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Previous studies on biocatalytic transformations of pinenes by cytochrome P450 (CYP) enzymes reveal the formation of different oxygenated products from a single substrate due to the multistate reactivity of CYP and the many reactive sites in the pinene scaffold. Up until now, the detailed mechanism of these biocatalytic transformations of pinenes have not been reported. Hereby, we report a systematic theoretical study of the plausible hydrogen abstraction and hydroxylation reactions of α- and β-pinenes by CYP using the density functional theory (DFT) method. All DFT calculations in this study were based on B3LYP/LAN computational methodology using the Gaussian09 software. We used the B3LYP functional with corrections for dispersive forces, BSSE, and anharmonicity to study the mechanism and thermodynamic properties of these reactions using a bare model (without CYP) and a pinene-CYP model. According to the potential energy surface and Boltzmann distribution for radical conformers, the major reaction products of CYP-catalyzed hydrogen abstraction from β-pinene are the doublet trans (53.4%) and doublet cis (46.1%) radical conformer at delta site. The formation of doublet cis/trans hydroxylated products released a total Gibbs free energy of about 48 kcal/mol. As for alpha pinene, the most stable radicals were trans-doublet (86.4%) and cis-doublet (13.6%) at epsilon sites, and their hydroxylation products released a total of ~50 kcal/mol Gibbs free energy. Our results highlight the likely C-H abstraction and oxygen rebounding sites accounting for the multi-state of CYP (doublet, quartet, and sextet spin states) and the formation of different conformers due to the presence of cis/trans allylic hydrogen in α-pinene and β-pinene molecules. [ABSTRACT FROM AUTHOR]

Several psychosocial, sleep/circadian, and cardiometabolic disorders have intricately interconnected pathologies involving melatonin disruption. Therefore, we hypothesize that melatonin could be a therapeutic target for treating potential comorbid diseases associated with this triad of psychosocial-sleep/circadian-cardiometabolic disorders. We investigated melatonin's target prediction and tractability for this triad of disorders. The melatonin's target prediction for the proposed psychosocial-sleep/circadian-cardiometabolic disorder triad was investigated using databases from Europe PMC, ChEMBL, Open Targets Genetics, Phenodigm, and PheWAS. The association scores for melatonin receptors MT1 and MT2 with this disorder triad were explored for evidence of target–disease predictions. The potential of melatonin as a tractable target in managing the disorder triad was investigated using supervised machine learning to identify melatonin activities in cardiovascular, neuronal, and metabolic assays at the cell, tissue, and organism levels in a curated ChEMBL database. Target–disease visualization was done by graphs created using "igraph" library-based scripts and displayed using the Gephi ForceAtlas algorithm. The combined Europe PMC (data type: text mining), ChEMBL (data type: drugs), Open Targets Genetics Portal (data type: genetic associations), PhenoDigm (data type: animal models), and PheWAS (data type: genetic associations) databases yielded types and varying levels of evidence for melatonin-disease triad correlations. Of the investigated databases, 235 association scores of melatonin receptors with the targeted diseases were greater than 0.2; to classify the evidence per disease class: 37% listed psychosocial disorders, 9% sleep/circadian disorders, and 54% cardiometabolic disorders. Using supervised machine learning, 546 cardiovascular, neuronal, or metabolic experimental assays with predicted or measured melatonin activity scores were identified in the ChEMBL curated database. Of 248 registered trials, 144 phase I to IV trials for melatonin or agonists have been completed, of which 33.3% were for psychosocial disorders, 59.7% were for sleep/circadian disorders, and 6.9% were for cardiometabolic disorders. Melatonin's druggability was evidenced by evaluating target prediction and tractability for the triad of psychosocial-sleep/circadian-cardiometabolic disorders. While melatonin research and development in sleep/circadian and psychosocial disorders is more advanced, as evidenced by melatonin association scores, substantial evidence on melatonin discovery in cardiovascular and metabolic disorders supports continued R&D in cardiometabolic disorders, as evidenced by melatonin activity scores. A multiplatform analysis provided an integrative assessment of the target–disease investigations that may justify further translational research. [ABSTRACT FROM AUTHOR]

This is a cross-sectional study that was conducted at Jordan University Hospital (JUH) to evaluate the appropriateness of Urinary Tract Infection (UTI) empiric treatment based on microbial culture data and susceptibility testing. All urine cultures requested for adult patients (≥18 years) admitted to JUH within the period from January 2019–July 2021 were reviewed and only those cultures with positive episodes of infection were considered. In this study, 6950 urine culture episodes were screened; among them, 34.5% (n = 2400) revealed positive results. Among those patients with positive culture episodes, 1600 patients (66.7%) were discharged before the availability of culture results and were excluded. Of the remaining eligible 800 patients, 701 (87.6%) received empiric treatment. In 26.8% of the eligible cases (n = 214), the prescribed empiric agents failed to have appropriate coverage of the identified pathogens, and in 14.6% of the cases (n = 117) the identified microorganisms were reported as resistant to the prescribed empiric agents. Furthermore, only 13.4% of the patients (n = 107) were appropriately treated for their UTI with empiric antibacterial agents. We were not able to judge the appropriateness of UTI treatment for one third (n = 263, 32.9%) of the patients, because they did not have susceptibility reports performed. This study revealed an alarmingly high rate of inappropriate treatment of UTIs, which encourages the emergence of bacterial resistance and affects health-related outcomes negatively. Therefore, antimicrobial stewardship programs must be applied to optimize antibiotic consumption in hospital settings. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate health professionals' perceptions regarding the level of implementation of the Antimicrobials Stewardship (AMS) programs in Jordanian tertiary hospitals and to assess the perceived barriers to its implementation. During this cross-sectional study, a total of 157 healthcare providers agreed to participate (response rate 96.3%). Participants were asked to complete an electronic survey after meeting them at their working sites. Only 43.9% of the healthcare providers (n = 69) reported having an AMS committee in their hospital settings. The results suggested that private hospitals have significantly better AMS implementation compared to public hospitals among four areas (p ≤ 0.05). Moreover, the results showed that the most widely available strategies to implement AMS were infectious disease/microbiology advice (n = 112, 71.3%), and treatment guidelines (n = 111, 70.7%). Additionally, the study revealed that the main barrier to AMS implementation was the lack of information technology support (n = 125, 79.6%). These findings could draw managers' attention to the importance of AMS and support the health care provider's practice of AMS in Jordanian tertiary hospitals by making the right decisions and the required modifications regarding the strategies needed for the implementation of AMS programs. [ABSTRACT FROM AUTHOR]

