
COVID-19 vaccination, both in healthy individuals and those with comorbid medical disorders, has proven highly effective in mitigating critical disease progression and mortality rates. Nevertheless, although rare, induction of autoantibodies and new-onset autoimmune conditions in apparently healthy individuals receiving COVID-19 vaccination have been documented. These autoimmune phenomena can be broadly classified into organ-specific autoimmune disorders (e.g., subacute thyroiditis (SAT)) and systemic autoimmune disorders, with many being generally transient (e.g., vaccine-induced thrombotic thrombocytopenia (VITT)) and others causing chronic disability (e.g., systemic vasculitis). Recent studies have highlighted significant associations between COVID-19 vaccine-associated autoimmunity and human leukocyte antigen (HLA) loci. For example, HLA class I alleles such as HLA-B*35 and HLA-C*04 have been associated with COVID-19 vaccine-induced SAT, while HLA class II alleles, including HLA-DRB1*11:04, HLA-DQA1*05:01, HLA-DQB1*02:01, and HLA-DPB1*17:01, have been linked to VITT. This review synthesizes the reported associations between classical HLA loci and COVID-19 vaccine-induced autoimmunity, providing insights into potential mechanisms and clinical implications.
BACKGROUND:Cholesteatoma recurrence is relatively common and often requires repeat surgical interventions, imposing a significant burden on patients and healthcare systems. Although clinical factors such as age, disease aggressiveness, surgical technique, and surgeon experience influence recurrence risk, accurate prediction remains challenging. Genetic Risk Scores (GRS), which aggregate the effects of multiple genetic variants, offer a promising approach to individualized recurrence risk estimation. OBJECTIVE:To evaluate the contribution of specific genetic variants to cholesteatoma recurrence by constructing a GRS using data from the UK Biobank. METHODS:A systematic review of PubMed identified six genes previously associated with cholesteatoma recurrence: KGF (FGF7), KGF-R (FGFR2), MMP9, KRT1, KRT10, and MIF. Corresponding single nucleotide polymorphisms (SNPs) were analyzed using the UK Biobank, a large-scale biomedical database of approximately 500,000 participants. Individuals with recurrent cholesteatoma were identified using ICD-10 code H95.0. SNPs with minor allele frequency <5% or in linkage disequilibrium were excluded. A weighted GRS was calculated by summing the number of risk alleles for each SNP, multiplied by their β coefficients (log odds ratios). RESULTS:A total of 39 SNPs were included in the final GRS calculation. Among 502,164 UK Biobank participants, 55 individuals were identified with recurrent cholesteatoma. The mean GRS for these individuals was 3.86, compared to 3.72 in the general population, indicating a 15.6% relative increase in genetically determined recurrence risk (OR ≈ 1.156). CONCLUSIONS:This study demonstrates a modest but measurable contribution of genetic variation to cholesteatoma recurrence. While the effect size is limited, future studies with larger cohorts and genome-wide data may improve predictive accuracy. Even at this stage, the GRS may help guide surgical decision-making and follow-up planning, moving toward more personalized management of cholesteatoma.
OBJECTIVES:Epstein-Barr virus (EBV) associated gastric cancer (EBVaGC) represents a distinct subtype of gastric carcinoma clinically characterized by low frequency of lymph node metastasis and better prognosis as compared to the EBV-negative gastric cancer (EBVnGC). Differential expression analysis of the transcriptome from tumor tissues revealed frequent involvement of immune genes which emphasizes the exclusive significance of immune response in EBVaGC patients. Considering the reported over-expression of toll-like receptor (TLR) genes in EBV infection and giving the crucial roles of TLRs in the innate immune system, we assumed that the entire TLR signaling pathway could have been differentially regulated in EBVaGC. METHODS:We tested our hypothesis by performing a differential expression analysis of the whole TLR signaling pathway using gene set enrichment test. RESULTS:A self-matched test detected a significant upregulation of the TLR signaling pathway in tumor as compared with non-tumor gastric tissues of EBVaGCs (P = 4×10-3) but no significant differential regulation of the pathway in EBVnGCs. A comparison of tumor gastric tissue in EBVaGCs versus non-tumor gastric tissue in EBVnGCs showed an even more significant upregulation of the pathway with a high enrichment of overexpressed genes (P = 2.5×10-4). CONCLUSIONS:Briefly, this study revealed a distinct pattern of activation of the TLR signaling pathway in EBVaGCs which can be seen as a specific feature of molecular pathology in the disease. This feature characterizes the disease as a distinct subtype of gastric cancer in oncogenesis which can be linked to its clinical manifestation and prognosis to motivate improved treatment strategies for both EBVaGC and EBVnGC patients.
