Large Doses Research Articles

Electrochemical behaviour of 5-fluorouracil at electrochemically pre-treated glassy carbon electrode

The right dosage for a medication is crucial and a large dosage accumulation could have an instantaneous effect. Hence for the analysis of concentration of 5-fluorouracil (5-FU) in human blood tissues, an electrochemical sensor was developed using pre-treatment Glassy carbon electrode (GCE) for the efficient detection of 5-FU an anticancer medication, using differential pulse voltammetry (DPV) and cyclic voltammetric (CV) methods. In order to decrease the expense of the suggested sensor, a straightforward surface alteration was made to the GCE. The examination of scan rate, concentration, pH, simultaneous, and interference analysis produced results that were acceptable. Based on the examination of the aforementioned factors, the electrode procedure, the quantity of protons and electrons transferred, the quantification limit for 5-FU was determined and discussed. Thus the developed pre-treated GCE sensor for 5-FU shows promising platform for the investigation of 5-FU with excellent selectivity and sensitivity.

Therapeutic delivery of siRNA for the management of breast cancer and triple-negative breast cancer.

Breast cancer is the leading cause of cancer-related deaths among women globally. The difficulties with anticancer medications, such as ineffective targeting, larger doses, toxicity to healthy cells and side effects, have prompted attention to alternate approaches to address these difficulties. RNA interference by small interfering RNA (siRNA) is one such tactic. When compared with chemotherapy, siRNA has several advantages, including the ability to quickly modify and suppress the expression of the target gene and display superior efficacy and safety. However, there are known challenges and hurdles that limits their clinical translation. Decomposition by endonucleases, renal clearance, hydrophilicity, negative surface charge, short half-life and off-target effects of naked siRNA are obstacles that hinder the desired biological activity of naked siRNA. Nanoparticulate systems such as polymeric, lipid, lipid-polymeric, metallic, mesoporous silica nanoparticles and several other nanocarriers were used for effective delivery of siRNA and to knock down genes involved in breast cancer and triple-negative breast cancer. The focus of this review is to provide a comprehensive picture of various strategies utilized for delivering siRNA, such as combinatorial delivery, development of modified nanoparticles, smart nanocarriers and nanocarriers that target angiogenesis, cancer stem cells and metastasis of breast cancer.

Potential mechanisms underlying podophyllotoxin-induced cardiotoxicity in male rats: toxicological evidence chain (TEC) concept.

Podophyllotoxin (PPT) is a high-content and high-activity compound extracted from the traditional Chinese medicinal plant Dysosma versipellis (DV) which exhibits various biological activities. However, its severe toxicity limits its use. In clinical settings, patients with DV poisoning often experience adverse reactions when taking large doses in a short period. The heart is an important toxic target organ, so it is necessary to conduct 24-h acute cardiac toxicity studies on PPT to understand its underlying toxicity mechanism. Based on the concept of the toxicological evidence chain (TEC), we utilized targeted metabolomic and transcriptomic analyses to reveal the mechanism of the acute cardiotoxicity of PPT. The manifestation of toxicity in Sprague-Dawley rats, including changes in weight and behavior, served as Injury Phenotype Evidence (IPE). To determine Adverse Outcomes Evidence (AOE), the hearts of the rats were evaluated through histopathological examination and by measuring myocardial enzyme and cardiac injury markers levels. Additionally, transcriptome analysis, metabolome analysis, myocardial enzymes, and cardiac injury markers were integrated to obtain Toxic Event Evidence (TEE) using correlation analysis. The experiment showed significant epistaxis, hypokinesia, and hunched posture in PPT group rats within 24h after exposure to 120mg/kg PPT. It is found that PPT induced cardiac injury in rats within 24h, as evidenced by increased serum myocardial enzyme levels, elevated concentrations of cardiac injury biomarkers, and altered cardiac cell morphology, all indicating some degree of cardiac toxicity. Transcriptome analysis revealed that primary altered metabolic pathway was arachidonic acid metabolism after PPT exposure. Cyp2e1, Aldob were positively correlated with differential metabolites, while DHA showed positive correlation with differential genes Fmo2 and Timd2, as well as with heart injury markers BNP and Mb. This study comprehensively evaluated cardiac toxicity of PPT and initially revealed the mechanism of PPT-induced acute cardiotoxicity, which involved oxidative stress, apoptosis, inflammatory response, and energy metabolism disorder.

