Antimicrobial Stewardship: Knowledge and Attitudes of Pharmacy Staff on Antibiotic Dispensing Patterns, Use and Resistance in Benin

Background: One of the key drivers for the emergence and spread of antimicrobial resistance (AMR) is non-prudent antibiotic use, which results in selection pressure toward relevant bacteria. Pharmacy staffs have pivotal roles in facilitating the prudent use of antibiotics through antimicrobial stewardship programs. Due to limited information in Benin, this study assessed the knowledge and attitudes of pharmacy staffs on antibiotic use and resistance. Materials and Methods: This cross-sectional study was conducted among 159 pharmacy staffs using a structured questionnaire from August 2018 to December 2018 in Benin. Data analysis was done by using Stata version 13.0. Results: Of the 159 participants, 54.8% knew the definition of antibiotic therapy and 66.9% knew the definition of probabilistic antibiotic therapy. The majority (88.1%) of the participants thought that the choice of antibiotics was made according to the pathology, while 60.4% thought that it depended on the pathology and the germ involved. 49.02% of dispensers in pharmacies stated that half of the patients had requested treatment without providing a prescription at the pharmacy. The top three antibiotics that were dispensed without a prescription include amoxicillin (98.1%), cloxacillin (76.7%) and metronidazole (57.2%), all from the Access group of antibiotics. Conclusion: These results underscore the need for educational and training interventions targeting specific professional groups. There is an urgent need for regulatory measures and public awareness through improved antimicrobial stewardship to limit this practice.

Pathogenesis and research progress of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis

In this editorial,we comment on the article by Mei et al.Nonalcoholic steatohep-atitis(NASH)is a severe inflammatory subtype of nonalcoholic fatty liver disease(NAFLD)with pathological features including steatosis,hepatocellular damage,and varying degrees of fibrosis.With the epidemic of metabolic diseases and obesity,the prevalence of NAFLD in China has increased,and it is now similar to that in developed countries;thus,NAFLD has become a major chronic liver disease in China.Human epidemiological data suggest that estrogen has a protective effect on NASH in premenopausal women and that sex hormones influence the development of liver disease.This review focuses on the path-ogenesis,treatment,and relationship between NASH and other diseases as well as on the relationship between NASH and sex hormone metabolism,with the aim of providing new strategies for the treatment of NASH.

Understanding the Novel Approach of Nanoferroptosis for Cancer Therapy

As a new form of regulated cell death,ferroptosis has unraveled the unsolicited theory of intrinsic apoptosis resistance by cancer cells.The molecular mechanism of ferroptosis depends on the induction of oxidative stress through excessive reactive oxygen species accumulation and glutathione depletion to damage the structural integrity of cells.Due to their high loading and structural tunability,nanocarriers can escort the delivery of ferro-therapeutics to the desired site through enhanced permeation or retention effect or by active targeting.This review shed light on the necessity of iron in cancer cell growth and the fascinating features of ferroptosis in regulating the cell cycle and metastasis.Additionally,we discussed the effect of ferroptosis-mediated therapy using nanoplatforms and their chemical basis in overcoming the barriers to cancer therapy.

Global Burden of Fungal Infections and Antifungal Resistance from 1961 to 2024: Findings and Future Implications

Background: Antifungal resistance (AFR) is a global public health problem with devastating effects, especially among immunocompromised individuals. Addressing AFR requires a One Health approach including Antifungal Stewardship (AFS). This study aimed to comprehensively review global studies published on fungal infections and AFR and to recommend solutions to address this growing problem. Materials and Methods: This was a narrative review that was conducted using published papers on fungal infections, AFR, and AFS between January 1961 and March 2024. The literature was searched using PubMed, Google Scholar, Web of Science, and EMBASE. Results: This found that there has been an increase in fungal infections globally, especially among immunocompromised patients. Due to this increase in fungal infections, there has been a proportionate increase in the use of antifungal agents to prevent and treat fungal infections. This increased use of antifungal agents has worsened the problem of AFR contributing to increased morbidity and mortality. Globally, fungal infections have contributed to 150 million infections annually and 1.7 million deaths per year. By the year 2023, over 3.8 million people died from fungal infections. Addressing AFR remains a challenge because the treatment of antifungal-resistant infections is difficult. Finally, the treatment of fungal infections is a global challenge exacerbated by the limited number of antifungal agents to treat invasive fungal infections. Conclusion: The results of this study indicated that fungal infections and AFR are prevalent across humans, animals, agriculture, and the environment. Addressing this problem requires the provision of solutions such as improving the awareness of AFR, conducting further research on the discovery of new antifungal agents, and implementing AFS programs. If this global problem is not addressed, the morbidity and mortality associated with AFR will continue to rise in the future.

