KRAS G12C-Mutant Non-Small-Cell Lung Adenocarcinoma: First Documented Report in the Arabian Gulf.

We report the first documented case series of two lung adenocarcinoma patients demonstrating Kirsten rat sarcoma viral oncogene homolog (KRAS) G12C mutations by reverse transcription-polymerase chain reaction techniques from Saudi Arabia. Both patients were males aged 64 and 76 years. The first had a heavy smoking history, while the second did not report any history of smoking. The tumor subtype was identified to be non-mucinous lung adenocarcinoma in both cases. The younger patient presented with generalized lymphadenopathy and a right-sided lung mass lesion, while the older patient exhibited stage III-A left lung adenocarcinoma that required rapid response. An initial examination of the first case showed a right-sided mediastinal shift, bilateral neck lymphadenopathy, and poorly differentiated neoplasm from a right supraclavicular core biopsy, leading to treatment with palliatives along with regular checkups. The second case was afebrile after being confirmed to be vitally stable and laboratory testing (Neutr 100). Further studies, specifically on large numbers of patients from the Arabian Gulf, are needed to confirm significant differences between the national and international populations. Additionally, future studies should investigate more differences in the differentiation of KRAS-mutant lung adenocarcinoma between patients from the Arabian Gulf and others.

Stability and validity of intact parathyroid hormone levels in different sample types and storage conditions.

BACKGROUND: Several pre-analytical factors can affect the measurement of intact Parathyroid Hormone (IPTH). In this study, we have investigated the effects of using different types of tubes, time elapsed before separation, and storage conditions over time on the measured values of IPTH. METHOD: Blood samples from 30 subjects were collected into plain, SST, and EDTA tubes. All serum and plasma were separated immediately (first set) and after 2 hrs delay (second set). The first set of samples were aliquoted and stored at RT (25°C), at fridge (4°C), and freezer (-20°C). IPTH was measured in all the stored aliquots at 2,4, and 8 days after collection using Architect analyzer. RESULTS: Paired T test and ANOVA repeated measures showed no significant difference between IPTH levels in all tubes. The second set of serum and plasma were significantly lower (3.8% and 7.4%, p < 0.001, respectively) when compared to samples measured initially. Serum samples stored at RT were significantly lower (by 45%,59%, and 77%) on days 2,4, and 8 when compared to the initial time (p < 0.001 in all cases). Plasma samples stored at RT, were significantly lower on day 8 after collection, by 30.8% (p < 0.001). These differences would be clinically important. CONCLUSION: Plasma IPTH can be stored at RT for up to four days. Both plasma and serum IPTH are not affected by a delay in the separation of up to two h and they can be stored for up to 8 days in a fridge or freezer without any clinically significant changes in their values.

Zika Virus Targeting by Screening Inhibitors against NS2B/NS3 Protease.

Zika flavivirus is suspected to cause Guillain-Barre syndrome in adults and microcephaly, along with other congenital abnormalities in infants. Presently, no vaccines or therapeutics are available. Here, we report novel compounds identified by high-throughput virtual screening of Maybridge chemical database and molecular docking studies. We selected viral enzyme NS2B/NS3 serine protease as the therapeutic target because of its important role in viral replication. We selected seven potential compounds as antiviral drug candidates because of their high GOLD fitness score, high AutoDock Vina score, or X-Score binding energy and analyzed the strength of molecular interactions between the active site amino acids and selected compounds. Our study also provides a foundation for similar studies for the search of novel therapeutics against Zika virus.

RNA interference for viral infections.

The treatment of viral infections has relied on pre-emptive vaccination or use of a limited range of anti-viral drugs. However, the majority of viruses have no available drugs and treatment is merely supportive. RNA interference (RNAi) offers the ability to directly and rapidly treat virus infections via the targeting of viral genes. Indeed, clinical trials have already been undertaken with promising results. Here we review the current state of the RNAi field for the treatment of viral infections such as HIV, human papillomavirus and HCV. We also review novel strategies including the concept of targeting self-genes to limit viral infection and activating the immune system for improved outcomes. Finally we examine innovative approaches being pursued at the Australian Infectious Diseases Research Centre including the use of high-throughput siRNA screens to identify new antiviral targets.

Nucleic acid amplification technology screening for hepatitis C virus and human immunodeficiency virus for blood donations.

OBJECTIVE: To investigate the performance of the commercial Roche COBAS AmpliScreen assay, and demonstrate whether the COBAS AmpliScreen human immunodeficiency virus-1 (HIV-1) test, v1.5, and COBAS AmpliScreen hepatitis C virus (HCV) v 2.0 for screening for HIV-1 and HCV RNA in the donated blood units from which plasma mini pools were collected, by nucleic acid amplification technology (NAT), could detect the positive pools and reduce the risk of transmission of infections for those routinely tested by serological assays. METHODS: The study was performed on 3288 plasma samples collected from blood donors in a period of 13 months, from August 2004 to August 2005, at Al-Hada Armed Forces Hospital, Molecular Pathology Laboratory, Taif, Kingdom of Saudi Arabia. The samples were tested by the reverse transcriptase polymerase chain reaction (RT-PCR) after RNA extraction (this represents the major method in NAT assays), in parallel with the routine serological testing to detect qualitatively for HIV-1 and HCV. RESULTS: The NAT assays that include an automated COBAS AmpliPrep system for RNA extraction and COBAS Amplicor Analyzer using AmpliScreen kits for RT-PCR assays, and the routine serological screening assays for the detection of the HIV-1 and HCV RNA in the plasma samples from the blood donors have shown to be a reliable combination that would meet our requirements. The collected data further confirms the results from the serological assays and enables us to decrease the residual risk of transmission to a minimum with the finding of no seronegative window period donation. The results demonstrate that out of 3288 samples, the percentages of RT-PCR (NAT) negative blood donations that were also confirmed as seronegative were 99% for HCV, and 99.1% for HIV-1. CONCLUSION: The modified combined systems (automated COBAS AmpliPrep system for RNA extraction and COBAS Amplicor Analyzer using AmpliScreen kits for RT-PCR assays) for NAT screening assays has allowed the release of all blood donations supplied in the specified period of the study with no seronegative window period donations. This facilitates keeping the residual risk of transmission of HIV-1 and HCV to its minimum through blood transfusion.