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Summary Parasomnias and sleep‐related movement disorders (SRMD) are major causes of sleep disorders and may be drug induced. The objective of this study was to conduct a systematic review of the literature to examine the association between drug use and the occurrence of parasomnias and SRMD. Following Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines for reporting systematic reviews, we searched PubMed databases between January 2020 and June 2023. The searches retrieved 937 records, of which 174 publications were selected for full‐text screening and 73 drugs were identified. The most common drug‐induced parasomnias were nightmares and rapid eye movement (REM) sleep behaviour disorders and sleepwalking. In terms of drug‐induced SRMD, restless legs syndrome, periodic limb movement disorders (PLMD), and sleep‐related bruxism were most frequent. Medications that inhibit noradrenergic, serotonergic, or orexin transmission could induce REM sleep (e.g., nightmares). Regarding sleepwalking, dysregulation of serotoninergic neurone activity is implicated. Antipsychotics are mentioned, as well as medications involved in the gamma‐aminobutyric acid (GABA) pathway. A mechanism of desensitisation‐autoregulation of GABA receptors on serotoninergic neurones is a hypothesis. SRMD and PLMD could involve medications disrupting the dopamine pathway (e.g., antipsychotics or opioids). Opioids would act on mu receptors and increase dopamine release. The role of adenosine and iron is also hypothesised. Regarding bruxism, the hypotheses raised involve dysregulation of mesocortical pathway or a downregulation of nigrostriatal pathway, related to medications involving dopamine or serotonin. Parasomnias are rarely identified in drug product labels, likely due to the recent classification of their diagnoses. An analysis of pharmacovigilance data could be valuable to supplement existing literature data. [ABSTRACT FROM AUTHOR]

Cannabidiol (CBD)-containing products are widely marketed as over the counter products. Adverse effects reported in anecdotal consumer reports or during clinical studies were first assumed to be due to acid-catalysed cyclization of CBD to psychotropic Δ 9-tetrahydrocannabinol (Δ 9-THC) in the stomach after oral consumption. However, research of pure CBD solutions stored in simulated gastric juice or subjected to various storage conditions such as heat and light with specific liquid chromatographic/tandem mass spectrometric (LC/MS/MS) and ultra-high pressure liquid chromatographic/quadrupole time-of-flight mass spectrometric (UPLC-QTOF) analyses was unable to confirm THC formation. Another hypothesis for the adverse effects of CBD products may be residual Δ 9-THC concentrations in the products as contamination, because most of them are based on hemp extracts containing the full spectrum of cannabinoids besides CBD. Analyses of 413 hemp-based products of the German market (mostly CBD oils) confirmed this hypothesis: 48 products (12%) contained Δ 9-THC above the lowest observed adverse effect level (2.5 mg/day). Hence, it may be assumed that the adverse effects of some commercial CBD products are based on a low-dose effect of Δ 9-THC, with the safety of CBD itself currently being unclear with significant uncertainties regarding possible liver and reproductive toxicity. The safety, efficacy and purity of commercial CBD products is highly questionable, and all of the products in our sample collection showed various non-conformities to European food law such as unsafe Δ 9-THC levels, hemp extracts or CBD isolates as non-approved novel food ingredients, non-approved health claims, and deficits in mandatory food labelling requirements. In view of the growing market for such lifestyle products, the effectiveness of the instrument of food business operators' own responsibility for product safety and regulatory compliance must obviously be challenged, and a strong regulatory framework for hemp products needs to be devised.

Copyright of Revista ADM is the property of Asociacion Dental Mexicana and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Medical professionals, particularly in regions with a high burden of human immunodeficiency virus (HIV), should be alert to the hematological complications of HIV, which may include cytopenias, malignancy, and coagulation disturbances. Patients may present with these conditions as the first manifestation of HIV infection. Hematological abnormalities are often multifactorial with opportunistic infections, drugs, malignancy, and HIV infection itself contributing to the clinical presentation, and the diagnosis should consider all these factors. Life-threatening hematological complications requiring urgent diagnosis and management include thrombotic thrombocytopenic purpura, superior mediastinal syndrome, spinal cord compression, and tumor lysis syndrome due to aggressive lymphoma. Antiretroviral therapy is the therapeutic backbone, including for patients with advanced HIV, in addition to specific therapy for the complication. This article reviews the impact of HIV on the hematological system and provides a clinical and diagnostic approach, including the role of a bone marrow biopsy, focusing on perspectives from sub-Saharan Africa. [ABSTRACT FROM AUTHOR]

This study explores the antiarrhythmic and hypotensive potential of pyridyl-substituted nitronyl nitroxides derivatives, uncovering the crucial role of a single carbon moiety of the pyridine cycle alongside radical and charged oxygen centers of the imidazoline fragment. Notably, the introduction of fluorine atoms diminished the antiarrhythmic effect, while the most potent derivatives featured the nitronyl nitroxide pattern positioned at the third site of the pyridine cycle. Gender-dependent responses were observed in lead compounds LCF3 and LMe, with LMe inducing temporary bradycardia and hypotension specifically in female rats, and LCF3 causing significant blood pressure reduction followed by rebound in females compared to milder effects in males. Mechanistic insights point towards β 1 adrenoceptor blockade as an underlying mechanism, supported by experiments on isolated rat atria. This research underscores the interplay between structure, cardiovascular effects and gender-specific responses, offering insights for therapeutic strategies for treating free radical-associated cardiovascular disorders. [Display omitted] • Distinctive antiarrhythmic and hypotensive properties. • The third-positioned nitronyl nitroxide fragment is a must. • Gender variations in compound activity are observed. • Stable aqueous solutions and lower toxicity compared to established HNO donors. [ABSTRACT FROM AUTHOR]

Copyright of Revista Ciencias de la Salud is the property of Colegio Mayor de Nuestra Senora del Rosario and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Sodium lauryl sulfate (SLS) is an anionic surfactant, which has a wide range of usage in the health sector and in dental pharmaceutical products, especially in toothpastes. The objective of this review was to investigate the effects of SLS containing dentifrices on oral and periodontal health, possible side effects, and its benefits. A thorough literature search was done using databases of PubMed and Google Scholar and finally, 40 articles were included in the study. This narrative review revealed the sources of discrepancy and conflicting results regarding the impact of SLS on oral cavity as well as a lack of sufficient evidence in most topics. Hence, the evidence suggests improved drug bioavailability when used as a solubilizer, improved plaque control, and reduction in bad breath. On the other hand, SLS can serve as a risk indicator of prolonged oral wound healing time, recurrent aphthous stomatitis.