Patients’Knowledge, Attitude and Practices on Disposal Methods of Expired and Unused Medicines: Implication for Creation of Drug Take-Back Program

Background: Handling of medicines is a day-to-day activity by patients and many health care providers. However, multiple studies have brought to light inappropriate disposal methods for expired and unused medication (EUM). Improper disposal of expired and unused medicines is hazardous both to humans and the environment. Objective: This sought to measure patients’ knowledge, attitude, and practices on disposal methods of EUM. Methods: A cross-sectional study was carried out among 384 patients at three outpatient pharmacies at the University Teaching Hospitals (UTHs). The structured questionnaire was used to collect data and STAT version 15.1 was used to analyse the data. Results: 384 respondents participated in this study and, at some point, had EUM. In this study, 356 (92.7%) of the participants reported that they had never heard of a drug take-back system. Most of the participants 285 (74.2%) and 239 (62.2%) kept and donated their unused medicine, respectively. Additionally, 244 (63.5%), 212 (55.2%), and 176 (44.8%) of the participants disposed of expired medicines in the bin or garbage, flushed them in toilets or sinks, or burned them, respectively. Occupation was significantly associated with unsafe disposal of unused medicine [P-value = 0.019]. Conclusion and Relevance: Knowledge of safe disposal methods for EUM was good amongst most participants. However, used unsafe disposal methods. The majority of the participants exhibited positive attitude concerning safe disposal methods. This study highlights the need for drug-take-back program creation in Zambia.

Roles of Community Pharmacists in Screening and Disseminating of Information about Non-Steroidal Anti-Inflammatory Drugs Risks: Implications for Drug Safety Assessment

Background: The increasing use of non-steroidal anti-inflammatory drugs (NSAIDs) both on prescription and over the counter raises a major global health concern because of the risks associated with their use if no proper guidance is given by the health care provider. This study assessed the roles of community pharmacists in screening and disseminating information about the risks associated with NSAID use in Zambia. Methodology: This was a national cross-sectional study in which a structured self-administered questionnaire was administered to 245 registered community pharmacists in Zambia. Stata/BE, version 15.1 (Stata Corporation, College Station, Texas, USA) and multivariate logistic regression model was used to determine factors associated with information dissemination about ADRs of NS-NSAIDs. Results: 231 of the 245 distributed questionnaires were returned giving a response rate of 94.3%. All (100%) participating community pharmacists claimed to have practiced dispensing NSAIDs. However, only 26 (11.0%) and 71 (30.8%) regularly screened for risk factor of selective COX-2 NSAIDS (SC2-NSAIDS) and non-selective NSAIDS (NS-NSAIDs) respectively. Information dissemination on adverse drug reactions (ADRs) of SC2-NSAIDS was regularly provided by only 22 (9.5%) of pharmacists while that of NS-NSAIDs was regularly provided by 49 (21.2%). In the multivariate logistic regression model, being the owner of a pharmacy (AOR: 5.4, CI: 1.84 - 16.4) was significantly associated with information dissemination about ADRs of NS-NSAIDs while an hour increase in the working hours per day (AOR: 0.9, CI: 0.64 - 0.95) was associated with less likelihood of information dissemination. Conclusion: Pharmacists working in community pharmacies in Zambia did not regularly screen and disseminate information about the risks associated with NSAID use. Therefore, pharmacists should be able to screen and monitor patients at risk and be aware of the majority of risk factors while dispensing NSAIDs to minimize the associated complications.

