Genotypic distribution of human papillomavirus and phylogenetic analysis of E6 and E7 gene of HR-HPV variants isolated from Pakistani population.

High-risk-human papillomavirus (HR-HPV)-induced cervical cancer is the second most common cause of death among females worldwide. HPV16 is the most prevalent HR-HPV infection worldwide. This study found the genotypic distribution of HR-HPV in the local population and investigated the sequence variations among the E6 and E7 oncogenes of the local HPV16 genotype to the E6 and E7 oncogenes of the foreign HPV16 genotypes and constructed a phylogenetic relationship based on nucleotide sequence comparison among the variants identified in our study along with previously reported isolates that were obtained from different regions of the world. The samples were collected from patients with cervical cancer. Genomic DNA was extracted, and HR-HPV genotypes were determined using real-time PCR. The HPV16 E6 and E7 genes were amplified and sequenced. A HPV16 phylogenetic tree was constructed using the maximum likelihood method with MEGA 7. HPV16 was the most prevalent human papillomavirus (HPV) type identified in the present study. HPV16 isolates belonged to the A1 sublineage of the European branch. Twenty-one nucleotide sequences were included in this analysis. The first, second, and third codon positions are also included. The final dataset included 776 positions.

Cytogenetical and hematological analysis of chronic myelogenous leukemia patients with a novel case 52XX, t (1;9;22) (q23.3; q34; q11.2), +6, +8, i(9) (q10;q10), +18,+19,+21+der22 t(9;22)(q34;q11).

(9;22) (q34; q11) translocation is appear in above ninety percent of chronic myelogenous leukemia patients while variant/complex translocations were observed in almost 5% to 8% chronic myelogenous leukemia (CML) positive cases. Gleevec (Imatinib Mesylate) is the first choice breakpoint cluster region (BCR)/ABL targeted oral therapy that produced a complete response almost in 71% to 80% of patients affected with CML. A complete blood count (CBC) of 37 patients was done during diagnosis, however only 21 showed abnormal CBC values which were selected for the study. Karyotyping study using bone marrow samples was performed on 21 CML patients for the conformation of 9;22, however, fluorescence in situ hybridisation was performed for the detection of the BCR-ABL fusion gene of 15 patients. Out of 21, 17 patients showed Ph-positive (9;22) (q34; q11) translocation. Sixteen CML patients showed standard translocation however only CML patients showed a three-way variant/complex translocation with six additional chromosomes, 52XX, t(1;9;22) (q23.3;q34;q11),+6,+8, i(9)(q10;q10), +18,+19,+21 + der22 t(9;22)(q34;q11)). Here we report we report a novel case of six additional chromosomes with the three-way translocation of 52XX, t(1;9;22) (q23.3;q34;q11),+6,+8, i(9)(q10;q10), +18,+19,+21 + der22 t(9;22)(q34;q11) in blast phase.

COVID-19 morbidity in Afghanistan: a nationwide, population-based seroepidemiological study.

OBJECTIVE: The primary objectives were to determine the magnitude of COVID-19 infections in the general population and age-specific cumulative incidence, as determined by seropositivity and clinical symptoms of COVID-19, and to determine the magnitude of asymptomatic or subclinical infections. DESIGN, SETTING AND PARTICIPANTS: We describe a population-based, cross-sectional, age-stratified seroepidemiological study conducted throughout Afghanistan during June/July 2020. Participants were interviewed to complete a questionnaire, and rapid diagnostic tests were used to test for SARS-CoV-2 antibodies. This national study was conducted in eight regions of Afghanistan plus Kabul province, considered a separate region. The total sample size was 9514, and the number of participants required in each region was estimated proportionally to the population size of each region. For each region, 31-44 enumeration areas (EAs) were randomly selected, and a total of 360 clusters and 16 households per EA were selected using random sampling. To adjust the seroprevalence for test sensitivity and specificity, and seroreversion, Bernoulli's model methodology was used to infer the population exposure in Afghanistan. OUTCOME MEASURES: The main outcome was to determine the prevalence of current or past COVID-19 infection. RESULTS: The survey revealed that, to July 2020, around 10 million people in Afghanistan (31.5% of the population) had either current or previous COVID-19 infection. By age group, COVID-19 seroprevalence was reported to be 35.1% and 25.3% among participants aged ≥18 and 5-17 years, respectively. This implies that most of the population remained at risk of infection. However, a large proportion of the population had been infected in some localities, for example, Kabul province, where more than half of the population had been infected with COVID-19. CONCLUSION: As most of the population remained at risk of infection at the time of the study, any lifting of public health and social measures needed to be considered gradually.

Role of tyrosine kinase inhibitor in chronic myeloid leukemia patients with SARS-CoV-2 infection: A narrative Review.

Severe acute respiratory syndrome (SARS) caused by a novel coronavirus-2 (CoV-2), also known as COVID-19, has spread rapidly worldwide since it is recognized as a public health emergency and has now been declared a pandemic on March 11, 2020, by the World Health Organization. The genome of SARS-CoV-2 comprises a single-stranded positive-sense RNA approximately 27 to 30 kb in size. The virus is transmitted through droplets from humans to humans. Infection with the SARS virus varies from asymptomatic to lethal, such as fever, cough, sore throat, and headache, but in severe cases, pneumonia and acute respiratory distress syndrome. Recently, no specific and effective treatment has been recommended for patients infected with the SARS virus. However, several options can be investigated to control SARS-CoV-2 infection, including monoclonal antibodies, interferons, therapeutic vaccines, and molecular-based targeted drugs. In the current review, we focus on tyrosine kinase inhibitor management and their protective role in SARS-CoV-2 patients with chronic myelogenous leukemia.