Objectives: Women are at a significantly higher risk of osteoporotic fractures, largely due to progressive bone demineralization and impaired bone microarchitecture. Low bone mineral density (BMD) is a common condition in women worldwide. Disrupted homocysteine (Hcy) metabolism has been linked to reduced BMD and increased risk of osteoporotic fractures. Hyperhomocysteinemia (Hhcy) affects osteoblast and osteoclast activity, interferes with collagen cross-linking in the extracellular matrix, and has a detrimental effect on bone health. This study aimed to establish the association between hematological and biochemical parameters and osteoporosis in adult females. Methods: We measured Hcy, creatinine, uric acid (UA), vitamin B12, and vitamin D levels. Significantly elevated Hcy (27.322 ± 0.816 vs 10.152 ± 0.381 µmol/L), creatinine (0.670 ± 0.012 vs 0.587 ± 0.011 mg/dL), and UA (5.118 ± 0.083 vs 2.786 ± 0.060 mg/dL) were found in osteoporotic females, while reduced concentrations of vitamin B12 (148.883 ± 2.192 vs 294.14 ± 6.505 pg/mL) and vitamin D (24.98 ± 0.621 vs 33.7 ± 0.652 ng/mL) were observed. Results: Hematological parameters were found differentially expressed in osteoporotic females. Elevated Hcy levels, combined with reduced vitamin B12 and vitamin D, were strongly associated with decreased BMD and a higher susceptibility to osteoporotic fractures. Women with increased Hcy levels also had lower T-scores compared to those without Hhcy. Conclusions: These findings suggest that Hcy plays a critical role in bone resorption and osteoporotic fractures. Regulating Hcy metabolism may serve as an effective therapeutic strategy for managing bone resorption and osteoporosis. We hypothesize that elevated Hcy levels are closely related to low BMD and an increased risk of osteoporosis.
Artemisinin Combination Therapies (ACT) stand as the most potent antimalarial treatments. In response to the emergence of ACT-resistant malaria parasites in Southeast Asia, the World Health Organization (WHO) has recommended continuous monitoring of the effectiveness of ACT and other antimalarials. To address this need, we collected dried blood spots from malaria patients during a 42-days drug efficacy trial evaluating the efficacy of Artesunate plus Amodiaquine (ASAQ), Artemether Plus Lumefantrine (AL) and Dihydroarthemisinine plus Piperaquine (DHAPQ) on simple P. falciparum malaria in 2017. Blood samples were collected on Day 0, prior to the patients' initial ACT dose, and on any days of recurrent parasitemia. Genetic markers such as Merozoite Surface Protein 1 (MSP1) and Merozoite Surface Protein 2 (MSP2) were genotyped to differentiate between recrudescence and re-infestation cases. Furthermore, PCR Single Specific Oligonucleotide Probes combined with-ELISA platform (PCR-SSOP-ELISA) and PCR-RFLP techniques were used to identify Pfcrt 72-76 mutant haplotype and Pfmdr1_86Y allele associated with chloroquine and amodiaquine resistance, respectively. Out of the 320 patients enrolled in the study, only 43 (13.43%) experienced relapses. Upon PCR correction, our analysis revealed that recrudescent infections affected 13 patients, with 8 in the ASAQ group, 5 in the AL group, and none in the DHAPQ group. Notably, no early treatment failures (within the first 3 days of treatment) were observed, and all recurrences occurred between Day 21 and Day 42. The prevalence of the Pfcrt wild-type haplotype CVMNK and Pfmdr N86 allele was 67.03% and 97.70%, respectively. In contrast, the mutant types CVIET and 86Y were found at 32.97% and 2.3%, respectively. The high prevalence of the CVMNK wild haplotype suggests that the parasites remain sensitive to chloroquine, while the low prevalence of the 86Y mutants indicates continued effectiveness of amodiaquine. Furthermore, the low prevalence of strains exhibiting the combination of CVIET and 86Y suggests that the use of multiple antimalarials is valuable for resistance control. Notably, none of the relapse cases carried the 86Y mutation or the combination of 86Y and CVIET.
