucosal fibrosis of the oral cavity and the oropharynx. People affected by this disease mostly live in south Asia, but migrants from these countries to the United States and Europe may present with OSF. We provide a historical background of the disease, and the objective of this review is to update the current knowledge on the etiology and etiopathogenesis of OSF.

Residential Appliance Identification Based on Spectral Information of Low Frequency Smart Meter Measurements

Abstract: A nonintrusive load monitoring (NILM) method for residential appliances based on uncorrelated spectral components of an active power consumption signal is presented. This method utilizes the Karhunen Loeve expansion to breakdown the active power signal into subspace components (SCs) so as to construct a unique information rich appliance signature. Unlike existing NILM techniques that rely on multiple measurements at high sampling rates, this method works effectively with a single active power measurement taken at a low sampling rate. After constructing the signature data base, SC level power conditions were introduced to reduce the number of possible appliance combinations prior to applying the maximum a posteriori estimation. Then, an appliances matching algorithm was presented to identify the turned-on appliance combination in a given time window. After identifying the turned-on appliance combination, an energy estimation algorithm was introduced to disaggregate the energy contribution of each individual appliance in that combination. The proposed NILM method was validated by using two public databases: 1) tracebase; and 2) reference energy disaggregation data set. The presented results demonstrate the ability of the proposed method to accurately identify and disaggregate individual energy contributions of turned-on appliance combinations in real households.

Impact of paraquat regulation on suicide in South Korea

Abstract: BACKGROUND: Ingestion of pesticides (mainly paraquat) accounted for one-fifth of suicides in South Korea in 2006-10. We investigated the effect on suicide mortality of regulatory action, culminating in a ban on paraquat in South Korea in 2011-12. METHODS: We calculated age-standardized method-specific suicide mortality rates among people aged ≥15 in South Korea (1983-2013) using registered death data. Negative binomial regression was used to estimate changes in the rate and number of pesticide suicides in 2013, compared with those expected based on previous trends (2003-11). RESULTS: Pesticide suicide mortality halved from 5.26 to 2.67 per 100 000 population between 2011 and 2013. Compared with the number expected based on previous trends, the regulations were followed by an estimated 847 [95% confidence interval (CI) -1180 to -533] fewer pesticide suicides, a 37% reduction in rates (rate ratio = 0.63, 95% CI 0.55 to 0.73) in 2013. The decline in pesticide suicides after the regulations was seen in all age/sex/geographical groups. The absolute reduction in the number of suicides was greatest among men, the elderly and in rural areas. The reduction in pesticide suicides contributed to 56% of the decline in overall suicides that occurred between 2011 and 2013. There was no impact of the regulations on crop yield. CONCLUSIONS: The regulation of paraquat in South Korea in 2011-12 was associated with a reduction in pesticide suicide. Further legislative interventions to prevent the easy availability of highly lethal suicide methods are recommended for reducing the number of suicides worldwide. Language: en

MiRNA Transcriptome Profiling of Spheroid-Enriched Cells with Cancer Stem Cell Properties in Human Breast MCF-7 Cell Line

Abstract: Breast cancer is the second leading cause of cancer-related mortality worldwide as most patients often suffer cancer relapse. The reason is often attributed to the presence of cancer stem cells (CSCs). Recent studies revealed that dysregulation of microRNA (miRNA) are closely linked to breast cancer recurrence and metastasis. However, no specific study has comprehensively characterised the CSC characteristic and miRNA transcriptome in spheroid-enriched breast cells. This study described the generation of spheroid MCF-7 cell in serum-free condition and the comprehensive characterisation for their CSC properties. Subsequently, miRNA expression differences between the spheroid-enriched CSC cells and their parental cells were evaluated using next generation sequencing (NGS). Our results showed that the MCF-7 spheroid cells were enriched with CSCs properties, indicated by the ability to self-renew, increased expression of CSCs markers, and increased resistance to chemotherapeutic drugs. Additionally, spheroid-enriched CSCs possessed greater cell proliferation, migration, invasion, and wound healing ability. A total of 134 significantly (p<0.05) differentially expressed miRNAs were identified between spheroids and parental cells using miRNA-NGS. MiRNA-NGS analysis revealed 25 up-regulated and 109 down-regulated miRNAs which includes some miRNAs previously reported in the regulation of breast CSCs. A number of miRNAs (miR-4492, miR-4532, miR-381, miR-4508, miR-4448, miR-1296, and miR-365a) which have not been previously reported in breast cancer were found to show potential association with breast cancer chemoresistance and self-renewal capability. The gene ontology (GO) analysis showed that the predicted genes were enriched in the regulation of metabolic processes, gene expression, DNA binding, and hormone receptor binding. The corresponding pathway analyses inferred from the GO results were closely related to the function of signalling pathway, self-renewability, chemoresistance, tumorigenesis, cytoskeletal proteins, and metastasis in breast cancer. Based on these results, we proposed that certain miRNAs identified in this study could be used as new potential biomarkers for breast cancer stem cell diagnosis and targeted therapy.

