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Purpose: This study was motivated by the need for better positron emission tomography (PET)-compatible tools to image bacterial infection. Our previous efforts have targeted bacteria-specific metabolism via assimilation of carbon-11 labeled d-amino acids into the bacterial cell wall. Since the chemical determinants of this incorporation are not fully understood, we sought a high-throughput method to label d-amino acid derived structures with fluorine-18. Our strategy employed a chemical biology approach, whereby an azide (-N3) bearing d-amino acid is incorporated into peptidoglycan muropeptides, with subsequent "click" cycloaddition with an 18F-labeled strained cyclooctyne partner. Procedures: A water-soluble, 18F-labeled and dibenzocyclooctyne (DBCO)-derived radiotracer ([18F]FB-sulfo-DBCO) was synthesized. This tracer was incubated with pathogenic bacteria treated with azide-bearing d-amino acids, and incorporated 18F was determined via gamma counting. In vitro uptake in bacteria previously treated with azide-modified d-amino acids was compared to that in cultures treated with amino acid controls. The biodistribution of [18F]FB-sulfo-DBCO was studied in a cohort of healthy mice with implications for future in vivo imaging. Results: The new strain-promoted azide-alkyne cycloaddition (SPAAC) radiotracer [18F]FB-sulfo-DBCO was synthesized with high radiochemical yield and purity via N-succinimidyl 4-[18F]fluorobenzoate ([18F]SFB). Accumulation of [18F]FB-sulfo-DBCO was significantly higher in several bacteria treated with azide-modified d-amino acids than in controls; for example, we observed 7 times greater [18F]FB-sulfo-DBCO ligation in Staphylococcus aureus cultures incubated with 3-azido-d-alanine versus those incubated with d-alanine. Conclusions: The SPAAC radiotracer [18F]FB-sulfo-DBCO was validated in vitro via metabolic labeling of azide-bearing peptidoglycan muropeptides. d-Amino acid-derived PET radiotracers may be more efficiently screened via [18F]FB-sulfo-DBCO modification.

BackgroundVertebral discitis-osteomyelitis (VDO) is a devastating infection of the spine that is challenging to distinguish from noninfectious mimics using computed tomography and magnetic resonance imaging. We and others have developed novel metabolism-targeted positron emission tomography (PET) radiotracers for detecting living Staphylococcus aureus and other bacteria in vivo, but their head-to-head performance in a well-validated VDO animal model has not been reported.MethodsWe compared the performance of several PET radiotracers in a rat model of VDO. [11C]PABA and [18F]FDS were assessed for their ability to distinguish S aureus, the most common non-tuberculous pathogen VDO, from Escherichia coli.ResultsIn the rat S aureus VDO model, [11C]PABA could detect as few as 103 bacteria and exhibited the highest signal-to-background ratio, with a 20-fold increased signal in VDO compared to uninfected tissues. In a proof-of-concept experiment, detection of bacterial infection and discrimination between S aureus and E coli was possible using a combination of [11C]PABA and [18F]FDS.ConclusionsOur work reveals that several bacteria-targeted PET radiotracers had sufficient signal to background in a rat model of S aureus VDO to be potentially clinically useful. [11C]PABA was the most promising tracer investigated and warrants further investigation in human VDO.

