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Acute heart failure, advanced cardiac failure, cardiac surgery, and sepsis are conditions that require simultaneous treatment to stimulate contractility and/or reduce systemic vascular resistance, with levosimendan and milrinone being treatment options. This research's aim is to review the current indications and evidence for these medications across various scenarios. Evidence suggests that levosimendan is a non-inferior alternative to dobutamine and superior to milrinone in treating low cardiac output syndrome following cardiac surgery. In cases of septic shock, levosimendan has been linked to lower mortality rates compared to placebo, while milrinone's efficacy remains inconclusive. Furthermore, postoperative patients undergoing correction for congenital heart disease have shown reduced mechanical ventilation time and intensive care unit stays when treated with levosimendan, although differences exist between the populations assigned to each intervention. In conclusion, levosimendan, compared to milrinone, appears to offer better hemodynamic favorability in patients undergoing cardiac surgery. However, additional research is necessary to further understand its impact on hemodynamic outcomes, mortality, intensive care unit, and hospital stays in patients with cardiogenic shock of both ischemic and non-ischemic etiologies, as well as septic shock.

This study aims to elucidate the anti-hypoxia mechanism of sesamoside, an active component of Phlomis younghusbandii Mukerjee , through a network pharmacology approach. Sesamoside has demonstrated potential anti-oxidant and antiglycation activities. The hypoxia-related disease targets were collected from databases like GeneCards and OMIM. Protein-protein interaction (PPI) networks were constructed using the STRING database. GO/KEGG enrichment analysis was performed using the Metascape database to identify biological processes and signaling pathways. Our results indicate that sesamoside interacts with multiple targets related to glucose and lipid metabolism, nucleotide metabolism, and inflammatory, and we find that AKR1B1 (AR) plays a crucial role in sesamoside responses to hypoxia. Molecular docking studies were performed using Autodock software, revealing good binding activity between sesamoside and AR. We then use CCK-8 assay, qPCR, WB, and ELISA analysis to validate the role of sesamoside in regulating AR and participating in anti-hypoxia through cell experiments. The results show that compared with the hypoxia group, sesamoside treatment significantly improves the expression of AR and inflammation cytokines. In summary, this study sheds light on the anti-hypoxia mechanism of sesamoside using a network pharmacology approach, providing a theoretical basis and experimental foundation for its application in the prevention and treatment of hypoxic diseases.

Background: The use of antineoplastic agents is one of the important triggers of tumor lysis syndrome (TLS), but there is still a lack of comprehensive understanding of antineoplastic agents that may trigger TLS and the TLS risk differences between different antineoplastic agents. Objectives: This study aims to investigate the TLS risk of different antineoplastic agents and provide reference information for clinical practice. Design: Real-world adverse events data in the FDA Adverse Event Reporting System (FAERS) database were used as the basis for the disproportionality analysis. Methods: We reviewed the TLS reports in the FAERS database from 2004 to 2022 to summarize an antineoplastic agent list that was reported to trigger TLS, based on which we conducted disproportionality analysis to assess the TLS risk of each antineoplastic agent. Results: In all, 164 antineoplastic agents were reported to trigger TLS. On the whole, rituximab was the most reported antineoplastic agent in TLS reports, followed by cyclophosphamide, venetoclax, doxorubicin, and etoposide, while tagraxofusp was the antineoplastic agent with the highest adverse drug reaction (ADR) signal strength in signal detection, followed by floxuridine, pentostatin, tebentafusp, and venetoclax. Integrating ADR signal detection results, 129 of 164 antineoplastic agents showed at least one positive ADR signal, and six antineoplastic agents (bevacizumab, carboplatin, cisplatin, fluorouracil, lenvatinib, and paclitaxel) have the highest total number of positive signals. Further classifying the 164 antineoplastic agents into 46 chemical subgroups to conduct ADR signal detection, nitrogen mustard analogs were the most reported antineoplastic agent subclasses, followed by clusters of differentiation 20 inhibitors, and pyrimidine analogs, while clusters of differentiation 22 inhibitors were the antineoplastic agent subclass with the highest ADR signal strength, followed by podophyllotoxin derivatives and actinomycines. Conclusion: Our study showed the TLS risk characteristics of 164 antineoplastic agents by detecting and integrating ADR signals, which may help to optimize clinical practice.

The current radiation dose estimates used in medical imaging, radiation oncology or environmental assessments are not entirely accurate from a fundamental physics perspective, let alone for biological consequences. The “one cloth fits all” approach of radiation-matter interactions cannot assess the effects of interactions of the same species of radiation of different energies on the same isotope of an element. Preliminary steps to set the radiation dosimetry in the right direction are suggested.

Introduction: Epilepsy is a neurological disorder characterized by recurrent seizures. Although antiepileptic drugs (AEDs) reduce the frequency of epileptic seizures, they can cause renal and hepatic damage. Several preclinical studies have indicated that Emblica officinalis Gaertn (AMLA) exerts an anticonvulsant effect related to its tannin and polyphenol content. Objective: We aim to evaluate the anticonvulsant effects of chronic oral AMLA administration and its impact on biochemical and hematological parameters in rats. Methods: Twenty-eight male Wistar rats (250 to 300 g) were divided into four experimental groups (n = 7): vehicle (purified water), AMLA (500 and 700 mg/kg), and carbamazepine (CBZ) (300 mg/kg) as the pharmacological control of anticonvulsant activity. Treatments were administered orally every 24 hours for 28 days, while carbamazepine was administered every 48 hours for 5 days before the behavioral, biochemical, and hematological test. On day 29, Status epilepticus (SE) was induced using the lithium-pilocarpine model (3 mEq/kg, i . p . and 30 mg/kg, s . c .), after which the behavioral and biochemical effects were evaluated. Results: The AMLA 500 mg/kg and CBZ 300 mg/kg groups presented fewer phase V seizures than the vehicle group did. None of the treatments modified biochemical or hematological parameters. Conclusion: AMLA could be considered as a potential alternative therapy for the treatment of epilepsy.

Introduction Cell repair dynamics are crucial in optimizing anti-cancer therapies. Various assays (eg, comet assay and γ-H2AX) assess post-radiation repair kinetics, but interpreting such data is challenging and model-based data analyses are required. However, ambiguities in parameter calibration remain an unsolved challenge. To address this, we propose combining survival dose-rate effects with computer simulations to gain knowledge about repair kinetics. Methods After a literature review, theoretical discriminators based on common fractionation/dose-rate-related effects were defined to discard unrealistic model dynamics. The Multi-Hit Repair (MHR) model was calibrated with canine osteosarcoma Abrams cell line data to study the discriminators’ efficacy in scenarios with limited survival data. Additionally, survival dose-rate-dependent data from the human SiHa cervical cancer cell line were used to illustrate the survival behavior at diverse dose-rates and the capability of the MHR to model these data. Results SiHa data confirmed the validity of the proposed discriminators. The discriminators filtered 99% of parameter sets, improving the calibration of Abrams cells data. Furthermore, results from both cell lines may hint universal aspects of cellular repair. Conclusions Dose-rate theoretical discrimination criteria are an effective method to understand repair kinetics and improve radiobiological model calibration. Moreover, this methodology may be used to analyze diverse biological data using dynamic models in-silico .

