Assessment of satisfaction of attendees of healthcare centers in Jordan with community pharmacy services of pharmacies they usually use.

Before extending the range of services provided, maximizing the usefulness of current procedures within community pharmacy settings is needed, as the scope of pharmacy services is evolving in different dimensions. The present study aims to assess the degree of factors affecting the satisfaction of traditional community pharmacy services using population data collected from patients attending academic and public healthcare centers in Jordan. A validated, pretested, and adapted survey instrument has been utilized to assess the satisfaction of contemporary services delivered by community pharmacists in different dimensions. Linear regression analysis evaluated the predictors associated with higher total satisfaction scores with community pharmacy services. The present study included 642 patients attending healthcare centers. Different dimension scores, such as explanation and consideration, scored similarly, with values ranging from 64.5% - 69.7% of the maximum possible score. The mean total scale score was 67.2% of the total possible scores. Using the linear regression analysis, respondents who were satisfied with their treatment plans were likely to have higher satisfaction with community pharmacy services. The increased number of prescription medications and increased age were associated with lower satisfaction with community pharmacy services. Results indicated that healthcare policymakers might be confident in the services within the community pharmacy setting; however, there is always room for more robust quality control activities.

Costs saved and avoided from pharmacist interventions to address drug-related problems identified from outpatient clinics in Jordan.

BACKGROUND: The pharmacist plays an essential role in identifying and managing drug-related problems. The aim of this research was to assess the costs avoided by clinical pharmacist interventions to resolve drug-related problems. RESEARCH DESIGN AND METHODS: Clinical pharmacists identified drug-related problems and interventions to address them in consecutive outpatients visiting internal medicine clinics at major teaching and public hospitals in Jordan from September 2012 to December 2013. The costs avoided by each intervention to address drug-related problems were collected from the literature. The collected data were used to calculate the overall cost saved and avoided by the interventions implemented to address the identified drug-related problems, adopting a Jordanian healthcare system perspective. RESULTS: A total of 2747 patients were enrolled in the study. Diagnostic interventions, such as the need for additional diagnostic testing, were employed in 95.07% of the 13935 intervention to address the drug-related problem "Miscellaneous" which was the most frequent drug-related problems. Other common drug-related problems categories included inappropriate knowledge (n = 6972), inappropriate adherence (4447), efficacy-related drug-related problem (3395) and unnecessary drug therapy (1082). The total cost avoided over the research period was JOD 1418720 per month and total cost saved over the study period was JOD 17250.204. Drug-related problems were associated the number of prescription medications (odds ratio = 1.105; 95% confidence interval = 1.069-1.142), prescribed gastrointestinal drugs (3.485; 2.86-4.247), prescribed antimicrobials (3.326; 1.084-10.205), and prescribed musculoskeletal drugs (1.385; 1.011-1.852). CONCLUSIONS: The study revealed that pharmacists have provided cognitive input to rationalize and optimize the medication use and prevent errors, that led to the reported projected avoided and saved expenditures via various interventions to address drug-related problems. This highlights the added economic impact to the clinical impact of drug-related problems on patients and the healthcare system. The high prevalence and cost of drug-related problems offer strong rationale for pharmacists to provide more vigilant intervention to improve patient outcomes while maintaining cost effectiveness.

Mechanistic safety assessment via multi-omic characterisation of systemic pathway perturbations following in vivo MAT2A inhibition.