Chemoenzymatic techniques have been applied extensively to pharmaceutical development, most effectively when routine synthetic methods fail. The regioselective and stereoselective construction of structurally complex glycans is an elegant application of this approach that is seldom applied to positron emission tomography (PET) tracers. We sought a method to dimerize 2-deoxy-[18F]-fluoro-d-glucose ([18F]FDG), the most common tracer used in clinical imaging, to form [18F]-labeled disaccharides for detecting microorganisms in vivo based on their bacteria-specific glycan incorporation. When [18F]FDG was reacted with β-d-glucose-1-phosphate in the presence of maltose phosphorylase, the α-1,4- and α-1,3-linked products 2-deoxy-[18F]-fluoro-maltose ([18F]FDM) and 2-deoxy-2-[18F]-fluoro-sakebiose ([18F]FSK) were obtained. This method was further extended with the use of trehalose (α,α-1,1), laminaribiose (β-1,3), and cellobiose (β-1,4) phosphorylases to synthesize 2-deoxy-2-[18F]fluoro-trehalose ([18F]FDT), 2-deoxy-2-[18F]fluoro-laminaribiose ([18F]FDL), and 2-deoxy-2-[18F]fluoro-cellobiose ([18F]FDC). We subsequently tested [18F]FDM and [18F]FSK in vitro, showing accumulation by several clinically relevant pathogens including Staphylococcus aureus and Acinetobacter baumannii, and demonstrated their specific uptake in vivo. Both [18F]FDM and [18F]FSK were stable in human serum with high accumulation in preclinical infection models. The synthetic ease and high sensitivity of [18F]FDM and [18F]FSK to S. aureus including methicillin-resistant (MRSA) strains strongly justify clinical translation of these tracers to infected patients. Furthermore, this work suggests that chemoenzymatic radiosyntheses of complex [18F]FDG-derived oligomers will afford a wide array of PET radiotracers for infectious and oncologic applications.

For the past several decades, chimeric antigen receptor T-cell therapies have shown promise in the treatment of cancers. These treatments would greatly benefit from companion imaging biomarkers to follow the trafficking of T cells in vivo. Methods: Using synthetic biology, we engineered T cells with a chimeric receptor synthetic intramembrane proteolysis receptor (SNIPR) that induces overexpression of an exogenous reporter gene cassette on recognition of specific tumor markers. We then applied a SNIPR-based PET reporter system to 2 cancer-relevant antigens, human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor variant III (EGFRvIII), commonly expressed in breast and glial tumors, respectively. Results: Antigen-specific reporter induction of the SNIPR PET T cells was confirmed in vitro using green fluorescent protein fluorescence, luciferase luminescence, and the HSV-TK PET reporter with 9-(4-18F-fluoro-3-[hydroxymethyl]butyl)guanine ([18F]FHBG). T cells associated with their target antigens were successfully imaged using PET in dual-xenograft HER2+/HER2- and EGFRvIII+/EGFRvIII- animal models, with more than 10-fold higher [18F]FHBG signals seen in antigen-expressing tumors versus the corresponding controls. Conclusion: The main innovation found in this work was PET detection of T cells via specific antigen-induced signals, in contrast to reporter systems relying on constitutive gene expression.

Abstract: For the past several decades, chimeric antigen receptor T cell (CAR T) therapies have shown promise in the treatment of cancers. These treatments would greatly benefit from companion imaging biomarkers to follow the trafficking of T cells in vivo. Using synthetic biology, we engineered T cells with a chimeric receptor SyNthetic Intramembrane Proteolysis Receptor (SNIPR) that induces overexpression of an exogenous reporter gene cassette upon recognition of specific tumor markers. We then applied a SNIPR-based positron emission tomography (PET) reporter system to two cancer-relevant antigens, human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor variant III (EGFRvIII), commonly expressed in breast and glial tumors respectively. Antigen-specific reporter induction of the SNIPR-PET T cells was confirmed in vitro using GFP fluorescence, luciferase luminescence, and the HSV-TK PET reporter with [18F]FHBG. T cells associated with their target antigens were successfully imaged using PET in dual xenograft HER2+/HER2- and EGFRvIII+/EGFRvIII-animal models, with > 10-fold higher [18F]FHBG signals seen in antigen-expressing tumors versus the corresponding controls. The main innovation described is therefore PET detection of T cells via specific antigen-induced signals, in contrast to reporter systems relying on constitutive gene expression.