Sodium lauryl sulfate (SLS) is an anionic surfactant, which has a wide range of usage in the health sector and in dental pharmaceutical products, especially in toothpastes. The objective of this review was to investigate the effects of SLS containing dentifrices on oral and periodontal health, possible side effects, and its benefits. A thorough literature search was done using databases of PubMed and Google Scholar and finally, 40 articles were included in the study. This narrative review revealed the sources of discrepancy and conflicting results regarding the impact of SLS on oral cavity as well as a lack of sufficient evidence in most topics. Hence, the evidence suggests improved drug bioavailability when used as a solubilizer, improved plaque control, and reduction in bad breath. On the other hand, SLS can serve as a risk indicator of prolonged oral wound healing time, recurrent aphthous stomatitis. [ABSTRACT FROM AUTHOR]

Background: Observational studies evaluating the effect of a drug versus "non-use" are challenging, mainly when defining cohort entry for non-users. The approach using successive monthly cohorts to emulate the randomized trial can be perceived as somewhat opaque and complex. Alternatively, the prevalent new-user design can provide a potentially simpler more transparent emulation. This design is illustrated in the context of statins and cancer incidence. Methods: We used the Clinical Practice Research Datalink to identify a cohort of subjects with low-density lipoprotein cholesterol level <5 mmol/L. We used a prevalent new-user design, matching each statin initiator to a non-user from the same time-based exposure set on time-conditional propensity scores with all subjects followed for 10 years for cancer incidence. We estimated the hazard ratio and 95% confidence interval (CI) of cancer incidence with statin use versus non-use using a Cox proportional hazards model, and the results were compared with those using the method of successive monthly cohorts. Results: The study cohort included 182,073 statin initiators and 182,073 matched non-users. The hazard ratio of any cancer after statin initiation versus non-use was 1.01 (95% CI = 0.98, 1.04), compared with 1.04 (95% CI = 1.02, 1.06) under the successive monthly cohorts approach. We estimated similar effects for specific cancers. Conclusion: Using the prevalent new-user design to emulate a randomized trial when compared to "non-use" led to results comparable with the more complex successive monthly cohorts approach. The prevalent new-user design emulates the trial in a potentially more intuitive and palpable manner, providing simpler data presentations in line with those portrayed in a classical trial while producing comparable results. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The popularity of intravenous immunoglobulin (IVIG) therapy in Acute Respiratory Distress Syndrome (CARDS) secondary to COVID-19 infection is increasing day by day. In this study, we aimed to retrospectively evaluate the possible cardiac effects in our CARDS patients treated with IVIG. METHODS: Demographic and clinical characteristics, mortality, sequential electrocardiography (ECG), echocardiography, cardiac markers, and other laboratory parameters of CARDS patients who received IVIG treatment were recorded. RESULTS: The mean age of the patients was 68.7±13.6%, and 70.5% were female. The mean number of days of hospitalization in the intensive care unit was 18.2±9.7, and the mortality rate was recorded as 35.2%. No pathological rhythm or ischemic change was observed in sequential ECG follow-ups. However, in consecutive ECO follow-ups, the sPAP values at the treatment end were numerically lower, although not statistically significant. CONCLUSION: Our study suggests that IVIG therapy may be used safely in COVID-19 patients with cardiovascular side effects. However, due to the high risk of coagulopathy in these patients, the use of IVIG therapy in COVID-19 infection should be monitored with close monitoring, as it may increase the potential for cardiovascular risk. Furthermore, monitoring cardiac parameters are also essential as it may predict high cardiovascular risk in patients. For this reason, patients need lower infusion rates, steroid combination, adequate hydration, and effective anticoagulation therapy to avoid these side effects. [ABSTRACT FROM AUTHOR]

Objectives: Drug reference databases provide information on potential drug-related medical complications in a dental patient. It is important that database entries and recommendations are supported by evidence-based original studies focused on drug-related dental management complications. The aim of this study was to review and identify database drug categories associated with evidence-based drug-related medical complications during dental treatment. Data sources: Relevant publications on adverse drug reactions and dental management complications were thoroughly reviewed from the literature published between July 1975 and July 2019. Method and materials: The drug reference database "Lexicomp Online for Dentistry" was reviewed to identify medications associated with the highest propensity to trigger drug-related dental management complications, and these were correlated with published original studies in PubMed, Embase, and Scopus databases that associated drug actions with dental treatment complications. Results: Fifty-four publications (1.2% of all fulltext articles) reported original studies that directly tested drug associations with dental management complications. The cautions in the drug reference database on drug-related dental treatment mainly focused on local anesthetic precaution (P < .001), xerostomia (P < .001), bleeding (P < .001), and a combination of xerostomia and bleeding (P < .001). Antipsychotics/ antidepressants were mostly associated with local anesthetic complications (80.95%), xerostomia (81.93%), and a combination of xerostomia and bleeding (22.89%). Bleeding complication was associated with anticoagulants (80.00%) and cancer chemotherapeutic agents (59.21%). Conclusions: Similarities exist within and across different drug categories in the database entries on drug-related medical complications in a dental patient. There were a relatively limited number of publications that directly tested the association between drug-related medical complications and dental therapies. Clinical relevance: The most common drug cautions during dental treatment reported in Lexicomp Online for Dentistry were limited to drugdrug interactions with local anesthetic actions, excessive bleeding, xerostomia, or a combination of any of these. These recommendations were supported by limited evidence-based studies. [ABSTRACT FROM AUTHOR]

Therapeutic psychedelic administration and contact with nature have been associated with the same psychological mechanisms: decreased rumination and negative affect, enhanced psychological connectedness and mindfulness-related capacities, and heightened states of awe and transcendent experiences, all processes linked to improvements in mental health amongst clinical and healthy populations. Nature-based settings can have inherently psychologically soothing properties which may complement all stages of psychedelic therapy (mainly preparation and integration) whilst potentiating increases in nature relatedness, with associated psychological benefits. Maximising enhancement of nature relatedness through therapeutic psychedelic administration may constitute an independent and complementary pathway towards improvements in mental health that can be elicited by psychedelics.

