Probing the Increased Virulence of Severe Acute Respiratory Syndrome Coronavirus 2 B.1.617 (Indian Variant) From Predicted Spike Protein Structure.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to an outbreak of a pandemic worldwide. The spike (S) protein of SARS-CoV-2, which plays a key role in the receptor recognition and cell membrane fusion process, is composed of two subunits, S1 and S2. The S1 subunit contains a receptor-binding domain that recognizes and binds to the host receptor angiotensin-converting enzyme 2 (ACE2), while the S2 subunit mediates viral cell membrane fusion with the cell membrane and subsequent entry into cells. Mutations in the spike protein (S) are of particular interest due to their potential for reduced susceptibility to neutralizing antibodies or increasing the viral transmissibility and infectivity. Recently, many mutations in the spike protein released new variants, including the Delta and Kappa ones (known as the Indian variants). The variants Delta and Kappa are now of most recent concern because of their well-increased infectivity, both a spin-off of the B.1.617 lineage, which was first identified in India in October 2020. This study employed homology modeling to probe the potential structural effects of the mutations. It was found that the mutations, Leu452Arg, Thr478Lys, and Glu484Gln in the spike protein increase the affinity for the hACE2 receptor, which explains the greater infectivity of the SARS-Cov-2 B.1.617 (Indian Variant).

Probing the Colorectal Cancer Incidence in Lebanon: an 11-Year Epidemiological Study.

BACKGROUND AND OBJECTIVES: Lebanon has witnessed an increase in the rates of several cancer sub-types over the past couple of years. The aim of our study is to investigate the incidence rates of colorectal cancer over 11 years in Lebanon and compare them with other countries. MATERIALS AND METHODS: Data was collected from the National Cancer Registry (NCR) of Lebanon from the years of 2005 till 2015 inclusive. Data of other countries was retrieved from the online database "Cancer Incidence in Five Continents". The age-specific and age-standardized incidence rates (ASR(w)) were calculated and analyzed using Joinpoint regression. RESULTS: Colorectal cancer ranked as the 5th most common cancer in Lebanon. The average ASR(w) was 12.6 per 100,00 for males and 10.7 per 100,00 for females. Colorectal cancer ASR (w) showed a significantly increasing trend in both males and females. Lebanon had the second highest incidence of colorectal cancer in the MENA region. CONCLUSION: Incidence of colorectal cancer has been increasing significantly over the course of our study. It is important to study the risk factors associated with colorectal cancer and develop proper preventive and screening policies in order to decrease exposure and therefore decrease incidence rates in the future.

Effect of Leishmaniasis on the Performance of Elementary School Students: A Case Study among Syrian Refugees in Some Bekaa (Lebanon) Area Schools.

Since the Syrian conflict started, Lebanon became a common destination receiving a huge number of Syrian refugees that are living in camps spread all over the country, with the largest concentration in the Bekaa Valley. Generous steps are being taken to increase the access to formal education, such as offering free public education and opening second shifts in the public schools in the afternoon. Yet barriers, such as child labor and health-related factors like the spreading of some communicable diseases, like Leishmania, are keeping children out of classroom. The present study was done with the aim of investigating the effect of leishmaniasis on the performance and the academic achievement of Syrian refugee children. The results showed varying degrees of knowledge and dealing with the case of leishmaniasis. The disease clearly had an effect on the students' attendance in schools, and by proxy on their academic performance.

Current State of Hypertrophic Cardiomyopathy Clinical Trials.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a genetic disorder with a very large global burden for which more therapeutic management regimens are required. OBJECTIVES: In this study, the authors explore HCM-related clinical trials, determine the shortcomings leading to the lack of development of new HCM therapies, and attempt to shed light on potential areas for improvement. METHODS: In January 2019, the authors completed a search on ClinicalTrials.gov for all therapeutic and interventional clinical trials involving HCM, without any limits for location or date. Information on trial characteristics such as phase, start and end dates, sample size, experimental intervention, publications, study design, selection criteria, and results were collected and analyzed. RESULTS: Sixty-three trials met the selection criteria. The average trial duration across phases was around 3 years. Around one-half of the trials were conducted in North America (United States and Canada) and 44% of the trials were in their early phases (I and II). Approximately one-third of the trials were completed. Only 14 publications were produced from all the clinical trials studied. CONCLUSIONS: The study revealed a low number of trials, lack of geographic diversity, and scarcity of published results concerning HCM clinical trials. Proper management of HCM trials is of vast importance to achieve effective therapies.

Breast Cancer Epidemiology among Lebanese Women: An 11-Year Analysis.