Lack of medication adherence among patients with dyslipidemia negatively affects health-related outcomes. This study aims to evaluate medication adherence; we also aim to investigate the predictors of non-adherence among patients with dyslipidemia in Jordan. Medication adherence was evaluated in a total of 228 dyslipidemia patients. The Beliefs about Medicines Questionnaire was also used to assess patients' beliefs about medications. The majority of the current study participants (73.2%) reported non-adherence to the prescribed medications. There were significant negative associations between medication adherence and concerns of prescription drug use (B = −0.41, p-value < 0.01), duration of dyslipidemia (B = −0.22, p-value < 0.01), and the number of medications (B = −0.64, p-value < 0.01). Positive associations were found between medication adherence and the necessity of prescription drug use (B = 0.43, p-value < 0.01), taking statin and fibrate (B = 2.04, p-value < 0.01), and moderate-intensity statin (B = 2.34, p-value < 0.01). As for patients' beliefs about medications, the item "My medicine to lower my cholesterol disrupted my life" had the highest mean (3.50 ± 0.99). This study revealed a low adherence rate to medication among patients with dyslipidemia. It also demonstrates modifiable factors such as beliefs regarding perceived risk, medication harms, treatment duration, and the number of medications associated with poor adherence in patients with dyslipidemia. [ABSTRACT FROM AUTHOR]

The Center for Disease Control and Prevention and the World Health Organization issued a practical approach and Global Action Plan to control the threatening emerging antibacterial resistance. One of the main bases of this plan is the Antimicrobial Stewardship Program (ASPs). This study aimed to evaluate community pharmacists' awareness and perception towards antimicrobial resistance and ASPs in Jordan. Thus, a qualitative study was conducted through in-depth interviews with twenty community pharmacists. Convenience sampling was used in the study. Qualitative analysis of the data yielded four themes and eleven sub-themes. All the respondents showed a good understanding of the causes of antimicrobial resistance. The most important cause reported by them was the non-restricted prescription of antimicrobials. Most of the pharmacists believed that they are competent to provide ASPs, however, they believed that there are several barriers against the implementation of ASPs in community pharmacies in Jordan. Barriers demonstrated by the pharmacists, included organizational obstacles, resources obstacles, and personal obstacles. In conclusion, this study revealed several barriers against the implementation of ASPs in community pharmacies in Jordan. Incorporating ASPs in the community pharmacy settings requires proper pharmacist training, several academic disciplines team efforts, and good pharmacy practice of antimicrobial guidelines. [ABSTRACT FROM AUTHOR]

Sneezing (sternutatio) is a poorly understood polysynaptic physiologic reflex phenomenon. Sneezing has exerted a strange fascination on humans throughout history, and induced sneezing was widely used by physicians for therapeutic purposes, on the assumption that sneezing eliminates noxious factors from the body, mainly from the head. The present contribution examines the various mixtures used for inducing sneezes (remedia sternutatoria) over the centuries. The majority of the constituents of the sneeze-inducing remedies are modulators of transient receptor potential (TRP) channels. The TRP channel superfamily consists of large heterogeneous groups of channels that play numerous physiological roles such as thermosensation, chemosensation, osmosensation and mechanosensation. Sneezing is associated with the activation of the wasabi receptor, (TRPA1), typical ligand is allyl isothiocyanate and the hot chili pepper receptor, (TRPV1), typical agonist is capsaicin, in the vagal sensory nerve terminals, activated by noxious stimulants. [ABSTRACT FROM AUTHOR]

The term ionone is derived from "iona" (Greek for violet) which refers to the violet scent and "ketone" due to its structure. Ionones can either be chemically synthesized or endogenously produced via asymmetric cleavage of β-carotene by β-carotene oxygenase 2 (BCO2). We recently proposed a possible metabolic pathway for the conversion of α-and β-pinene into α-and β-ionone. The differences between BCO1 and BCO2 suggest a unique physiological role of BCO2; implying that β-ionone (one of BCO2 products) is involved in a prospective biological function. This review focuses on the effects of ionones and the postulated mechanisms or signaling cascades involved mediating these effects. β-Ionone, whether of an endogenous or exogenous origin possesses a range of pharmacological effects including anticancer, chemopreventive, cancer promoting, melanogenesis, anti-inflammatory and antimicrobial actions. β-Ionone mediates these effects via activation of olfactory receptor (OR51E2) and regulation of the activity or expression of cell cycle regulatory proteins, pro-apoptotic and anti-apoptotic proteins, HMG-CoA reductase and pro-inflammatory mediators. α-Ionone and β-ionone derivatives exhibit anti-inflammatory, antimicrobial and anticancer effects, however the corresponding structure activity relationships are still inconclusive. Overall, data demonstrates that ionone is a promising scaffold for cancer, inflammation and infectious disease research and thus is more than simply a violet's fragrance. [ABSTRACT FROM AUTHOR]