Phytochemical analysis and protective effects of Vaccinium macrocarpon (cranberry) in rats (Rattus norvegicus) following ethylene oxide-induced oxidative insult.

The Vaccinium genus comprises more than 126 genera of perennial flowering plants that are commonly adapted to poor and acidic soils or epiphytic environments. Their molecular and genomic characterization is a result of the recent advent in next-generation sequencing technology. In the current research, extracts were prepared in different media, such as petroleum ether, methanol and ethanol. An extract of Vaccinium macrocarpon (cranberry) was used at a dose of 200-400 mg/kg by weight (B.wt). Levels of oxidative stress markers, i.e., superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), advanced oxidation protein products (AOPPs) and malondialdehyde (MDA), were measured. A histopathological study of six vital organs in rats was also conducted. The results indicated that the antioxidant levels were lower in the group given only ethylene oxide (EtO) but higher in the groups receiving cranberry extract as a treatment. Major improvements were also observed in stress markers such as advanced oxidation protein products (AOPPs) and MDA following cranberry treatment. Histopathological changes induced by EtO were observed in the heart, kidney, liver, lung, stomach and testis and were reversed following cranberry treatment. The major toxic effects of EtO were oxidative stress and organ degeneration, as observed from various stress markers and histopathological changes. Our study showed that this extract contains strong antioxidant properties, which may contribute to the amelioration of the observed toxic effects.

Discovery of a novel and a rare Kristen rat sarcoma viral oncogene homolog (KRAS) gene mutation in colorectal cancer patients.

Colorectal cancer (CRC) is one of the most important causes of morbidity and mortality in the developed world and is gradually more frequent in the developing world including Saudi Arabia. According to the Saudi Cancer Registry report 2015, CRC is the most common cancer in men (14.9%) and the second most prevalent cancer. Oncogenic mutations in the KRAS gene play a central role in tumorigenesis and are mutated in 30-40% of all CRC patients. To explore the prevalence of KRAS gene mutations in the Saudi population, we collected 80 CRC tumor tissues and sequenced the KRAS gene using automated sequencing technologies. The chromatograms presented mutations in 26 patients (32.5%) in four different codons, that is, 12, 13, 17, and 31. Most of the mutations were identified in codon 12 in 16 patients (61.5% of all mutations). We identified a novel mutation c.51 G>A in codon 17, where serine was substituted by arginine (S17R) in four patients. We also identified a very rare mutation, c.91 G>A, in which glutamic acid was replaced by lysine (E31K) in three patients. In conclusion, our findings further the knowledge about KRAS mutations in different ethnic groups is indispensable to fully understand their role in the development and progression of CRC.

Toward male individualization with rapidly mutating y-chromosomal short tandem repeats.

Relevant for various areas of human genetics, Y-chromosomal short tandem repeats (Y-STRs) are commonly used for testing close paternal relationships among individuals and populations, and for male lineage identification. However, even the widely used 17-loci Yfiler set cannot resolve individuals and populations completely. Here, 52 centers generated quality-controlled data of 13 rapidly mutating (RM) Y-STRs in 14,644 related and unrelated males from 111 worldwide populations. Strikingly, >99% of the 12,272 unrelated males were completely individualized. Haplotype diversity was extremely high (global: 0.9999985, regional: 0.99836-0.9999988). Haplotype sharing between populations was almost absent except for six (0.05%) of the 12,156 haplotypes. Haplotype sharing within populations was generally rare (0.8% nonunique haplotypes), significantly lower in urban (0.9%) than rural (2.1%) and highest in endogamous groups (14.3%). Analysis of molecular variance revealed 99.98% of variation within populations, 0.018% among populations within groups, and 0.002% among groups. Of the 2,372 newly and 156 previously typed male relative pairs, 29% were differentiated including 27% of the 2,378 father-son pairs. Relative to Yfiler, haplotype diversity was increased in 86% of the populations tested and overall male relative differentiation was raised by 23.5%. Our study demonstrates the value of RM Y-STRs in identifying and separating unrelated and related males and provides a reference database.

Y-chromosomal STR analysis in the Pashtun population of Southern Afghanistan.

Afghanistan is a landlocked country in the heart of Asia and since the dawn of humankind Afghanistan has faced centuries of turmoil, strife, conflict, warfare, distress, social unrest, difficult climate, harsh terrain and due to its unique geostrategic position in Eurasia which has historically attracted commerce and conflict. It is an important stop along the Silk Road, connecting the far eastern civilizations to the western world. A 5000-year history of constant invasion. Afghanistan has been repeatedly invaded and conquered by rulers and super powers, neighboring interference in this conflict-tattered land for centuries yet rarely leading to the conquest of this rugged and challenging terrain nation. Afghans are not only shepherds, farmers and nomads but also intense fighters and fierce warriors. Currently very limited genetic studies have been performed in Afghan populations. 17 Y chromosomal short tandem repeats (Y-STRs) were analyzed in 125 unrelated Pashtun (in hindi: Pathan) males residing in the Kandahar region of Southern Afghanistan. A total of 92 unique haplotypes were observed. The predominant haplotype reached a frequency of 9.6%. The haplotype diversity was 0.987 and the discrimination capacity 73.6%. Analysis of molecular variance (AMOVA) reveals a considerable regional stratification within the country as well as between different Pashtun (Pathan) groups from Afghanistan, Pakistan and India.