Expanding the Boundaries of the Chemical Space of DNA Methyltransferase 1 Modulators

DNA methyltransferase 1 (DNMT1), one of the main epigenetic targets, is involved in the duplication of the DNA methylation pattern during replication, and it is essential for proper mammalian development. Small molecule DNMT1 modulators are attractive for biochemical epigenetic studies and have the potential to become drugs. So far, more than five hundred small molecules have been reported as DNMT1 inhibitors. However, only a limited number of DNMT1 activators have been disclosed because, at least in part, DNMT1 activators are typically regarded as negative data in virtual screening campaigns or optimization projects. This manuscript aims to report the chemical structures and biological activity of small molecules that increase the enzymatic activity of DNMT1. Results of the biochemical experimental assays are discussed. It was found that small molecule activators have a large variety of chemical scaffolds but share pharmacophore features. Visual analysis of the chemical space and multiverse based on molecular fingertips supported that activators are structurally diverse. This is the first report of eight small molecules that increase the enzymatic activity of DNMT1 by more than 400% in an enzymatic-based assay. The outcome warrants further investigation of the epigenetic activity of the compounds in a counter-screen assay, e.g., cell-based and in vivo context.

COVID-19 Vaccine Acceptance and Hesitancy among Pregnant Women: A Knowledge, Attitude, and Perceived Risks Survey in Lusaka, Zambia

Introduction: The coronavirus disease 2019 (COVID-19) is an infectious disease of the respiratory tract caused by SARS-CoV-2. Since its emergence, there have been increased rates of transmission and spread, morbidity and mortality which led to the development of COVID-19 vaccines to address the pandemic. This study assessed acceptance, knowledge, attitude, and perceived risks regarding COVID-19 vaccines among pregnant women attending antenatal care at two First-Level Hospitals in Lusaka, Zambia. Materials and Methods: This was a cross-sectional study that was conducted among 241 pregnant women using a questionnaire from August 2023 to October 2023 in two First-Level Hospitals in Lusaka district, Zambia. The collected data were analyzed using IBM Statistical Package for Social Sciences (SPSS) version 22.0. Statistical analysis was performed using a Chi-square test. The statistical significance was set at a 95% confidence level. Results: Of the 241 participants, 107 (42.7%) were aged between 24 and 34 years. Overall, 64.3% accepted the COVID-19 vaccines, of which 122 (50.6%) were already vaccinated. Further, 203 (84.6%) of the pregnant women had good knowledge, and 199 (82.6%) had positive attitudes towards COVID-19 vaccines. However, 58.5% thought COVID-19 vaccines were not safe and could cause infertility. Alongside this, 70.1% thought that COVID-19 vaccines were harmful during pregnancy. Having good knowledge of COVID-19 vaccines was associated with age (p = 0.049), education status (p = 0.001), and employment status (p = 0.001). Having a positive attitude towards COVID-19 vaccines was associated with education status (p = 0.001) and employment status (p = 0.001). Conclusion: This study found that most pregnant women had good knowledge, and positive attitudes, and the majority accepted the COVID-19 vaccine. Encouragingly, most of the pregnant women who accepted the COVID-19 vaccines were already vaccinated. Most pregnant women thought that COVID-19 vaccines had side effects, were not safe, and could be harmful during pregnancy. Consequently, this could have contributed to the hesitancy to receive a vaccine among some participants. The findings of this study demonstrate the need to provide pregnant women with continuous educational programs on the benefits of vaccinations for themselves and their children.

Study on improving hematopoietic function of rats with blood deficiency syndrome by Shengxuebao mixture

Background:Shengxuebao mixture(SXBM)is a novel herbal drug approved by China State Food and Drug Administration for the treatment of Leukopenia and iron deficiency anemia caused by radiotherapy and chemotherapy.Methods:To explore the mechanism of SXBM in treating blood deficiency syndrome(BDS).Firstly,network pharmacology and in vivo experiments were used to screen candidate targets and important signaling pathways of SXBM,GO functional enrichment and KEGG pathway analysis were performed.Secondly,a BDS rat model was established to verify the results of the analysis of network pharmacological enrichment.Histopathology and routine peripheral blood examination were observed.The expressions of tumor necrosis factor-α,interleukin(IL)-6,HIF-1αand NF-κB were detected by Western blot,and the expressions of IL-6,IL-1βwere detected by ELISA.Results:62 bioactive components,66 potential targets and 131 signaling pathways of BDS were successfully identified by network pharmacology.Molecular docking simulation techniques showed that key targets tumor necrosis factor-α,IL-6,IL-1βcan dock well with crucial components,and the BDS-related signaling pathways HIF-1 and JAK-STAT play a vital role.The combined model experiment of acetylphenylhydrazine and cyclophosphamide showed that the model group had obvious blood deficiency,and the histopathology and blood routine were effectively restored after administration.Our findings indicate that SXBM’s therapeutic effect on BDS primarily involves the mediation of the HIF-1α/NF-κB signaling pathway and the regulation of hematopoietic factor expression.Conclusion:This study not only affirmed the protective properties of SXBM against BDS but also provided insights into a potential mechanism for blood replenishment in the treatment of BDS using SXBM.