Background Hemolacria, the excretion of blood-tinged tears, merges biological oddity with mysticism. This report discusses a unique case of hemolacria in a patient with possible idiopathic intracranial hypertension without papilledema (IIHWOP), resolving after acetazolamide treatment, exploring a potential pathogenic link. Case Presentation A 50-year-old male experienced daily hemolacria for three months along with occasional epistaxis and otorrhagia. He also suffered from chronic migraine, often accompanied with blurred vision and vertigo, and primary stabbing headache. Systemic and neurological assessments, along with computed tomography (CT) brain scans, ophthalmological and hematological tests revealed no underlying diseases. Brain magnetic resonance imaging (MRI) along with magnetic resonance venography, indicated left transverse sinus aplasia, bilateral ocular bulb flattening and enlargement of optic nerve sheaths, suggesting increased intracranial pressure. The patient began acetazolamide treatment. In the next three months, he experienced only four bleeding episodes and a dramatic reduction of monthly migraine days. Discussion Our report first associates hemolacria with possible IIHWOP, proposing a new pathogenic pathway. A derangement in the glymphatic system, implicated in idiopathic intracranial hypertension pathophysiology, could explain its ocular symptoms, including hemolacria. Our findings may contribute to understanding IIHWOP and the glympathic system's role in ocular physiology.

Background Medication overuse headache (MOH) presents a considerable challenge in patient care, with physicians playing a critical role in its prevention and management. However, awareness, knowledge, and practices regarding MOH among physicians are often found to be inadequate. Methods A cross-sectional study was conducted at King Chulalongkorn Memorial Hospital to investigate the awareness, knowledge, and practices concerning MOH among residents from family medicine, internal medicine, and neurology specialties. Participants were surveyed using an internet-based questionnaire. Results Of the 130 residents, 70 participated in the study. Ten percent were unaware that analgesics could exacerbate headaches, a finding particularly notable among family medicine residents. Furthermore, 11.4% of participants were uncertain about the classification of MOH, while 31.4% and 44.3% were uncertain about the frequency with which the use of simple analgesics and migraine-specific drugs could lead to MOH, respectively. This uncertainty was prevalent among residents in internal medicine and family medicine. Additionally, 22.9% of participants, especially those in internal medicine, prescribed opioids for abortive treatment in migraine patients. Residents in neurology generally performed better across various aspects compared to those in other specialties. Conclusion The study highlights a significant gap in the awareness, knowledge, and practices regarding MOH, particularly in non-neurology residency programs. Addressing these issues may require continuous medical education utilizing a multifaceted approach, encompassing undergraduate courses, postgraduate training, and public outreach.

Background: Ultrasound therapy is a non-invasive technique used to address a variety of health issues. Objectives: This systematic review and meta-analysis aim to assess the effectiveness of ultrasound therapy in alleviating pain associated with musculoskeletal diseases. Design: This study was conducted following PRISMA guidelines, with relevant articles identified through comprehensive searches in electronic databases. Data sources and methods: We conducted searches across multiple databases, including Scopus, PubMed, MEDLINE, ProQuest, Science Direct, CINAHL, AIM, and ELDIS. Two independent reviewers screened the titles and abstracts of the retrieved articles. We included randomized controlled trials (RCTs) and observational cohort studies published between 2010 and 2023 that evaluated ultrasound therapy for knee and shoulder skeletal disorders. The selected data were analyzed qualitatively and synthesized, with the risk of bias assessed using the RoB2 tool. Results: Initially, 117 articles were reviewed using the search strategy, and 10 trials that met the inclusion criteria were identified. In seven of these studies, the primary musculoskeletal disorder was osteoarthritis, while three studies focused on shoulder pain and impingement. Most studies indicated that ultrasound therapy significantly reduced pain. The meta-analysis showed that ultrasound therapy was significantly more effective than other interventions for knee disorders ( I 2 = 51%, Z = 2.65, p = 0.008). However, for shoulder disorders, both ultrasound and other intervention methods were found to be ineffective ( I 2 = 93%, Z = 0.73, p = 0.46). Conclusion: The current evidence supports the effectiveness of ultrasound therapy in reducing pain and aiding rehabilitation for knee conditions. However, there are mixed results regarding its efficacy for shoulder conditions, highlighting the need for further research in this area.

Introduction The management of acute exacerbations of trigeminal neuralgia remains a major clinical challenge due to the limited availability of clinical evidence. This retrospective case series aims to evaluate the effectiveness and safety of intravenous phenytoin in the treatment of these exacerbations. Methods We retrospectively analyzed the outcome of patients treated with intravenous phenytoin for acute exacerbations of trigeminal neuralgia at the University Hospital Zurich between January 2016 and December 2023. Statistical analyses were performed to assess the associations of patient and disease characteristics with phenytoin response. Results In our sample of 45 cases, treatment with phenytoin resulted in a significant or complete relief in 30 cases (66.7%), while 11 (24.4%) experienced slight relief and 4 (8.9%) none. Patient or disease characteristics were not associated with treatment response. Side effects were rare, with skin itching occurring in only one case. Conclusion This retrospective case series demonstrates, that phenytoin is a safe and effective treatment for acute exacerbations of trigeminal neuralgia. However, larger prospective studies are needed.

Background: Psychedelics are receiving growing interest among clinical researchers for their effects on mood and cognition. Psilocybin is one of the most widely studied classic psychedelics which has shown good safety and clinical benefit for major depression and substance use disorders. Athletes frequently sustain concussions and often experience myriad symptoms, including cognitive and mood issues, which can persist for weeks or months in 10%–30% of athletes. Psilocybin may be a potential symptom management option for athletes with persisting concussion symptoms. Objectives: This study sought to summarize athlete psychedelic use, among other substances, and to examine the willingness of the sports community to engage in or support psilocybin-assisted therapy (PAT) for concussion recovery and management of persisting concussion symptoms. Methods: In total, 175 ( n = 85 athletes; n = 90 staff) respondents completed an online survey distributed in Canada and the United States which queried sport involvement and demographics, substance use, concussion history, and knowledge and willingness about psilocybin. The reporting of this study conforms to the Checklist for Reporting Results of Internet E-Surveys (CHERRIES) statement. Design: Substance use rates were summarized across athletes and team staff members and a path analysis was used for each sample to identify predictors of willingness to use PAT (athletes) or support PAT (staff) for concussion recovery. Participants were also asked to identify perceived barriers to the implementation of PAT for sports-related concussions, and to indicate their overall willingness. Results: Psychedelics were the third most used substance in the past year among athletes (35.8%) while regular psychedelic use was quite low in athletes (7.5%). A path analysis conducted in RStudio found that attitudes toward psilocybin and knowledge of psilocybin were significant predictors for both athletes and staff members of their willingness to use or support PAT for concussion recovery. Athletes reported likely engaging in PAT (61.2%) and staff (71.1%) reported that they would support their athletes using PAT. Conclusion: The results of this study suggest that the sports community may be receptive to PAT and athletes would be willing to engage in it for concussion recovery and/or the management of persisting post-concussion symptoms (PPCS). Future research should examine the effects of psilocybin for PPCS to inform whether there is any impact while addressing concerns regarding long-term effects of psilocybin use.

Although it is well established that a vegetable-rich (Mediterranean) diet is associated with health benefits in later life, the mechanisms and biological origins of this benefit are not well established. This review seeks to identify the components a healthful diet that reduce the individual’s suffering from non-communicable disease and extend longevity. We note the difference between the claims made for an essential diet (that prevents deficiency syndromes) and those argued for a diet that also prevents or delays non-communicable diseases and ask: what chemicals in our food induce this added resilience, which is effective against cardiovascular and neurodegenerative diseases, diabetes and even cancer? Working in the framework of acquired resilience (tissue resilience induced by a range of stresses), we arguethat the toxins evolved by plants as part of allelopathy (the competition between plant species) are key in making the ‘healthful difference’. We further suggest the recognition of a category of micronutrients additional to the established ‘micro’ categories of vitamins and trace elements and suggest also that the new category be called ‘trace toxins’. Implications of these suggestions are discussed.