Objective: The healing effects of two different dilutions (5 & 100%) of N-Chromosome Royal Jelly and ANGIPARS ointment were investigated and measured on experimental injuries in streptozotocin (STZ)-induced diabetic rats. This study investigated the healing effects of 2 different N Chromosome Royal Jelly dilutions on injuries of STZ-induced diabetic rats. Materials and Methods: For diabetes induction, male Wistar rats received STZ (55 mg/kg) intraperitoneally and plasma glucose level measurement after 72 hours demonstrated diabetes induction. Rats were randomly divided into 5 groups of 6 members and one square centimeter (cm2) wound was surgically induced in the dorsal region of each rat. The test groups were treated with ANGIPARS, undiluted royal jelly N chromosome, and royal jelly N chromosome 5% separately. The control groups were including non-diabetic and untreated diabetic rats. Results: The findings indicate a significant acceleration in wound healing of the diabetic rats treated by ANGIPARS ointment or royal jelly N chromosomes 5%. RJ also shortened the healing period of desquamated skin lesions. Thus, RJ possesses an anti-inflammatory action and is able to augment wound healing, but does not have an insulin-like action in streptozotocin-diabetic rats. Conclusion: Regarding the mentioned findings, royal jelly as a natural product may play an effective role in treating chronic wounds in mice, which makes it a proper candidate for use in human wound repair. Nonetheless, it seems that determination of the suitable dilution of this compound will result in better effects, thus more studies are recommended.

Cannabidiol (CBD)-containing products are widely marketed as over the counter products, mostly as food supplements. Adverse effects reported in anecdotal consumer reports or during clinical studies were first assumed to be due to acid-catalysed cyclization of CBD to psychotropic Δ 9tetrahydrocannabinol (Δ 9-THC) in the stomach after oral consumption. However, research of pure CBD solutions stored in simulated gastric juice or subjected to various storage conditions such as heat and light with specific liquid chromatographic/tandem mass spectrometric (LC/MS/MS) and ultra-high pressure liquid chromatographic/quadrupole time-of-flight mass spectrometric (UPLC-QTOF) analyses was unable to confirm THC formation. Another hypothesis for the adverse effects of CBD products may be residual Δ 9-THC concentrations in the products as contamination, because most of them are based on hemp extracts containing the full spectrum of cannabinoids besides CBD. Analyses of 362 hemp-based products of the German market (mostly CBD oils) confirmed this hypothesis: 39 products (11%) contained Δ 9-THC above the lowest observed adverse effect level (2.5 mg/day). Hence, it may be assumed that the adverse effects of some commercial CBD products are based on a low-dose effect of Δ 9-THC, with the safety of CBD itself currently being unclear with significant uncertainties regarding possible liver and reproductive toxicity. The safety, efficacy and purity of commercial CBD products is highly questionable, and all of the products in our sample collection showed various non-conformities to European food law such as unsafe Δ 9-THC levels, hemp extracts or CBD isolates as non-approved novel food ingredients, non-approved health claims, and deficits in mandatory food labelling requirements. In view of the growing market for such lifestyle products, the effectiveness of the instrument of food business operators' own responsibility for product safety and regulatory compliance must obviously be challenged, and a strong regulatory framework for hemp products needs to be devised.

Introduction: Essential oils are considered a potential alternative to synthetic drugs in the management of diseases such as peptic ulcer (PU) and ulcerative colitis (UC). This study is concerned with comparing the therapeutic effects of Cuminum cyminum L, Carum carvi L, and Thymus vulgaris L. essential oils on PU and UC models induced by ethanol. Methods: Rats were divided into 10 groups; control groups were treated with saline and experimental groups with 500 mg/kg body weight of C. cyminum, C. carvi, or T. vulgaris essential oil. Curative effects were determined by measuring tissue oxidative markers, such as reduced glutathione (GSH), malondialdehyde (MDA), and myeloperoxidase (MPO), as well as the inflammatory marker prostaglandin E2 (PGE2), stomach pepsin (PEP), and colon alkaline phosphatase (ALP). Biochemical and histological examinations were done on stomach and colon tissues. Results: The current study proved the anti-ulcer effects of C. cyminum, C. carvi, and T. vulgaris essential oils. They improved the oxidative and inflammatory markers in both stomach and colon tissues and modulated stomach PEP and colon ALP activities. T. vulgaris essential oil modulated GSH and MDA levels resulting in a significant elevation in GSH levels by 120.43% and 99.46% and a significant reduction in MDA levels by 20.05% and 24.1% in PU and UC models, respectively. C. carvi essential oil was the most effective in restoring PGE2 by 71.51% compared to UC group. Results were confirmed by the morphological and histopathological changes. Conclusion: C. cyminum, C. carvi, or T. vulgaris essential oils might be used in the management of acute PU and UC.

Cardiovascular diseases (CVDs) are the leading cause of death. Of CVDs, congenital heart diseases are the most common congenital defects, with a prevalence of 1 in 100 live births. Despite the widespread knowledge that prenatal and postnatal drug exposure can lead to congenital abnormalities, the developmental toxicity of many FDA-approved drugs is rarely investigated. Therefore, to improve our understanding of drug side effects, we performed a high-content drug screen of 1,280 compounds using zebrafish as a model for cardiovascular analyses. Zebrafish are a well-established model for CVDs and developmental toxicity. However, flexible open-access tools to quantify cardiac phenotypes are lacking. Here, we provide pyHeart4Fish, a novel Python-based, platform-independent tool with a graphical user interface for automated quantification of cardiac chamber-specific parameters, such as heart rate (HR), contractility, arrhythmia score, and conduction score. In our study, about 10.5% of the tested drugs significantly affected HR at a concentration of 20 µM in zebrafish embryos at 2 days post-fertilization. Further, we provide insights into the effects of 13 compounds on the developing embryo, including the teratogenic effects of the steroid pregnenolone. In addition, analysis with pyHeart4Fish revealed multiple contractility defects induced by seven compounds. We also found implications for arrhythmias, such as atrioventricular block caused by chloropyramine HCl, as well as (R)-duloxetine HCl-induced atrial flutter. Taken together, our study presents a novel open-access tool for heart analysis and new data on potentially cardiotoxic compounds.

