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Background: Polycythemia is a common medical problem, frequently acquired and reactive to secondary conditions. High-altitude-associated hypoxia contributes to the greater prevalence of polycythemia at altitude. Primary clonal polycythemia vera (PV), even though it is rare, requires a different therapeutic approach. Suspicion of PV usually drives the diagnostic workup of polycythemia. Methods: In this retrospective lab record study, we collected all JAK2 tests requested over a three-year period. We analyzed requests that were made for the evaluation of polycythemia. Complete blood count (CBC) and imaging of the abdomen were collected. Results: Out of 208 total requests, 136 were for the purpose of polycythemia evaluation. JAK2 mutation was positive (confirming the presence of PV) in 22 (16.7%) cases. PV patients have the usual demographics reported elsewhere. Additionally, PV patients exhibit distinct hemogram results featuring leukocytosis, thrombocytosis, and hypochromic microcytic red blood cells (RBCs) related to the associated iron deficiency. Conclusions: Many patients with polycythemia at altitude might be unnecessarily considered for an evaluation of PV, if hemoglobin/hematocrit is the sole deciding criterion. PV patients have a distinct CBC pattern that can be exploited to better select patients with polycythemia for further evaluation and thus reduce unnecessary workups. [ABSTRACT FROM AUTHOR]

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Copyright of Saudi Medical Journal is the property of Saudi Medical Journal and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The discovery of imatinib, a specific inhibitor of Abl kinase, revolutionized the therapeutic approach to chronic myeloid leukemia (CML); however, its efficacy can be impeded by the emergence of novel mutations within the kinase domain, particularly AblT315I, that lead to the development of drug resistance. It therefore remains necessary to identify specific inhibitors that can effectively target imatinib-resistant CML harboring the AblT315I mutation. A natural product library sourced from the ZINC database was screened against the experimental structure of AblT315I kinase to identify compounds that selectively target the mutated kinase. The top-scoring compound was empirically tested for inhibition of AblT315I kinase using a luminescence-based kit and for impact on cellular proliferation using the BaF3-BCR-ABL-T315I stable cell line. Computational docking and molecular dynamic simulations identified the compound SISB-A1, N-[1-(4-bromophenyl)-3-methyl-1H-pyrazol-5-yl]-2-[(2-oxo-4-phenyl-2H-chromen-7-yl)oxy] acetamide, to effectively bind the catalytic domain of the mutant AblT315I kinase. Moreover, SISB-A1 exhibited greater preference than imatinib for amino acid residues of the mutant kinase's active site, including isoleucine 315. MMPBSA-based Gibbs binding free energy estimation predicted SISB-A1 to have a free energy of −51.5 versus −65.0 kcal/mol for the conventional AblT315I inhibitor ponatinib. Cell proliferation assays showed SISB-A1 to have a GI50 of 164.0 nM against the ABL-T315I stable cell line, whereas imatinib had a GI50 of 5035 nM. The IC50 value obtained for SISB-A1 against the AblT315I kinase was 197.9 nM. The results indicate SISB-A1 to have a notable ability to bind the catalytic domain of the AblT315I mutant kinase and effectively suppress its activity, thereby surpassing the associated resistance to imatinib. Continued advancement of this lead compound has the potential to yield innovative therapeutics for imatinib-resistant CML. [ABSTRACT FROM AUTHOR]

Background: It was observed that the severe acute respiratory syndrome-Coronavirus (SARS-CoV-2) virus is more transmissible in places that are more clustered and where mosquitoes breed in significant numbers. Therefore, we wanted to study the potential influence of mosquitoes in the COVID-19 transmission in the field settings. Materials and Methods: This research was applied in the Asir region of Saudi Arabia. A questionnaire survey was meted out to the quarantined participants diagnosed with the COVID-19 infection. Mosquito traps were located at places with the high rate of human vector contact. A total of 464 female mosquitos were screened for the SARS-CoV-2 S gene utilizing real time reverse transcriptase–polymerase chain reaction. In addition, blood-fed mosquitoes were tested through sequencing of the cytochrome b gene region to identify the source of blood meals. Results: People having low economic status and places with high population density, such as parks and malls, resulted in the individuals "high risk of being infected with the COVID-19 infection. Most of the collected blood-fed mosquitoes exhibited a high match-sequencing with human. All tested mosquitoes had not manifested any SARS-CoV-2S gene amplification. Conclusion: Our results highlight the association of low economic status of individuals and the individuals" behavior of frequently visiting parks, with an elevated risk of contracting the COVID-19 infection. Moreover, using a field experiment for the first time in Saudi Arabia, our data supported the theory that the SARS-CoV-2 virus cannot be transmitted through mosquitoes, either by blood meal or by mechanical transmission. [ABSTRACT FROM AUTHOR]