Response Detection of Castrate-Resistant Prostate Cancer to Clinically Utilised and Novel Treatments by Monitoring Phospholipid Metabolism

The authors gratefully acknowledge funding from Grampian NHS Endowment. The use of Professor Zanda’s and Jaspar’s NMR equipment and Russell Gray’s assistance are also gratefully acknowledged.Peer reviewedPublisher PD

CDP-choline accumulation in breast and colorectal cancer cells treated with a GSK-3-targeting inhibitor

Open via Springer Compact Agreement Funding from the University of Aberdeen Development Trust is gratefully acknowledged. Professor Zanda is gratefully acknowledged for the use of his NMR system.Peer reviewedPublisher PD

Probing the PI3K/Akt/mTor pathway using 31P-NMR spectroscopy : routes to glycogen synthase kinase 3

Professor Matteo Zanda and Professor Marcel Jaspars are gratefully acknowledged for the use of the NMR system and Russell Gray for running some of the NMR samples.Peer reviewedPublisher PD

Development of Fluorinated Analogues of Perhexiline with Improved Pharmacokinetic Properties and Retained Efficacy

We designed and synthesized perhexiline analogues that have the same therapeutic profile as the parent cardiovascular drug but lacking its metabolic liability associated with CYP2D6 metabolism. Cycloalkyl perhexiline analogues 6a–j were found to be unsuitable for further development, as they retained a pharmacokinetic profile very similar to that shown by the parent compound. Multistep synthesis of perhexiline analogues incorporating fluorine atoms onto the cyclohexyl ring(s) provided a range of different fluoroperhexiline analogues. Of these, analogues 50 (4,4-gem-difluoro) and 62 (4,4,4′,4′-tetrafluoro) were highly stable and showed greatly reduced susceptibility to CYP2D6-mediated metabolism. In vitro efficacy studies demonstrated that a number of derivatives retained acceptable potency against CPT-1. Having the best balance of properties, 50 was selected for further evaluation. Like perhexiline, it was shown to be selectively concentrated in the myocardium and, using the Langendorff model, to be effective in improving both cardiac contractility and relaxation when challenged with high fat buffer

A Semi-automatic Approach to Identifying and Unifying Ambiguously Encoded Arabic-Based Characters

In this study, we outline a potential problem in normalising texts that are based on a modified version of the Arabic alphabet. One of the main resources available for processing resource-scarce languages is raw text collected from the Internet. Many less-resourced languages, such as Kurdish, Farsi, Urdu, Pashtu, etc., use a modified version of the Arabic writing system. Many characters in harvested data from the Internet may have exactly the same form but encoded with different Unicode values (ambiguous characters). The existence of ambiguous characters in words leads to word duplication, thus it is important to identify and unify ambiguous characters during the normalisation stage. Here, we demonstrate cases related to ambiguous Kurdish and Farsi characters and propose a semi-automatic approach to identifying and unifying them

Genetic analysis of fish iridoviruses isolated in Taiwan during 2001–2009

To investigate the genetic relationships between field strains of iridoviruses gathered from various fish species in Taiwan, viruses that were collected from 2001 to 2009 were analyzed. Open reading frames encoding the viral major capsid protein (MCP) and adenosine triphosphatase (ATPase) were sequenced for phylogenetic analysis. Our results indicated that iridoviruses from Taiwan aquaculture fishes could be classified into two groups: prior to 2005, the viruses were closely related to members of the genus Ranavirus; and after 2005, they were similar to members of the genus Megalocytivirus. Based on the analysis of MCP amino acid sequences, virus isolates were divided into 4 major genotypes that were related to ISKNV, RSIV, FLIV, and GIV, respectively. Pairwise comparisons of MCP genes showed that the ranavirus was an epidemic pathogen for economically important species in the major production regions and cultured marine fish, while the megalocytivirus isolates were sensitive to host range. In addition, the distribution of synonymous and non-synonymous changes in the MCP gene revealed that the iridoviruses were evolving slowly, and most of the variations were synonymous mutations. The Ka/Ks values were lower than one, and hence, the viruses were under negative selection

Acute Kidney Injury Biomarkers for Patients in a Coronary Care Unit: A Prospective Cohort Study