Objective: The healing effects of two different dilutions (5 & 100%) of N-Chromosome Royal Jelly and ANGIPARS ointment were investigated and measured on experimental injuries in streptozotocin (STZ)- induced diabetic rats. This study investigated the healing effects of 2 different N Chromosome Royal Jelly dilutions on injuries of STZ-induced diabetic rats. Materials and Methods: For diabetes induction, male Wistar rats received STZ (55 mg/kg) intraperitoneally and plasma glucose level measurement after 72 hours demonstrated diabetes induction. Rats were randomly divided into 5 groups of 6 members and one square centimeter (cm² ) wound was surgically induced in the dorsal region of each rat. The test groups were treated with ANGIPARS, undiluted royal jelly N chromosome, and royal jelly N chromosome 5% separately. The control groups were including non-diabetic and untreated diabetic rats. Results: The findings indicate a significant acceleration in wound healing of the diabetic rats treated by ANGIPARS ointment or royal jelly N chromosomes 5% . RJ also shortened the healing period of desquamated skin lesions. Thus, RJ possesses an anti-inflammatory action and is able to augment wound healing, but does not have an insulin-like action in streptozotocin-diabetic rats. Conclusion: Regarding the mentioned findings, royal jelly as a natural product may play an effective role in treating chronic wounds in mice, which makes it a proper candidate for use in human wound repair. Nonetheless, it seems that determination of the suitable dilution of this compound will result in better effects, thus more studies are recommended . [ABSTRACT FROM AUTHOR]

Neural stem cell (NSC) transplantation is an emerging and promising approach to combat neurodegenerative diseases. While NSCs can differentiate into neural cell types, many therapeutic effects are mediated by paracrine, “drug-like” mechanisms. Neurodegenerative diseases are predominantly a burden of the elderly who commonly suffer from comorbidities and thus are subject to pharmacotherapies. There is substantial knowledge about drug-drug interactions but almost nothing is known about a potential impact of pharmacotherapy on NSCs. Such knowledge is decisive for designing tailored treatment programs for individual patients. Previous studies revealed preliminary evidence that the anti-depressants fluoxetine and imipramine may affect NSC viability and proliferation. Here, we derive a hypothesis on how commonly applied drugs, statins and antihypertensives, may affect NSC viability, proliferation, and differentiation. We conducted a systematic review and meta-analysis looking at potential effects of commonly prescribed antihypertensive and antihyperlipidemic medication on NSC function. PubMed and Web of Science databases were searched on according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Publications were assessed against a priori established selection criteria for relevancy. A meta-analysis was then performed on data extracted from publications eligible for full text review to estimate drug effects on NSC functions. Our systematic review identified 1,017 potential studies, 55 of which were eligible for full text review. Out of those, 21 were included in the qualitative synthesis. The meta-analysis was performed on 13 publications; the remainder were excluded as they met exclusion criteria or lacked sufficient data to perform a meta-analysis. The meta-analysis revealed that alpha- 2 adrenoceptor agonists, an anti-hypertensive drug class [p < 0.05, 95% confidence intervals (CI) = –1.54; –0.35], and various statins [p < 0.05, 95% CI = –3.17; –0.0694] had an inhibiting effect on NSC proliferation. Moreover, we present preliminary evidence that L-type calcium channel blockers and statins, particularly lovastatin, may reduce NSC viability. Although the data available in the literature is limited, there are clear indications for an impact of commonly applied drugs, in particular statins, on NSC function. Considering the modes of action of the respective drugs, we reveal plausible mechanisms by which this impact may be mediated, creating a testable hypothesis, and providing insights into how future confirmative research on this topic may be conducted. [ABSTRACT FROM AUTHOR]

Autacoids are substances that released locally from cells with various stimuli to elicit normal physiological responses and lose activity in a very short time providing local communication between adjacent cells in the organism. Disproportion in their synthesis, release or transmission contribute significantly to pathological conditions such as inflammation, allergy, hypersensitivity, and ischemia-reperfusion injury. These messenger molecules participate in all physiological and pathological processes, and assume very important roles in inflammation. Autacoids, which take part in different stages or types of inflammation, work both as a trigger and as a regulator. These substances mediate the communication network of the cells involved in the inflammation, enabling the organism to eliminate the damaged/foreign/harmful factor. Either autacoids can be found in immune cells as storage or enzymes whose activity or expression increase with inflammatory stimulus can also synthesize them. According to their chemical structure, autacoids are classified in groups of gaseous (NO, H2S, CO), lipid (prostaglandins, leukotrienes, lipoxins, PAF), peptide (angiotensins, kinins, Substance P, endothelins, natriuretic peptides), amine (histamine, serotonin) and protein autacoids (cytokines) and they can be secreted from many cells in the inflammation. There are various differences in acute and chronic inflammation in terms of both the types of autoacoids involved and the inflammatory cells that synthesize them. However, how much of these molecules are secreted from each cell during the process has not been revealed in real time yet. While they are secreted under the dominance of neutrophils and macrophages in the acute stage, lymphocytes and macrophages take over the secretory function according to the type of inflammation in the chronic stage. Despite the use of many drugs as enzyme inhibitors, receptor antagonists / agonists or analogues in the treatment of inflammation, intensive studies are underway to develop new drugs, which will be more selective, highly effective and have less side effects. The aim of this review was to discuss autacoids involved in inflammation in the context of participating cells and inflammatory processes and to evaluate their situation as a drug target in inflammation. [ABSTRACT FROM AUTHOR]

Cannabidiol (CBD)-containing products are widely marketed as over the counter products, mostly as food supplements. Adverse effects reported in anecdotal consumer reports or during clinical studies were first assumed to be due to hydrolytic conversion of CBD to psychotropic Δ 9-tetrahydrocannabinol (Δ 9-THC) in the stomach after oral consumption. However, research of pure CBD solutions stored in simulated gastric juice or subjected to various storage conditions such as heat and light with specific liquid chromatographic/tandem mass spectrometric (LC/MS/MS) and ultra-high pressure liquid chromatographic/quadrupole time-of-flight mass spectrometric (UPLC-QTOF) analyses was unable to confirm THC formation. Another hypothesis for the adverse effects of CBD products may be residual Δ 9-THC concentrations in the products as contamination, because most of them are based on hemp extracts containing the full spectrum of cannabinoids besides CBD. Analyses of 293 food products of the German market (mostly CBD oils) confirmed this hypothesis: 28 products (10%) contained Δ 9-THC above the lowest observed adverse effect level (2.5 mg/day). Hence, it may be assumed that the adverse effects of some commercial CBD products are based on a low-dose effect of Δ 9-THC, with the safety of CBD itself currently being unclear with significant uncertainties regarding possible liver and reproductive toxicity. The safety, efficacy and purity of commercial CBD products is highly questionable, and all of the products in our sample collection showed various non-conformities to European food law such as unsafe Δ 9-THC levels, hemp extracts or CBD isolates as non-approved novel food ingredients, non-approved health claims, and deficits in mandatory food labelling requirements. In view of the growing market for such lifestyle products, the effectiveness of the instrument of food business operators' own responsibility for product safety and regulatory compliance must obviously be challenged, and a strong regulatory framework for hemp products needs to be devised.