Dynamics of drug delivery determines course of evolution of antibiotic responses in bacteria.

To adjust to sudden shifts in conditions, microbes possess regulated genetic mechanisms that sense environmental challenges and induce the appropriate responses. The initial evolution of microbes in new environments is thought to be driven by regulatory mutations, but it is not clear how this evolution is affected by how quickly conditions change (i.e. dynamics). Here, we perform experimental evolution on continuous cultures of tetracycline resistant E. coli in different dynamical regimens of drug administration. We find that cultures evolved under gradually increasing drug concentrations acquire fine- tuning mutations adapting an alternative efflux pump to tetracycline. However, cultures that are instead periodically exposed to large drug doses evolve transposon insertions resulting in loss of regulation of the main mechanism of tetracycline resistance. A mathematical model shows that sudden drug exposures overwhelm regulated responses, which cannot induce resistance fast enough. These results help explain the frequent loss of regulation of resistance in clinical pathogens.

The effect of DMSO on Saccharomyces cerevisiae yeast with different energy metabolism and antioxidant status

We studied the effect of dimethyl sulfoxide (DMSO) on the biochemical and physiological parameters of S. cerevisiae yeast cells with varied energy metabolism and antioxidant status. The wild-type cells of varied genetic backgrounds and their isogenic mutants with impaired antioxidant defences (Δsod mutants) or response to environmental stress (ESR) (Δmsn2, Δmsn4 and double Δmsn2msn4 mutants) were used. Short-term exposure to DMSO even at a wide range of concentrations (2–20%) had little effect on the metabolic activity of the yeast cells and the stability of their cell membranes, but induced free radicals production and clearly altered their proliferative activity. Cells of the Δsod1 mutant showed greater sensitivity to DMSO in these conditions. DMSO at concentrations from 4 to 10–14% (depending on the strain and genetic background) activated the ESR programme. The effects of long-term exposure to DMSO were mainly depended on the type of energy metabolism and antioxidant system efficiency. Yeast cells with reduced antioxidant system efficiency and/or aerobic respiration were more susceptible to the toxic effects of DMSO than cells with a wild-type phenotype and respiro-fermentative or fully fermentative metabolism. These studies suggest a key role of stress response programs in both the processes of cell adaptation to small doses of this xenobiotic and the processes related to its toxicity resulting from large doses or chronic exposure to DMSO.

Cannabis, cannabinoids and health: a review of evidence on risks and medical benefits

AbstractThe legalization of cannabis for medical and recreational purposes has progressed internationally. Cannabis and cannabinoids are advocated for a plethora of medical indications. An increasing number of medical and nonmedical users regularly consume large doses of delta-9-Tetrahydrocannabinol (THC), the main active component of cannabis. Aim: to summarize the evidence on (1) risks of recreational cannabis use and (2) effectiveness and safety of medicinal cannabis. Findings on recreational use: Cannabis is mostly used to experience its acute rewarding effects. Regular use of high THC products can produce addiction (cannabis use disorder or CUD). Acute consumption of high THC doses (including unintentionally) can cause time-limited mental, gastrointestinal, and cardiovascular problems and motor vehicle accidents. Chronic patterns of cannabis use have been associated with multiple adverse outcomes that are of particular concern among adolescents and young adults, such as, disrupted learning, impaired cognitive performance, reduced educational attainment and an increased risk of CUD, psychosis/schizophrenia, mood and anxiety disorders and suicidal behaviors. There is debate about the extent to which cannabis use is a cause of these adverse outcomes. Physical health risks (e.g., respiratory and cardiovascular, prematurity and restricted fetal growth, hyperemesis syndrome among others) have also been linked with repeated consumption of cannabis with a high THC content. Findings on medical cannabis use: Herbal cannabis, medicines from extracted or synthetized cannabinoids—often used as adjuvants to standard medicines—may produce small to modest benefits. This is primarily the case in treating chronic pain, muscle spasticity, chemotherapy-induced nausea and vomiting, and refractory epilepsy (in the case of cannabidiol, CBD). The evidence is inconclusive on their value in treating mental disorders and other medical conditions. Safety: Cannabis-based medicine is generally well tolerated. There is a risk of mild to moderate adverse effects and CUD.

