Morphology of the Roots and Canals of Mandibular Third Molars, Their Symmetry and Related Factors Using Cone-Beam Computed Tomography

Introduction: Adequate knowledge about the anatomy of the roots and canals of mandibular third molars is imperative for a successful treatment. This study aimed to use cone-beam computed tomography (CBCT) to evaluate the morphology of the roots and canals of mandibular third molars and their symmetry. Methods and Materials: Totally, 110 CBCT images of bilateral mandibular third molars were evaluated in terms of the number of roots and canals, canal type, isthmus location, location of accessory canals, degree of root curvature and its direction, age and sex of patients and the symmetry of variables in the right and left sides of the mandible. The descriptive statistics, t-test and chi-square test were applied to analyze data. Results: Of all, 71.36% of mandibular third molars had two roots, 20.9% had one single root and 7.72% had three roots. The distal root had one single canal in 89.08%. The mesial root had one single canal in 44.25% and two canals in 49.42%. The Vertucci’s types I (45.40%) and IV (34.48%) had the highest frequency in the mesial root while type I (91.95%) had the highest frequency in the distal root. The deviation of mesial root was towards the distal while distal roots were mainly straight. Conclusion: The symmetry between the right and left mandibular third molars was significantly high. In case of encountering anatomical complexities in dental treatment of a mandibular third molar, dental clinicians should consider the high possibility of presence of the same condition in the contralateral mandibular third molar.Keywords: Anatomy; Cone-Beam Computed Tomography; Mandible; Third Mola

Status of Central Libraries at Iranian Universities of Medical Sciences for Joining an Integrated Network of Medical Libraries

The aim of the study is to offer integrated access to information and data sources in the libraries of Iranian universities of medical sciences (UMS) as an important feature enhancing the quality and quantity of research. Thus, it is essential to study the status of Iranian libraries of UMS in terms of integration features. Accordingly, the main objective of the present study was the identification of integration in libraries of Iranian UMS in terms of metadata, digital contents, software, hardware, and human force. The quantitative study was conducted with an analytic survey method. The statistical population consists of 66 Iranian UMS, of this, 59 libraries completed the researcher-made questionnaire. To ensure the accuracy of data, interviews and, in some cases, observations were also performed. Statistical estimates of frequency, percentage, cumulative frequency, and diagrams were utilized for data analysis. The results demonstrated that the library software programs of UMS do not have a desirable status in terms of content, human force, software infrastructure, and integration features. These libraries enjoyed an optimal status in terms of hardware which was, however, not properly used. To create integrated access to the contents of libraries of Iranian UMS, it is essential to provide the required infrastructure, including integration features, human force, and appropriate contents such as the metadata and digital contents of data source

Vitamin D enhances type I IFN signaling in COVID-19 patients

The ability of Vitamin D (VitD) to modulate antiviral responses through induction of antimicrobial peptide is well established. However, the effect of VitD on host responses to SARS-CoV-2 is not well investigated. We here report the ability of VitD to enhance host IFN-alpha/beta (a/β) signaling both in vitro and among severe COVID-19 patients treated with VitD. Blood and saliva specimens were obtained from severe COVID-19 patients treated (43 patients), or not (37 patients), with vitD, during their stay in intensive care unit. Patients were followed up to 29 days following admission, and patient survival outcomes were collected. Higher activity levels of RIG-1/MDA-5 and JAK-STAT signaling pathways were observed with significantly higher gene and protein levels of antiviral interferon stimulating genes (ISGs) such as MX-1 and ISG-15; both in vitro, following treatment of PBMCs with vitD, and in whole blood and saliva specimens of VitD treated patients. Moreover, VitD treated patients had lower risk of all-cause mortality by day 29 compared to untreated patients (adjusted hazard ratio, 0.37, 95% confidence interval of 0.14–0.94; P = 0.038). The herein uncovered regulatory role of VitD on type I IFNs suggests the importance of insuring a normal level of VitD for the prevention and probably treatment of SARS-CoV-2 infection. Additional mechanistic studies, however, are needed to fully elucidate the antiviral effects of VitD particularly in the setting of COVID-19 infection