BackgroundCerebral microbleeds (CMB) are MRI-demonstrable cerebral microhemorrhages (CMH) which commonly coexist with ischemic stroke. This creates a challenging therapeutic milieu, and a strategy that simultaneously protects the vessel wall and provides anti-thrombotic activity is an attractive potential approach. Phosphodiesterase 3A (PDE3A) inhibition is known to provide cerebral vessel wall protection combined with anti-thrombotic effects. As an initial step in the development of a therapy that simultaneously treats CMB and ischemic stroke, we hypothesized that inhibition of the PDE3A pathway is protective against CMH development.MethodsThe effect of PDE3A pathway inhibition was studied in the inflammation-induced and cerebral amyloid angiopathy (CAA)-associated mouse models of CMH. The PDE3A pathway was modulated using two approaches: genetic deletion of PDE3A and pharmacological inhibition of PDE3A by cilostazol. The effects of PDE3A pathway modulation on H&E- and Prussian blue (PB)-positive CMH development, BBB function (IgG, claudin-5, and fibrinogen), and neuroinflammation (ICAM-1, Iba-1, and GFAP) were investigated.ResultsRobust development of CMH in the inflammation-induced and CAA-associated spontaneous mouse models was observed. Inflammation-induced CMH were associated with markers of BBB dysfunction and inflammation, and CAA-associated spontaneous CMH were associated primarily with markers of neuroinflammation. Genetic deletion of the PDE3A gene did not alter BBB function, microglial activation, or CMH development, but significantly reduced endothelial and astrocyte activation in the inflammation-induced CMH mouse model. In the CAA-associated CMH mouse model, PDE3A modulation via pharmacological inhibition by cilostazol did not alter BBB function, neuroinflammation, or CMH development.ConclusionsModulation of the PDE3A pathway, either by genetic deletion or pharmacological inhibition, does not alter CMH development in an inflammation-induced or in a CAA-associated mouse model of CMH. The role of microglial activation and BBB injury in CMH development warrants further investigation.

Fatal opioid poisonings often involve methadone or morphine. This study aimed to elucidate if quetiapine, a widely used sedative antipsychotic medication, may increase the risk of fatal opioid poisoning by additive inhibitory effects on the central nervous system. We used data from 323 cases of fatal methadone or/and morphine poisonings autopsied from 2013 to 2020, a survey of 34 drug users, and performed blinded placebo-controlled studies in 75 Flinders Resistant Line rats receiving three cumulative intraperitoneal doses of vehicle, methadone (2.5, 10 and 15 mg/kg), morphine (3.75, 15 and 22.5 mg/kg), quetiapine (3, 10 and 30 mg/kg) or quetiapine combined with methadone or morphine. Quetiapine was detected in 20.4% of fatal opioid poisonings with a significantly increased frequency over time, primarily in low or therapeutic concentrations, and was not associated with methadone or morphine concentrations. Use of quetiapine, most commonly in low-to-moderate doses to obtain a sleep-inducing or tranquillizing effect, was reported by 67.6% of survey respondents. In the animal studies, a significant impairment of sedation score, performance on the rotarod and open field mobility was observed in all treatment groups compared with vehicle. However, the effect of quetiapine plus the opioid was not significantly different from that of the opioid alone. Thus, no additive sedative effects were observed in rats. Our results suggest that quetiapine is more often an innocent bystander than a contributor to fatal opioid poisoning. However, the combined effects on other parameters, including blood pressure, cardiac rhythm and respiratory rate, need investigation. [ABSTRACT FROM AUTHOR]

Proton pump inhibitors (PPIs) are widely prescribed medications that have effects on both enteric and urinary solute handling with an unknown effect on risk of nephrolithiasis. Our objectives were to examine the association between PPI exposure and incident nephrolithiasis and to determine its effect on 24H urine chemistry. We performed a single-center retrospective study on patients diagnosed with gastroesophageal reflux disease (GERD) without a history of kidney stones. Exposure to PPIs was abstracted, and then subsequent kidney stone diagnoses were identified. Multivariable Cox models with time-varying covariates were used to estimate the hazard of PPI use on incident nephrolithiasis. We used multivariable linear regression to analyze a subset of patients who went through 24-h urine analysis. We identified n = 55,765 PPI-naïve GERD patients without prior kidney stone diagnoses of whom 40,866 (73.2%) were exposed to PPI over a median of 3 year follow up. On multivariable analysis, PPI use was associated with higher risk of incident kidney stone diagnoses (HR 1.19, 95% CI 1.06–1.34). Among 593 patients with GERD with 24-H urine data, the PPI-exposed group (n = 307) had significantly lower mean urinary citrate (mean 3.0 vs 3.4 mmol, p = 0.029) and urinary magnesium (mean 3.6 vs 4.3 mmol, p < 0.001) on multivariable analyses. Exposure to PPIs is associated with an increased risk of kidney stones among patients with GERD. Hypomagnesemia and hypocitraturia associated with PPI exposure may contribute to kidney stone risk. [ABSTRACT FROM AUTHOR]

Metabolomics is an emerging and powerful bioanalytical method supporting clinical investigations. Serum and plasma are commonly used without rational prioritization. Serum is collected after blood coagulation, a complex biochemical process involving active platelet metabolism. This may affect the metabolome and increase the variance, as platelet counts and function may vary substantially in individuals. A multiomics approach systematically investigating the suitability of serum and plasma for clinical studies demonstrated that metabolites correlated well ( n = 461, R 2 = 0.991), whereas lipid mediators ( n = 83, R 2 = 0.860) differed substantially between specimen. Independently, analysis of platelet releasates identified most biomolecules significantly enriched in serum compared to plasma. A prospective, randomized, controlled parallel group metabolomics trial with acetylsalicylic acid administered for 7 days demonstrated that the apparent drug effects significantly differ depending on the analyzed specimen. Only serum analyses of healthy individuals suggested a significant downregulation of TXB2 and 12-HETE, which were specifically formed during coagulation n = 322, R 2 = 0.860) differed substantially between specimen. Independently, analysis of platelet releasates identified most biomolecules significantly enriched in serum compared to plasma. A prospective, randomized, controlled parallel group metabolomics trial with acetylsalicylic acid administered for 7 days demonstrated that the apparent drug effects significantly differ depending on the analyzed specimen. Only serum analyses of healthy individuals suggested a significant downregulation of TXB2 and 12-HETE, which were specifically formed during coagulation in vitro . Plasma analyses reliably identified acetylsalicylic acid effects on metabolites and lipids occurring in vivo such as an increase in serotonin, 15-deoxy-PGJ2 and sphingosine-1-phosphate and a decrease in polyunsaturated fatty acids. The present data suggest that plasma should be preferred above serum for clinical metabolomics studies as the serum metabolome may be substantially confounded by platelets.