Research, Development and Pharmacological Activity of Sinomenine and Its Derivatives

Abstract: In this manuscript, the resource distribution, pharmacological activity, pharma-cokinetics of sinomenine and the structure, synthesis, biological activity and mechanism of sinomenine derivatives reported from 2000 to December 2023 were reviewed. The lit-erature was retrieved through Web of Science, PubMed, Science Direct, SciFiner Scholar and other websites. Sinomenine belongs to isoquinoline alkaloids and was extracted from the Chinese herb Sinomenium acutum root. In Asian countries such as China and Japan, it is commonly prescribed as a treatment for rheumatoid arthritis. In addition, sinomenine also has sedative, analgesic, anti-inflammatory, immunosuppressive, neuroprotective, an-ti-drug dependence, anti-tumor and other biological activities. Sinomenine limited its ap-plication prospects because of its large dosage, poor epidermal permeability and short half-life. To overcome these defects, new sinomenine derivatives have been synthesized. Based on the comprehensive analysis of relevant literature at home and abroad, this paper reviews the recent progress in the study of sinomenine's pharmacological effects and structural modifications. Future research on sinomenine will focus on improving its thera-peutic effect, and developing new drug preparations and structural modifications. It is hoped that this review will help to better understand the research progress of sinomenine and provide constructive suggestions for further research of sinomenine.

Outcome of Levofloxacin in the Treatment of Lower Respiratory Tract Infection

Background: Levofloxacin, a broad-spectrum fluoroquinolone antibiotic, is commonly used in treating lower respiratory tract infections (LRTIs) like pneumonia and chronic bronchitis. Its effectiveness lies in its ability to inhibit bacterial DNA gyrase, leading to bacterial cell death. Clinical outcomes of levofloxacin in LRTI treatment have generally been positive, with high rates of bacterial eradication and symptom resolution. Objective: The present research aimed to determine whether levofloxacin is an effective and safe option for treating lower respiratory tract infections. Method: From January 2022 to January 2023, researchers analyzed data from 120 patients with a lower respiratory tract infection at a tertiary hospital. Sixty patients were split evenly between a control group and an observation group. Levofloxacin was administered at the standard dosage to the control group and at a significantly higher dose to the observation group. Both the clinical efficacy and adverse reaction rates were compared and contrasted between the two groups statistically. Results: The cure rate in the observation group was 53.33 percent, which was substantially greater than the cure rate in the control group, which was 36.67 percent. There is a statistically significant difference between them (P 0.05). The overall efficacy rate of the observation group was 93.33%, significantly higher than that of the control group (73.33%). There is a statistically significant difference between them (P 0.05). There was no statistically significant difference (P>0.05) between the two groups due to the low incidence of adverse responses in both the observation and control groups. Conclusion: This research demonstrates that large dosages of levofloxacin have a stronger clinical curative impact on treating lower respiratory infections than lesser doses. It is worthwhile to promote the widespread adoption of this technique since it has the potential to greatly enhance the quality of patient care

Study examines psychosis risk with amphetamine prescriptions

Large doses of prescription amphetamine have been associated with a more than five‐fold increased risk of new‐onset psychosis or mania, according to Belmont, Massachusetts‐based McLean Hospital researchers of a new study published online Sept. 12 in the American Journal of Psychiatry.

Obesity, Metabolic Syndrome, and Sugar-Sweetened Beverages (SSBs) in America: A Novel Bioethical Argument for a Radical Public Health Proposal.