Vitamin D modulates systemic inflammation in patients with severe COVID-19

Aims The ability of vitamin D (VitD) to modulate immune responses in the clinical setting of COVID-19 infection is not well investigated. This study aimed to evaluate the ability of VitD to attenuate inflammatory responses in patients with severe COVID-19. Materials and methods Blood samples and nasopharyngeal swabs were obtained from patients with severe COVID-19 who had been treated (20 patients), or not (25 patients), with VitD, during their stay in the intensive care unit. Western blotting was used to evaluate the expressions of STAT3, JNK and AKT signaling pathways and ELISA was used to measure levels of IL-6, IL-17, and IL-1β in blood of these patients. Key findings Reduced levels of STAT3, JNK and AKT pathways and lower levels of proinflammatory cytokines such as IL-6, IL-17, and IL-1β were observed in VitD treated patients (50,000 IU of cholecalciferol weekly for 3 weeks), and in vitro following treatment of poly I:C stimulated PBMCs with VitD (50 nM of calcitriol). Moreover, lower circulatory levels of these proinflammatory cytokines following treatment with VitD were associated with lower serum levels of COVID-19-related severity markers such as D-dimer and C-reactive proteins (

Multiple inborn errors of type I IFN immunity in a 33-year-old male with a fatal case of COVID-19

The host genetic inborn errors of immunity (IEIs) have been shown to contribute to susceptibility to life-threatening coronavirus disease 2019 (COVID-19), as it had been associated previously with other viral infections. Most genetic association studies have described IEIs as a monogenic defect, while there have been no reports of patients with multiple inherited immune deficiencies. This is a complex case of IEIs predisposing to severe viral infections in an unvaccinated 33-year-old male patient. The patient was admitted with no respiratory symptoms, showed a SARS-CoV-2 PCR positive test on the second day of admission, started developing progressive lung consolidation within three days of hospitalization, and was moved from non-invasive to mechanical ventilation within 12 days of hospitalization. Impaired production of type I IFN was detected in patient PBMCs treated with poly(I:C), at both mRNA and protein levels. Whole exome sequencing revealed three mutations across type I IFN production pathway, which were predicted to be loss-of-function (pLOF). The three mutations were predicted to predispose to severe viral infections: monoallelic R488X TLR3, monoallelic His684Arg TLR3, and biallelic Val363Met IRF3. Functional analysis confirmed that all these mutations dysregulated the type I IFN pathway. Evaluation of TLR3 and IRF3 IFN-β1 luciferase reporter activity showed a hypomorphic suppression of function. TOPO TA cloning was used to ascertain the positioning of both TLR3 variants, indicating that both variants were on the same allele. We have described a unique complex IEI patient with multiple mutations, particularly along type I IFN production pathway

Design, synthesis and mechanistic anticancer activity of new acetylated 5-aminosalicylate-thiazolinone hybrid derivatives

The development of hybrid compounds has been widely considered as a promising strategy to circumvent the difficulties that emerge in cancer treatment. The well-established strategy of adding acetyl groups to certain drugs has been demonstrated to enhance their therapeutic efficacy. Based on our previous work, an approach of accommodating two chemical entities into a single structure was implemented to synthesize new acetylated hybrids (HH32 and HH33) from 5-aminosalicylic acid and 4-thiazolinone derivatives. These acetylated hybrids showed potential anticancer activities and distinct metabolomic profile with antiproliferative properties. The in-silico molecular docking predicts a strong binding of HH32 and HH33 to cell cycle regulators, and transcriptomic analysis revealed DNA repair and cell cycle as the main targets of HH33 compounds. These findings were validated using in vitro models. In conclusion, the pleiotropic biological effects of HH32 and HH33 compounds on cancer cells demonstrated a new avenue to develop more potent cancer therapies

Disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE) in Iran and its neighboring countries, 1990–2015

BACKGROUND: Summary measures of health are essential in making estimates of health status that are comparable across time and place. They can be used for assessing the performance of health systems, informing effective policy making, and monitoring the progress of nations toward achievement of sustainable development goals. The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) provides disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) as main summary measures of health. We assessed the trends of health status in Iran and 15 neighboring countries using these summary measures. METHODS: We used the results of GBD 2015 to present the levels and trends of DALYs, life expectancy (LE), and HALE in Iran and its 15 neighboring countries from 1990 to 2015. For each country, we assessed the ratio of observed levels of DALYs and HALE to those expected based on socio-demographic index (SDI), an indicator composed of measures of total fertility rate, income per capita, and average years of schooling. RESULTS: All-age numbers of DALYs reached over 19 million years in Iran in 2015. The all-age number of DALYs has remained stable during the past two decades in Iran, despite the decreasing trends in all-age and age-standardized rates. The all-cause DALY rates decreased from 47,200 in 1990 to 28,400 per 100,000 in 2015. The share of non-communicable diseases in DALYs increased in Iran (from 42% to 74%) and all of its neighbors between 1990 and 2015; the pattern of change is similar in almost all 16 countries. The DALY rates for NCDs and injuries in Iran were higher than global rates and the average rate in High Middle SDI countries, while those for communicable, maternal, neonatal, and nutritional disorders were much lower in Iran. Among men, cardiovascular diseases ranked first in all countries of the region except for Bahrain. Among women, they ranked first in 13 countries. Life expectancy and HALE show a consistent increase in all countries. Still, there are dissimilarities indicating a generally low LE and HALE in Afghanistan and Pakistan and high expectancy in Qatar, Kuwait, and Saudi Arabia. Iran ranked 11th in terms of LE at birth and 12th in terms of HALE at birth in 1990 which improved to 9th for both metrics in 2015. Turkey and Iran had the highest increase in LE and HALE from 1990 to 2015 while the lowest increase was observed in Armenia, Pakistan, Kuwait, Kazakhstan, Russia, and Iraq. CONCLUSIONS: The levels and trends in causes of DALYs, life expectancy, and HALE generally show similarities between the 16 countries, although differences exist. The differences observed between countries can be attributed to a myriad of determinants, including social, cultural, ethnic, religious, political, economic, and environmental factors as well as the performance of the health system. Investigating the differences between countries can inform more effective health policy and resource allocation. Concerted efforts at national and regional levels are required to tackle the emerging burden of non-communicable diseases and injuries in Iran and its neighbors

Association of specific ACE2 and TMPRSS2 variants with circulatory cytokines of COVID-19 Emirati patients

IntroductionThe COVID-19 pandemic represented one of the most significant challenges to researchers and healthcare providers. Several factors determine the disease severity, whereas none alone can explain the tremendous variability. The Single nucleotide variants (SNVs) in angiotensin-converting enzyme-2 (ACE2) and transmembrane serine protease type-2 (TMPRSS2) genes affect the virus entry and are considered possible risk factors for COVID-19.MethodsWe compiled a panel of gene variants from both genes and used in-silico analysis to predict their significance. We performed biological validation to assess their capacity to alter the ACE2 interaction with the virus spike protein. Subsequently, we conducted a retrospective comparative genome analysis on those variants in the Emirati patients with different disease severity (total of 96) along with 69 healthy control subjects.ResultsOur results showed that the Emirati population lacks the variants that were previously reported as associated with disease severity, whereas a new variant in ACE2 “Chr X:g.15584534” was associated with disease severity specifically among female patients. In-silico analysis revealed that the new variant can determine the ACE2 gene transcription. Several cytokines (GM-CSF and IL-6) and chemokines (MCP-1/CCL2, IL-8/CXCL8, and IP-10/CXCL10) were markedly increased in COVID-19 patients with a significant correlation with disease severity. The newly reported genetic variant of ACE2 showed a positive correlation with CD40L, IL-1β, IL-2, IL-15, and IL-17A in COVID-19 patients.ConclusionWhereas COVID-19 represents now a past pandemic, our study underscores the importance of genetic factors specific to a population, which can influence both the susceptibility to viral infections and the level of severity; subsequently expected required preparedness in different areas of the world