Background Buprenorphine (BPN) is a widely used analgesic in the pediatric population, although there are few studies on the pharmacokinetics and pharmacodynamics of this drug. Objective The objective was to characterize the pharmacokinetics of BPN after intravenous administration and analyze the effect of age, gender, weight, height, body mass index (BMI), and drug-drug interactions as covariates. Methods Ninety-nine children (2-10 years), who underwent orthopedic surgery under regional, general, or combined anesthesia were included. Patients evaluated according to the American Society of Anesthesiologists Physical Status Classification, who received intravenous BPN 2 μg/kg were enrolled. Blood was collected from 1-240 min. Drug plasma concentrations were determined by LC-MS/MS. Population pharmacokinetic parameters were obtained with Monolix 2021R1 software. Pearson’s correlation and/or ANOVA were used for statistical analysis. Results Age was associated with changes in clearance and central compartment volume and the female gender was associated with lower intercompartmental clearance, while BMI modified clearance, central and peripheral compartment volume. Concomitant administration of BPN with fentanyl and dexamethasone produced decreases in clearance. Conclusions The covariates of sex, age, and BMI are directly related to the increase or decrease in BPN pharmacokinetic parameters.

Background: Metabolic associated fatty liver disease (MAFLD) stands as the leading cause of chronic liver disease globally. Notably, individuals with metabolic risk factors, such as diabetes and obesity, exhibit a staggering prevalence of MAFLD, with estimates reaching up to 70%. However, despite its widespread occurrence, there’s a noticeable gap in understanding and awareness about MAFLD among these high-risk groups. Objectives: The main objective of this study was to assess the awareness and prevalence of MAFLD among diabetic patients who regularly receive secondary care focusing particularly on how multiethnic backgrounds and associated lifestyle preferences influence these health outcomes. Design: Cross-sectional study. Methods: Patients with type 2 diabetes (T2D) who regularly attend Lambeth Diabetes Intermediate Care Team clinics were invited to undergo MAFLD screening using FibroScan. Those who agreed to participate were provided with structured questionnaires on diet, physical activity, and MAFLD knowledge by a hepatologist. For each participant, anthropometric data, medical history, liver stiffness measurement, and controlled attenuation parameter (CAP) were documented. Steatosis was identified with a CAP value of ⩾275 dB/m, and advanced fibrosis was flagged at values of ⩾8 kPa. Results: The FibroScan data was valid in 96.4% (215), 53.5% (115/215) had steatosis and 26.2% (58/215) had liver fibrosis in this multiethnic high-risk group. Awareness of MAFLD was notably low at 30.9%. Alarmingly, 69% of patients diagnosed with liver fibrosis were unfamiliar with the condition. Additionally, understanding of MAFLD showed variation among different ethnic groups with highest levels were demonstrated in the Caucasian/White population (46%). Majority (96%) of these subjects were receiving specific lifestyle advice from healthcare professionals due to metabolic conditions and comorbidities. However, most patients preferred diets that were rich in carbohydrates (65.8%) and only 43% subjects performed moderate exercise daily highlighting lack of understanding regarding MAFLD and lifestyle management. Conclusion: There’s a pressing need for increased awareness of MAFLD, especially in multiethnic high-risk groups. Additionally, the development of cost-effective strategies to stratify risk is essential to address this growing health concern.

Background: Prolonged or excessive use of acid suppressants may increase the risk of Clostridioides difficile infection (CDI) by altering the intestinal microecosystem. Vonoprazan, a novel potassium-competitive acid blocker, exhibits a faster and more sustained acid-suppressive effect than proton pump inhibitors (PPIs). Therefore, vonoprazan may have a greater impact on the gut microbiota, potentially resulting in CDI. Objectives: This study aimed to explore the potential relationship between acid suppressants and CDI by the Japan Adverse Drug Event Report (JADER) and the FDA Adverse Event Reporting System (FAERS) databases. Design: A retrospective analysis of the JADER and FAERS databases was examined by disproportionality analysis. Methods: We performed signal detection analyses of CDI induced by vonoprazan and PPIs using the JADER and FAERS databases. The association between acid suppressants and CDI was calculated using the reporting odds ratio (ROR) and corresponding 95% confidence interval (95% CI). When the lower limit of the 95% CI is exceeded by 1, the association is considered statistically significant. Results: In the JADER database, the ROR (95% CI) for vonoprazan and PPIs based on suspect drug reports was 15.84 (12.23–20.50) and 2.51 (1.92–3.28), respectively. In the FAERS database, the ROR (95% CI) for vonoprazan and PPIs based on primary and secondary suspect drug reports was 11.50 (6.36–20.82) and 1.42 (1.34–1.51), respectively. Subgroup analysis showed that elderly patients aged 60 years and older were more strongly associated with CDI. The ROR (95% CI) for vonoprazan and PPIs in patients aged 60 years and older in the JADER database was 15.35 (11.59–20.33) and 1.65 (1.14–2.39), respectively. Similarly, the ROR (95% CI) for vonoprazan and PPIs in the FAERS database was 12.56 (6.26–25.20) and 1.43 (1.31–1.57), respectively. Excluding the effect of Helicobacter pylori ( H. pylori ) infection, the use of acid suppressants was still associated with CDI. Conclusion: While signal detection analysis based on the JADER and FAERS databases could not establish causality, our study demonstrated that both vonoprazan and PPIs were significantly associated with CDI. Vonoprazan showed a stronger association with CDI in both databases.

Effective management of schizophrenia (SZ) requires long-term treatment with antipsychotics (APs) to prevent clinical relapse, attain remission and improve patients’ personal and social functioning, and quality of life. Although APs remain the cornerstone treatment for patients with SZ, despite their potential benefits, long-acting injectable APs (LAI-APs) remain underused, most notably in women with SZ. The efficacy and tolerability of APs differ significantly between men and women, and some of these differences are more noticeable depending on the patient’s age and the stage of the disorder. Although sex differences may influence treatment outcomes in SZ, their pertinence has been insufficiently addressed, especially regarding the use of LAI-APs. Some biological and social experiences, such as pregnancy, lactation, contraception and menopause, are specific to women, but these remain under-researched issues. Implications of this disorder in parenting are also of special pertinence regarding women; therefore, taking sex differences into account when treating SZ patients is now recommended, and improving personalized approaches has been proposed as a priority in the management of psychosis. In this narrative, critical review, we address some aspects specific to sex and their implications for the clinical management of women with SZ, with a special focus on the potential role of LAI-AP treatments.

Background: The perioperative arena is a unique and challenging environment that requires coordination of the complex processes and involvement of the entire care team. Pharmacists’ scope of practice has been evolving to be patient-centered and to expand to variety of settings including perioperative settings. Objectives: To critically appraise, synthesize, and present the available evidence of the characteristics and impact of pharmacist-led interventions on clinically important outcomes in the perioperative settings. Design: A systematic review and meta-analysis. Methods: We searched PubMed, Embase, and CINAHL from index inception to September 2023. Included studies compared the effectiveness of pharmacist-led interventions on clinically important outcomes (e.g. length of stay, readmission) compared to usual care in perioperative settings. Two independent reviewers extracted the data using the DEPICT-2 (Descriptive Elements of Pharmacist Intervention Characterization Tool) and undertook quality assessment using the Crowe Critical Appraisal (CCAT). A random-effect model was used to estimate the overall effect [odds ratio (OR) for dichotomous and standard mean difference (SMD) for continuous data] with 95% confidence intervals (CIs). Results: Twenty-five studies were eligible, 20 (80%) had uncontrolled study design. Most interventions were multicomponent and continuous over the perioperative period. The intervention components included clinical pharmacy services (e.g. medication management/optimization, medication reconciliation, discharge counseling) and education of healthcare professionals. While some studies provided a minor description in regards to the intervention development and processes, only one study reported a theoretical underpinning to intervention development. Pooled analyses showed a significant impact of pharmacist care compared to usual care on length of stay (11 studies; SMD −0.09; 95% CI −0.49 to −0.15) and all-cause readmissions (8 studies; OR 0.60; 95% CI 0.39–0.91). The majority of included studies ( n = 21; 84%) were of moderate quality. Conclusion: Pharmacist-led interventions are effective at improving clinically important outcomes in the perioperative setting; however, most studies were of moderate quality. Studies lacked the utilization of theory to develop interventions; therefore, it is not clear whether theory-derived interventions are more effective than those without a theoretical element. Future research should prioritize the development and evaluation of multifaceted theory-informed pharmacist interventions that target the whole surgical care pathway.