Background: Renal dysfunction is an established predictor of all-cause mortality in intensive care units. This study analyzed the outcomes of coronary care unit (CCU) patients and evaluated several biomarkers of acute kidney injury (AKI), including neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18) and cystatin C (CysC) on the first day of CCU admission. Methodology/Principal Findings: Serum and urinary samples collected from 150 patients in the coronary care unit of a tertiary care university hospital between September 2009 and August 2010 were tested for NGAL, IL-18 and CysC. Prospective demographic, clinical and laboratory data were evaluated as predictors of survival in this patient group. The most common cause of CCU admission was acute myocardial infarction (80%). According to Acute Kidney Injury Network criteria, 28.7 % (43/150) of CCU patients had AKI of varying severity. Cumulative survival rates at 6-month follow-up following hospital discharge differed significantly (p,0.05) between patients with AKI versus those without AKI. For predicting AKI, serum CysC displayed an excellent areas under the receiver operating characteristic curve (AUROC) (0.89560.031, p,0.001). The overall 180-day survival rate was 88.7 % (133/150). Multiple Cox logistic regression hazard analysis revealed that urinary NGAL, serum IL-18, Acute Physiology, Age and Chronic Health Evaluation II (APACHE II) and sodium on CCU admission day one were independent risk factors for 6-month mortality. In terms of 6-month mortality, urinary NGAL had the best discriminatory power, the best Youden index, and the highest overall correctness of prediction

Associations between COVID-19 outcomes and asthmatic patients with inhaled corticosteroid

Background: The impact of inhaled corticosteroid (ICS) in the interaction between asthma, COVID-19 and COVID-19 associated outcomes remain largely unknown. The objective of this study is to investigate the risk of COVID-19 and its related outcomes in patients with asthma using and not using inhaled corticosteroid (ICS).Methods: We used the TriNetX Network, a global federated network that comprises 55 healthcare organizations (HCO) in the United States, to conduct a retrospective cohort study. Patients with a diagnosis of asthma with and without ICS between January 2020 and December 2022 were included. Propensity score matching was used to match the case cohorts. Risks of COVID-19 incidence and medical utilizations were evaluated.Results: Out of 64,587 asthmatic patients with ICS and without ICS, asthmatic patients with ICS had a higher incidence of COVID-19 (Hazard ratio, HR: 1.383, 95% confidence interval, CI: 1.330–1.437). On the contrary, asthmatic patients with ICS revealed a significantly lower risk of hospitalization (HR: 0.664, 95% CI: 0.647–0.681), emergency department visits (HR: 0.774, 95% CI: 0.755–0.793), and mortality (HR:0.834, 95% CI:0.740–0.939). In addition, subgroup or sensitivity analyses were also conducted to examine the result of different vaccination status, disease severity, or COVID-19 virus variants.Conclusion: For asthmatic patients using ICS, risk of COVID-19 was significantly higher than non-users. The observed association could provide potential guidance for primary care physicians regarding the risk of COVID-19 in asthmatic patients

Mortality risk factors in patients with Acinetobacter baumannii ventilator-associated pneumonia

Background/PurposeVentilator-associated pneumonia (VAP) caused by Acinetobacter baumannii has contributed to high mortality rate, prolonged stays in the intensive care unit, and the rapid development of antimicrobial resistance to commonly used antimicrobials. This study sought to determine predictors of mortality and carbapenem resistance for patients with A baumannii VAP.MethodsWe retrospectively reviewed 541 adult patients with A baumannii pneumonia, who were admitted to a medical center between 2005 and 2007; of which 180 (33.3%) had been treated with mechanical ventilation. Of the 180 patients, 98 (54.4%) who survived were categorized as the survivor group, and 82 (45.6%) who died as the mortality group. Eighty-seven (48.3%) with imipenem-sensitive A baumannii VAP were categorized as the IS-AB group, and the remaining 93 (51.7%) with imipenem-resistant VAP as the IR-AB group.ResultsCompared with the survivor group, the mortality group had significantly higher Charlson comorbidity index scores, and more neoplastic disease, other sites of infection, bloodstream infections, altered mental status, confusion, urea >7 mmol/L, respiratory rate >30/min, low blood pressure (systolic <90 mmHg or diastolic <60 mmHg), age >65 years (CURB-65) ≥ 3, creatinine > 1.6 mg/dL, C-reactive protein ≥ 100 mg/L, and imipenem resistance. The survivor group had more cases of tracheostomy and diabetes mellitus than the mortality group had. Compared with the IS-AB group, the IR-AB group had higher Charlson comorbidity index scores, longer stays before VAP onset, an increase in other sites of infection, white blood cell count <4/μL or >1.1 × 104/μL, and higher hospital mortality rates.ConclusionInadequate initial empiric antimicrobial therapy and higher disease severity scores, including CURB ≥ 3 and C-reactive protein ≥ 120 mg/L, were independent risk factors associated with higher mortality rates for A baumannii pneumonia. Length of stay before VAP and white blood cell count <4/μL or >1.1 × 104/μL were independent risk factors for carbapenem resistance