The tumour suppressor p16/CDKN2A and the metabolic gene, methyl-thio-adenosine phosphorylase (MTAP), are frequently co-deleted in some of the most aggressive and currently untreatable cancers. Cells with MTAP deletion are vulnerable to inhibition of the metabolic enzyme, methionine-adenosyl transferase 2A (MAT2A), and the protein arginine methyl transferase (PRMT5). This synthetic lethality has paved the way for the rapid development of drugs targeting the MAT2A/PRMT5 axis. MAT2A and its liver- and pancreas-specific isoform, MAT1A, generate the universal methyl donor S-adenosylmethionine (SAM) from ATP and methionine. Given the pleiotropic role SAM plays in methylation of diverse substrates, characterising the extent of SAM depletion and downstream perturbations following MAT2A/MAT1A inhibition (MATi) is critical for safety assessment. We have assessed in vivo target engagement and the resultant systemic phenotype using multi-omic tools to characterise response to a MAT2A inhibitor (AZ'9567). We observed significant SAM depletion and extensive methionine accumulation in the plasma, liver, brain and heart of treated rats, providing the first assessment of both global SAM depletion and evidence of hepatic MAT1A target engagement. An integrative analysis of multi-omic data from liver tissue identified broad perturbations in pathways covering one-carbon metabolism, trans-sulfuration and lipid metabolism. We infer that these pathway-wide perturbations represent adaptive responses to SAM depletion and confer a risk of oxidative stress, hepatic steatosis and an associated disturbance in plasma and cellular lipid homeostasis. The alterations also explain the dramatic increase in plasma and tissue methionine, which could be used as a safety and PD biomarker going forward to the clinic.

Proteomics of prostate cancer serum and plasma using low and high throughput approaches.

Despite progress, MS-based proteomics in biofluids, especially blood, faces challenges such as dynamic range and throughput limitations in biomarker and disease studies. In this work, we used cutting-edge proteomics technologies to construct label-based and label-free workflows, capable of quantifying approximately 2,000 proteins in biofluids. With 70µL of blood and a single depletion strategy, we conducted an analysis of a homogenous cohort (n = 32), comparing medium-grade prostate cancer patients (Gleason score: 7(3 + 4); TNM stage: T2cN0M0, stage IIB) to healthy donors. The results revealed dozens of differentially expressed proteins in both plasma and serum. We identified the upregulation of Prostate Specific Antigen (PSA), a well-known biomarker for prostate cancer, in the serum of cancer cohort. Further bioinformatics analysis highlighted noteworthy proteins which appear to be differentially secreted into the bloodstream, making them good candidates for further exploration.

Assessment of adherence to carbamazepine using plasma and saliva samples, a study from Jordan.

Background: The measurement of carbamazepine levels in a biological sample is required to guide dosing, and prevent toxicity, and can be useful to assess medication adherence. Aim: The primary aim of the presented study is to analyze carbamazepine levels in saliva and plasma samples of outpatients and to assess adherence to carbamazepine using saliva and plasma levels. Methods: Adults who used carbamazepine for at least one month were recruited from the outpatient clinic department of Princess Basma Hospital, a public hospital in Irbid. Saliva and blood samples (1 ml) were collected simultaneously from subjects, and using a microanalytical method with high-performance liquid chromatography coupled with an ultraviolet detector, the level of carbamazepine (in micrograms per milliliter) was ascertained. Analysis of adherence to carbamazepine was carried out using plasma and saliva levels. Results: A total of 69 consecutive patients attending the neurology clinic were recruited, of whom 85.5% had epilepsy. Approximately one-third (34.8%) used carbamazepine as monotherapy, whereas the remainder used a combination of antiepileptic drugs to control seizures. Overall, about two-thirds (71.9%) of the studied samples were non-adherent in either plasma or saliva samples. By referring to the plasma sample carbamazepine concentration, 75.4% of the respondents were adherents, 15.9% had under-adherence, and 8.7% had over-adherence. A total of 85.9% of the responders were adherent using the carbamazepine level in saliva samples. Plasma and saliva carbamazepine levels were linearly correlated to one another. Polypharmacy was commonly utilized with the patients, as 42% of the patients used two medications, with a range of 1-7 drugs used concomitantly. The predictor associated with higher plasma and saliva carbamazepine levels, as determined by multiple linear regression analysis, was the occurrence of seizures less than once a month, as compared to seizures with higher frequencies. Conclusion: Saliva carbamazepine levels show the potential to be used as an alternative matrix to assess medication adherence, with a considerable correlation with the plasma carbamazepine level. Healthcare professionals can address routine care non-adherence through such measures.