The global, regional, and national burden of stomach cancer in 195 countries, 1990-2017 : a systematic analysis for the Global Burden of Disease study 2017

Background: Stomach cancer is a major health problem in many countries. Understanding the current burden of stomach cancer and the differential trends across various locations is essential for formulating effective preventive strategies. We report on the incidence, mortality, and disability-adjusted life-years (DALYs) due to stomach cancer in 195 countries and territories from 21 regions between 1990 and 2017. Methods: Estimates from GBD 2017 were used to analyse the incidence, mortality, and DALYs due to stomach cancer at the global, regional, and national levels. The rates were standardised to the GBD world population and reported per 100 000 population as age-standardised incidence rates, age-standardised death rates, and age-standardised DALY rates. All estimates were generated with 95% uncertainty intervals (UIs). Findings: In 2017, more than 1·22 million (95% UI 1·19–1·25) incident cases of stomach cancer occurred worldwide, and nearly 865 000 people (848 000–885 000) died of stomach cancer, contributing to 19·1 million (18·7–19·6) DALYs. The highest age-standardised incidence rates in 2017 were seen in the high-income Asia Pacific (29·5, 28·2–31·0 per 100 000 population) and east Asia (28·6, 27·3–30·0 per 100 000 population) regions, with nearly half of the global incident cases occurring in China. Compared with 1990, in 2017 more than 356 000 more incident cases of stomach cancer were estimated, leading to nearly 96 000 more deaths. Despite the increase in absolute numbers, the worldwide age-standardised rates of stomach cancer (incidence, deaths, and DALYs) have declined since 1990. The drop in the disease burden was associated with improved Socio-demographic Index. Globally, 38·2% (21·1–57·8) of the age-standardised DALYs were attributable to high-sodium diet in both sexes combined, and 24·5% (20·0–28·9) of the age-standardised DALYs were attributable to smoking in males. Interpretation: Our findings provide insight into the changing burden of stomach cancer, which is useful in planning local strategies and monitoring their progress. To this end, specific local strategies should be tailored to each country's risk factor profile. Beyond the current decline in age-standardised incidence and death rates, a decrease in the absolute number of cases and deaths will be possible if the burden in east Asia, where currently almost half of the incident cases and deaths occur, is further reduced. Funding: Bill & Melinda Gates Foundation

Neonatal, infant, and under-5 mortality and morbidity burden in the Eastern Mediterranean region: findings from the Global Burden of Disease 2015 study

Objectives Although substantial reductions in under-5 mortality have been observed during the past 35 years, progress in the Eastern Mediterranean Region (EMR) has been uneven. This paper provides an overview of child mortality and morbidity in the EMR based on the Global Burden of Disease (GBD) study. Methods We used GBD 2015 study results to explore under-5 mortality and morbidity in EMR countries. Results In 2015, 755,844 (95% uncertainty interval (UI) 712,064–801,565) children under 5 died in the EMR. In the early neonatal category, deaths in the EMR decreased by 22.4%, compared to 42.4% globally. The rate of years of life lost per 100,000 population under 5 decreased 54.38% from 177,537 (173,812–181,463) in 1990 to 80,985 (76,308–85,876) in 2015; the rate of years lived with disability decreased by 0.57% in the EMR compared to 9.97% globally. Conclusions Our findings call for accelerated action to decrease child morbidity and mortality in the EMR. Governments and organizations should coordinate efforts to address this burden. Political commitment is needed to ensure that child health receives the resources needed to end preventable deaths