This article explores the transformative impact of Artificial Intelligence (AI) in oncology pharmacy. Oncology pharmacists, traditionally pivotal to cancer management, are now navigating a landscape revolutionized by AI advancements, including machine learning and predictive analytics. Their role has expanded beyond conventional boundaries to encompass data-driven decision-making, AI-guided clinical support, and comprehensive patient counseling on AI-based treatment protocols. This evolution necessitates an augmented skill set encompassing technological proficiency, data interpretation, and ethical considerations in patient care. Despite the promise of AI in personalizing treatment and enhancing patient outcomes, challenges persist, including data privacy concerns, integration complexities, and ethical quandaries. Oncology pharmacy is transitioning to a more patient-focused practice, driven by continuous innovation and adaptation to AI technologies. This shift underscores the critical role of oncology pharmacists in shaping an AI-integrated future in healthcare, pivotal for advancing cancer treatment and improving patient care.

Warfarin is favored over newer direct oral anticoagulants (DOACs) for many older adults. However, its use necessitates rigorous monitoring due to the fine line between toxic and therapeutic doses. Few studies have evaluated the anticoagulation quality of warfarin among elderly patients in Saudi Arabia. This study aimed to assess and identify factors affecting the anticoagulation quality of warfarin using the time in the therapeutic range (TTR) among older adults attending two hospitals in Saudi Arabia. Additionally, we aimed to evaluate differences in the anticoagulation quality of warfarin when managed by pharmacists or physicians. This cross-sectional study was conducted at King Abdullah bin Abdulaziz University Hospital (KAAUH) and King Fahad Medical City (KFMC) in Riyadh, Saudi Arabia. After calculating the TTR of each patient, the anticoagulation control level was determined using these values: a) good control: >70 %; b) intermediate control: 50–70 %; c) poor control:

BACKGROUND: The rate of severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) infection and immunogenicity of a single dose of ChAdOx1 vaccine at 16 weeks post-vaccination among young and healthy participants remains unclear in Saudi Arabia. OBJECTIVES: Assess the rate of subsequent infection and immunogenicity of a single dose of ChAdOx1 vaccine at 16 weeks post-vaccination in a sample of healthy and young participants. DESIGN: Cross-sectional study SETTING: Academic teaching hospital in Riyadh, Saudi Arabia SUBJECTS AND METHODS: Healthy participants 18–50 years of age, who received one dose of ChAdOx1 vaccine and had no history of SARS CoV-2 infection were recruited, and blood samples were obtained 16 weeks after vaccination to assess immunogenicity using a commercially available kit. MAIN OUTCOME MEASURES: The rate of SARS-CoV-2 infection within 16 weeks post-vaccination. SAMPLE SIZE: 385 participants with median (IQR) age of 34 (29-38) years. RESULTS: Eleven (2.8%) participants acquired polymerase chain reaction (PCR)-confirmed infection within 16 weeks after a single dose of ChAdOx1 vaccine (mean [SD] 42.5 [28] days post-vaccination). No hospital or intensive care unit admissions occurred among the subjects in this sample. Females were significantly over-represented in PCR-confirmed cases of SARS-CoV-2 infection, with 10 of 11 infections occurring in females (P=.006). Antibody response against anti-spike IgG were detectable in 92.7% of subjects at 16 weeks’ post-vaccination. The median anti-spike IgG level after vaccination was 273.1 (IQR 107-1052 AU/mL). However, the anti-nucleocapsid IgG antibody demonstrated a sensitivity of only 20%. CONCLUSION: A single dose of ChAdOx1 vaccine in healthy and young individuals was associated with a low, single-digit rate of PCR-confirmed infection, most of which were mild. LIMITATIONS: Small sample size and single-center. CONFLICT OF INTEREST: None.

BACKGROUND: The rise in the incidence of implantation is one of the main causes behind the increased rate of CIED infection, which is considered as a serious life-threatening complication. The need of risk factor assessment has become a necessity to prevent further complications and provide prompt management. OBJECTIVES: Identify the risk factors of infection postoperatively among patients who have implantable cardiac devices. DESIGN: A retrospective case-control study. SETTINGS: Cardiac center for adults. PATIENTS AND METHODS: The study included all adult patients (≥14 years of age) of all nationalities who underwent cardiac electronic device implantation that was managed in the cardiac center between January 2012 to December 2018. MAIN OUTCOME MEASURES: Cardiac device infection and associated risk factors. SAMPLE SIZE: 213, including 23 (10.8%) infected case patients and 190 (89.2%) non-infected controls. RESULTS: The mean (SD) age of non-infected patients was 45.0 (12.7) years compared with 61.7 (13.7) for infected patients (P

