Pharmacokinetics of d- and l-norfenfluramine following their administration as individual enantiomers in rats.

The effect of fenfluramine and norfenfluramine enantiomers in rodent seizure models and their correlation with the pharmacokinetics of d- and l-fenfluramine in rats have been reported recently. To complement these findings, we investigated the pharmacokinetics of d- and l- norfenfluramine in rat plasma and brain. Sprague-Dawley rats were injected intraperitoneally with 20 mg/kg and 1 mg/kg l- norfenfluramine. A 1 mg/kg dose of d-norfenfluramine was used because higher doses caused severe toxicity. The concentration of each enantiomer in plasma and brain was determined at different time points by liquid chromatography/mass spectrometry. Pharmacokinetic parameters were compared between norfenfluramine enantiomers, and with those reported previously for fenfluramine enantiomers after a 20 mg/kg, i.p., dose. All enantiomers were absorbed rapidly and eliminated, with half-lives ranging from 0.9 h (l-fenfluramine) to 6.1 h (l- norfenfluramine, 20 mg/kg) in plasma, and from 3.6 h (d-fenfluramine) to 8.0 h (l-fenfluramine) in brain. Brain-to-plasma concentration ratios ranged from 15.4 (d-fenfluramine) to 27.6 (d-norfenfluramine), indicating extensive brain penetration. The fraction of d- and l-fenfluramine metabolized to norfenfluramine was estimated to be close to unity. This work is part of ongoing investigations to determine the potential value of developing enantiomerically pure l-fenfluramine or l-norfenfluramine as follow-up compounds to the marketed racemic fenfluramine.

Factors affecting judgment accuracy when scoring children's responses to non-word repetition stimuli in real time.

BACKGROUND: Non-word repetition (NWR) tests are an important way speech and language therapists (SaLTs) assess language development. NWR tests are often scored whilst participants make their responses (i.e., in real time) in clinical and research reports (documented here via a secondary analysis of a published systematic review). AIMS: The main aim was to determine the extent to which real-time coding of NWR stimuli at the whole-item level (as correct/incorrect) was predicted by models that had varying levels of detail provided from phonemic transcriptions using several linear mixed method (LMM) models. METHODS & PROCEDURES: Live scores and recordings of responses on the universal non-word repetition (UNWR) test were available for 146 children aged between 3 and 6 years where the sample included all children starting in five UK schools in one year or two consecutive years. Transcriptions were made of responses to two-syllable NWR stimuli for all children and these were checked for reliability within and between transcribers. Signal detection analysis showed that consonants were missed when judgments were made live. Statistical comparisons of the discrepancies between target stimuli and transcriptions of children's responses were then made and these were regressed against live score accuracy. Six LMM models (three normalized: 1a, 2a, 3a; and three non-normalized: 1b, 2b, 3b) were examined to identify which model(s) best captured the data variance. Errors on consonants for live scores were determined by comparison with the transcriptions in the following ways (the dependent variables for each pair of models): (1) consonants alone; (2) substitutions, deletions and insertions of consonants identified after automatic alignment of live and transcribed materials; and (3) as with (2) but where substitutions were coded further as place, manner and voicing errors. OUTCOMES & RESULTS: The normalized model that coded consonants in non-words as 'incorrect' at the level of substitutions, deletions and insertions (2b) provided the best fit to the real-time coding responses in terms of marginal R2, Akaike's information criterion (AIC) and Bayesian information criterion (BIC) statistics. CONCLUSIONS & IMPLICATIONS: Errors that occur on consonants when non-word stimuli are scored in real time are characterized solely by the substitution, deletion and insertion measure. It is important to know that such errors arise when real-time judgments are made because NWR tasks are used to assess and diagnose several cognitive-linguistic impairments. One broader implication of the results is that future work could automate the analysis procedures to provide the required information objectively and quickly without having to transcribe data. WHAT THIS PAPER ADDS: What is already known on this subject Children and patients with a wide range of cognitive and language difficulties are less accurate relative to controls when they attempt to repeat non-words. Responses to non-words are often scored as correct or incorrect at the time the test is conducted. Limited assessments of this scoring procedure have been conducted to date. What this study adds to the existing knowledge Live NWR scores made by 146 children were available and the accuracy of these judgements was assessed here against ones based on phonemic transcriptions. Signal detection analyses showed that live scoring missed consonant errors in children's responses. Further analyses, using linear mixed effect models, showed that live judgments led to consonant substitution, deletion and insertion errors. What are the practical and clinical implications of this work? Improved and practicable NWR scoring procedures are required to provide SaLTs with better indications about children's language development (typical and atypical) and for clinical assessments of older people. The procedures currently used miss substitutions, deletions and insertions. Hence, procedures are required that provide the information currently only available when materials are transcribed manually. The possibility of training automatic speech recognizers to provide this level of detail is raised.