Statistical 3-D Beamforming for Large-Scale MIMO Downlink Systems Over Rician Fading Channels

Abstract: In this paper, we investigate a downlink transmission algorithm for single-cell multiuser systems with two-dimensional (2-D) large-scale antenna array at the base station (BS) over Rician fading channels. We first derive some properties of the channel’s line-of-sight (LOS) component in the large-scale antenna array scenario. Next, based on these properties and under the assumption of only statistical channel state information (CSI), i.e., the LOS component and Rician $K$ -factor, at the BS, we derive the optimal beamforming vector for each user in maximizing an approximation of the ergodic sum rate. The main guidelines for user scheduling are also presented. Then, a three-dimensional (3-D) beamforming downlink transmission algorithm exploiting only the statistical CSI of each user is proposed. For this algorithm, we derive an exact analytical closed-form expression for the achievable ergodic rate and present tractable approximations. Based on our analysis, we gain some valuable insights. The proposed algorithm is shown to perform well in achieving considerable sum rate while requiring much less CSI at the BS. It requires three scalar values at the BS for each user, and can achieve an ergodic sum rate closer to the ergodic sum rate achieved by the matched-filter precoding with perfect CSI at the BS.

Processor Design for Soft Errors: Challenges and State of the Art

Abstract: Today, soft errors are one of the major design technology challenges at and beyond the 22nm technology nodes. This article introduces the soft error problem from the perspective of processor design. This article also provides a survey of the existing soft error mitigation methods across different levels of design abstraction involved in processor design, including the device level, the circuit level, the architectural level, and the program level.

Descriptive study of 896 Oral squamous cell carcinomas from the only University based Oral Pathology Diagnostic Service in Sri Lanka

Abstract: The main objective of this study was to describe selected clinico-pathological characteristics of Oral Squamous Cell Carcinoma (OSCC) in Sri-Lanka. The study sample comprised of eight hundred and ninety six biopsies diagnosed as OSCC. The clinical and histopathological features were analyzed using the Chi-square test. Of the 896 biopsies, 801 were primary OSCCs, while 95 were recurrent OSCCs. Majority of the patients (78 %) were in the 5th to 7th decades of life and showed a male predilection. The buccal mucosa was the commonest site of primary OSCC comprising of 43 % of the sample. Of the primary OSCCs, with known TNM stage, 86 % were in stage 3&4 and majority (59 %) of stage 4 tumours showed tumour at one or more excision margins. Of the recurrent OSCC, 46 % developed their recurrences within one year of the excision of the primary tumour. In Sri-Lanka, OSCC is a major problem. Only half the patients had completely excised tumours (with clearance of >5 mm at all excision margins) at operation, and recurrences appeared early. This data should be considered in the future management policy of OSCC in Sri-Lanka.

Adsorption of Cd2+ and Pb2+ onto coconut shell biochar and biochar-mixed soil.