Background: Oxaliplatin-associated shock (referred to as shock) is a rare but life-threatening adverse event. Objectives: This pioneering cohort study aimed to quantitatively investigate the association between oxaliplatin use and shock in patients with stage III colorectal cancer (CRC), identify potential independent risk factors for shock, and assess the cycle-to-shock during oxaliplatin treatment. Design: The study utilized a nested case–control (NCC) design to assess the association between oxaliplatin and shock and employed a case-crossover approach to address unmeasured confounders. Methods: All newly diagnosed stage III CRC patients were identified from the CRC Health Database (2012–2016). Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CIs) for oxaliplatin’s link to shock incidence. Results: Among 6932 oxaliplatin recipients, 331 suffered shock. In all, 3309 controls were selected via risk-set sampling for the shock cases. Oxaliplatin use is associated with a doubled risk of shock (adjusted OR: 2.08, 95% CI: 1.23–3.52). Two independent risk factors were male sex (adjusted OR: 1.33, 95% CI: 1.05–1.69) and heart diseases (adjusted OR: 1.65, 95% CI: 1.17–2.32). The case-crossover analysis revealed a more than fourfold risk (OR: 4.4, 95% CI: 1.67–11.62). In total, 22 of 331 shock cases were exposed to oxaliplatin within 2 days of shock onset, with a median cycle-to-shock time at the seventh cycle. Conclusion: Oxaliplatin use significantly increased shock risk in stage III CRC patients. Male sex and heart disease are two independent risk factors.

Due to their high specificity and scalability, Monoclonal IgY antibodies have emerged as a valuable alternative to traditional polyclonal IgY antibodies. This abstract provides an overview of the production and purification methods of monoclonal IgY antibodies, highlights their advantages over polyclonal IgY antibodies, and discusses their recent applications. Monoclonal recombinant IgY antibodies, in contrast to polyclonal IgY antibodies, offer several benefits. such as derived from a single B-cell clone, monoclonal antibodies exhibit superior specificity, ensuring consistent and reliable results. Furthermore, it explores the suitability of monoclonal IgY antibodies for low- and middle-income countries, considering their cost-effectiveness and accessibility. We also discussed future directions and challenges in using polyclonal IgY and monoclonal IgY antibodies. In conclusion, monoclonal IgY antibodies offer substantial advantages over polyclonal IgY antibodies regarding specificity, scalability, and consistent performance. Their recent applications in diagnostics, therapeutics, and research highlight their versatility.

Gastric malabsorptive conditions may prevent patients from deriving benefit from orally administered medications intended for enteric absorption. While malabsorption is an increasingly common issue, current data on alternative oral options for agitation in these patients are very sparse. Sublingual (SL) asenapine is absorbed transmucosally, bypassing gut absorption, making it a viable consideration. We report on three patients, one with short bowel syndrome, one with viral gastritis, and one with aortic dissection who were trialed on SL asenapine for agitation after failing alternative antipsychotics. Two of these patients had an extensive history of psychiatric admissions for bipolar disorder and substance-induced psychosis. All three patients had significant reductions in agitation within 1–5 days, with no reported adverse effects. However, benefit of SL asenapine was hindered in two of these patients as they began inappropriately swallowing the medication, reducing bioavailability to nil. Clinicians should consider the use of SL asenapine for medically complex agitated patients where gastric absorption is questionable. There is an urgent need for guidelines on this matter, as well as more, alternative dosage forms for various medications that may help with agitation in this population.

Background Rasagiline mesylate, a monoamine oxidase-B inhibitor, is used in Parkinson's disease (PD) treatment. We report a case of reversible cerebral vasoconstriction syndrome (RCVS) developed after rasagiline mesylate initiation. Case presentation A 59-year-old woman was diagnosed with PD at the age of 54 years. She experienced frequent episodes of nausea after increasing the dose of levodopa-carbidopa hydrate, and her nausea worsened with the addition of rasagiline mesylate. Three months later, the patient experienced recurrent thunderclap headaches. Brain imaging revealed subarachnoid hemorrhage with segmental vasoconstriction in the main trunks of multiple cerebral arteries. The subsequent clinical course was consistent with RCVS. Her headache and nausea were completely resolved by the discontinuation of rasagiline mesylate and addition of verapamil hydrochloride. Discussion Worsened nausea was the only sign implicating the elevated monoamine levels, potentially linked to the development of RCVS. RCVS should be considered when a patient taking rasagiline mesylate experiences thunderclap headache.

Background: Elexacaftor/tezacaftor/ivacaftor (ETI) has reduced many symptoms of cystic fibrosis (CF). Objectives: We sought to identify the impact of ETI on both symptoms and treatment decisions among adults with CF. Design: Participants were enrolled in a cross-sectional study. Surveys were sent via a RedCap link. Semistructured interviews were administered remotely via Microsoft Teams. Interviews were audio recorded and professionally transcribed. Methods: We assessed Cystic Fibrosis Questionnaire-Revised (CFQ-R) subscales for physical, respiratory, emotion, and treatment, and analyzed semistructured interviews covering CF treatment regimens and daily living. Quantitative and qualitative results were analyzed separately and via a mixed-methods convergence coding matrix. Results: Twenty-four adults with CF taking ETI were included. CFQ-R subscale scores (mean scores/standard deviation) were physical (82.1/22.8), respiratory (83.7/11.2), emotion (65.3/14.2), and treatment (57.5/20.1). Three themes about decision-making for non-ETI-treatments emerged: (1) How I’m feeling, (2) Not noticing a difference, and (3) Uncertainty about long-term impact of modifying treatment regimens, and we found participants weighed each of these factors in their treatment decisions. Key findings from mixed-methods analysis show that among individuals experiencing higher CFQ-R scores for physical and respiratory compared to emotion and treatment, there were statements indicating that while those participants were experiencing better physical health, many continued their burdensome treatment regimens. Conclusion: With little long-term data on the impact of reducing non-ETI treatments, participants weighed how they were feeling, treatment efficacy beliefs, and risk tolerance when making treatment decisions.