The prevalence of obesity, metabolic syndrome, and the associated long-term chronic diseases (cardiovascular disease, type II diabetes, cancer, Alzheimer's disease, depression) have reached epidemic levels in the United States and Western nations. In response to this public health calamity, the author of this paper presents and defends a novel bioethical argument: the consistency argument for outlawing SSBs (sugar-sweetened beverages) for child consumption (the "consistency argument"). This argument's radical conclusion states that the government is justified in outlawing SSBs consumption for child consumption. The reasoning is as follows: if one accepts that the physical harm caused by chronic alcohol consumption justifies the government outlawing alcoholic beverages for child consumption, and there is strong evidence that comparable physical harms result from chronic SSBs consumption, then, mutatis mutandis, the government is also justified in outlawing child consumption of SSBs. To support this argument, the author provides extensive evidence based on epidemiological observational studies, interventional studies, controlled trials, large meta-analyses, and the pathophysiology and biological mechanisms of action behind SSBs and chronic disease. Chronic consumption of large doses of SSBs and alcoholic beverages both drive the same diseases: obesity and insulin resistance, cardiovascular disease, hypertension, and cancer. Chronic SSB consumption carries the additional risk of Alzheimer's disease, dementia, and depression. The author concludes this paper by considering prominent objections to the consistency argument, and then demonstrating that each objection is unsound.

Structural reconstruction of mouse acute aortic dissection by intravenously administered human Muse cells without immunosuppression

BackgroundStanford type B-acute aortic dissection (type B-AAD) is often life-threatening without invasive surgery. Multilineage-differentiating stress enduring cell (Muse cells), which comprise several percent of mesenchymal stem cells (MSCs), are endogenous pluripotent-like stem cells that selectively home to damaged tissue and replace damaged/apoptotic cells by in-vivo differentiation.MethodsMortality, aortic diameter expansion, cell localization, cell differentiation, and inflammation of the dissected aorta were evaluated in type B-AAD model mice intravenously injected with human-Muse cells, -elastin-knockdown (KD)-Muse cells, -human leukocyte antigen-G (HLA-G)-KD-Muse cells, or MSCs, all without immunosuppressant.ResultsHere, we show the Muse (50,000 cells) group has a lower incidence of aortic rupture and mortality of AAD compared with the MSC-50K (50,000 human-MSCs) and vehicle groups. Spectrum computed tomography in-vivo dynamics and 3-dimensional histologic analyses demonstrate that Muse cells more effectively home to the AAD tissue and survive for 8 weeks in the Muse group than in the MSC-750K (750,000 human-MSCs containing 50,000 Muse cells) group. Homing of Muse cells is impeded in the HLA-G-KD-Muse (50,000 cells) group. Differentiation of homed Muse cells into CD31(+) and alpha-smooth muscle actin (+) cells, production and reorganization of elastic fibers in the AAD tissue, and suppression of diameter expansion are greater in the Muse group than in the MSC-750K and elastin-KD-Muse (50,000 cells) groups.ConclusionsIntravenously administered Muse cells reconstruct the dissected aorta and improve mortality and diameter enlargement rates. Moreover, small doses of purified Muse cells are more effective than large doses of MSCs. HLA-G is suggested to contribute to the successful survival and homing of Muse cells.

Various aspects of radiosurgery – a review

Introduction and purpose Radiosurgery (RS) is an innovative treatment method that involves the precise administration of a large dose of ionizing radiation to the diseased area of ​​the body sparing healthy tissues maximally. The treatment is non-invasive and usually painless for the patient, and its greatest advantage is the immediate destruction of cancer cells. The method enables the treatment of tumors which are located within the brain tissue, but also of extracranial lesions in almost all organs of the human body. The aim of this article is to compare the structure, principles of operation, advantages, disadvantages and the use of Gamma Knife and CyberKnife in neurosurgery. These devices are used to perform radiosurgery and stereotactic radiotherapy procedures. They are an alternative to neurosurgical procedures, especially for cancerous tumors located in hard-to-reach places, and significantly reduce the risk of postoperative complications. Materials and methods The literature included in the PubMed, BioMed Central and Polish Medical Platform databases is searched by means of the words such as Gamma Knife, CyberKnife, radiosurgery, stereotactic radiotherapy. Quoted sources in selected works were also used. Conclusions Stereotactic radiosurgery is an element of radical, palliative or analgesic treatment of well-circumscribed small lesions, less than 5 cm in diameter. Gamma Knife and CyberKnife enable cancerous and non-cancerous treatment lesions. Both procedures are performed on an outpatient basis and are considered minimally invasive procedures, especially recommended for patients who cannot undergo neurosurgical surgery or require less invasive cancer treatment. Gamma Knife was designed for radiosurgery of lesions located intracranially and covering the upper parts of the cervical spine up to the level of the fourth cervical vertebra, while CyberKnife or modern linear accelerators are used for intracranial and extracranial radiosurgery.