Background and Objectives: Breast cancer is the most prevalent cancer in women worldwide. Lebanon is a developing country in the Middle East with a prominent breast cancer incidence. The aim of our study was to explore the incidence rates of breast cancer in Lebanon from 2005 to 2015, and compare them to the rates of other countries. Materials and Methods: Breast cancer data for the years 2005-2015 was collected from the National Cancer Registry of Lebanon and stratified by gender and age group. Age-specific and age-standardized incidence rates were calculated and analyzed using joinpoint regression. Age-standardized incidence rates in the world population (ASR(w)) were obtained for other countries, from two online databases. Results: Breast cancer was found to be the most prevalent cancer in Lebanon, accounting for 20% of all cancer cases. The average ASR(w) was 96.5 per 100,000. Over the studied period, breast cancer ASR(w) in Lebanon showed a significantly increasing trend with an annual percent change (APC) of +4.6. Moreover, the APC of breast cancer age-specific rates significantly increased for the age groups 45-49 (p = 0.013), 50-54 (p < 0.001), 55-59 (p = 0.001), 60-64 (p = 0.002), 65-69 (p = 0.003), 70-74 (p < 0.001), and 75+ years (p < 0.001). Lebanon had the highest breast cancer ASR(w), when compared to other regional countries, and trailed only behind Denmark, when compared to selected countries from different parts of the world. Conclusions: Breast cancer incidence in Lebanon is among the highest in the world. Future studies should focus on exploring the genetic profile of the Lebanese population in an aim to extrapolate proper prevention guidelines.

Epidemiological Study of Lung Cancer Incidence in Lebanon.

Background and Objectives: Lung cancer (LC) is the most common cancer in the world. Developing countries in the Middle East and North Africa (MENA) region, including Lebanon, have witnessed a great increase in the incidence rates of this disease. The aim of our study is to investigate the incidence rates of lung cancer in Lebanon from 2005 to 2015 and to compare these rates to other countries from the MENA region and other regions of the world. Material and Methods: Lung cancer data for the years 2005-2015 were collected from the National Cancer Registry of Lebanon and stratified by gender and age group. Age-specific and age-standardized incidence rates were calculated and analyzed using joinpoint regression. Age-standardized incidence rates to the world population (ASR(w)) for other countries were obtained from two online databases. Results: Lung cancer ranked as the second most common cancer in Lebanon and accounted for 9.2% of all newly diagnosed cancers. Lung cancer ASR(w) showed a significantly increasing trend over the period studied for males and females. Lung cancer ASR(w) among males in Lebanon came second after Malta when compared to other MENA countries, but it was among the lowest when compared to non-MENA countries. For females, Lebanon ranked first when compared to other MENA countries but was among the lowest when compared to countries in other regions of the world. The lung cancer incidence rate increased with age in both sexes and 89.2% of patients were 50 years of age or older. Conclusion: Lebanon has the highest incidence of LC in females and the second highest for males in the MENA region. The lung cancer incidence rate is on the rise and older age groups are much more burdened by this disease than the young ones. Several risk factors, particularly smoking, play a role in increased LC incidence among the Lebanese population.

Conformation and stability properties of B17: II. Analytical investigations using differential scanning calorimetry.

Thermal and stability properties of B17, the 17% N-terminal domain of apo B, were carried out using differential scanning calorimetry spectroscopy, where the thermal characteristics of the polypeptide were studied and analyzed. The heat capacity data of B17 showed that the protein undergoes two transitions between 50 and 90 °C, with T m's at 65.9 and 74.8 °C. While the first transition showed immediate reversibility, the second one-with the higher T m-necessitated a longer cooling (several days) period for its reversibility to be observed and both transitions could be seen in the heat capacity profile of B17. Moreover, the van't Hoff enthalpies determined via calorimetric measurements agreed with the values calculated from the CD analysis reported previously.

Conformation and stability properties of B17: I. Analytical investigations using circular dichroism.

Structural characterization of B17, the 17% N-terminal domain of apo B, was carried out using circular dichroic (CD) spectroscopy, where secondary and tertiary structures were studied as a function of temperature and pH. Mild acidic conditions that correlate with histidine protonation invoked a change in the α-helix and random coil contents of the protein, with no apparent change in the ß-sheet structural content. Specific changes in the structure of the protein that occur in response to temperature were also investigated to understand the stability and conformational changes of B17. Far- and near-UV CDs were used to probe the thermal changes in the protein. The protonation of some histidine residues was attributed to underlie the increase in the helical content of the protein.

The N-terminal domain of apolipoprotein B-100: structural characterization by homology modeling.

BACKGROUND: Apolipoprotein B-100 (apo B-100) stands as one of the largest proteins in humans. Its large size of 4536 amino acids hampers the production of X-ray diffraction quality crystals and hinders in-solution NMR analysis, and thus necessitates a domain-based approach for the structural characterization of the multi-domain full-length apo B. RESULTS: The structure of apo B-17 (the N-terminal 17% of apolipoprotein B-100) was predicted by homology modeling based on the structure of the N-terminal domain of lipovitellin (LV), a protein that shares not only sequence similarity with B17, but also a functional aspect of lipid binding and transport. The model structure was first induced to accommodate the six disulfide bonds found in that region, and then optimized using simulated annealing. CONCLUSION: The content of secondary structural elements in this model structure correlates well with the reported data from other biophysical probes. The overall topology of the model conforms with the structural outline corresponding to the apo B-17 domain as seen in the EM representation of the complete LDL structure.