OBJECTIVE:In recent years, Acinetobacter baumannii has been appearing in hospitals with high drug resistance and strong vitality, which brings many difficulties to clinical treatment. In this study, 255 strains of A. baumannii were isolated from Youjiang Medical University for Nationalities Affiliated Hospital clinical samples and found to be highly resistant to carbapenems. The drug resistance, biofilm-forming ability, and carbapenase gene distribution of 145 carbapenem-resistant A. baumannii (CRAB) strains were analyzed statistically.METHODS:The clinically isolated strains were detected using Vitek mass spectrometry and Vitek2-compact for bacterial identification and susceptibility testing, respectively. The biofilms of clinical isolates were quantitatively detected by microplate crystal violet staining, and qualitatively observed by confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM). And the common carbapenemase genes were detected by polymerase chain reaction (PCR).RESULTS:The 255 clinical isolates from the Youjiang District of western Guangxi Province had a high resistance rate to carbapenems antibiotics. The main specimens were from the intensive care unit (49%), and the most important specimens were sputum specimens (80%). All 145 strains of CRAB produced different degrees of biofilm, and six carbapenenase genes were detected. We found that there were significant differences in biofilm formation between resistant and sensitive strains of tobramycin, levofloxacin, ciprofloxacin, tigecycline, and doxycycline (P<0.05). The distribution of blaOXA-23 and blaOXA51 genes was significantly different from CRAB biofilm formation (P<0.05). In addition, AmpC, blaOXA-23, blaOXA-51, and TEM genes were more distributed in antibiotic-resistant strains.CONCLUSION:The clinical strains have a high resistance rate to carbapenems, and the CRAB with blaOXA-51 and blaOXA-23 genes has a high resistance to antibiotics and a strong biofilm.
University campus communities consist of dynamic and diverse human populations originated from different regions of the country or the world. Their national/global movement to and from campus may contribute to the spread and buildup of methicillin-resistant (MR) bacteria, including MR Staphylococci (MRS) on high-touch surfaces, sinks, and toilets. However, studies on MR bacteria contamination of surfaces, sinks, and toilets are scarce in workplaces outside of healthcare settings. Hence, little is known whether university communities contaminate campus bathrooms by MR bacteria. This study evaluated the abundance, identity, and phylogenetics of MR bacteria grown on CHROMagar MRSA media from bathrooms at workplaces. We collected 21 sink and 21 toilet swab samples from 10 buildings on campus and cultured them on CHROMagar MRSA media, extracted DNA from MR bacteria colonies, sequenced PCR products of 16S and dnaJ primers, determined the sequence identities by BLAST search, and constructed a phylogenetic tree. Of 42 samples, 57.1% (24/42) harbored MR bacteria. MR bacteria were more prevalent on the sink (61.9%) than in the toilet (52.2%) and in male bathrooms (54.2%) than in female bathrooms (41.7%). The colony count on the bathroom surfaces of 42 samples varied in that 42.9% (18/42), 33.3, 14.3, and 9.5% of samples harbored 0, 100, and > 1000 MR bacteria colonies, respectively. Of MR bacteria sequenced, BLAST search and phylogenetic analysis showed that Staphylococcus accounted for 60% of the MR bacteria and the rest were non-Staphylococci. Of Staphylococcus carrying MR (n = 15), 53.3% were S. hemolyticus followed by S. lugdunensis (26.7%), S. epidermidis (8%), and a newly discovered S. borealis in 2020 (4%). Of non-Staphylococci MR bacteria, 20% accounted for Sphingomonas koreensis. Campus bathrooms serve as a reservoir for diverse bacteria carrying MR, which pose a direct risk of infection and a potential source of horizontal gene transfer. To reduce the health risk posed by MR bacteria in high traffic areas such as bathrooms additional environmental monitoring and improved decontamination practices are needed.