Postoperative ileus in obstetric and gynecological practice: a prospective solution to the problem

Proton pump inhibitors (PPIs) are the undisputed leaders in the treatment of acid-related diseases. In actual clinical practice, the use of PPIs has been growing exponentially in recent decades. For a long time, PPIs were considered completely safe drugs for both short-term and long-term use. However, modern clinical guidelines and reviews and meta-analyses of the current decade on the safety of PPI use note that when prescribing PPIs in large doses for a long period, the possibility of developing numerous side effects should be taken into account. We searched the PubMed and Scopus information databases for publications on the safety of PPI use, including sources up to 12/01/2023. The review addresses issues of drug interactions between PPIs and chemotherapeutic drugs, which should certainly be taken into account in real clinical practice. In addition, recent reviews and meta-analyses have examined side effects of long-term PPI use, such as increased risk of infection (Clostridium difficile infection, community-acquired pneumonia), electrolyte disturbances, kidney damage, increased risk of hip, wrist and spine fractures; increased cardiovascular risk and a number of others, which can also have an adverse effect on the prognosis of cancer patients. The risk of developing gastric cancer with long-term PPI therapy can be considered as a likely side effect, since their association with PPI use is not denied or questioned in recent reviews and meta-analyses. There is still uncertainty regarding the increased risk of other cancers, since there are publications that do not confirm their association with PPI use. However, the presented review, despite a number of contradictions, allows us to conclude that the increased cancer risk with long-term use of PPIs is real and must be taken into account when prescribing PPIs for a long term.

The role of anti-osteoporosis drugs in fall risk

Osteoporosis is a common skeletal disease characterized by reduced bone mass and micro-architectural deterioration, which leads to an increased risk of fractures. A significant concern associated with osteoporosis is the risk of falls, which can result in fractures and other related complications. This review examines the role of anti-osteoporosis drugs in the prevention of falls, focusing on pharmacological interventions that have shown promise in reducing the incidence of falls in osteoporotic patients. Falls in older people often lead to fractures, decreased mobility and reduced quality of life. Given that individuals with osteoporosis are more susceptible to fractures, it is essential to explore therapeutic strategies aimed at mitigating fall risk in this population. Anti-osteoporosis drugs have been developed primarily to improve bone mineral density and strength. The most extensively explored in this sense is probably vitamin D. Several meta-analyses have indicated that vitamin D could reduce the risk of falling compared with placebo. For this nutrient, important in vitro and experimental research data are available showing, overall, a positive effect on muscle. However, there is emerging evidence that large bolus doses and/or high levels of vitamin D may increase the risk of falls. Denosumab, a monoclonal antibody against RANKL (receptor activator of nuclear factor-кB ligand), is widely used to treat osteoporosis, and its influence on falls, although supported by a recent systematic review, is currently under investigation. Understanding the relationship between anti-osteoporosis medications and fall prevention is critical in comprehensive management of osteoporosis. Although these drugs are primarily used to improve bone health, their influence on falls is an intriguing topic. KEY WORDS: Falls, denosumab, vitamin D, romosozumab.

GLP-1 Receptor Agonists - An Anaesthesiologist’s Perspective – A Comprehensive Review

GLP-1 receptor agonists help in regulating blood sugar levels and encouraging weight reduction in individuals with non-insulin-dependent diabetes mellitus who adhere to dietary guidelines and exercise regularly. Semaglutide is a commonly utilized type of GLP-1 receptor agonist. The injection is usually administered once every seven days subcutaneously, beginning at 0.25 mg, with the highest weekly dosage is between 2.0 and 2.4 mg (larger doses are employed to promote weight loss instead of regulating blood sugar). Semaglutide’s half-life is approximately one week, indicating it remains active in the body for a long duration. So, it requires roughly five weeks to reach its stable level in the body, and it also takes the same amount of time for its effects to cease after discontinuation. There is now an oral formulation, and its effects might resemble those of the injection (1,2)