Aims In patients with atrial fibrillation (AF) and stroke risk factors, randomized trials have demonstrated that anticoagulation decreases the risk of ischemic stroke. However, all trials to date have excluded patients with significant liver disease, leaving guidelines to extrapolate recommendations. We aim to evaluate the impact of anticoagulation on safety events in patients with AF and cirrhosis. Methods and Results In this retrospective cohort study, we obtained de-identified health record data to extract anticoagulation strategy, comorbidities, prescriptions, lab values, and procedures for a cohort of patients with cirrhosis who develop AF. After selecting a propensity matched population to match patients with various anticoagulation strategies, we tracked data on outcomes for death, transfusion requirements, hospital and ICU admissions. After propensity score weighting and multivariable adjustment, anticoagulation strategy was associated with increased hospital admission count (OR = 1.74 per admission, P

Background: Transmural healing (TH) has emerged as a potential treatment goal for Crohn’s disease (CD). However, further research is needed to confirm its benefits and risk factors associated with TH remain unclear. Objectives: We aimed to assess the value of TH based on magnetic resonance enterography (MRE) in Chinese CD patients regarding the long-term outcomes and its associated factors. Design: Retrospective, observational cohort study. Methods: Patients with CD diagnosed by colonoscopy and MRE examination between 2015 and 2022 were included. All patients were evaluated with endoscopy together with MRE within 6–12 months after baseline and followed up for at least 6 months after evaluation. The primary endpoint was the occurrence of major outcomes during the follow-up, including drug escalation, hospitalization, and surgery. The cumulative probabilities of major outcomes were calculated using Kaplan–Meier survival curves. Logistic regression analyses were used to predict TH within 6–12 months after baseline. Results: A total of 175 patients were included in the study. Of these, 69 (39.4%) patients achieved mucosal healing (MH), but only 34 (19.4%) of them achieved TH. The median follow-up duration was 17.4 months (interquartile range, 11.6–25.5), and major outcomes occurred in 58.3% of patients. A lower occurrence rate of major outcomes was noted in patients who achieved TH than in those who achieved MH only ( p = 0.012). The baseline lymphocyte/C-reactive protein ratio (LCR) [odds ratio (OR), 1.60; 95% confidence interval (CI), 1.02–2.50; p = 0.039] and bowel wall thickness (BWT) (OR, 0.72; 95% CI, 0.59–0.90; p = 0.003) were independent predictors associated with TH. According to multivariate Cox regression analysis, low LCR [hazard ratio (HR), 2.34; 95% CI, 1.51–3.64; p

Background: Vaccination is a fundamental tenet of public and population health. Several barriers to vaccine uptake exist, exacerbated post-COVID-19, including misconceptions about vaccine efficacy and safety, vaccine hesitancy, vaccine inequity, costs, religious beliefs, and insufficient education and guidance for healthcare professionals. Vaccine uptake may be aided using microarray patches (MAPs) due to reduced pain, no hypodermic needle, enhanced thermostability, and potential for self and lay administration. Objectives: This protocol outlines the development of a scale that aims to accurately measure the perceived safety, usability, and acceptability of MAPs for vaccination among laypeople, MAP recipients, clinicians, and parents or guardians of children. Methods and analysis: This study will follow three phases of scale development and validation, including (1) item development, (2) scale development, and (3) scale evaluation. Inductive (interviews) and deductive methods (literature searches) will be used to develop scale items, which experts from target populations will assess through an online survey. Cognitive interviews will be conducted to observe their processes of answering the draft survey. Thematic analysis will be conducted to analyse qualitative data. Lastly, four surveys will be administered online to our target populations over two time points to determine their repeatability. Exploratory and confirmatory factor analyses, Cronbach’s alpha, and construct validity will be performed. Ethics: This study was approved by Metro South Health (HREC/2021/QMS/81653) and Western Sydney Local Health District (2023/ETH00705) Human Research Ethics Committees. Discussion: The scale will support a standardised approach to assessing the social and behavioural aspects of MAP vaccines, enabling comparison of outcomes across studies. Once validated, this scale will assist vaccination programmes in developing effective strategies for integrating MAPs and overcoming barriers to vaccination. This includes improving vaccine equity and accessibility, especially in lower- and middle-income countries and rural or remote locations.

Background and Purpose Artificial intelligence (AI) is a technique which tries to think like humans and mimic human behaviors. It has been considered as an alternative in a lot of human-dependent steps in radiotherapy (RT), since the human participation is a principal uncertainty source in RT. The aim of this work is to provide a systematic summary of the current literature on AI application for RT, and to clarify its role for RT practice in terms of clinical views. Materials and Methods A systematic literature search of PubMed and Google Scholar was performed to identify original articles involving the AI applications in RT from the inception to 2022. Studies were included if they reported original data and explored the clinical applications of AI in RT. Results The selected studies were categorized into three aspects of RT: organ and lesion segmentation, treatment planning and quality assurance. For each aspect, this review discussed how these AI tools could be involved in the RT protocol. Conclusions Our study revealed that AI was a potential alternative for the human-dependent steps in the complex process of RT.

Objective To investigate the biological role of miR-143 and miR-199a in mediating the progression of osteosarcoma (OS) by targeting cyclooxygenase (COX-2). Introduction COX-2 plays a crucial role in the development and progression of OS. However, the specific regulatory mechanisms of COX-2 in OS are still not well understood. Methods The expression levels of COX-2, miR-143 and miR-199a in OS tissues were detected using immunohistochemistry, qPCR, or western blot assays. The targeting relationship between miRNAs and COX-2 was determined. The effect of miRNA and COX-2 on OS cells was evaluated in vitro and in vivo. Results COX-2 expression was upregulated while miR-143 and miR-199a were downregulated in OS tissues. miR-143 and miR-199a suppressed the proliferation, migration, and invasion of OS cells. The dual-luciferase reporter gene assay showed that COX-2 was a direct target of miR-143 and miR-199a. Genetic knockdown of COX-2 significantly suppressed cell proliferation, induced apoptosis, and inhibited migration and invasion of OS cells. The expression levels of COX-2 and PGE2 were decreased after the overexpression of miR-143 and miR-199a. Additionally, COX-2 silencing inhibited the tumorigenesis of OS and the synthesis of PGE2 in vivo. Conclusions miR-143 and miR-199a/COX-2 axis modulates the proliferation, invasion, and migration in osteosarcoma.

This study focuses on the investigation of the significance of polymers in drug delivery approaches. The carboxymethyl cellulose (CMC), polyvinyl alcohol (PVA) and dextrin-based hydrogel membrane were prepared and employed for the sustained release of third-generation oral antibiotic (cefixime). Different proportions of CMC, PVA and dextrin were blended and hydrogel membranes were fabricated via solvent casting method. The prepared membrane was characterized by FTIR, SEM, UV-visible, TGA and swelling analysis. Cefixime drug was incorporated in the CMC/PVA/dextrin matrix and drug release was investigated. The sustained release of the tested drug (cefixime) was investigated and the drug was released in 120 min in the phosphate-buffered saline (PBS) solution. The antibacterial activity of the prepared membrane was promising against Proteus vulgaris , salmonella typhi, Escherichia coli and Bacillus subtilis strains. The swelling capabilities, thermal stability and non-toxic nature of the prepared CMC/PVA/dextrin membrane could have potential applications for cefixime drug in delivery in a controlled way for the treatment of infectious diseases.

This research investigated the anticancer properties of punicalagin, a prominent bioactive polyphenol extracted from Punica granatum L, in human gastric cancer cell lines. Normal and gastric cancer cells were exposed to different doses of punicalagin for various durations. Punicalagin exhibited cytotoxic effects on gastric cancer cells in a dose- and time-dependent fashion, while sparing normal gastric epithelial cells. It is noteworthy that among the 3 gastric cancer cells, HGC-27 cells were more resistant to punicalagin than 23,132/87 and AGS cells. Furthermore, punicalagin triggered apoptosis in gastric cancer cells, evidenced by a rise in both early and late apoptotic cell percentages. Western blot analysis further revealed that punicalagin elevated the levels of activated caspase-3. Conversely, punicalagin curtailed cell invasion and reduced the expression of MMP-2, MMP-9, Snail, and Slug. From a mechanistic standpoint, Western blotting indicated that punicalagin might inhibit the Erk and NF-κB pathways, leading to apoptosis induction and the inhibition of cell invasion in gastric cancer cells. These results indicate that punicalagin promotes apoptosis and inhibits cell invasion in gastric cancer cells by activating caspase-3 and suppressing MMP-2, MMP-9, Snail, and Slug through the inhibition of the Erk and NF-κB pathways.