Comparative activity of the enantiomers of fenfluramine and norfenfluramine in rodent seizure models, and relationship with their concentrations in plasma and brain.

OBJECTIVES: To investigate the comparative antiseizure activity of the individual enantiomers of fenfluramine and its major active primary metabolite norfenfluramine in rodent seizure models, and its relationship with the pharmacokinetics of these compounds in plasma and brain. METHODS: The antiseizure potency of d,l-fenfluramine (racemic fenfluramine) was compared with the respective potencies of its individual enantiomers and the individual enantiomers of norfenfluramine using the maximal electroshock (MES) test in rats and mice, and the 6-Hz 44 mA test in mice. Minimal motor impairment was assessed simultaneously. The time course of seizure protection in rats was compared with the concentration profiles of d-fenfluramine, l-fenfluramine, and their primary active metabolites in plasma and brain. RESULTS: All compounds tested were active against MES-induced seizures in rats and mice after acute (single-dose) administration, but no activity against 6-Hz seizures was found even at doses up to 30 mg/kg. Estimates of median effective doses (ED50 ) in the rat-MES test were obtained for all compounds except for d-norfenfluramine, which caused dose-limiting neurotoxicity. Racemic fenfluramine had approximately the same antiseizure potency as its individual enantiomers. Both d- and l-fenfluramine were absorbed and distributed rapidly to the brain, suggesting that seizure protection at early time points (≤2 h) was related mainly to the parent compound. Concentrations of all enantiomers in brain tissue were >15-fold higher than those in plasma. SIGNIFICANCE: Although there are differences in antiseizure activity and pharmacokinetics among the enantiomers of fenfluramine and norfenfluramine, all compounds tested are effective in protecting against MES-induced seizures in rodents. In light of the evidence linking the d-enantiomers to cardiovascular and metabolic adverse effects, these data suggest that l-fenfluramine and l-norfenfluramine are potentially attractive candidates for a chiral switch approach leading to development of a novel, enantiomerically-pure antiseizure medication.

Giant Cell Tumor of the Temporal Bone and Skull Base.

Giant cell tumor (GCT) is a benign tumor that originates from undifferentiated mesenchymal cells of the bone marrow. The craniums as well as temporal bone are extremely rare locations for GCTs. Clinical, radiological, and anatomical diagnosis of this locally aggressive disease poses a major challenge in clinical practice. In this article, we present a clinical study for a 35-year-old female who was found to have left-sided temporal bone GCT with extension to middle cranial fossa and temporomandibular joint (TMJ) with its clinical features and management.

The Hydrophobic Residues in Amino Terminal Domains of Cx46 and Cx50 Are Important for Their Gap Junction Channel Ion Permeation and Gating.

Lens gap junctions (GJs) formed by Cx46 and Cx50 are important to keep lens transparency. Functional studies on Cx46 and Cx50 GJs showed that the Vj-gating, single channel conductance (γj), gating polarity, and/or channel open stability could be modified by the charged residues in the amino terminal (NT) domain. The role of hydrophobic residues in the NT on GJ properties is not clear. Crystal and cryo-EM GJ structures have been resolved, but the NT domain structure has either not been resolved or has showed very different orientations depending on the component connexins and possibly other experimental conditions, making it difficult to understand the structural basis of the NT in Vj-gating and γj. Here, we generated missense variants in Cx46 and Cx50 NT domains and studied their properties by recombinant expression and dual whole-cell patch clamp experiments on connexin-deficient N2A cells. The NT variants (Cx46 L10I, N13E, A14V, Q15N, and Cx50 I10L, E13N, V14A, N15Q) were all able to form functional GJs with similar coupling%, except Cx46 N13E, which showed a significantly reduced coupling%. The GJs of Cx46 N13E, A14V and Cx50 E13N, N15Q showed a reduced coupling conductance. Vj-gating of all the variant GJs were similar to the corresponding wild-type GJs except Cx46 L10I. The γj of Cx46 N13E, A14V, Cx50 E13N, and N15Q GJs was reduced to 51%, 82%, 87%, and 74%, respectively, as compared to their wild-type γjs. Structural models of Cx46 L10I and A14V predicted steric clashes between these residues and the TM2 residues, which might be partially responsible for our observed changes in GJ properties. To verify the importance of hydrophobic interactions, we generated a variant, Cx50 S89T, which also shows a steric clash and failed to form a functional GJ. Our experimental results and structure models indicate that hydrophobic interactions between the NT and TM2 domain are important for their Vj-gating, γj, and channel open stability in these and possibly other GJs.