Kesterite‐Type Narrow Bandgap Piezoelectric Catalysts for Highly Efficient Piezocatalytic Fenton System

AbstractPiezocatalytic Fenton (PF) system emerges as a promising approach to wastewater treatment by leveraging piezocatalysis to enhance Fenton‐like reactions. However, conventional piezocatalysts encounter challenges because they often compromise catalytic properties in biased favor of superior piezoelectricity, resulting in sluggish catalytic kinetics. To tackle this trade‐off, here a novel class of kesterite‐type narrow bandgap piezoelectrics, Cu2XSnS4 (CXTS, X = Zn, Ni, Co), is developed for PF reactions, which exhibit a unique combination of physicochemical attributes favorable for catalysis such as narrow bandgap (1.2–1.5 eV), high free charge density (1 × 1018 cm−3), mobility, and redox activity while retaining excellent piezoelectricity (62–142 pm V−1). With the well‐balanced piezoelectric, semiconducting, and catalytic properties, CXTS‐based PF systems demonstrate outstanding performance for tetracycline degradation, delivering a notable reaction kinetics of 0.34 min−1 only with a minor H2O2 dosage (1.2 mm), outperforming most of the conventional Fenton‐like reactions requiring a large amount H2O2 dosage by a factor up to 10. Such a remarkable performance is fulfilled by the simultaneously effective H2O2 activation and in situ generation of reactive oxygen species from oxygen and water via piezocatalysis. Additionally, the distinctive hierarchical morphology consisting of 2D nanosheets enables easy crystal domain deformation to trigger the piezoelectric effect, thereby drastically reducing the mechanical energy input required to drive redox reactions. Rigorous testing has validated the viability and practical feasibility of this system. The study offers a new design strategy for highly efficient piezocatalysts in the PF systems, enabling a cost‐effective and sustainable water treatment approach.

High-Dose Propranolol for Severe and Chronic Aggression in Autism Spectrum Disorder: A Pilot, Double-Blind, Placebo-Controlled, Randomized Crossover Study.

Despite the use of behavioral interventions and psychotropic medications, many individuals with autism spectrum disorder (ASD) who engage in severe aggression remain refractory to conventional treatment. Propranolol, a beta-blocker, has accumulated much anecdotal evidence as a promising option. However, well-designed studies are rare, and the apprehension about cardiovascular side effects from large doses continues to exist. The aims of this study were (1) to demonstrate the feasibility of treating aggression with high-dose propranolol using telehealth study visits and (2) to document cardiac safety. This study utilized a randomized, double-blind, placebo-controlled, crossover design. Dosing was titrated up in a flexible but stepwise fashion until therapeutic response was obtained or up to 200 mg tid. Following washout, those who were assigned propranolol were crossed over to placebo and vice versa. Six participants between the ages 12-19 participated. The primary outcome measures were the final Clinical Global Impression Improvement Scale (CGI-I) and the Aberrant Behavior Checklist-Community Irritability (ABC-C/I) scores at 200 mg tid. The CGI-I indicated a 50% reduction in symptoms in the propranolol phase, while the ABC-I indicated a 37% reduction in comparison to placebo. The effect sizes ( r ) for the CGI-I and the ABC-C/I were large, -0.74 and -0.64, respectively. The average blood pressure was 122/68 during the placebo phase and 109/72 during the propranolol phase. All Holter monitor exams were unremarkable. These results suggest that propranolol is an effective option in decreasing aggression in individuals with ASD. As this was a small study, a larger clinical trial is needed.

Identifying Three Psilocybin Use Patterns by Frequency and Quantity.