Giant left sinus of Valsalva aneurysm as a rare cause of acute myocardial infarction: a case report.

Background: Sinus of Valsalva aneurysm (SVA) is a rare but potentially life-threatening condition. Acute myocardial infarction (MI) is a rare consequence of aneurysmal dilatation of one or more sinuses of Valsalva. We present a case of an unruptured and partially thrombosed left SVA, presenting as anterior MI and congestive heart failure. Case summary: A 55-year-old gentleman was admitted with pulmonary oedema and a late presenting ST-elevation MI with Q wave. After initial treatment on furosemide infusion, a coronary angiography showed significant stenosis in both his left main stem (LMS) and left anterior descending artery (LAD). This is likely a result of external compression, potentially from the enlarged left sinus of Valsalva. A subsequent transthoracic echocardiogram and transoesophageal echocardiogram (TOE) confirmed large SVA involving the left coronary cusp measured 9.9 cm compressing both LMS and LAD. Discussion: Left SVAs are rare and frequently asymptomatic, typically being identified incidentally. Due to the close proximity of the left coronary system, they can present with myocardial ischaemia due to extrinsic compression of the coronary system. We were able to perform a comprehensive multi-modality assessment of left SVA, which helped establish this unusual diagnosis and guide management. Transthoracic echocardiogram and TOE helped assess the SVA and demonstrated the thrombus in situ, aortic valve insufficiency, and cardiac function. The computed tomography scan aided in accurately defining the extent of the aneurysm and the extent of compression of the left coronary system and cardiac magnetic resonance scan was able to demonstrate viability in LAD and circumflex territory.

Public Patterns and Determinants of Antibiotic Self-Medication and Antibiotic Knowledge in Southern Jordan.

Antibiotic self-medication, which refers to acquisition and using antibiotics to treat infections based on personal experience and/or without a doctor's advice or prescription, is a significant public health issue jeopardizing patient health outcomes. The purpose of the present cross-sectional online survey was to assess the frequency of self-medication among the general public in various geographical locations in southern Jordan, as well as to examine the determinants to self-medication. The survey was distributed through several social media networks over the period November-December 2022, and included demographic information as well as items related to the use and abuse of antibiotics, information sources about antibiotics, the duration of use of antibiotics, and assessment of the public knowledge about appropriate antibiotic use. Inferential analysis, such as the Chi-Square test and logistic regression, were adopted to assess the associations between the different variables with self-medication. A total of 984 respondents were enrolled in the study. Of these, 752 had been using antibiotics during the last year. However, the self-medicating cases were 413 of the 752. The main source of information about the utilization of antibiotics among participants in the survey was pharmacists. The participants commonly (36.0%) tended to use antibiotics until the symptoms disappeared. Nearly half of the respondents reported usually taking antibiotics for treating a runny nose (rhinorrhea). The logistic regression analysis indicated that self-medication with antibiotics was significantly associated with female gender (p-value < 0.001), low educational level (p-value = 0.014), rural living location (p-value 0.003), no health insurance (p-value = 0.001) and occupation (p-value = 0.005). Meanwhile age had no significant relationship to self-medication. Finally, the results revealed poor understanding of key appropriate antibiotic usage, which inevitably influences self-medication practice. It is crucial to come up with several programs and governmental policies to suppress widespread antibiotic self-medication as it will affect the health of future generations of Jordanian citizens.

Routine postaccess-closure angiography to detect vascular complications following transfemoral TAVR.