Anaesthesiologists commonly use intravenous labetalol to adjust patient haemodynamics during surgical procedures. Cases of profound hypotension after continuous labetalol infusions have been reported; however, there is limited evidence regarding the safety of intraoperative labetalol boluses. This audit examined the frequency of postoperative hypotension and bradycardia in 292 adult non-cardiac surgery patients treated with intraoperative labetalol boluses. Blood pressure and heart rate data were collected from the post-anaesthesia care unit and on the floor units for 24 hours after surgery. The median total intraoperative labetalol dose was 10mg. A total of 30/292 patients had all-cause postoperative hypotension within 24 hours of surgery, 26 of which had other medical or surgical precipitants. Fifteen patients developed bradycardia. There were no deaths or intensive care unit admissions attributed to labetalol. This audit demonstrates a low risk of all-cause postoperative hypotension (10%) and bradycardia (5%) after the use of small IV doses of intraoperative labetalol.

The prevalence of functional gastrointestinal (FGI) symptoms and irritable bowel syndrome (IBS) is high in the society, but the etiology is mainly unknown. This population-based, cross-sectional study aimed to examine the associations between self-reported IBS or gastrointestinal (GI) symptoms within the past 2 weeks and concomitant diseases, drug consumption and family history of diseases. Participants from the Malmö Offspring Study (MOS) answered a questionnaire about lifestyle habits, medical history and GI symptoms. Associations between self-reported IBS or GI symptoms and other diseases, drugs, and family history of diseases were calculated by logistic regression, adjusted for false discovery rate (FDR; q < 0.05). Of 2648 included patients, 316 had IBS and 459 had GI symptoms. There was an association between IBS and asthma (OR: 1.66; 95% confidence interval [CI]: 1.19–2.32; q = 0.018), and between IBS and using of prescription (OR: 1.44; 95% CI: 1.10–1.89; q = 0.028) and nonprescription drugs (OR: 1.92; 95% CI: 1.43–2.59; q < 0.001), specifically adrenergic beta-antagonists, antihistamines and hypnotics. Regarding family history, GI disease in the family (OR: 2.44; 95% CI: 1.78–3.35; q < 0.001) and the subgroups celiac disease, gastric ulcer, functional dyspepsia, IBS and reflux, as well as prostate cancer were associated with IBS, while GI diseases (OR: 2.56; 95% CI: 1.89–3.46; q < 0.001), joint diseases (OR: 1.61; 95% CI: 1.19–2.16; q = 0.009), and myocardial infarction (OR: 1.48; 95% CI: 1.09–2.99; q = 0.043) were associated with GI symptoms. Abdominal pain was the specific symptom with strongest associations. IBS and GI symptoms were mainly associated with GI diseases in the family and drug consumption. To take a family and drug history is pertinent to all clinical history taking, irrespective of the symptomatology. [ABSTRACT FROM AUTHOR]

We report the cases of 2 women who had urethral bulking injections with polydimethylsiloxane for stress urinary incontinence with intrinsic sphincter deficiency and reported initial improvement of symptoms followed by rapid return of stress urinary incontinence several weeks later associated with extrusion of the bulking material. We hypothesize this unique adverse outcome could represent immune rejection of this urethral bulking agent.

Background: Weight loss clinics are common in the United States. Unfortunately, some offer dubious weight loss methods such as self-administered human chorionic gonadotropin (HCG) injections. HCG products are unregulated, yet, widely available. Infection is among the risks potentially associated with this treatment. We report a case of skin infection caused by Mycobacterium fortuitum after HCGinjection.Case Presentation: A 51-year-old woman with a history of hypogammaglobulinemia presented with an eight week history of a tender abdominal lesion. The lesion was at the site of a previous HCG injection.Acid-fast bacilli (AFB) culture grew Mycobacterium fortuitum. Based on the organism’s susceptibility profile, sulfamethoxazole-trimethoprim 800-160mg and ciprofloxacin 500 mg were both prescribed. The case was referred to the Missouri Department of Health. Based on clinical progress treatment was continued for a total of six months.Conclusions: This case illustrates the potential for cutaneous infection by Mycobacterium fortuitum and other rapidly growing mycobacteria after HCGinjections. Clinicians should maintain a high index for suspicion for rapidly growing mycobacteria when evaluating persistent skin lesions at sites of trauma or skin puncture.

BackgroundCerebral microhemorrhages (CMH) are tiny deposits of blood degradation products in the brain and are pathological substrates of cerebral microbleeds. The existing CMH animal models are β-amyloid-, hypoxic brain injury-, or hypertension-induced. Recent evidence shows that CMH develop independently of hypoxic brain injury, hypertension, or amyloid deposition and CMH are associated with normal aging, sepsis, and neurodegenerative conditions. One common factor among the above pathologies is inflammation, and recent clinical studies show a link between systemic inflammation and CMH. Hence, we hypothesize that inflammation induces CMH development and thus, lipopolysaccharide (LPS)-induced CMH may be an appropriate model to study cerebral microbleeds.MethodsAdult C57BL/6 mice were injected with LPS (3 or 1 mg/kg, i.p.) or saline at 0, 6, and 24 h. At 2 or 7 days after the first injection, brains were harvested. Hematoxylin and eosin (H&E) and Prussian blue (PB) were used to stain fresh (acute) hemorrhages and hemosiderin (sub-acute) hemorrhages, respectively. Brain tissue ICAM-1, IgG, Iba1, and GFAP immunohistochemistry were used to examine endothelium activation, blood-brain barrier (BBB) disruption, and neuroinflammation. MRI and fluorescence microscopy were used to further confirm CMH development in this model.ResultsLPS-treated mice developed H&E-positive (at 2 days) and PB-positive (at 7 days) CMH. No surface and negligible H&E-positive CMH were observed in saline-treated mice (n = 12). LPS (3 mg/kg; n = 10) produced significantly higher number, size, and area of H&E-positive CMH at 2 days. LPS (1 mg/kg; n = 9) produced robust development of PB-positive CMH at 7 days, with significantly higher number and area compared with saline (n = 9)-treated mice. CMH showed the highest distribution in the cerebellum followed by the sub-cortex and cortex. LPS-induced CMH were predominantly adjacent to cerebral capillaries, and CMH load was associated with indices of brain endothelium activation, BBB disruption, and neuroinflammation. Fluorescence microscopy confirmed the extravasation of red blood cells into the brain parenchyma, and MRI demonstrated the presence of cerebral microbleeds.ConclusionsLPS produced rapid and robust development of H&E-positive (at 2 days) and PB-positive (at 7 days) CMH. The ease of development of both H&E- and PB-positive CMH makes the LPS-induced mouse model suitable to study inflammation-induced CMH.