Turner-type X-linked syndromic intellectual developmental disorder (MRXST) is a rare neurodevelopmental disorder. MRXST is caused by pathogenic variants in the HUWE1 gene on chromosome Xp11.22. The HUWE1 gene encodes a ubiquitin ligase, which has downstream effects on the n-MYC protein and DLL3 Notch ligand, ultimately affecting neuronal differentiation. In addition to intellectual disability and developmental delay, other clinical features such as absent or delayed speech, skeletal abnormalities, abnormalities in hands or feet, seizures, and hypotonia have been described in case reports. Facial dysmorphic features and eye manifestations have been reported in patients with MRXST, but have not been identified as distinctive to this condition. We report two cases of individuals affected by HUWE1-Related Intellectual Developmental Disorder and present a review of literature of male patients affected by this disorder. Based on the literature review and findings in our two patients, it is our observation that patients with MRXST present with distinctive features, which include broad nasal tip, root, or prominent nose (39%), blepharophimosis (27%), epicanthic folds (25%), ear abnormalities (25%), thin upper lip (23%), and deep set eyes (23%). Furthermore, we note that oculofacial abnormalities are seen more frequently in patients with missense variants than patients with duplications in the HUWE1 gene. The findings noted in this paper may help clinicians suspect a diagnosis of MRXST when presented with these distinctive ocular and facial features.
OBJECTIVE:The aim of this study was to identify the potential risk factors and genetic variants associated with dental caries incidence using survival analysis. METHODS:The Center for Oral Health Research in Appalachia recruited and prospectively followed pregnant women and their children. A total of 909 children followed from birth for up to 7 years were included in this study. Annual intra-oral examinations were performed to assess dental caries experience including the approximate time to first caries incidence in the primary dentition. Cox proportional hazards models were used to assess the associations of time to first caries incidence with self-reported risk factors and 4.9 million genetic variants ascertained using a genome-wide genotyping array. RESULTS:A total of 196 of 909 children (21.56%) had their first primary tooth caries event during follow-up. Household income, home water source, and mother's educational attainment were significantly associated with time to first caries incidence in the stepwise Cox model. The heritability (i.e., proportion of variance explained by genetics) of time to first caries was 0.54. Though no specific genetic variants were associated at the genome-wide significance level (P < 5E-8), we identified 14 loci at the suggestive significance level (5E-8 < P < 1E-5), some of which were located within or near genes with plausible biological functions in dental caries. CONCLUSION:Our findings indicate that household income, home water source, and mother's educational attainment are independent risk factors for dental caries incidence. We nominate several suggestive loci for further investigation.