BACKGROUND: Vascular complications following transfemoral TAVR are associated with increased morbidity and mortality. Measures that may mitigate this risk are important. AIM: To evaluate the utility of routine, access-vessel angiography post sheath-removal in the detection and management of complications in patients undergoing transcatheter aortic valve replacement (TAVR). METHODS: This was a retrospective study of 512 consecutive patients who underwent transfemoral TAVR with routine post access-closure angiography from the radial artery. Rates of mild angiographically evident bleeding, bleeding requiring surgery/interventional-radiology, ischemia, 90-day access-site-related events, and major and minor vascular complications using Valve Academic Research Consortium 3 definitions were recorded. RESULTS: Of 512 patients, digital subtraction angiography (DSA) was undertaken via the radial artery in 467 patients (91%). In the remaining patients (9%) DSA was either not attempted, due to concerns regarding kidney disease and contrast volume, or failed due to anatomical factors (aortic tortuosity/calcification). Significant chronic kidney disease was present at baseline in 72.4% of this cohort (stages III-IV or dialysis). Ninety-four percent of cases underwent TAVR using a balloon-expandable platform. Mild iliofemoral extravasation was observed in 7.7% of the DSA cases. These cases were managed by manual compression with none requiring any vascular intervention subsequently. Valve Academic Research Consortium 3 major and minor access-site-related complications were observed in 0.4% and 12.2%, respectively. Access-site-related bleeding and ischemic events requiring interventional-radiology or vascular-surgery were observed in 0.9% and 1.7% of the DSA cases, respectively. No new renal replacement therapy was needed in any of the DSA cases. Discharge to 90-day access-related complications was 0.8%. CONCLUSIONS: Routine post access-closure angiography is feasible via the radial artery in patients undergoing transfemoral TAVR and appears safe. It facilitates early identification of complications and mitigates risk by enabling prompt action to be taken. Larger studies are needed to confirm these findings.

First Measurement of the Nuclear-Recoil Ionization Yield in Silicon at 100 eV.

We measured the nuclear-recoil ionization yield in silicon with a cryogenic phonon-sensitive gram-scale detector. Neutrons from a monoenergetic beam scatter off of the silicon nuclei at angles corresponding to energy depositions from 4 keV down to 100 eV, the lowest energy probed so far. The results show no sign of an ionization production threshold above 100 eV. These results call for further investigation of the ionization yield theory and a comprehensive determination of the detector response function at energies below the keV scale.

Affi-BAMS™: A Robust Targeted Proteomics Microarray Platform to Measure Histone Post-Translational Modifications.

For targeted protein panels, the ability to specifically assay post-translational modifications (PTMs) in a quantitative, sensitive, and straightforward manner would substantially advance biological and pharmacological studies. The present study highlights the effectiveness of the Affi-BAMS™ epitope-directed affinity bead capture/MALDI MS platform for quantitatively defining complex PTM marks of H3 and H4 histones. Using H3 and H4 histone peptides and isotopically labelled derivatives, this affinity bead and MALDI MS platform achieves a range of >3 orders of magnitude with a technical precision CV of <5%. Using nuclear cellular lysates, Affi-BAMS PTM-peptide capture resolves heterogeneous histone N-terminal PTMs with as little as 100 µg of starting material. In an HDAC inhibitor and MCF7 cell line model, the ability to monitor dynamic histone H3 acetylation and methylation events is further demonstrated (including SILAC quantification). Affi-BAMS (and its capacity for the multiplexing of samples and target PTM-proteins) thus provides a uniquely efficient and effective approach for analyzing dynamic epigenetic histone marks, which is critical for the regulation of chromatin structure and gene expression.

Aortic cusp perforation during rotational atherectomy: a case report.

Background: Rotational atherectomy has become increasingly utilised over the past decade. Although a relatively safe procedure in appropriately trained physicians' hands, there are a number of recognised complications. Case summary: We describe the case of a 64-year-old female who presented with chest pain and was diagnosed with non-ST-segment elevation acute coronary syndrome. A transthoracic echocardiogram (TTE) showed normal biventricular function and no valve disease. Invasive coronary angiogram was performed which revealed a severely calcified ostial right coronary artery (RCA) disease which was felt to be the culprit of the presentation. Balloon dilatation was unsuccessful, therefore, rotational atherectomy with an Amplatz left 0.75 guide and a 1.5 mm rota-burr was utilised and improved calcium burden. This was complicated by ostial dissection, treated with stenting. A TTE following the procedure revealed moderate aortic regurgitation (AR). The patient was discharged as she remained asymptomatic. An outpatient transoesophageal echocardiogram performed eight months later showed evidence of severe eccentric AR. Cardiac magnetic resonance imaging confirmed severe AR with left ventricular dilatation. Repeat angiogram 10 months after index procedure revealed in-stent restenosis, and the patient was accepted by heart multidisciplinary team for aortic valve replacement and grafting of RCA. Discussion: As the field of rotational atherectomy continues to expand, we propose that novel complications such as reported in this case may become recognised. Finally, we stress the importance of multi-modality imaging in the investigation and timely planning of interventions in the management of these patients.