Diagnosing Coronary Artery Disease on the Basis of Hard Ensemble Voting Optimization.

Background and Objectives: Recently, many studies have focused on the early diagnosis of coronary artery disease (CAD), which is one of the leading causes of cardiac-associated death worldwide. The effectiveness of the most important features influencing disease diagnosis determines the performance of machine learning systems that can allow for timely and accurate treatment. We performed a Hybrid ML framework based on hard ensemble voting optimization (HEVO) to classify patients with CAD using the Z-Alizadeh Sani dataset. All categorical features were converted to numerical forms, the synthetic minority oversampling technique (SMOTE) was employed to overcome imbalanced distribution between two classes in the dataset, and then, recursive feature elimination (RFE) with random forest (RF) was used to obtain the best subset of features. Materials and Methods: After solving the biased distribution in the CAD data set using the SMOTE method and finding the high correlation features that affected the classification of CAD patients. The performance of the proposed model was evaluated using grid search optimization, and the best hyperparameters were identified for developing four applications, namely, RF, AdaBoost, gradient-boosting, and extra trees based on an HEV classifier. Results: Five fold cross-validation experiments with the HEV classifier showed excellent prediction performance results with the 10 best balanced features obtained using SMOTE and feature selection. All evaluation metrics results reached > 98% with the HEV classifier, and the gradient-boosting model was the second best classification model with accuracy = 97% and F1-score = 98%. Conclusions: When compared to modern methods, the proposed method perform well in diagnosing coronary artery disease, and therefore, the proposed method can be used by medical personnel for supplementary therapy for timely, accurate, and efficient identification of CAD cases in suspected patients.

Real-time data of COVID-19 detection with IoT sensor tracking using artificial neural network.

The coronavirus pandemic has affected people all over the world and posed a great challenge to international health systems. To aid early detection of coronavirus disease-2019 (COVID-19), this study proposes a real-time detection system based on the Internet of Things framework. The system collects real-time data from users to determine potential coronavirus cases, analyses treatment responses for people who have been treated, and accurately collects and analyses the datasets. Artificial intelligence-based algorithms are an alternative decision-making solution to extract valuable information from clinical data. This study develops a deep learning optimisation system that can work with imbalanced datasets to improve the classification of patients. A synthetic minority oversampling technique is applied to solve the problem of imbalance, and a recursive feature elimination algorithm is used to determine the most effective features. After data balance and extraction of features, the data are split into training and testing sets for validating all models. The experimental predictive results indicate good stability and compatibility of the models with the data, providing maximum accuracy of 98% and precision of 97%. Finally, the developed models are demonstrated to handle data bias and achieve high classification accuracy for patients with COVID-19. The findings of this study may be useful for healthcare organisations to properly prioritise assets.

Pharmacy service accreditation: Raising the bar of practice standards.

PURPOSE: To summarize the journey of a tertiary and quaternary care hospital outside the United States in receiving American Society of Health-System Pharmacists (ASHP) accreditation for its pharmacy services. SUMMARY: Tertiary and quaternary care hospitals have gained their reputation owing to the high quality and advanced services that they provide. Our organization, King Faisal Hospital & Research Center (KFSH&RC), Riyadh, Saudi Arabia, is a 1300-bed capacity hospital that serves as a center of excellence in solid organ transplant, genetic and metabolic diseases, hematology and oncology, and cardiology, in addition to a diversity of medical services. Accreditation of the pharmacy services by ASHP represents an important recognition of the quality and breadth of the services performed at KFSH&RC. The process of accreditation and the accreditation standards have also continued to serve as a guide for the hospital to maintain pharmacy service standards as they evolve. CONCLUSION: As the first internationally accredited pharmacy services, KFSH&RC now demonstrates the path forward for other international hospitals seeking to reach the same standards of practice defined by ASHP.