INTRODUCTION:miR-132-3p acts in normal breast development and its downregulation has been documented in breast cancer. One of the targets of miR-132-3p is RB1 which is also inactivated in breast cancer. The interactions between RB1 and miR-132 have been reported in several pathological conditions. We aimed to investigate the correlation between expression levels of miR-132 and RB1 in ductal carcinoma of the breast.METHODS:The study was carried out on tissues obtained from female patients with primary breast cancer. Tumor samples were classified using clinical and pathological data. Following RNA extraction and cDNA synthesis, relative gene expressions in tumors were compared to non-cancerous adjacent tissues. The link between RB1 and miR-132 was assessed by the correlation coefficient test.RESULTS:Our findings revealed a significant decrease in miR-132 and RB1 expressions with a ratio of 0.165 and 0.365, respectively. Tumor grade showed an association with miRNA-132 levels. The expression of miR-132 in grade I tumors was almost equal to that of normal adjacent tissues, but was intensely decreased in grades II and III. The correlation analysis showed a small linear association between RB1 and miR-132 levels.CONCLUSION:The reduction of miR-132 and RB1 expression confirmed the tumor-suppressive role of both genes in breast cancer. Considering that RB1 is one of the miR-132 targets, further studies are required to discover any miRNA-mediated upregulation role for miR-132. Our finding discovered a small linear association between miR-132 and RB1, which can be concluded towards their independent function in breast cancer pathogenesis.
PURPOSE:Childhood cataracts and strabismus are among the most common causes of visual impairment in children worldwide, and prompt diagnosis and correction can significantly reduce disease burden. In certain regions, including the Eastern Caribbean, access to adequate treatment can be limited and epidemiological data scarce. This study aims to analyze the epidemiological data of pediatric strabismus and cataract cases in St. Vincent and the Grenadines.METHODS:The setting of the study is a clinical practice including 201 patients between the age of 0 to 19 who received care with World Pediatric Project (WPP). Factors analyzed include patient age, sex, and type of cataract or strabismus. The findings were compared to publicly available demographic information.RESULTS:The cases were divided into cataract (n=51), strabismus (n=134), and both strabismus and cataract (n=16). Mean ages (years) were 5.96, 5.54, and 4.50, respectively. The most frequent type of cataract and strabismus were congenital (n=25) and esotropia (n=95), respectively. The highest annual cumulative incidence was 31 and 49 cases per 100,000 people for cataracts and strabismus, respectively.CONCLUSION:This study provides regional epidemiological data on pediatric strabismus and cataracts. Further studies can expand the patient population by increasing collaboration with local providers. Ultimately, these findings can offer a basis for which additional epidemiological studies can be performed and help guide public health efforts to prevent visual impairment in St. Vincent and the Grenadines.
Nabais Sa-de Vries syndrome (NSDVS) is a neurodevelopmental disorder first described in 2020. The syndrome is caused by de novo missense mutations in speckle-type pox virus and zinc finger protein (SPOP) on chromosome 17q21. The syndrome is divided into two forms (NSDVS Type 1 and NSDVS Type 2) based on the consequence of the mutation involved. In this report, we present the clinical features in a young male patient with suspected NSDVS1 and summarize the features of the reported affected individuals thus far, with a focus on the ophthalmic manifestations. Similar to other individuals with NSDVS1, he had features of congenital microcephaly, developmental delay, behavioral abnormalities, hearing loss, and facial dysmorphisms. Ocular and periorbital manifestations in this patient included thick high-arched eyebrows, mild synophrys, long eyelashes, ptosis, and downslanting palpebral fissures; comparable to features described in other individuals with NSDVS1. In addition, this patient had esotropia that required multiple strabismus surgeries and a refractive error that required the use of corrective lenses. Although the consequences of specific mutations may result in a portion of the phenotypic differences between NSDVS1 and NSDVS2, the ophthalmic abnormalities between the two types may have significant overlap not explained by these bidirectional mutational effects.