Knowledge, Attitude, and Behavior about Antimicrobial Use and Resistance among Medical, Nursing and Pharmacy Students in Jordan: A Cross Sectional Study.

The present study aimed to survey medical, nursing and pharmacy students' knowledge, attitude and practice regarding antimicrobial use and resistance. Additionally, the study assessed the teaching and assessment activities received regarding antibiotic use. A cross sectional online survey was distributed to undergraduate students currently in clinical studies in their degree program. A total of 716 medicine, nursing and pharmacy undergraduate students were included. Respondents scored more than 76% on knowledge on effective use, unnecessary use and associated side effects of antibiotics, and 65.2% regarding knowledge on the spread of antibiotic resistance. Some participants (21.0%) agreed or strongly agreed that there has been good promotion of prudent antimicrobial use. Students were aware (13.1%), unaware (29.1%), or unsure (57.8%) that there is a national action plan relating to antimicrobial resistance. A total of 62.8% of the respondents strongly agreed or agreed that they have a key role in helping control antibiotic resistance. Participants reported that they require more information about resistance to antibiotics (53.9%), medical conditions for which antibiotics are used (51.7%) and how to use antibiotics (51.0%). Discussion of clinical cases and vignettes and small group teaching were reported as very useful or useful teaching strategies (79.9% and 74.2%, respectively). The findings from this study determined the current situation in relation to education on prudent antimicrobial use for undergraduates and highlighted areas for informing better curriculum design.

Antibiotic use and resistance: Information sources and application by dentists in Jordan.

INTRODUCTION: The availability of evidence-based information sources for dentists is essential to influence antibiotic prescribing practices and we need to understand how dentists interact with such sources and how this influences their practice. The present study aimed to evaluate dentists' preferred sources of information and their awareness of available information and initiatives on prudent antibiotic prescribing practices in Jordan. METHODOLOGY: An online cross-sectional questionnaire was administered to dentists between July to September 2021. It was an adapted version of the European Centre for Disease Prevention and Control (ECDC) survey for antibiotic use and resistance. RESULTS: A total of 204 dentists responded to the survey. The main sources of information regarding avoiding unnecessary antibiotic prescribing were published guidelines (35.5%), the dental professional body (20.0%), colleagues or peers (18.6%), and scientific organizations (17.2%), with the influence of these sources on changing prescribers' views being 40.7%, 9.8%, 10.3%, and 14.2%, respectively. Of the surveyed dentists, 9.3%, 33.8%, and 56.9% were aware, unaware, and unsure of the presence of national action plans on antimicrobial resistance, respectively. Dentists reported their desire to receive more information about resistance to antibiotics (57.8%), medical conditions for which antibiotics are used (52.9%), how to use antibiotics (41.2%), prescribing of antibiotics (39.7%), and links between the health of humans, animals, and the environment (26.0%). CONCLUSIONS: The study provided insights into the information available to and used by dentists, which can inform effective antimicrobial stewardship strategies for improving antibiotic prescribing.

Solanum Procumbens-Derived Zinc Oxide Nanoparticles Suppress Lung Cancer In Vitro through Elevation of ROS.