Developing a multidisciplinary HCV direct-acting antivirals utilization management and assessment program.

BACKGROUND: The introduction of direct-acting antivirals (DAAs) for the treatment of hepatitis C virus (HCV) infections has revolutionized outcomes for patients with HCV. Cost-effective use of these antivirals in addition to ensuring patient adherence is of paramount importance. OBJECTIVES: The goal of this article is to describe the processes by which a tertiary care, multisite institution managed the complexities involved in administering DAA treatment and managing the increased cost of therapy. Specifically, the objectives of this article are to describe the development of a multidisciplinary HCV management program and the role of pharmacists in this program, including formulary management strategies and monitoring of DAAs use in our institution, development of guidelines, electronic prescribing protocols and order sets, and specific outcomes based on a concurrent medication use evaluation. PRACTICE DESCRIPTION: King Faisal Specialist Hospital and Research Centre is a tertiary care referral hospital. As a tertiary referral hospital, it offers primary and highly specialized inpatient and outpatient medical care. The process of selecting and developing institutional HCV management program is described. PRACTICE INNOVATION: This article provides key details regarding how a multidisciplinary HCV program using DAAs can be implemented successfully at a tertiary care facility. Key facets of our innovation include establishing formulary guidelines, setting up eligibility criteria for patients, and establishing an HCV taskforce and multidisciplinary HCV program clinic. EVALUATION: Medication use evaluations were regularly conducted to monitor sustained virologic response rates, adherence to guidelines, adverse reactions, and drug interactions. METHODS: Formulary guidelines, setting up an eligibility criterion for patients, and an HCV taskforce and multidisciplinary HCV program clinic were established. RESULTS: The involvement of pharmacists in a multidisciplinary HCV program in outpatient settings resulted in improved formulary decision making, reduction of costs, and improvement of adherence to institutional guidelines. PRACTICE IMPLICATIONS: The role of a pharmacist in the management of patients with HCV with DAAs is important. Pharmacists play an integral part in medication management and overall reduction in health care expenditure. Many disease management programs can be complemented with pharmacists to improve patient care and reduce cost. CONCLUSION: HCV treatment is challenging, and a multidisciplinary approach to treat HCV is critical. It is a rapidly evolving field; therefore, it requires dynamic formulary management and collaborative practice approaches to monitor pharmacotherapy carefully and efficiently. Clinical pharmacists play a pivotal role within the multidisciplinary team by providing support to both patients and health care providers with regard to the treatment of HCV.

Impact of prior hysterectomy on surgical outcomes for laparoscopic adnexal surgery.

BACKGROUND: Adnexal surgery is believed to be more complex in patients with prior hysterectomy; however, there is little data regarding surgical outcomes. Understanding of individualized risks improves counseling, informed consent, and preoperative planning. METHODS: We performed a retrospective cohort study with a control group; we evaluated 744 patients undergoing laparoscopic adnexal surgery at an academic tertiary care center from 2011 to 2015. Comparisons were made using Chi square, Fisher's exact, or Wilcoxon-rank sum tests. We used log-binomial regression to calculate risk ratio and 95% confidence interval. RESULTS: Patients with prior hysterectomy were more likely to have intraoperative or postoperative complications at the time of laparoscopic adnexal surgery when compared to patients without prior hysterectomy [17.7% vs. 10.2%, p = 0.02, risk ratio (RR) 1.7, 95% confidence interval (CI) 1.1-2.7]. Patients with prior hysterectomy were four times more likely to have intraoperative complications (3.2% vs. 0.8%, p = 0.047, RR 4.0, 95% CI 1.1-14.7), and five times more likely to have conversion to laparotomy (5.6% vs. 1.1%, p = 0.004, RR 5.0, 95% CI 1.8-14.0). Patients with prior hysterectomy were more likely to need additional procedures, including lysis of adhesions (69.4% vs. 26.0%, p < 0.001), ureterolysis (15.3% vs. 4.8%, p < 0.001), and cystoscopy (28.2% vs. 8.1%, p < 0.001). They had longer operative time [101.5 min (IQR 59.5-135.0) vs. 78.0 min (IQR 53.0-109.0, p < 0.001)], and were less likely to have outpatient surgery (56.5% vs. 84.8%, p < 0.01). Postoperative complications were also more common (15.3% vs. 9.4%, p = 0.046). CONCLUSIONS: Patients with prior hysterectomy were 70% more likely to have a complication at the time of laparoscopic adnexal surgery than patients without hysterectomy. Increased risk of complications in subsequent adnexal surgery may influence the informed consent process or decisions regarding ovarian conservation. Awareness of potential need for additional surgical procedures may guide availability of equipment, choice of operating site, or referral to an advanced pelvic surgeon.