Genetics is responsible for 80% of androgenetic alopecia (AGA) predisposition. Several single nucleotide polymorphisms (SNPs) have been linked to AGA risk and the metabolism of its first-line therapies. Genotypic and allelic frequencies have not been described in Mexican individuals; therefore, the aim of this study was to describe the genetic distribution of SNPs associated with AGA predisposition and drug metabolism. Using Real Time-PCR, we genotyped SNPs rs4827528 (AR), rs7680591 (FGF5), rs1042028, rs1042157, rs788068 and rs6839 (SULT1A1) and rs776746 (CYP3A5) in 125 (controls = 60, cases = 65) male volunteers from Northern and Western Mexico. The SULT1A1 SNPs rs1042028 (C/T) and rs788068 (T/A/C) resulted in a 100% distribution of the ancestral allele C and mutated allele A, respectively; rs1042028 diverges from the previously reported frequency, while the rs788068 ancestral allele was found to be more predominant than the reported frequency. Rs1042028, rs788068 and rs4827528, were not in Hardy-Weinberg (HW) equilibrium; conversely, rs1042157 and rs6839, rs776746, and rs7680591 followed HW principles. A statistically significant difference (P<0.05) was obtained for the rs1042157 allelic frequency between cases and controls in Western Mexico. We reported the genotypic and allelic frequencies of seven polymorphisms in Mexican individuals from Northern and Western Mexico.
The Alternaria genus has pathogenic, endophytic, and saprobic characteristics. Alternaria genus causes respiratory diseases, fungal allergenicity and the production of mycotoxin in food. Ahvaz city is one of the areas where the presence of dust and high humidity cause the growth and spread of fungal species in the air. Identification of Alternaria species is difficult based on morphology solely. For the first time in Ahvaz, the classification of this fungus was performed using ITS region, alta1 gene, and morphology. For the identification of Alternaria isolates in the Ahvaz city air using morphological and molecular characteristics, potato dextrose agar (PDA) media were used to culture 40 Alternaria isolates recovered from the Ahvaz city air. Afterward, the appearance of the colonies was examined. The DNAs of the isolates were extracted and amplified using the specific primers of the ITS and, Alt a1 regions. The amplified DNA products were sequenced. Then, they were compared with the sequences in the NCBI GeneBank. Based on the morphological results, the isolates included four different species and A. alternata had the highest frequency. Alt a1 gene was present in all the isolates of Alternaria species recovered in our research. Finally, identifying the varieties of Alternaria species based on morphological characteristics as well as ITS or Alt a1 regions is useful but difficult.
Some blood group antigens are reported as a susceptibility marker for some diseases. For instance, HBGA (Histo-blood group antigen) which is controlled by gene FUT2 also considered as a susceptible marker. The FUT2 gene which exhibits the expression of alpha-1, 2-L-fucosyltransferase enzyme also leads to HBGA expression for the gut, and it provides a composition of the phenotypical profile that exists in some populations with unique histories of evolution and it can be considered as a marker of the genetic population. It is found to have an association with many diseases which is discussed in this review. Polymorphic mutations are known to inhibit and reduce its function which are population specific. Detailed understanding and deeper knowledge of its role in the pathogenesis and prevention of many diseases is required. FUT2 may also have a potential role in the case of COVID-19 as a susceptible marker due to its association with respiratory diseases and the ABO blood group. There is an utmost need for this kind of review knowing its importance and owing to limited collective information.
INTRODUCTION:Activating mutations in the BRAF gene have been reported in 0.8%-8% cases of NSCLC. Traditionally, diagnostics have mainly focused on detection of V600E and modalities like mutation specific IHC, allele specific real-time PCR have been utilized. This may underestimate true prevalence of the non-V600E variants. Broader panel NGS testing offers a one stop solution and may identify newer potentially targetable variants. This is a retrospective single center experience of patients with BRAF mutated NSCLC characterizing the molecular spectrum and clinicopathologic characteristics.METHODS:260 patients underwent panel based NGS testing at our center, between 2017-2020. 13 BRAF mutant cases, were detected and were clinically reviewed.RESULTS:Thirteen cases of BRAF alterations were seen in out of 260 (5%) patients. Median age of the cohort was 62 years (range: 39-86 years) with a female predilection). Canonical BRAF V600E mutation was seen in 6 (46.2%) patients and 7 (53.8%) harbored a non-V600E alteration. Spectrum of non V600E alterations included G466E, G469A, N581I, V600_K601delins, D594G, L597Q, G649V and were commonly female (P>0.01) with a higher trend for liver metastases (P=0.09). Median PFS was 4.8 months on chemotherapy (P=0.8). All patients (13/13, 100%) were never smokers with an adenocarcinoma histology.CONCLUSION:This is a single center experience from an Indian NSCLC cohort and shows higher prevalence of non-V600E than V600E mutation reported in literature. This may be attributed to increased use of NGS testing revealing otherwise missed alterations on sequential single gene testing.