Lung cancer is one of the cancers with high mortality rate. The current therapeutic regimens have only limited success rate. The current work highlights the potential of Solanum procumbens-derived zinc oxide nanoparticle (SP-ZnONP)-induced apoptosis in A549 lung cancer cells. Synthesized nanoparticles were confirmed by UV-Vis spectrophotometry, X-ray diffraction (XRD), dynamic light scattering analysis (DLS), scanning electron microscopy (SEM), Fourier transform infrared (FT-IR), and photoluminescence analysis. Lactate dehydrogenase (LDH), cytotoxicity, and cell viability assays revealed that the SP-ZnONP caused the cell death and the inhibition concentration (IC50) was calculated to be 61.28 µg/mL. Treatment with SP-ZnONPs caused morphological alterations in cells, such as rounding, which may have been caused by the substance's impact on integrins. Acridine orange/ethidium bromide dual staining revealed that the cells undergo apoptosis in a dose-dependent manner, which indicates the cell death. Furthermore, reactive oxygen species (ROS) were examined and it was shown that the nanoparticles elevated ROS levels, which led to lipid peroxidation. In short, the SP-ZnONPs increase the level of ROS, which in turn causes lipid peroxidation results in apoptosis. On the other hand, the SP-ZnONPs decrease nitric oxide level in A549 cells in a dose-dependent manner, which also supports the apoptosis. In conclusion, SP-ZnONPs would become a promising treatment option for lung cancer.

Proprotein convertase PCSK9 affects expression of key surface proteins in human pancreatic beta cells via intracellular and extracellular regulatory circuits.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is involved in the degradation of the low-density lipoprotein receptor. PCSK9 also targets proteins involved in lipid metabolism (very low-density lipoprotein receptor), immunity (major histocompatibility complex I), and viral infection (cluster of differentiation 81). Recent studies have also indicated that PCSK9 loss-of-function mutations are associated with an increased incidence of diabetes; however, the expression and function of PCSK9 in insulin-producing pancreatic beta cells remain unclear. Here, we studied PCSK9 regulation and function by performing loss- and gain-of-function experiments in the human beta cell line EndoC-ßH1. We demonstrate that PCSK9 is expressed and secreted by EndoC-ßH1 cells. We also found that PCSK9 expression is regulated by cholesterol and sterol regulatory element-binding protein transcription factors, as previously demonstrated in other cell types such as hepatocytes. Importantly, we show that PCSK9 knockdown using siRNA results in deregulation of various elements of the transcriptome, proteome, and secretome, and increases insulin secretion. We also observed that PCSK9 decreases low-density lipoprotein receptor and very low-density lipoprotein receptor levels via an extracellular signaling mechanism involving exogenous PCSK9, as well as levels of cluster of differentiation 36, a fatty acid transporter, through an intracellular signaling mechanism. Finally, we found that PCSK9 regulates the cell surface expression of PDL1 and HLA-ABC, proteins involved in cell-lymphocyte interaction, also via an intracellular mechanism. Collectively, these results highlight PCSK9 as a regulator of multiple cell surface receptors in pancreatic beta cells.

A Survey of Knowledge and Barriers of Healthcare Professionals toward Opioid Analgesics in Cancer Pain Management.