After long eras of socialism, wars and economic embargo when Iraqi people were severely exhausted, Iraq finally adopts free market economy. Its Gross Domestic Product (GDP) increased rapidly. The fortune was to flow in a proper frame of legislations to Iraqis. Since wealth needs time to grow for a person, and housing commodity is of high costs, then legislation were to be issued to organize flow of the national wealth to support private sector in housing finance. In respond, the Law of Iraqi Housing Bank (IHB) No. 32 was issued in 2011. This research is to solve the conflicts of the (IHB) Law and to support Iraqi legislators regarding this aspect. This research claims that this law should be revised by the Iraq Parliament. The research comes to help in this mission. The law of (IHB) should not conflict with The Iraqi Constitution. The range of this research is the “Status-in-force” Iraqi legislations only. It discusses the housing finance relations in various Iraqi legislations.

Purpose: Numerous studies have shown that students of health professions report higher perceived stress and lower quality of life (QOL) levels than those in other disciplines. The purpose of this cross-sectional survey study is to assess variations in students’ QOL and perceived stress levels by demographic and college-related factors. Methods: The World Health Organization QOL (WHOQOL) – BREF and Perceived Stress Scale (PSS-14) were used to assess QOL and stress levels among students at King Saud Bin Abdul-Aziz University for Health Sciences (KSAU-HS), Riyadh, during December 2015–June 2016. The WHOQOL-BREF comprises four broad QOL domains: physical health, psychological health, social relationships and environment. A total score from responses to the 14 questions in the PSS was computed. Univariate statistical analyses were performed using the Chi-square/Fisher's exact test or the t-test/Mann-Whitney U test, as appropriate. Linear regression models were used to examine the independent effect of numerous demographic and college-related factors on QOL and PSS. Results: A total of 479 students completed the questionnaire, representing a response rate of 95%. Fifty nine percent of the respondents were females. Then vast majority of respondents were single (96%) and reported a household income of SAR 10,000 or higher (82%). The distribution of college enrollment was as follows: Medicine 37%, Applied Medical Sciences 18%, Nursing 16%, Dentistry 13% and Pharmacy 14%. Scores in a number of QOL domains were significantly different by gender, household income, college, academic level and smoking status. Scores in all four QOL domains were negatively correlated with PSS, indicating that better QOL is strongly and highly significantly related to lower perceived stress levels with correlations ranging from −0.27 to −0.58 (p

Background: The internet has become a primary source of health information, particularly for cancer patients. This study evaluated the quality of online health information related to colon cancer in Arabic. Objective: To assess the reliability, accountability, legitimacy, and readability of Arabic websites providing information on colon cancer. Methods: A search was conducted on major search engines using Arabic keywords related to colon cancer. After initial screening, 13 websites were selected for evaluation. The Journal of the American Medical Association (JAMA) benchmarks, DISCERN instrument and website certification (Health on the Net - HON code) were used for assessment. Readability was analyzed using the Flesch Reading Ease Score and Flesch-Kincaid Grade Level. Results: Non-government websites, particularly Wikipedia, msdmanuals.com, and primomedico.com, demonstrated higher compliance with JAMA benchmarks. Six websites scored high on the DISCERN instrument, indicating reliable treatment information. Only one website was HON-code certified. Readability analysis revealed that text comprehension is challenging for most websites. Conclusion: Private agencies and hospitals managed non-government websites generally outperformed government websites' reliability, quality, and readability. However, overall improvement in Arabic's online health information landscape is essential to enhance accessibility and credibility for colon cancer patients. [ABSTRACT FROM AUTHOR]