Glucocorticoid-induced osteoporosis (GIOP) changes the microarchitecture of bones and often leads to the reduction of bone-mineral density (BMD) and increased fracture rates. Zebrafish has been used as an alternative model for GIOP, however, the interaction of GIOP, and its treatment, with zebrafish bone morphometrics and mechanical properties, remains a challenge. Thus, this study aimed to evaluate the effects of prednisolone and alendronate on the properties of zebrafish vertebrae. Adult 7-month-old zebrafish were distributed into four groups: control (CTRL), prednisolone-only (PN), alendronate-only (ALN), and the sequential use of both medicines (PN + ALN). Fish skeletons were scanned via micro-tomography (n = 3) to obtain vertebra morphometrics (e.g., BMD). Bone morphology was assessed using scanning electron microscopy (n = 4) and the biomechanical behaviour with nanoindentation technique (n = 3). The BMD decreased in PN (426.08 ± 18.58 mg/cm3) and ALN (398.23 ± 10.20 mg/cm3) groups compared to the CTRL (490.43 ± 41.96 mg/cm3) (p < 0.001); however, administering the medicines in sequence recovered the values to healthy levels (495.43 ± 22.06 mg/cm3) (p > 0.05). The bone layered structures remain preserved in all groups. The vertebrae of the groups that received ALN and PN + ALN, displayed higher modulus of elasticity (27.27 ± 1.59 GPa and 25.68 ± 2.07 GPa, respectively) than the CTRL (22.74 ± 1.60 GP) (p < 0.001). ALN alone increased the hardness of zebrafish vertebrae to the highest value among the treatments (1.32 ± 0.13 GPa) (p < 0.001). Conversely, PN + ALN (1.25 ± 0.11 GPa) showed unaltered hardness from the CTRL (1.18 ± 0.13 GPa), but significantly higher than the PN group (1.08 ± 0.12 GPa) (p < 0.001). ALN administered after GIOP development, rescued osteoporotic condition by recovering the BMD and bone hardness in zebrafish vertebrae. [Display omitted] • The intake of prednisolone-only decreased the BMD of zebrafish vertebrae. • Neither prednisolone nor alendronate altered the morphology of zebrafish backbone. • Bone hardness was not affected by the sequential use of medicines. • Osteoporosis showed no influence on zebrafish vertebrae elastic modulus. • Prednisolone followed by alendronate intake rescued osteoporosis phenotype. [ABSTRACT FROM AUTHOR]

Simple Summary: The main problem in treating advanced cancers is a metastatic spread when individual cancer cells leave the primary tumor and colonize to distant organs. In drug development, it is important to quantitatively assess effects of novel drug candidates on both primary tumors and metastasis. Unfortunately, current methods of monitoring metastasis in mouse models have low sensitivity and are not quantitative. Here, we developed a methodology to monitor drug effects on metastasis that is quantitative and has a very high sensitivity and resolution. In fact, it allows monitoring effects of drugs on individual cancer cells in animals. Imaging in monitoring metastasis in mouse models has low sensitivity and is not quantitative. Cell DNA barcoding, demonstrating high sensitivity and resolution, allows monitoring effects of drugs on the number of tumor and metastatic clones. However, this technology is not suitable for comparison of sizes of metastatic clones in different animals, for example, drug treated and untreated, due to high biological and technical variability upon tumor and metastatic growth and isolation of barcodes from tissue DNA. However, both numbers of clones and their sizes are critical parameters for analysis of drug effects. Here we developed a modification of the barcoding approach for monitoring drug effects on tumors and metastasis that is quantitative, highly sensitive and highly reproducible. This novel cell double-barcoding system allows simultaneously following the fate of two or more cell variants or cell lines in xenograft models in vivo, and also following the fates of individual clones within each of these populations. This system allows comparing effects of drugs on different cell populations and thus normalizing drug effects by drug-resistant lines, which corrects for both biological and technical variabilities and significantly increases the reproducibility of results. Using this barcoding system, we uncovered that effects of a novel DYRK1B kinase inhibitor FX9847 on primary tumors and metastasis is clone-dependent, while a distinct drug osimertinib demonstrated clone-independent effects on cancer cell populations. Overall, a cell double-barcoding approach can significantly enrich our understanding of drug effects in basic research and preclinical studies. [ABSTRACT FROM AUTHOR]

Metformin is a widely accepted first-line hypoglycemic agent in current clinical practice, and it has been applied to the clinic for more than 60 years. Recently, researchers have identified that metformin not only has an efficient capacity to lower glucose but also exerts anti-aging effects by regulating intracellular signaling molecules. With the accelerating aging process and mankind's desire for a long and healthy life, studies on aging have witnessed an unprecedented boom. Osteoporosis, sarcopenia, degenerative osteoarthropathy, and frailty are age-related diseases of the musculoskeletal system. The decline in motor function is a problem that many elderly people have to face, and in serious cases, they may even fail to self-care, and their quality of life will be seriously reduced. Therefore, exploring potential treatments to effectively prevent or delay the progression of aging-related diseases is essential to promote healthy aging. In this review, we first briefly describe the origin of metformin and the aging of the movement system, and next review the evidence associated with its ability to extend lifespan. Furthermore, we discuss the mechanisms related to the modulation of aging in the musculoskeletal system by metformin, mainly its contribution to bone homeostasis, muscle aging, and joint degeneration. Finally, we analyze the protective benefits of metformin in aging-related diseases of the musculoskeletal system. [ABSTRACT FROM AUTHOR]