Purpose: Pain is among the most frequent and troubling symptoms in cancer patients. Despite the availability of updated treatment guidelines and effective pharmacological therapies, undertreatment of cancer pain remains a global problem. Opioids are the mainstay analgesics to treat moderate-to-severe cancer pain. The goal of this study was to assess the knowledge and barriers towards opioid analgesics for cancer pain management among healthcare professionals in Oncology Units in Jordan. Methods: A structured questionnaire was administered to healthcare professionals (consultant doctors, resident doctors, pharmacists, and nurses) at three Oncology Units in a cross-sectional study design. Results: A total of 201 healthcare professionals completed the questionnaire. The average age was 34.8 ± 8.1 years (range 23-58) and 49.3% of respondents were nurses. The mean score for the knowledge of opioids was 12.5 ± 3.2 out of 24 points (range 2-20). An acceptable level of knowledge was observed in 50.7% of participants, while 49.3% had poor knowledge. Knowledge items mostly answered incorrectly were related to opioid administration, pharmacology, dosing, adverse events, rotation, and toxicity. Knowledge scores were significantly higher for consultant doctors compared to pharmacists and nurses (p=0.016 and p < 0.001, respectively). Healthcare professionals who handled opioid analgesics had significantly higher mean knowledge scores than those who did not (p=0.012). Linear regression analysis revealed that being a consultant physician has an independent, statistically significant association with higher knowledge scores. Among perceived barriers to using opioids, fear of addiction by patients was the most frequently reported barrier by respondents (79.6%). Other highly recognized barriers were fear of adverse effects by patients (67.2%) and lack of training programs on opioid dosing and monitoring (63.7%). Conclusions: This study revealed major gaps in the knowledge of opioids and pain management among healthcare professionals. There is an urgent need for developing innovative interventions to improve the knowledge of opioid analgesics and the understanding of pain management guidelines among healthcare professionals in Jordan.

Community pharmacists' routine provision of drug-related problem-reduction services.

OBJECTIVES: The present study aimed to assess the degree of the provision of services for drug-related problems (DRPs) and the factors affecting provision within the community pharmacy setting in Irbid, a large city in Northern Jordan. METHODS: A cross-sectional survey was developed and administered to community pharmacists in Irbid, Jordan during the period from January to May 2017. The survey is composed of background and practice characteristics, services provided routinely by the community pharmacists to address DRPs, and barriers and facilitators for DRP-reduction services. A summated score quantifying the degree of DRP-reduction service provision was calculated, which included overall scores and scores for the different scales and domains. Statistical analysis included descriptive statistics and a multivariate linear regression model for factors associated with the high provision of DRP-reduction service. RESULTS: Two hundred community pharmacists out of 210 pharmacists approached completed the surveys yielding a response rate of 95.2%. The most frequent DRPs encountered within the routine practice in the community pharmacy were economic aspects (76.0%). The mean total score relating to different DRP-reduction services was 32.9 (58.8%) out of 56 as the maximum possible score. It was estimated that 28.2% of the responding pharmacists provided the service overall (scored more than 50% of the scale). For the assessment, intervention, and referral dimensions, similar percentages of providers of the services were achieved: 59.7%, 61.9%, and 49.0%, respectively. Lower rates of providers were achieved on the documentation scale (12.9%). The lack of recognition of the pharmacist role by physicians was the most commonly reported barrier to effective DRP-reduction services among community pharmacists (78.9%). The ability to receive external guidance was indicated by the majority of surveyed pharmacists (94.5%) as a potential facilitator to DRP-reduction services in this study. Predictors associated with high total scores were the presence of medical records for the patients in the pharmacy, patients contact the pharmacy using email, a high satisfaction in professional relationships with physicians, and pharmacists' age. CONCLUSION: Even though community pharmacists in this study have been shown to deliver certain activities to address DRPs to a high degree, the overall rate of DRPs services was suboptimal. Community pharmacists reported several barriers that should be taken into consideration to facilitate the role of community pharmacists in providing adequate DRP reduction services to patients.

Characterization of the Secretome, Transcriptome, and Proteome of Human ß Cell Line EndoC-ßH1.