Factors affecting the viability of Staphylococcus aureus and production of enterotoxin during processing and storage of white-brined cheese.

Staphylococcus aureus is a major foodborne pathogen that causes severe disease in humans. It is commonly found in milk and dairy products, particularly in fresh brined cheese. Our aim was to investigate the behavior of Staph. aureus and enterotoxin production during the storage of white-brined cheese prepared with or without a starter culture and stored in a 10 or 15% NaCl brine at 10°C and 25°C for 28 d. NaCl concentration, water activity, pH, and number of Staph. aureus and lactic acid bacteria were determined in cheese and brine. Only 1 of 4 Staph. aureus strains (ATCC 439) was positive for enterotoxin production, and its production was detected in unsalted UHT milk, but not in salted milk or in any of the cheese treatments held at 37°C for 1, 3, or 7 d. Staphylococcus aureus grew in the cheese stored in both brines at 10°C and 25°C, regardless of the presence of a starter culture, although the latter significantly reduced Staph. aureus growth in cheese or its brine at 10°C. Staphylococcus aureus numbers were increased by 2.26 and 0.47 log10 cfu/g in cheese stored in 10 and 15% NaCl brine, respectively, in the presence of starter culture, and by 2.78 and 2.96 log10 cfu/g, respectively, in the absence of starter culture at 10°C. Nonetheless, the pathogen grew, but at a lower number in the brines. The salt concentration of cheese stored in 10% brine remained at approximately 5% during storage; however, in 15% brine, the salt concentration increased to almost 8% (wt/wt) by 28 d. The addition of a starter culture, high salt concentration, low temperature, and pH (∼5.2) had inhibitory effects on the growth of Staph. aureus. Moreover, lactic acid bacterial numbers increased considerably in cheese and brine by d 28. The use of starter cultures, salt (15%), and low storage temperature (10°C) reduced the growth of Staph. aureus, and salt may have prevented enterotoxin production in white-brined cheese.

An evaluation of TAZ and YAP crosstalk with TGFß signalling in canine osteosarcoma suggests involvement of hippo signalling in disease progression.

BACKGROUND: Osteosarcoma (OSA) is the most common bone cancer in canines. Both transforming growth factor beta (TGFß) and Hippo pathway mediators have important roles in bone development, stemness, and cancer progression. The role of Hippo signalling effectors TAZ and YAP has never been addressed in canine OSA. Further, the cooperative role of TGFß and Hippo signalling has yet to be explored in osteosarcoma. To address these gaps, this study investigated the prognostic value of TAZ and YAP alone and in combination with pSmad2 (a marker of active TGFß signalling), as well as the involvement of a TGFß-Hippo signalling crosstalk in tumourigenic properties of OSA cells in vitro. An in-house trial tissue microarray (TMA) which contained 16 canine appendicular OSA cases undergoing standard care and accompanying follow-up was used to explore the prognostic role of TAZ, YAP and pSmad2. Published datasets were used to test associations between TAZ and YAP mRNA levels, metastasis, and disease recurrence. Small interfering RNAs specific to TAZ and YAP were utilized in vitro alone or in combination with TGFß treatment to determine their role in OSA viability, proliferation and migration. RESULTS: Patients with low levels of both YAP and pSmad2 when evaluated in combination had a significantly longer time to metastasis (log-rank test, p = 0.0058) and a longer overall survival (log rank test, p = 0.0002). No similar associations were found for TAZ and YAP mRNA levels. In vitro, TAZ knockdown significantly decreased cell viability, proliferation, and migration in metastatic cell lines, while YAP knockdown significantly decreased viability in three cell lines, and migration in two cell lines, derived from either primary tumours or their metastases. The impact of TGFß signaling activation on these effects was cell line-dependent. CONCLUSIONS: YAP and pSmad2 have potential prognostic value in canine appendicular osteosarcoma. Inhibiting YAP and TAZ function could lead to a decrease in viability, proliferation, and migratory capacity of canine OSA cells. Assessment of YAP and pSmad2 in larger patient cohorts in future studies are needed to further elucidate the role of TGFß-Hippo signalling crosstalk in canine OSA progression.