56 Years of the Marburg Virus—A Review of Therapeutics

Background: The Marburg virus (MARV) is the causative agent of Marburg virus disease (MVD). This filovirus first appeared in 1967 and has since caused several outbreaks with case fatality rates between 23% and 90%. The earliest cases of MVD are thought to be caused by exposure to an infected animal, either a reservoir host (some bat species, e.g., Rousettus aegyptiacus) or a spill-over host, such as non-human primates. The virus is spread between people by direct contact with blood or other bodily fluids (including saliva, sweat, faeces, urine, tears, and breast milk) from infected individuals. Despite the high fatality rate, the Marburg virus has no vaccine or drug treatment. Recent outbreaks of the virus in 2023 in Tanzania and Equatorial Guinea have reignited the need to develop effective therapeutics, especially in the wake of the COVID-19 pandemic. Purpose: This review seeks to highlight the drug discovery efforts aimed at developing vaccines or possible treatments as potential therapeutics. Several existing antiviral agents are being probed, and vaccines are in pre-clinical and clinical stages. Natural products are also an important source of possible drugs or lead compounds and when coupled with computational techniques, these strategies offer possible therapeutics for the Marburg virus, especially in Africa, which has a high disease burden. Methods: Using the search engines Google Scholar and PubMed;keywords e.g. Marburg virus, Marburg treatments, Marburg virus drug discovery were utilized. Several results were yielded, and articles published in recent years were accepted into the final list.Results and Conclusion: This study shows there is a growing interest in therapeutics for the Marburg virus, especially with the recent outbreaks and pandemic preparedness. Initiatives that to support vaccine development and access like the MARVAC consort time are critical to fighting this public health threat.

Evidence-based expert consensus on clinical management of safety of Bruton’s tyrosine kinase inhibitors(2024)

Bruton’s tyrosine kinase inhibitors(BTKis)have revolutionized the treatment of B-cell lymphomas.However,safety issues related to the use of BTKis may hinder treatment continuity and further affect clinical efficacy.A comprehensive and systematic expert consensus from a pharmacological perspective is lacking for safety issues associated with BTKi treatment.A multidisciplinary consensus working group was established,comprising 35 members from the fields of hematology,cardiovascular disease,cardio-oncology,clinical pharmacy,and evidencebased medicine.This evidence-based expert consensus was formulated using an evidence-based approach and the Delphi method.The Joanna Briggs Institute Critical Appraisal(JBI)tool and Grading of Recommendations Assessment,Development,and Evaluation(GRADE)approach were used to rate the quality of evidence and grade the strength of recommendations,respectively.This consensus provides practical recommendations for BTKis medication based on nine aspects within three domains,including the management of common adverse drug events such as bleeding,cardiovascular events,and hematological toxicity,as well as the management of drug-drug interactions and guidance for special populations.This multidisciplinary expert consensus could contribute to promoting a multi-dimensional,comprehensive and standardized management of BTKis.

Violence study of healthcare workers and systems in the Caribbean:ViSHWaS-Caribbean study

BACKGROUND Violence against healthcare workers(HCWs)in the Caribbean continues to prevail yet remains underreported.Our aim is to determine the cause,traits,and consequences of violence on HCWs in the Caribbean.AIM To determine the cause,traits,and consequences of violence on HCWs in the Caribbean.METHODS This research adopted an online cross-sectional survey approach,spanning over eight weeks(between June 6th and August 9th,2022).The survey was generated using Research Electronic Data Capture forms and followed a snowballing strategy to contact individuals using emails,social media,text messages,etc.Logistic regression analysis was performed to evaluate the variables that influence violence,including gender,age,years of experience,institution type,and night shift frequency.RESULTS The survey was completed by 225 HCWs.Females comprised 61%.Over 51%of respondents belonged to the 21 to 35 age group.Dominica(n=61),Haiti(n=50),and Grenada(n=31)had the most responses.Most HCWs(49%)worked for government academic institutions,followed by community hospitals(23%).Medical students(32%),followed by attending physicians(22%),and others(16%)comprised the most common cadre of respondents.About 39%of the participants reported experiencing violence themselves,and 18%reported violence against colleague(s).Verbal violence(48%),emotional abuse(24%),and physical misconduct(14%)were the most common types of violence.Nearly 63%of respondents identified patients or their relatives as the most frequent aggressors.Univariate logistic regression analyses demonstrated that female gender(OR=2.08;95%CI:1.16-3.76,P=0.014)and higher frequency of night shifts(OR=2.22;95%CI:1.08-4.58,P=0.030)were associated with significantly higher odds of experiencing violence.More than 50%of HCWs felt less motivated and had decreased job satisfaction post-violent conduct.CONCLUSION A large proportion of HCWS in the Caribbean are exposed to violence,yet the phenomenon remains underreported.As a result,HCWs’job satisfaction has diminished.