Early diabetes research is hampered by limited availability, variable quality, and instability of human pancreatic islets in culture. Little is known about the human ß cell secretome, and recent studies question translatability of rodent ß cell secretory profiles. Here, we verify representativeness of EndoC-ßH1, one of the most widely used human ß cell lines, as a translational human ß cell model based on omics and characterize the EndoC-ßH1 secretome. We profiled EndoC-ßH1 cells using RNA-seq, data-independent acquisition, and tandem mass tag proteomics of cell lysate. Omics profiles of EndoC-ßH1 cells were compared to human ß cells and insulinomas. Secretome composition was assessed by data-independent acquisition proteomics. Agreement between EndoC-ßH1 cells and primary adult human ß cells was ∼90% for global omics profiles as well as for ß cell markers, transcription factors, and enzymes. Discrepancies in expression were due to elevated proliferation rate of EndoC-ßH1 cells compared to adult ß cells. Consistently, similarity was slightly higher with benign nonmetastatic insulinomas. EndoC-ßH1 secreted 783 proteins in untreated baseline state and 3135 proteins when stressed with nontargeting control siRNA, including known ß cell hormones INS, IAPP, and IGF2. Further, EndoC-ßH1 secreted proteins known to generate bioactive peptides such as granins and enzymes required for production of bioactive peptides. EndoC-ßH1 secretome contained an unexpectedly high proportion of predicted extracellular vesicle proteins. We believe that secretion of extracellular vesicles and bioactive peptides warrant further investigation with specialized proteomics workflows in future studies.

Pharmacists' Knowledge, Attitudes, Behaviors and Information Sources on Antibiotic Use and Resistance in Jordan.

Antimicrobial resistance (AMR) is a serious healthcare problem that affects public health globally. Appropriate understanding and knowledge of prudent antimicrobial use and resistance, along with providing evidence-based information sources, are needed for informed antibiotic prescribing practices. This study aimed to assess the knowledge, opportunity, motivation, behavior of pharmacists and their information sources regarding antibiotic use and resistance in Jordan. An online cross-sectional questionnaire was developed and administered to pharmacists during the period of July-September 2021. The survey is an adapted version of the validated European Centre for Disease Prevention and Control (ECDC) survey for antibiotic use and resistance. Pharmacists from all sectors (n = 384), of whom 276 (71.9%) were community pharmacists, completed an online questionnaire. While respondents scored highly (>87%) on knowledge on effective use, unnecessary use, and associated side effects of antibiotics, lower scores were recorded for knowledge on the spread of antibiotic resistance (52.9%). Pharmacists support easy access to guidelines on managing infections in 56% of cases, and easy access to materials advising prudent antibiotic use and resistance in 39.8% of cases. One-third of respondents (37.0%) reported no knowledge of any initiatives on antibiotic awareness and resistance. Pharmacists were aware (13.3%), unaware (36.2%), or unsure (50.5%) of the existence of a national antibiotic resistance action plan. Pharmacists indicated an interest in receiving more information on resistance to antibiotics (55.2%), medical conditions for which antibiotics are used (53.1%), how to use antibiotics (45.1%), prescribing of antibiotics (34.4%), and links between the health of humans, animals, and the environment (28.6%). Findings can inform antimicrobial stewardship with required interventions to improve antibiotic use.

Mechanistic Insights into a CDK9 Inhibitor Via Orthogonal Proteomics Methods.

Cyclin-dependent-kinases (CDKs) are members of the serine/threonine kinase family and are highly regulated by cyclins, a family of regulatory subunits that bind to CDKs. CDK9 represents one of the most studied examples of these transcriptional CDKs. CDK9 forms a heterodimeric complex with its regulatory subunit cyclins T1, T2 and K to form the positive transcription elongation factor b (P-TEFb). This complex regulates transcription via the phosphorylation of RNA polymerase II (RNAPolII) on Ser-2, facilitating promoter clearance and transcription elongation and thus remains an attractive therapeutic target. Herein, we have utilized classical affinity purification chemical proteomics, kinobeads assay, compressed CEllular Thermal Shift Assay (CETSA)-MS and Limited Proteolysis (LiP) to study the selectivity, target engagement and downstream mechanistic insights of a CDK9 tool compound. The above experiments highlight the value of quantitative mass spectrometry approaches to drug discovery, specifically proteome wide target identification and selectivity profiling. The approaches utilized in this study unanimously indicated that the CDK family of kinases are the main target of the compound of interest, with CDK9, showing the highest target affinity with remarkable consistency across approaches. We aim to provide guidance to the scientific community on the available chemical biology/proteomic tools to study advanced lead molecules and to highlight pros and cons of each technology while describing our findings in the context of the CDKs biology.