Concetta Cafiero,1,* Agnese Re,2,* Alessandra Micera,3,* Raffaele Palmirotta,4 Delio Monaco,5 Francesca Romano,6 Claudia Fabrizio,7 Raffaele Di Francia,8 Andrea Cacciamani,3 Pier Luigi Surico,9 Gerardo D’Amato,10 Salvatore Pisconti1 1Medical Oncology, SG Moscati Hospital, Taranto, Italy; 2CNR-IASI, Catholic University of Sacred Heart, Rome, Italy; 3Research Laboratories in Ophthalmology, IRCCS — Fondazione Bietti, Rome, Italy; 4Department of Biomedical Sciences and Clinical Oncology, Oncogenomic Research Center, Aldo Moro University of Bari, Bari, Italy; 5Radiology, SG Moscati Hospital, Taranto, Italy; 6Department of Precision Medicine, Luigi Vanvitelli University of Campania, Napoli, Italy; 7Infectious Disease Unit, SG Moscati Hospital, Taranto, Italy; 8Italian Association of Pharmacogenomics and Molecular Diagnostics, Ancona, Italy; 9Oncology and Hematology Department, F Miulli Hospital, Acquaviva delle Fonti, Italy; 10Endocrine and Metabolic Surgery, A Gemelli Polyclinic Foundation, Rome, Italy*These authors contributed equally to this workCorrespondence: Alessandra MiceraResearch Laboratories in Ophthalmology, IRCCS — Fondazione Bietti, 6 via di Santo Stefano Rotondo, Rome 00184, ItalyTel +39-06-4554-1191Email alessandra.micera@fondazionebietti.itRaffaele PalmirottaDepartment of Biomedical Sciences and Clinical Oncology, Oncogenomic Research Center, Aldo Moro University of Bari, ItalyEmail raffaelepalmirotta@gmail.comAbstract: The latest developments in precision medicine allow the modulation of therapeutic approaches in different pathologies on the basis of the specific molecular characterization of the patient. This review of the literature coupled with in silico analysis was to provide a selected screening of interactions between single-nucleotide polymorphisms (SNPs) and drugs (repurposed, investigational, and biological agents) showing efficacy and toxicityin counteracting Covid-19 infection. In silico analysis of genetic variants related to each drug was performed on such databases as PharmGKB, Ensembl Genome Browser, www.drugs.com, and SNPedia, with an extensive literature review of papers (to May 10, 2020) on Covid-19 treatments using Medline, Embase, International Pharmaceutical Abstracts, PharmGKB, and Google Scholar. The clinical relevance of SNPs, known as both drug targets and markers, considering genetic variations with known drug responses, and the therapeutic consequences are discussed. In the context of clinical treatment of Covid-19, including infection prevention, control measures, and supportive care, this review highlights the importance of a personalized approach in the final selection of therapy, which is probably essential in the management of the Covid-19 pandemic.Keywords: Covid-19, SARS-CoV2, drug effects, pharmacogenomics, pharmacogenetics, in silico, ADR

Abstract Background While surgery is the first-line treatment for patients with endogenous hypercortisolism (Cushing syndrome [CS]), mifepristone has been shown to be a beneficial medical treatment option, as demonstrated in the SEISMIC (Study of the Efficacy and Safety of Mifepristone in the Treatment of Endogenous Cushing Syndrome) trial. Mifepristone is a competitive glucocorticoid receptor antagonist and progesterone receptor antagonist that is associated with several treatment effects and adverse events that clinicians need to be aware of when considering its use. The objective of this review was to provide updated clinical management recommendations for patients with CS treated with mifepristone. Methods A panel of endocrinologists from the US with extensive experience in treating patients with CS, including with mifepristone, convened as part of a clinical advisory board to develop a consensus on the practical, real-world clinical management of patients on mifepristone. Results Comprehensive considerations and recommendations are provided for managing mifepristone-associated effects, including symptoms of cortisol withdrawal, hypokalemia, and change in thyroid function; effects related to its antiprogesterone activity; and rash. Additional management strategies to address concomitant medications and special clinical situations, such as surgery and use in specific populations, are also provided. Conclusion Safe and effective use of mifepristone requires clinical judgment and close patient monitoring to ensure optimal clinical outcomes. These consensus recommendations provide useful, practical guidance to clinicians using mifepristone.

Metformin is a widely accepted first-line hypoglycemic agent in current clinical practice, and it has been applied to the clinic for more than 60 years. Recently, researchers have identified that metformin not only has an efficient capacity to lower glucose but also exerts anti-aging effects by regulating intracellular signaling molecules. With the accelerating aging process and mankind’s desire for a long and healthy life, studies on aging have witnessed an unprecedented boom. Osteoporosis, sarcopenia, degenerative osteoarthropathy, and frailty are age-related diseases of the musculoskeletal system. The decline in motor function is a problem that many elderly people have to face, and in serious cases, they may even fail to self-care, and their quality of life will be seriously reduced. Therefore, exploring potential treatments to effectively prevent or delay the progression of aging-related diseases is essential to promote healthy aging. In this review, we first briefly describe the origin of metformin and the aging of the movement system, and next review the evidence associated with its ability to extend lifespan. Furthermore, we discuss the mechanisms related to the modulation of aging in the musculoskeletal system by metformin, mainly its contribution to bone homeostasis, muscle aging, and joint degeneration. Finally, we analyze the protective benefits of metformin in aging-related diseases of the musculoskeletal system.

Independent retail pharmacies are required to have a technical manager responsible for the operation and adverse drug event reporting. In this context the following investigation is developed based on one objective: To establish factors related to the technical management and adverse drug event reporting in independent retail pharmacies in Cali. This is a cross-sectional observational study. Data was randomly collected from an estimated sample of 244 independent retail pharmacies. The results show that storage was the area of greatest implementation, 94% of the assessed pharmacies had a technical manager and 50% of them reported adverse drug events. A technical manager, being a chemist, pharmacist, or pharmacy manager, was associated with having computer equipment and dispensing homeopathic products. Adverse drug event reporting was directly associated with having bibliographic resources and inversely associated with the technical manager being a drug retailer. These data show the factors related to technical management of independent retail pharmacies and adverse drug event reporting were identified.