Background: Numerous studies report that anticholinergic burden (ACB) has been linked with several health consequences, including increased hospital admissions, prolonged hospitalization, and physical and cognitive impairment. However, low- and middle-income settings, as well as younger individuals, are underrepresented. Objectives: To assess the prevalence and determinants of ACB, and to assess the impact of ACB on in-hospital mortality among adult in-patients at University of Gondar Comprehensive Specialized Hospital (UOGCSH). Design: A cross-sectional study was conducted from June to August 2022 at UOGCSH among adult in-patients. Methods: A pre-tested questionnaire was utilized to collect data from patients and their corresponding medical charts. A consecutive sampling technique was used to select the participants. Descriptive statistics were used to summarize socio-demographic and clinical characteristics. Chi-squared, Fisher’s exact, and Wilcoxon rank sum tests, as appropriate, were used to determine associations between independent variables and ACB. Kaplan–Meier survival curve and Cox proportional hazards regression test were used to assess the impact of ACB on in-hospital mortality. Results: A total of 420 adult in-patients, median (interquartile range) age of 38 (26, 55) years, participated in this study. Over half (58.3%) were exposed to anticholinergic medicines, with a high ACB (⩾3) seen in 11.2% of participants. High ACB was associated with higher median number of medicines per patient ( p = 0.003) higher median hospital length of stay ( p = 0.033), and having mental and behavioral disorders ( p

Background: Cefuroxime has played a crucial role in the prevention and treatment of bacterial infections. However, the differences in adverse events across formulations and routes remain unclear. Objectives: This study aimed to investigate the post-marketing safety of cefuroxime, particularly concerning formulations and routes. Design: A retrospective pharmacovigilance study of cefuroxime was conducted using the data from Food and Drug Administration Adverse Event Reporting System database. Methods: The clinical characteristics and concomitant drugs reported with cefuroxime were investigated. Adverse event signals of cefuroxime were identified based on four disproportionality algorithms. The signal differences of cefuroxime across formulations and routes were further examined. Results: A total of 1810 adverse event reports associated with cefuroxime were identified, and 181 cefuroxime-associated signals were detected. Compared with tablets, injections were more likely to cause preferred terms ‘blood pressure decreased’ and ‘anaphylactic shock’. In addition, system organ class ‘eye disorders’ significantly increased when cefuroxime was administered intraocularly, underscoring the importance of exercising caution regarding ocular toxicity. Conclusion: The adverse events associated with cefuroxime were significantly different across formulations and routes, which deserve special attention in clinical use.

Background The use of walking aids is widely acknowledged as one of the most relied-on forms of assistive technology. Using stick-shaped devices, such as a cane, is often the entrance for many people to the world of assistive technologies, often accompanied by the negative stigma associated with ageing and disability. Objectives This study investigated the perception of disability and needs of the Hong Kong population using walking aids, aiming to inform device design and service provision. Methods We observed 391 individuals using cane-like devices in their natural environment and conducted semi-structured interviews with 28 participants to understand stigma, barriers to acquisition, training, and design requirements. Results Half of the interviewees (50%, n = 14) did not feel disabled when using a walking stick, while 39% felt slightly disabled. 56% of the observed sample used non-medical-looking aids like hiking poles or umbrellas. Most interviewees (79%) purchased off-the-shelf devices, but less than half received seller support in choosing appropriate aids. Conclusion The feelings associated with using walking sticks and similar devices are mostly positive. There is a preference in Hong Kong for using devices without a medical appearance to aid walking, such as umbrellas and hiking poles. There is a need to raise awareness of the risks of using umbrellas to aid walking and empower the user to make informed decisions when purchasing walking aid devices. In addition, there is a need to support the supply chain of walking aids, including umbrellas and hiking poles, to provide more information on device use, misuse, training, and maintenance.

Background Individuals with mobility disabilities are less likely to meet physical activity standards and are at greater risk of developing non-communicable chronic diseases at earlier ages. Public parks are an essential resource for participation in physical activity. However, environmental factors may limit the participation of wheelchair users. The objective of this study was to evaluate the feasibility of using the Path Environment Audit Tool (PEAT) and to explore the wheelchair accessibility of five public parks in Saudi Arabia through descriptive analysis. Methods A descriptive study design was implemented to evaluate wheelchair accessibility features of five public parks in Riyadh, Saudi Arabia, and process, resource, and management assessments were conducted. Phone GPS-App Strava was used to track the segments and measure their distances. Results Audits in multiple parks using PEAT were time-consuming despite being user-friendly. The descriptive analysis of paths and trails across the five parks showed some positive features, such as adequate bollard/gate clearance, but the path slope and condition of the path surfaces were more variable. Conclusion This study is the first to examine wheelchair accessibility in public parks in Saudi Arabia. Preliminary audits of paths/trials in five public parks revealed the strengths and weaknesses of accessibility and features that promote physical activity participation for wheelchair users. These findings can guide future use of PEAT in large-scale studies and inform environmental modifications.

Introduction Wearable sensors are increasingly applied to rehabilitation for arm movement analysis. However, simple and clinically relevant applications are scarce. Objectives To investigate the feasibility of single smart watch-based parameters for functional assessment in upper limb rehabilitation for musculoskeletal injuries using a commercial smart watch. Method Ten patients with unilateral shoulder pain and range-of-motion limitations were enrolled. They wore Galaxy Watch ® and performed three sets of upper extremity tasks consisting of gross activities-of-daily-living tasks, Wolf Motor Function Test (WMFT), and Upper Extremity Functional Index (UEFI), and the acceleration and angular velocities were acquired. The motion segment size (MSS), representing motion smoothness from a clinical perspective, and various sensor-based parameters were extracted. The correlation between the parameters and clinical outcome measures were analyzed. The percent relative range (PRR) of the significant parameters was also calculated. Results For overhead and behind body activity task set, mean MSS for elbow flexion/extension axis significantly correlated with WMFT score (R = 0.784, p = .012). For planar tasks, mean MSS for the forearm supination/pronation (R = 0.815, p = .007) and shoulder rotation (R = 0.870, p = .002) axes significantly correlated with WMFT score. For forearm and fine movement task set, mean MSS of the elbow flexion/extension angle showed significant correlation with WMFT (R = 0.880, p < .001) and UEFI (R = 0.718, p = .019). The total performance time (R = −0.741, p = .014) also showed significant correlation with WMFT score. The PRR for mean MSS in forearm supination (71.5%, planar tasks) and mean MSS in x -direction (49.8%, forearm and fine motor movements) were similar to the PRR of WMFT (58.5%), suggesting sufficient variation range across different degree of impairments. Conclusion The commercial smart watch-based parameters showed consistent potential for use in clinical functional assessments.

Introduction Currently studies indicate the need to incorporate the user`s perspective in the testing of new assistive technologies. The objective of this paper is to test a baropodometric insole prototype for monitoring and treatment weight-bearing asymmetry, according to the Participatory Design. Methods We used a qualitative case study approach during the testing phase of the baropodometric insole prototype. The focus group approach addressed topics related to the experience and accessibility of the potential user in conjunction with professionals, researchers, and physiotherapy students. Facilitators, barriers, and requirements for the device were collected through audio recordings of the discussions during and after prototype testing. Results Key steps in the prototype testing process were divided into (1) Test of the prototype according to the Participatory Design, divided into Who, When, How, and Why the potential user was involved in the study; and (2) Facilitators, barriers and requirements to improve the prototype. Conclusions The baropodometric insole prototype can be seen as a promising device for monitoring and treating weight-bearing asymmetry.

It has long been established that occupational therapists (OTs) play an important role in assisting clients suffering from a variety of physical and mental health conditions. Cyberpsychology is a relatively new field in medicine that pertains to how technology influences people's mental health and behavior. It covers the effects of social media, online gaming, virtual-augmented reality, artificial intelligence, and other forms of technology on individuals. Among the known psychological phenomena arising from individuals’ interactions with digital technologies are cyberbullying and technology addiction. This commentary explores how OTs in the cyberpsychology field can develop personalized interventions to enhance digital well-being and promote healthy technology use.