Patterns of psilocybin use in non-clinical settings are not well described in the literature. Psilocybin use can involve infrequent, large (i.e., macro) doses that produce hallucinogenic effects. In addition, some people report psilocybin use at particularly small (i.e., micro), sub-perceptual doses. Given the heterogeneity in reported use metrics, we sought to determine whether there are identifiable patterns of psilocybin use based on participants' self-described typical use frequencies and quantities and to describe how demographic characteristics are associated with each pattern of use. Participants were recruited from online communities via Reddit.com. We used Latent Profile Analysis to discern psilocybin use patterns defined by frequency and quantity of use. The analytic sample consisted of 664 participants (75.6% US residents; 83.1% white; 67.2% male). The Chipper Profile (18%) was associated with approximately 1-4 annual uses and using between 0.75g and 1.0g of dehydrated, psilocybin-containing mushrooms. The Tripper Profile (64%) was associated with approximately 2-6 annual uses and self-reported use quantities between 2-4g. The Microdoser Profile (18%) was related to substantively higher psilocybin use frequencies than the other profiles (between 2-4 times a week) and a lower range of preferred quantities (between 0.25g - 0.75g). Additionally, profiles differed by certain demographic measurements, lifetime psilocybin use, and timing of psilocybin use. Psilocybin use in non-clinical settings is heterogeneous. We identified three profiles that differed on frequency and quantity of use and their associated demographic characteristics. Next steps are to identify factors that affect one's likelihood of experiencing particular use outcomes and to explore use variability.

Current Approaches on Transfersomal Patch: A Noninvasive Innovative Booster for Improved Transdermal Drug Delivery.

Pharmaceutical research is increasingly focusing on transdermal drug delivery due to its potential for improved compliance and bioavailability. However, it is challenging due to the tight intracellular junctions present in the skin. Researchers have developed noninvasive methods, like transfersomes, to overcome these challenges. Transfersomes are ultra-deformable vesicles utilized for improved transdermal applications. They are made up of a phospholipid-rich lipid bilayer, an edge activator, and an ethanol/aqueous core. After topical treatment, transfersomes can penetrate deeper skin regions, delivering larger concentrations of active compounds. A transfersomal patch is applied to the skin and left for an extended period of time to allow a large dose of medication to permeate into the bloodstream. The transfersomal patch offers an advantage over the transfersomal gel because it allows the transfersomes to be applied under occlusive conditions, resulting in greater permeability, a lower amount of active medication, and a steady supply rather than a massive dose. This review represents the preparation and evaluation of transfersomal patches, recent research approaches, and future aspects of transfersomal patches. This study suggests that drug-loaded transfersomal patches could be a unique option to avoid invasive therapy.

A case report of elevated bromide levels from pyridostigmine bromide for treatment of myasthenia gravis.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Elevated serum bromide levels can cause dermatological, gastrointestinal, and neurological abnormalities. As bromide and chloride are both halogens, bromide may interfere with chloride assays, causing a falsely high serum chloride concentration and a low or negative anion gap. There is a paucity of data describing bromide toxicity from high doses of pyridostigmine bromide (PB). This case report describes a patient with an elevated bromide level with neurological symptoms from a therapeutic dose of PB. A 37-year-old male with myasthenia gravis secondary to type B2 thymoma status following thymectomy presented in myasthenic crisis. He required mechanical ventilation and was managed with steroids, intravenous immune globulin, plasmapheresis, and PB. On day 9, the patient experienced acute agitation. He had an anion gap of 2 mEq/L and a chloride concentration of 109 mEq/L. The plasma creatinine concentration was 0.63 to 1.15mg/dL and urine output was 0.76 to 1.79mL/kg/h throughout his admission. All other laboratory values were normal. The daily dose of PB was 660mg on day 9, but the patient received 76mg of intravenous PB over the first few days of his admission with the largest dose in 24 hours equal to 48mg. On day 10, the patient's bromide level was 37 μg/mL. His agitation was initially managed with quetiapine, followed by PB dose reduction. To our knowledge, there are 2 cases in the literature of bromide toxicity secondary to PB. These patients experienced neurological symptoms with bromide levels of 88 to 90 μg/mL. Bromide concentrations of more than 12 μg/mL are associated with a higher risk of neuronal dysfunction demonstrated as disturbances on an electroencephalogram, and levels greater than 50 μg/mL are considered toxic. While our patient's bromide level was not as high as those previously reported, no other causes for his agitation were identified. Elevated bromide levels from therapeutic PB can occur, and monitoring of these levels should be considered.