The NSUN2-intellectual disability syndrome is a rare disorder of the cellular transcriptome that prevents proper t-RNA splicing. This disorder interrupts cellular function and leads to an accumulation of RNA fragments, producing a constellation of symptoms including dysmorphic facies, hypotonia, microcephaly, and short stature. Eye manifestations have been reported but not well characterized. Our study presents a new case involving a 4-year-old boy with novel NSUN2 variants and clinical features consistent with the syndrome. In addition, through a systemic review, we discuss the 24 previously reported cases of the syndrome with an emphasis on the eye and ocular adnexa clinical features.
Dengue is an important vector borne viral infection. At present, it is endemic in many tropical countries. A molecular epidemiology of viral type in patients and mosquitoes can give useful epidemiology data for disease control. In Indochina, dengue is very common and the molecular epidemiology surveillance is continuously performed. Here, the authors reappraise on available local data from epidemiology studies of viral type in patients and mosquitoes in an endemic area of dengue in Indochina. According to analysis, the authors found that a considerable number of dengue patients do not have the same viral type with caught mosquito vector at their home. According to this study, a chance that a dengue patient gets pathogen from mosquito bite at home is 2.185%. The chance of getting dengue from the vector mosquito bite at home is not high. Hence, a public health policy to control of mosquito vector at home has to extend to universal control at any public places.
The outbreak of COVID-19 disease is an international public health concern. Therefore, the analysis of information related to mortality and disability due to COVID-19 is considered important, so the present study was designed and conducted with the aim of assessing COVID-19 Disability-Adjusted Life Years (DALYs) in Yazd. In Yazd province, all suspected cases of COVID-19 that would be referred to central hospitals in order to get confirmed through PCR or CT scan test, were recruited to our study. The fatality data of COVID-19 was gathered from the forensic medicine organization. The Disability-Adjusted Life Years (DALYs) combines in one measure years of life lost (YLL), the loss of healthy life due to premature mortality and years of life lived with disability (YLD), the loss of healthy life because of disease and disability. The total burden of COVID-19 was 23,472 years. The number of years lost due to premature death was 23385 and the number of years of life with disability due to COVID-19 was estimated to be 87 years. The disease burden was 12992 years for men and 10480 years for women. The overall incidence of COVID-19 was 1411 per 100,000, of which 1419 in men and 1402 in women per 100,000. The outbreak of COVID-19 pandemic affected a large population and the residents of Yazd Province lost many years of their lives due to this disease.
Oral submucous Fibrosis (OSMF) is a chronic disease that mainly affects the upper part of the aerodigestive tract. Areca nut and betel quid chewing has been established as the most significant causative factor for this condition. While OSMF is a predominantly Asian disease, the migrant populations from the region have taken the disease across the globe. Additionally, areca nut is now easily accessible in flavors and aggressively marketed. Many research activities have been undertaken for decades to understand the etiopathogenesis and risk factors of OSMF. Although OSMF is a slowly progressing disease, it has the potential to transform to an oral malignancy. This article is an attempt to review the literature and provide an update on its prevalence, etiopthogenesis and its diagnosis. We also highlight certain clinical, histopathological and molecular features that aid in the diagnosis and prognostication of OSMF, highlighting the importance of identifying the possibly high risk OSMF that is prone to malignant transformation. Using this information, future directions can be developed to include treatmentof OSMF through a dynamic gene-specific approach.