Determinants of alcohol drinking and its association with sexual practices among high school students in Addis Ababa, Ethiopia: Cross sectional study

Introduction: Alcohol drinking and risky sexual practices have become serious public health problem among teenagers and young adults globally, including many developing countries. The available reports are sparse, especially there is a lack of recent and representative data for high school students in developing countries including Ethiopia. The aim of this study was to estimate the prevalence, identify determinants, and examine the association of alcohol drinking with sexual practices among high school students in Addis Ababa, capital city of Ethiopia. Methods: School based cross sectional study was conducted from November to December 2010. Multivariate logistic regression analysis was used to determine the association between students’ background characteristics and alcohol use, and alcohol use and sexual practices. Results: Among 2551 students surveyed, lifetime and current (past month) alcohol drinking was reported by 1166 (45.7%) and 676 (26.5%) students, respectively. Having sexual intercourse at least once in their lifetime was reported by 412 (16.2%) with151 (5.9%) of them being sexually active during a month prior to the survey. Having multiple sexual partners (52.5%), drinking alcohol before sexual intercourse (26.4%), and having sexual intercourse without the use of condom (47.3%) were also common among sexually active students. In adjusted logistic regression model, age (18 and 19 and older), living with 2 parents, getting pocket money, having alcohol drinking friends and attending general secondary school (grade 9-10) were positive predictors of current alcohol drinking. Nergative predictors of current alcohol drinking were being Protestant Christian and living with relatives or siblings. Conclusion: Alcohol drinking before sexual intercourse was a major problem among high school students in Addis Ababa, Ethiopia. Male gender, older age and higher school grade, friends influence, religious affiliation, living with parents and getting pocket money were significant predictors of current alcohol drinking. Educating about substance use and risky sexual behaviors, engaging students in extracurricular activities and restrict access to alcohol to high school students may help in solution of these problems on a local scale.

The Alzheimer's disease-associated gene TREML2 modulates inflammation by regulating microglia polarization and NLRP3 inflammasome activation

Triggering receptor expressed on myeloid cells-like 2(TREML2)is a newly identified susceptibility gene for Alzheimer's disease(AD).It encodes a microglial inflammation-associated receptor.To date,the potential role of mic roglial TREML2 in neuroinflammation in the context of AD remains unclear.In this study,APP/PS1 mice were used to investigate the dynamic changes of TREML2 levels in brain during AD progression.In addition,lipopolysaccharide(LPS)stimulation of primary microglia as well as a lentivirus-mediated TREML2 overexpression and knockdown were employed to explore the role of TREML2 in neuroinflammation in the context of AD.Our res ults show that TREML2 levels gradually increased in the brains of AP P/PS1 mice during disease progression.LPS stimulation of primary microglia led to the release of inflammato ry cytokines including interleukin-1β,inte rleukin-6,and tumor necrosis factor-a in the culture medium.The LPS-induced mic roglial release of inflammatory cytokines was enhanced by TREML2 overexpression and was attenuated by TREML2 knoc kdown.LPS increased the levels of mic roglial M1-type polarization marker inducible nitric oxide synthase.This effect was enhanced by TREML2 overexpression and ameliorated by TREML2 knockdown.Furthermore,the levels of microglial M2-type polarization markers CD206 and ARG1 in the primary microglia were reduced by TREML2 overexpression and elevated by TREML2 knockdown.LPS stimulation increased the levels of NLRP3 in primary microglia.The LPS-induced increase in NLRP3 was further elevated by TREML2 overexpression and alleviated by TREML2 knockdown.In summary,this study provides the first evidence that TREML2 modulates inflammation by regulating microglial polarization and NLRP3 inflammasome activation.These findings reveal the mechanisms by which TREML2 regulates microglial inflammation and suggest that TREML2 inhibition may represent a novel therapeutic strategy for AD.