Accuracy of cast posts fabricated by the direct and the indirect techniques.

STATEMENT OF PROBLEM: Patterns for custom cast posts and cores can be fabricated either by the direct or the indirect technique. Which technique is more accurate is unknown. PURPOSE: The purpose of this in vitro study was to investigate the effect of pattern fabrication technique on the accuracy of post fit. MATERIAL AND METHODS: Ten intact extracted premolar teeth with a single canal and similar dimensions received root canal treatment. The teeth were sectioned 2 mm above the cementoenamel junction. A total of 20 cast post and core patterns, 2 for each tooth, were fabricated, 10 with the direct technique and 10 with the indirect technique. Patterns were cast to produce 20 cast post and cores. Each tooth was scanned using a microcomputed tomography (µCT) system with a resolution of 14.5 µm, once with the post of the direct technique and once with the post of the indirect technique. Ct analyzer software was used to calculate the overall space between the post and canal walls and the space areas in 3 different standardized sections. The Student paired t test was used to determine any significant difference in the scores of the groups. RESULTS: The overall space between the canal walls and posts made with the direct technique ranged between 7.86 and 17.39 mm(3), with a mean value of 12.25 mm(3), whereas with the indirect technique, the space ranged between 6.68 and 18.02 mm(3), with a mean of 11.92 mm(3). No significant differences were found between the results of either technique (P>.05). CONCLUSIONS: Within the limitations of this study, neither the indirect nor direct pattern fabrication technique influenced the accuracy of post fitting.

Retraction: An Aspirated Tooth Masquerading As Lung Cancer: A Unique Case Report.

[This retracts the article DOI: 10.7759/cureus.55890.].

An Aspirated Tooth Masquerading As Lung Cancer: A Unique Case Report.

Tooth aspiration, while commonly linked to predisposing conditions such as loose teeth, facial surgeries, or injuries, can also affect patients without apparent risk factors. Such small foreign body aspirations may go undiagnosed for many months as patients often tolerate the symptoms, such as chronic cough. However, the protracted course of unaddressed foreign body aspiration has the potential to resemble symptoms of malignancy, including persistent hemoptysis, weight loss, and fatigue. In this report, we detail the case of a 51-year-old man with underlying chronic obstructive pulmonary disease (COPD) whose history and symptoms initially suggested lung carcinoma. Further investigation uncovered an aspirated tooth as the culprit. The sequelae of pulmonary complications arising from endobronchial obstruction, such as post-obstructive pneumonia and atelectasis, as demonstrated in our case, further emphasize the importance of prompt detection and management of tooth aspiration.

Heavy metal and microbial testing of selected cosmetic products in the Palestinian market.

Excessive and continuous use of cosmetic products containing heavy metals can lead to harmful effects. International regulations mandate limited quantities of heavy metals contamination in cosmetic preparations to ensure consumer safety. This research aims to evaluate heavy metal and microbial contamination levels in selected cosmetic products available in the Palestinian market. We collected 35 samples randomly from 23 companies, representing four product types, and analyzed them for the presence of seven heavy metals: zinc (Zn), cadmium (Cd), lead (Pb), chromium (Cr), iron (Fe), copper (Cu), and arsenic (As) using an atomic absorption spectrometer. We also interviewed pharmacists who sold these cosmetics to assess their knowledge of allowed limits and toxic effects associated with increased heavy metal content in cosmetics. The results indicated that all tested products exceeded the allowed limit for Cd (9.5 ± 2.3 ppm), Cu (33.8 ± 9.2 ppm), and Zn (151.0 ± 7.4 ppm). However, none of the tested samples showed microbial contamination. These findings underscore the significant heavy metal contamination of cosmetics present in the Palestinian market. Thus, there is a pressing need to register and quality-test all cosmetic products sold in the Palestinian market and to raise the pharmacists' awareness and knowledge regarding heavy metals in cosmetics.

Challenges in Batch-to-Bed Translation Involving Inflammation-Targeting Compounds in Chronic Epilepsy: The Case of Cathepsin Activity-Based Probes.