The bronchodilator effect of the Achillea fragrantissima essential oil (AFO) was studied in guinea pigs’ tracheas and the influence of drying on the quantity and composition of AFO was studied using GC-MS and GC analyses. AFO produced a complete and potent relaxation against carbachol (CCh), while lower potency and partial efficacy were observed against high K+ (80 mM), thus producing dual inhibitory effects similar to dicyclomine. The anticholinergic-like action was further confirmed when pre-incubation tracheal tissues were used at lower concentrations with AFO displacing the CCh concentration‒response curves (CRCs) to the right in a competitive manner similar to atropine. However, non-parallel shifts in CCh CRCs were observed with higher doses, similar to dicyclomine. Further confirmation of the CCB-like effect was obtained from the non-specific deflection of Ca++ CRCs toward the right using the pre-incubated tissues with AFO in Ca++ free medium, similar to verapamil. When AFO was tested against low K+-mediated contractions to explore the possible involvement of additional antispasmodic mechanism(s), AFO interestingly showed a complete inhibition with a higher potency. This inhibition was found to be sensitive to tetraethylammonium (TEA) and 4-aminopyridine (4-AP), whereas glibenclamide (Gb) remained inactive. These results show that AFO possesses bronchodilator effects predominantly from its anticholinergic and K+ channel activation followed by weak Ca++ channels inhibition.

Aim/Background: Peripheral Arterial Disease (PAD) affects the lower limbs. Globally there is a growing disease burden among the patients suffering from cardio-vascular disease and metabolic disorders. The purpose of this review is to generate evidence on the efficacy of CAM therapies in PAD. Materials and Methods: This systematic review was performed across the five electronic databases i.e. PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Ovid SP, ISI Web of Science, Elsevier Science Direct, and Wiley Online Library as per the PRISMA guidelines from inception till April 2022. Results: After screening n=55,410 articles, n=77 articles were found to fulfill the eligibility criteria and were selected for this review. The nature of interventions investigated in the clinical trials were physical interventions including exercises of different forms, oral supplements, and other interventions such as chelation therapy, Tai Chi Chuan (TCC), Intermittent Mechanical Compression (IMC) device, connective tissue reflex massage, Remote Ischemic Preconditioning (RIC), Transcutaneous Electrical Nerve Stimulation (TENS) and heat therapy. Upon final assessment, it was revealed that physical activity had a positive effect on peripheral arterial disease patients' quality of life. In addition, Ginkgo biloba and nitrate supplements were found effective for Intermittent Claudication (IC) and PAD patients. Conclusion: This review suggests a positive impact of physical activity on peripheral arterial disease patients' quality of life. Evidence also shows that Physical activity/exercise-based intervention alone or in combination with the supplement is found to be effective among PAD patients and has shown significant results in intermittent claudication. [ABSTRACT FROM AUTHOR]

Background: Herbal medicine has been widely utilized by pregnant women despite the limited available evidence regarding the safety and efficacy of that practice. The current available studies, from different countries, estimated that the use of herbal medicine during pregnancy range from 7% up to 96%. The aim of this study is to determine the prevalence, attitude, source of information, and reasoning behind the use of herbal medicine among pregnant women in Saudia Arabia. Methods: A cross-sectional study conducted using a convenience sample including pregnant women who visited the obstetric clinics at King Abdulaziz Medical City in Riyadh, Saudi Arabia. A survey was administered in order to evaluate the prevalence and perception toward herbal medicine use among pregnant women in Saudi Arabia. Results: A total of 297 pregnant women completed the survey. The results showed that 56% of the respondents have used some type of herbal medicine during their pregnancy. Olive oil was utilized in 26% of the respondents followed by cumin 20% and garlic 15%. In addition, 37% of the respondents used herbal medicine by their own initiative, while 33% and 12% used herbal medicine based on recommendations from their families and friends, respectively. Furthermore, 19% of the respondents reported a positive attitude toward herbal medicine use during pregnancy. In addition, the percentage of women with positive attitude was marginally higher among respondents with lower educational level. Conclusion: The prevalence of using herbal medicine is considerably high among pregnant women in Saudi Arabia. Unfortunately, the majority of the users relied on informal sources to use herbal medicine during pregnancy. Keywords: Herbal medicine, Supplements, Pregnancy, Prevalence, Attitudes, Saudi Arabia