Ginsenoside Rb1 improves energy metabolism after spinal cord injury

Mitochondrial damage caused by oxidative stress and energy deficiency induced by focal ischemia and hypoxia are important factors that aggravate diseases.Studies have shown that ginsenoside Rb1 has neurotrophic and neuroprotective effects.However,whether it influences energy metabolism after spinal cord injury remains unclear.In this study,we treated mouse and cell models of spinal cord injury with ginsenoside Rb1.We found that ginsenoside Rb1 remarkably inhibited neuronal oxidative stress,protected mitochondria,promoted neuronal metabolic reprogramming,increased glycolytic activity and ATP production,and promoted the survival of motor neurons in the anterior horn and the recovery of motor function in the hind limb.Because sirtuin 3 regulates glycolysis and oxidative stress,mouse and cell models of spinal cord injury were treated with the sirtuin 3 inhibitor 3-TYP.When Sirt3 expression was suppressed,we found that the therapeutic effects of ginsenoside Rb1 on spinal cord injury were remarkably inhibited.Therefore,ginsenoside Rb1 is considered a potential drug for the treatment of spinal cord injury,and its therapeutic effects are closely related to sirtuin 3.

COVID-19 and liver injury: An ongoing challenge

The new coronavirus severe acute respiratory syndrome coronavirus 2(SARSCoV-2)was identified in December 2019,in Wuhan,China.The virus was rapidly spread worldwide,causing coronavirus disease 2019(COVID-19)pandemic.Although COVID-19 is presented,usually,with typical respiratory symptoms(i.e.,dyspnea,cough)and fever,extrapulmonary manifestations are also encountered.Liver injury is a common feature in patients with COVID-19 and ranges from mild and temporary elevation of liver enzymes to severe liver injury and,even,acute liver failure.The pathogenesis of liver damage is not clearly defined;multiple mechanisms contribute to liver disorder,including direct cytopathic viral effect,cytokine storm and immune-mediated hepatitis,hypoxic injury,and druginduced liver toxicity.Patients with underlying chronic liver disease(i.e.,cirrhosis,non-alcoholic fatty liver disease,alcohol-related liver disease,hepatocellular carcinoma,etc.)may have greater risk to develop both severe COVID-19 and further liver deterioration,and,as a consequence,certain issues should be considered during disease management.The aim of this review is to present the prevalence,clinical manifestation and pathophysiological mechanisms of liver injury in patients with SARS-CoV-2 infection.Moreover,we overview the association between chronic liver disease and SARS-CoV-2 infection and we briefly discuss the management of liver injury during COVID-19.

A benchtop brain injury model using resected donor tissue from patients with Chiari malformation

The use of live animal models for testing new therapies for brain and spinal cord repair is a controversial area. Live animal models have associated ethical issues and scientific concerns regarding the predictability of human responses. Alternative models that replicate the 3 D architecture of the central nervous system have prompted the development of organotypic neural injury models. However, the lack of reliable means to access normal human neural tissue has driven reliance on pathological or post-mortem tissue which limits their biological utility. We have established a protocol to use donor cerebellar tonsillar tissue surgically resected from patients with Chiari malformation(cerebellar herniation towards the foramen magnum, with ectopic rather than diseased tissue) to develop an in vitro organotypic model of traumatic brain injury. Viable tissue was maintained for approximately 2 weeks with all the major neural cell types detected. Traumatic injuries could be introduced into the slices with some cardinal features of post-injury pathology evident. Biomaterial placement was also feasible within the in vitro lesions. Accordingly, this ‘proof-of-concept’ study demonstrates that the model offers potential as an alternative to the use of animal tissue for preclinical testing in neural tissue engineering. To our knowledge, this is the first demonstration that donor tissue from patients with Chiari malformation can be used to develop a benchtop model of traumatic brain injury. However, significant challenges in relation to the clinical availability of tissue were encountered, and we discuss logistical issues that must be considered for model scale-up.