Our goal was to test the feasibility of a new theranostic strategy in chronic epilepsy by targeting cathepsin function using novel cathepsin activity-based probes (ABPs). We assessed the biodistribution of fluorescent cathepsin ABPs in vivo, in vitro, and ex vivo, in rodents with pilocarpine-induced chronic epilepsy and naïve controls, in human epileptic tissue, and in the myeloid cell lines RAW 264.7 (monocytes) and BV2 (microglia). Distribution and localization of ABPs were studied by fluorescence scanning, immunoblotting, microscopy, and cross-section staining in anesthetized animals, in their harvested organs, in brain tissue slices, and in vitro. Blood-brain-barrier (BBB) efflux transport was evaluated in transporter-overexpressing MDCK cells and using an ATPase activation assay. Although the in vivo biodistribution of ABPs to both naïve and epileptic hippocampi was negligible, ex vivo ABPs bound cathepsins preferentially within epileptogenic brain tissue and colocalized with neuronal but not myeloid cell markers. Thus, our cathepsin ABPs are less likely to be of major clinical value in the diagnosis of chronic epilepsy, but they may prove to be of value in intraoperative settings and in CNS conditions with leakier BBB or higher cathepsin activity, such as status epilepticus.

An evaluation of pharmacists' general attitudes, knowledge, and phobias regarding medications that include corticosteroids: a cross-sectional study.

BACKGROUND: Corticosteroid-containing medications are widely accessible in various forms, including topical, injectable, and inhaled formulations. Due to uncertain safety profiles, healthcare providers, including pharmacists, often express apprehension when dispensing these drugs. This cross-sectional study assesses the knowledge, attitudes, and phobia of Jordanian pharmacists regarding corticosteroid-containing medications. METHODS: Conducted through a self-administered online questionnaire. RESULTS: the study reveals that dermatological conditions and respiratory disorders are the primary indications for prescribing corticosteroid-containing drugs. The most reported side effects among pharmacists' patients include increased appetite, diabetes, and skin thinning. Pharmacists generally exhibit acceptable knowledge, with a median score of 9.0 out of 11.0 (IQR = 3.0). Over two-thirds of pharmacists (69.9%) achieve a high knowledge score (Bloom's cut-off point ≥ 8.8). However, only 55.7% are aware that corticosteroids may induce mood changes. High phobia scores, particularly concerning increased blood pressure and osteoporosis risks, indicate pharmacist reservations in corticosteroid dispensing. Interestingly, pharmacists in rural areas display lower knowledge scores, while those working outside community pharmacies exhibit lower phobia scores compared to their counterparts in urban areas and community pharmacies, respectively. CONCLUSION: Despite generally good knowledge levels, the study underscores high phobia scores among Jordanian pharmacists regarding corticosteroid dispensing, particularly due to concerns about blood pressure elevation and osteoporosis risks. This suggests a potential need for targeted educational interventions and support systems to enhance pharmacist confidence and optimize corticosteroid usage while minimizing associated risks.

Empowering brain cancer diagnosis: harnessing artificial intelligence for advanced imaging insights.

Artificial intelligence (AI) is increasingly being used in the medical field, specifically for brain cancer imaging. In this review, we explore how AI-powered medical imaging can impact the diagnosis, prognosis, and treatment of brain cancer. We discuss various AI techniques, including deep learning and causality learning, and their relevance. Additionally, we examine current applications that provide practical solutions for detecting, classifying, segmenting, and registering brain tumors. Although challenges such as data quality, availability, interpretability, transparency, and ethics persist, we emphasise the enormous potential of intelligent applications in standardising procedures and enhancing personalised treatment, leading to improved patient outcomes. Innovative AI solutions have the power to revolutionise neuro-oncology by enhancing the quality of routine clinical practice.

The Role of the Gut Microbiome in Inflammatory Bowel Disease: The Middle East Perspective.

The gut microbiome is of paramount importance in preserving internal balance in the gastrointestinal tract; therefore, disruptions in its regulation have been linked to the development of inflammatory bowel disease (IBD). This article explores the intricate details of the gastrointestinal microbiome as it pertains to inflammatory bowel disease (IBD), with an emphasis on the Middle East. The study reviews the typical gut microbiome, modifications in inflammatory bowel disease (IBD), determinants impacting the gut microbiome of the Middle East, and prospective therapeutic interventions.