Abstract: Permeable reactive barrier (PRB) systems containing effective and low-cost adsorbents for heavy metals are expected to function as in situ treatment methods for leachate from waste landfills and contaminated groundwater surrounding the landfills in developing countries. This study was conducted to characterize the adsorption of Cd2+ and Pb2+ onto coconut shell biochar (fine granules), a local soil from Sri Lanka (Entisol), and a biochar-mixed soil (1:1 mixture of biochar and soil) as potential adsorbents for PRB systems. Batch experiments were carried out to investigate the effects of solution pH, contact time, initial ion concentration, and competitive ions on the Cd2+ and Pb2+ adsorption. Results showed that the adsorption kinetics of Cd2+ and Pb2+ onto all adsorbents were well described by the pseudo second order kinetics model and that adsorption isotherms followed the Langmuir model. In the range of pH ≥3, the initial solution pH had a minor effect on efficiency of metal removal and the removal of metals mostly exceeded 80 % for all adsorbents. Measured maximum adsorptions onto soil and biochar-mixed soil were 30.1 mmol/g for Cd2+ and 44.8–46.7 mmol/g for Pb2+. These adsorption capacities are similar to or higher than the values of biosorbents tested for wastewater treatment in previous studies, suggesting our tested materials would be useful as adsorbents of Cd2+ and Pb2+ in PRB systems. Additional analysis by scanning electron microscopy linked with energy dispersive X-ray revealed that both Cd2+ and Pb2+ exhibited high adsorption affinity towards soil particles while adsorbing randomly to biochar granules.

Candida-bacteria interactions: Their impact on human disease

Abstract: Candida species are the most common commensal fungus that coexists with hundreds of species of bacteria in the human body. Between 24 and 70% of humans harbor Candida species in various body niches, including the oral and vaginal mucosa and the skin ( 1 ). Out of over 150 Candida species, Candida albicans is the principal pathogenic species that causes infections, especially in patient populations with immune dysfunction due to HIV infection, malignancy, immunosuppressive therapy, and organ transplantation. Therefore, these opportunistic infections of Candida in topical or systemic forms have become widespread and account for 8 to 10% of bloodstream infections in hospitals ( 2 ). Nearly 70% of denture wearers experience denture stomatitis, or inflammation of oral mucosa covered by denture prostheses, with C. albicans being a primary etiological factor ( 3 , 4 ). Almost 75% of the female population has experienced an episode of vulvovaginal candidiasis at least once in their lifetime, and many have recurring episodes ( 5 ). In many of these conditions, there is a phenotypic change for Candida from harmless commensal to invasive pathogen. Adhesion to various surfaces, morphogenesis, phenotypic and genotypic switching, and production of lytic enzymes are major virulence mechanisms facilitating this conversion ( 6 ). However, properties of the host are also commiserate in enabling Candida to act as an invasive pathogen since compromise in the interleukin-17 (IL-17)/Th17 arm of the host immune response (e.g., AIDS, Job’s syndrome, etc.) or an imbalance in the host microbiome ( 7 ) both can contribute to candidiasis ( 7 ). During this shift, commensal or transient organisms living with Candida species in various locations may play diverse roles in the process of pathogenesis; environmental bacteria may also be introduced via catheters, cannulae, and prosthetic appliances and interact with the already present Candida. Such interactions may be detrimental to the health of the human host, leading to mortality.

Oral submucous fibrosis: review on mechanisms of malignant transformation.

Abstract: Research studies focusing on various aspects of carcinogenesis in the background of fibrosis have advanced significantly in the recent past, allowing us to understand the mechanisms involved in malignant transformation of oral submucous fibrosis (OSF), the most prevalent potentially malignant oral disorder in South Asia. The role of areca nut as a carcinogen has been proven beyond doubt, with a large number of animal studies demonstrating its carcinogenicity, mutagenicity, and genotoxicity. Studies on the molecules implicated in cell cycle regulation, hypoxia, processes leading to DNA double-strand breaks, senescence, and many other pathways related to carcinogenesis have shown ample evidence for the malignant transformation in OSF induced by areca nut. More importantly, the understanding of the mechanisms of malignant transformation may lead to early diagnosis of oral squamous cell carcinoma arising in the background of OSF, which is now considered to constitute a clinicopathologically distinct disease, and the differences are believed to arise from the differential mechanisms of areca nut carcinogenesis. Therefore, the objective of this study is to review the literature on the various mechanisms leading to the malignant transformation of OSF.