Cases studies of application of model-informed drug development in early phase clinical trials

Model-informed drug develop⁃ment(MIDD)is the application of a various math⁃ematical,statistical,and biological models to facilitate drug development,decision making and regulatory review.As a quantitative tool,MIDD approaches allow an integration of information obtained from non-clinical studies and clinical trials in a drug development program.General understandings of the underlying biology,patho⁃physiology,and pharmacology can also be incor⁃porated into the model.MIDD is centered on knowledge and inferences generated from inte⁃grated models of the physicochemical character⁃istics of a molecule,its disposition in the body,and its mechanism of action,and how the drug might affect a disease from both an efficacy and a safety perspective.MIDD approaches have the potential to significantly streamline drug develop⁃ment,by improving clinical trial efficiency,opti⁃mizing dose and regimen and waive unneces⁃sary clinical studies.This presentation will use cases studies to demonstrate how to apply MIDD in early phase of clinical trials.

The role of selected medicinal plants from Iranian traditional medicine for the treatment of fatigue in metabolic syndrome

Background:Fatigue is a symptom of metabolic disorders such as metabolic syndrome,which is currently increasing in the world.There is no specific medication for fatigue,but in many cases,such as in metabolic disorders,it can be relieved by treating the underlying causes.Oxidative stress and inflammation are associated with fatigue and metabolic syndrome.Other mechanisms in metabolic syndrome are also involved in causing fatigue.Objective:The aim of this study was to investigate the role of selected medicinal plants from Iranian traditional medicine(ITM)in improving fatigue in patients with metabolic syndrome.Methods:ITM is one of the most ancient systems of medicine.In this article,we first explained fatigue,its types,and treatment from the perspective of ITM and then introduced a list of medicinal plants used in ITM to treat fatigue.Next,we reviewed the biological effects of these plants effective in treating the manifestations of the metabolic syndrome based on a search of electronic databases.Results:They have antioxidant,anti-inflammatory,and anti-diabetic activities.Among them,Matricaria chamomilla L.,Laurus nobilis L.,Origanum majorana L.,Vitex agnus-castus L.,Lawsonia inermis L.,Anethum graveolens L.,and Pistacia terebinthus L.improve the lipid profile and reduce dyslipidemia.Also,the antihypertensive effects of Matricaria chamomilla,Laurus nobilis,and Origanum majorana have been proven.Conclusion:These plants prevent fatigue and disease progression by countering oxidative stress and inflammation and affecting the properties of the metabolic syndrome.

Global Strategies to Combat Antimicrobial Resistance: A One Health Perspective

Background: Antimicrobial resistance (AMR) is a global health challenge that has escalated due to the inappropriate use of antimicrobials in humans, animals, and the environment. Developing and implementing strategies to reduce and combat AMR is critical. Purpose: This study aimed to highlight some global strategies that can be implemented to address AMR using a One Health approach. Methods: This study employed a narrative review design that included studies published from January 2002 to July 2023. The study searched for literature on AMR and antimicrobial stewardship (AMS) in PubMed and Google Scholar using the 2020 PRISMA guidelines. Results: This study reveals that AMR remains a significant global public health problem. Its severity has been markedly exacerbated by inappropriate use of antimicrobials in humans, animals, and the broader ecological environment. Several strategies have been developed to address AMR, including the Global Action Plan (GAP), National Action Plans (NAPs), AMS programs, and implementation of the AWaRe classification of antimicrobials. These strategies also involve strengthening surveillance of antimicrobial consumption and resistance, encouraging the development of new antimicrobials, and enhancing regulations around antimicrobial prescribing, dispensing, and usage. Additional measures include promoting global partnerships, combating substandard and falsified antimicrobials, advocating for vaccinations, sanitation, hygiene and biosecurity, as well as exploring alternatives to antimicrobials. However, the implementation of these strategies faces various challenges. These challenges include low awareness and knowledge of AMR, a shortage of human resources and capacity building for AMR and AMS, in adequate funding for AMR and AMS initiatives, limited laboratory capacities for surveillance, behavioural change issues, and ineffective leadership and multidisciplinary teams. Conclusion: In conclusion, this study established that AMR is prevalent among humans, animals, and the environment. Successfully addressing AMR calls for a collaborative, multifaceted One Health approach. Despite this, some gaps remain effectively implementing strategies currently recommended to combat AMR. As a result, it is essential to reinforce the strategies that are deployed to counter AMR across the human, animal, and environmental sectors.