Background Ensuring effective return to work following acquired brain injuries is crucial from the perspectives of both quality of life and the economy. However, techniques of occupational therapy support for return to work remain relatively unelucidated. Aims/Objectives To clarify the specific contents of occupational therapy required for work and work support for clients with acquired brain injuries. Material and Methods An interview-based survey was conducted with participants who had >10 years of occupational therapy experience and had provided work support. We selected participants via snowball sampling. Data were analyzed using thematic analysis. Results A total of 20 participants (15 women and 5 men; 6, 12, 1, and 1 in their 30s, 40s, 50s, and 60s, respectively) were included. Six concepts were generated on reviewing the support for work items considered important by the occupational therapist as follows: “Support for vocational life,” “Support for interpersonal skills,” “Support for work,” “Support for illness, disability, and awareness,” “Support for utilization of compensation measures,” and “Support for goal setting.” Conclusions We clarified the specific contents of work support, including support for vocational life and support for work, that is administered by occupational therapists who provide work support for clients with acquired brain injury. The insights from the study improve understanding of OTs’ roles and contributions in supporting clients with acquired brain injuries in returning to work.

Background: Long-acting injectable antipsychotics (LAIs) have advantages over oral antipsychotics (OAPs) in preventing relapse and hospitalization in chronically ill patients with schizophrenia-spectrum disorders (SSDs), but evidence in patients with first-episode/recent-onset, that is, early-phase-SSDs is less clear. Objectives: To assess the relative medium- and long-term efficacy and safety of LAIs versus OAPs in the maintenance treatment of patients with early-phase SSDs. Method: We searched major electronic databases for head-to-head randomized controlled trials (RCTs) comparing LAIs and OAPs for the maintenance treatment of patients with early-phase-SSDs. Design: Pairwise, random-effects meta-analysis. Relapse/hospitalization and acceptability (all-cause discontinuation) measured at study-endpoint were co-primary outcomes, calculating risk ratios (RRs) with their 95% confidence intervals (CIs). Subgroup analyses sought to identify factors moderating differences in efficacy or acceptability between LAIs and OAPs. Results: Across 11 head-to-head RCTs ( n = 2374, median age = 25.2 years, males = 68.4%, median illness duration = 45.8 weeks) lasting 13–104 (median = 78) weeks, no significant differences emerged between LAIs and OAPs for relapse/hospitalization prevention (RR = 0.79, 95%CI = 0.58–1.06, p = 0.13) and acceptability (RR = 0.92, 95%CI = 0.80–1.05, p = 0.20). The included trials were highly heterogeneous regarding methodology and patient populations. LAIs outperformed OAPs in preventing relapse/hospitalization in studies with stable patients (RR = 0.65, 95%CI = 0.45–0.92), pragmatic design (RR = 0.67, 95%CI = 0.54–0.82), and strict intent-to-treat approach (RR = 0.64, 95%CI = 0.52–0.80). Furthermore, LAIs were associated with better acceptability in studies with schizophrenia patients only (RR = 0.87, 95%CI = 0.79–0.95), longer illness duration (RR = 0.88, 95%CI = 0.80–0.97), unstable patients (RR = 0.89, 95%CI = 0.81–0.99) and allowed OAP supplementation of LAIs (RR = 0.90, 95%CI = 0.81–0.99). Conclusion: LAIs and OAPs did not differ significantly regarding relapse prevention/hospitalization and acceptability. However, in nine subgroup analyses, LAIs were superior to OAPs in patients with EP-SSDs with indicators of higher quality and/or pragmatic design regarding relapse/hospitalization prevention (four subgroup analyses) and/or reduced all-cause discontinuation (five subgroup analyses), without any instance of OAP superiority versus LAIs. More high-quality pragmatic trials comparing LAIs with OAPs in EP-SSDs are needed. Trial registration: CRD42023407120 (PROSPERO).

Background Moxonidine, an imidazoline I 1 receptor agonist, is an effective antihypertensive drug that was shown to improve insulin sensitivity. RAAS-blockers are recommended as first-line therapy in patients with diabetes, alone or in combination with a calcium-channel antagonist or a diuretic. Aims This study compared the effects of moxonidine and ramipril on blood pressure (BP) and glucose metabolism in overweight patients with mild-to-moderate hypertension and impaired fasting glucose or type 2 diabetes. Methods Treatment-naïve patients for hypertension and dysglycemia were randomized to 12 weeks of double-blind moxonidine 0.4 mg or ramipril 5 mg once-daily treatment. At 12 weeks, for a further 12 weeks non-responders received combination of mox/ram, while responders continued blinded treatment. Results Moxonidine and ramipril were equivalent in lowering SiDBP and SiSBP at the end of the first 12 weeks. The responder rate was approximately 50% in both groups, with a mean SiDBP and SiSBP decrease of 10 and 15 mm Hg in the responders, respectively. The normalization rate (SiDBP

Hidradenitis suppurativa (HS) is an inflammatory skin condition with an underlying inflammatory process. Due to the limited efficacy of available treatments, HS remains a therapeutic challenge. The safety and efficacy of tumor necrosis factor-α (TNF-α) inhibitors, adalimumab, infliximab, and etanercept, are well studied in this patient population, and in some cases, HS was unresponsive to them. In recent years, evidence has been growing regarding the application of other anti-TNFs, including certolizumab pegol (CPZ) and golimumab. We sought to evaluate the overall safety and efficacy of golimumab and CPZ in the management of HS. A comprehensive search was performed on the PubMed, Scopus, Web of Science, and Ovid Embase databases, as well as the Google Scholar search engine from initiation to 31 August 2023. A total of nine and four studies used CPZ and golimumab to treat HS, respectively. Individuals with concomitant inflammatory immune-mediated diseases, pregnant females, and patients who were refractory to previous treatments achieved a Hidradenitis Suppurativa Clinical Response following CPZ administration. Also, golimumab showed promise in treating recalcitrant HS after the failure of other treatments, such as adalimumab and anti-interleukin-1. CPZ and golimumab can be efficacious treatment options for moderate-to-severe HS, especially in patients who are unresponsive to other TNF inhibitors, such as adalimumab.

This case report examines the possible correlation between the clozapine/norclozapine ratio and the occurrence of constipation and paralytic ileus. We present the case of a 42-year-old patient diagnosed with schizoaffective disorder undergoing clozapine therapy. Despite intensive treatment with clozapine, haloperidol, valproic acid and biweekly electroconvulsive therapy sessions for over a year, florid psychotic symptoms and fluctuating mood swings persisted. Therefore, valproic acid was replaced by carbamazepine, a potent inducer of several CYP450-enzymes. To maintain clozapine plasma levels, fluvoxamine, a CYP1A2-inhibitor, was introduced at a dose of 25 mg before this switch. After addition of carbamazepine, there was a significant decline in clozapine levels, necessitating an increase in fluvoxamine dosage to 50 mg. Five weeks later the patient was admitted to a general hospital with a diagnosis of paralytic ileus. Treatment with enemas proved effective. Drug concentration analysis revealed a 2.5-fold increase in norclozapine levels in the weeks preceding hospital admission, resulting in an inverted clozapine/norclozapine ratio. Treatment with clozapine, carbamazepine and fluvoxamine was continued as the patient demonstrated clinical improvement on carbamazepine. Concurrently, an intensive laxative regimen was initiated. Two weeks later, the patient was readmitted to the general hospital due to suspected paralytic ileus and faecal vomiting, once again displaying an inverted clozapine/norclozapine ratio. We discuss potential mechanisms contributing to the occurrence of the paralytic ileus in this patient, including the antagonism of muscarinic M3 receptors by both clozapine and norclozapine, as well as the agonism of delta-opioid receptors by norclozapine. This case highlights the potential significance of both the clozapine/norclozapine ratio and absolute norclozapine levels as risk factors for constipation and paralytic ileus in patients on clozapine therapy.