Introduction Ventilator-associated pneumonia (VAP) is a common healthcare-associated infection in the intensive care unit (ICU). Probiotics are defined as live microorganisms that may confer health benefits when ingested. Prior randomised trials suggest that probiotics may prevent infections such as VAP and Clostridioides difficile–associated diarrhoea (CDAD). PROSPECT (Probiotics to Prevent Severe Pneumonia and Endotracheal Colonization Trial) is a multicentre, double-blinded, randomised controlled trial comparing the efficacy of the probiotic Lactobacillus rhamnosus GG with usual care versus usual care without probiotics in preventing VAP and other clinically important outcomes in critically ill patients admitted to the ICU.Methods and analysis The objective of E-PROSPECT is to determine the incremental cost-effectiveness of L. rhamnosus GG plus usual care versus usual care without probiotics in critically ill patients. E-PROSPECT will be performed from the public healthcare payer’s perspective over a time horizon from ICU admission to hospital discharge.We will determine probabilities of in-ICU and in-hospital events from all patients alongside PROSPECT. We will retrieve unit costs for each resource use item using jurisdiction-specific public databases, supplemented by individual site unit costs if such databases are unavailable. Direct costs will include medications, personnel costs, radiology/laboratory testing, operative/non-operative procedures and per-day hospital ‘hoteling’ costs not otherwise encompassed. The primary outcome is the incremental cost per VAP prevented between the two treatment groups. Other clinical events such as CDAD, antibiotic-associated diarrhoea and in-hospital mortality will be included as secondary outcomes. We will perform pre-specified subgroup analyses (medical/surgical/trauma; age; frailty status; antibiotic use; prevalent vs no prevalent pneumonia) and probabilistic sensitivity analyses for VAP, then generate confidence intervals using the non-parametric bootstrapping approach.Ethics and dissemination Study approval for E-PROSPECT was granted by the Hamilton Integrated Research Ethics Board of McMaster University on 29 July 2019. Informed consent was obtained from the patient or substitute decision-maker in PROSPECT. The findings of this study will be published in peer-reviewed journals.Trial registration number NCT01782755; Pre-results.

Feeling ashamed is a universal humanuniverse living experience. According to humanbecoming, all persons choose to feel ashamed or not from moment to moment. Therefore, it is significant to discover the newknowings of the phenomenon of feeling ashamed. The investigation method was Parsesciencing, a unique mode of inquiry within the humanbecoming paradigm. The investigation included 10 historians between the ages of 18 and 65 years, who were willing to share their experiences of feeling ashamed. The inquiry stance was: What is the discerning extant moment of the universal humanuniverse living experience of feeling ashamed? The major discovery of this Parsesciencing inquiry was the discerning extant moment: Feeling ashamed is profound agonizing regretfulness with persistent unwelcome recollections arising with desired concealment with distancing affiliations. [ABSTRACT FROM AUTHOR]

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The research dealt with the concepts of time and architectural thought and the extent of the influence of Ideas derived from the element of time on the variation and differentiation of architectural movements and schools, by reviewing a group of vocabulary such as nostalgia, present, and looking forward to the future, the null of the present and immortality in architecture and the null or deferred future, and the study of the duration of its reflection on architectural thought to lead to the differentiation of each of the architecture of Mesopotamia, Classical architecture, Modern architecture, Postmodernism, and Autonomous architecture, Deconstruction architecture according to these terms. The problem of the research was the lack of clarity on the influence of the element of time and its role in the differentiation of architectural thought. The main goal of the research is to focus on the role of the element of time in the differentiation and uniqueness of architectural thought. As for the research hypothesis, it focused on emphasizing the role of thought that distinguishes time in the differentiation of architectural thought, which in turn guarantees the uniqueness of societies, and the most important finding of the research is that Classical architecture is distinguished by its interest in the principle of nostalgia, and that there are some trends in Contemporary Iraqi Architecture based on the principle of nostalgia represented by nostalgia for formal elements, and that modern architecture urged in most of its buildings nostalgia for the present. [ABSTRACT FROM AUTHOR]