Background: Antipsychotic medications are associated with weight gain and metabolic derangement. However, comprehensive evidence for the efficacy of co-commenced pharmacological treatments to mitigate initial weight gain is limited. Metformin has been shown to be effective in reducing weight among people on antipsychotic medications who are already overweight, but the potential benefits of metformin co-commencement in mitigating antipsychotic-induced weight gain has not been systematically reviewed. Method: We conducted a systematic review of PubMed, EMBASE, PsychInfo, CINAHL, the Cochrane database, and China National Knowledge Infrastructure from inception to 18 November 2023. We undertook a meta-analysis of concomitant commencement of metformin versus placebo for attenuation of weight gain and metabolic syndrome for people with schizophrenia commencing a new antipsychotic. Results: Fourteen studies from Australia, United States, Venezuela, and China with 1126 participants were included. We found that metformin was superior to placebo in terms of attenuating weight gain (−3.12 kg, 95% CI −4.22 to −2.01 kg). Metformin also significantly attenuated derangement of fasting glucose levels, total cholesterol, and total triglyceride levels. Sensitivity analysis on study quality, duration, and antipsychotic agent did not impact the results. Meta-analysis was also conducted on adverse drug reactions (ADR) reported in each study which showed no significant difference in ADR incidence between metformin and placebo groups. Subgroup analysis on antipsychotic-naïve participants and participants switching to new antipsychotic did not impact the results. Conclusion: Metformin led to statistically significant and clinically meaningful attenuation of weight gain as well as attenuation of several other metabolic parameters when commenced concomitantly with antipsychotic medications. Co-commencement of metformin with antipsychotic medications, where tolerated, should be considered in the clinical setting with aim to improve long-term cardiometabolic outcomes for patients with long-term need of antipsychotic treatments.

Tricyclic antidepressants (TCAs) remain widely prescribed for depression and many other conditions. There may be important differences between individual TCA in regard to their overdose toxicity and their cardiac toxicity in clinical use. We conducted a systematic review to compare the toxicity of individual TCA in overdose and the risk of serious adverse cardiac events occurring with therapeutic doses. We used the fatal toxicity index (FTI) and case fatality ratio as markers of fatality in overdose, and hazard ratios or odds ratios for the risk of cardiovascular adverse events during normal clinical use. In all, 30 reports of mortality in overdose and 14 observational studies assessing the risk of cardiovascular adverse events in clinical use were included. FTI values were of the same order of magnitude (10 1 –10 2 ) for all TCAs except lofepramine. Desipramine appears to be somewhat more likely than other TCAs to lead to death in overdose. Amitriptyline, clomipramine, dothiepin/dosulepin, doxepin, trimipramine and imipramine showed broadly similar toxicity and were usually reported to be less toxic than desipramine. Data on nortriptyline were contradictory. Lofepramine had the lowest risk of death in overdose. The rank order of overdose toxicity was broadly consistent between different FTI definitions and between markers used. With respect to the risk of cardiovascular events at clinically relevant exposure, amitriptyline, nortriptyline and lofepramine were associated with a greater risk of in-use cardiotoxicity. All measures of overdose toxicity were subject to external influences and confounding. The continued use of TCAs in depression and other conditions should be minimized when considering their undoubted toxicity in overdose and possible toxicity in normal clinical use.

Background Arsenic (As) is a highly toxic and carcinogenic pollutant commonly found in soil and water, posing significant risks to human health and plant growth. Objective The objectives of this study to evaluate morphological, biochemical, and physiological markers, as well as ion homeostasis, to alleviate the toxic effects of As in sunflowers through the exogenous application of salicylic acid (SA), γ-aminobutyric acid (GABA), and their combination. Methods A pot experiment was conducted using two sunflower genotypes, FH-779 and FH-773, subjected to As stress (60 mg kg −1 ) to evaluate the effects of SA at 100 mg L −1 , GABA at 200 mg L −1 , and their combination on growth and related physiological and biochemical attributes under As stress. Results The study revealed that As toxicity had a detrimental effect on various growth parameters, chlorophyll pigments, relative water content, total proteins, and nutrient uptake in sunflower plants. It also led to increased oxidative stress, as indicated by higher levels of malondialdehyde (MDA) and hydrogen peroxide (H 2 O 2 ), along with As accumulation in the roots and leaves. However, the application of SA and GABA protected against As-induced damage by enhancing the enzymatic antioxidant defense system. This was achieved through the activation of superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) activities, as well as an increase in osmolytes. They also improved nutrient acquisition and plant growth under As toxicity. Conclusions We investigated the regulatory roles of SA and GABA in mitigating arsenic-induced phytotoxic effects on sunflower. Our results revealed a significant interaction between SA and GABA in regulating growth, photosynthesis, metabolites, antioxidant defense systems, and nutrient uptake in sunflower under As stress. These findings provide valuable insights into plant defense mechanisms and strategies to enhance stress tolerance in contaminated environments. In the future, SA and GABA could be valuable tools for managing stress in other important crops facing abiotic stress conditions.

Background/Hypothesis: Creativity is a cognitive process that affects the performance of many daily life activities. This process, in turn, is influenced not only by various environmental factors but also by numerous individual aspects. Chronic pain is one of the factors that has proven to negatively affect creativity. Our hypothesis is that people with migraine in the interictal phase also have lower levels of creativity than the control group. Methods: We collected data from participants with migraine ( n = 31) in the interictal phase and from a non-migraine control group ( n = 30). We used the Alternative Uses Task (AUT) test and the Creative Intelligence Test (CREA) to evaluate creativity. Results: Our results revealed lower creativity in participants with migraine. This was confirmed by both the AUT (fluency: controls 7.4 (4.35) vs. participants with migraine 4.4 (2.9); p < 0.001; originality: controls 2.353 (0.457) vs. participants with migraine 2.07 (0.278); p < 0.001; flexibility: controls 3.4 (1.55) vs. participants with migraine 2.0 (1.0); p < 0.001) and CREA (controls 14.0 (9.875) vs. participants with migraine 9.5 (5.0); p = 0.004) tests. Interpretation: The present pilot study provides evidence that migraine, even in the interictal period, reduces creative ideation and this may impact the quality of life of these individuals.

Background: Venous thromboembolism (VTE) has a serious impact on the prognosis of patients with spontaneous intracranial hemorrhage (sICH). However, the use of prophylactic heparin remains controversial. Objectives: This study investigated the safety and timing of prophylactic heparin for VTE in patients with sICH. Design: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. Methods: Two authors systematically searched Web of Science, Cochrane Library, Embase, and PubMed to find all published research before June 2023. The incidence of deep venous thrombosis (DVT) and mortality were set as primary endpoints. Results: This meta-analysis included seven randomized controlled trials (RCTs) and five observational studies involving a total of 4419 sICH patients in the heparin ( n = 2808) and control ( n = 1183) groups. Among these patients, 205 received early heparin administration, while 223 received late heparin administration. The results suggested that, compared to the control group, patients in the heparin group had a lower incidence of VTE [odds ratio (OR), 0.47; 95% CI, 0.31–0.71; p 0.05). There was no statistically significant difference in DVT, mortality, hematoma enlargement, and extracranial hemorrhage between the early heparin group ( 0.05). Conclusion: In patients with sICH, prophylactic use of heparin may be beneficial because it reduces the incidence of VTE and mortality without increasing the risk of additional bleeding. In addition, early prophylactic use of heparin appears to be safe. However, large-scale RCTs are lacking to support this evidence.