Adverse Actions Research Articles

Optimization and Performance Evaluation of Steel Slag Asphalt Mixture Modified with Fibers under Freeze–Thaw Cycles

Recycling waste steel slag for asphalt pavement construction can reduce energy consumption and preserve nonrenewable natural resources. However, the moisture susceptibility of steel slag asphalt mixture (SSAM) in severe freeze–thaw regions should be taken into consideration. In light of this, three types of fibers (basalt fiber, polyester fiber, and lignin fiber) and rubber powder were blended into the SSAMs, and their freeze–thaw damage characteristics were investigated. First, the optimum bitumen and fiber content of SSAMs were determined based on Marshall design using response surface methodology. Then, the air voids of SSAMs were identified through X-ray computed tomography (CT) technology, while the effects of the fiber and freeze–thaw cycles on the moisture stability of SSAMs were investigated. Moreover, the enhancement effects of the fibers were analyzed using scanning electron microscopy (SEM). The results show the optimum fiber content of different fiber-reinforced SSAMs are 0.35%, 0.29%, and 0.23%, respectively, and the optimum bitumen content is 6.7% for all cases. The effect of freezing–thawing leads to an increase of the air voids in the middle part of the specimen, whereas the incorporation of fibers weakens the adverse action of freezing–thawing and effectively improves the moisture stability of the SSAMs. Furthermore, the network structure formed by basalt fibers in asphalt mastic significantly improves the integrity of the SSAM. Additionally, basalt fiber reinforced SSAM shows the best resistance to moisture damage.

The Modernization of the Energy Charter Treaty: Fulfilled or Broken Promises?

On 24 June 2022, the Contracting Parties of the Energy Charter Treaty (ECT) finalized discussions on the modernization of the treaty. After fifteen rounds of negotiations, an agreement in principle was reached to be adopted by the Energy Charter Conference on 22 November 2022 in Ulaanbaatar, Mongolia.1 The ECT, adopted in 1994, establishes a legal framework that aims to promote international cooperation in the energy sector.2 It has a membership of 53 countries primarily from Europe and Central Asia, as well as the European Union (EU) and the European Atomic Energy Community. In recent years, the ECT attracted widespread public attention due to its impact on states’ environmental and climate policies. Particularly, the treaty’s provisions on investment protection, with investor-to-state dispute settlement (ISDS) at the centre, allow foreign investors in the energy sector to challenge adverse state action before international arbitration and claim compensation for measures affecting their business activities. Fossil fuel investors have increasingly used the ECT to challenge environmental and climate measures, such as phasing out coal-fired power generation, banning offshore oil drilling in coastal areas, and prohibiting gas fracking projects. Such cases have fuelled concerns regarding the abilities of governments to roll-out large-scale climate action. The Intergovernmental Panel on Climate Change (IPCC) has warned that international investment agreements (IIAs) like the ECT could ‘be used by fossil-fuel companies to block national legislation aimed at phasing out the use of their assets’.3 With some of these damage claims running into billions of euros, the ECT enables fossil fuel investors to offload the costs and risks associated with their affected assets onto society at large in the face of necessary climate action. This would go, in the words of the editorial board of the Financial Times, against the ‘heart of the capitalist social contract’ and the ‘ability of markets to deal adequately with the challenge of climate change’.4

Central Positions of Glucocorticoids and Stress in the Phenomena of Hormonal and Metabolic Programming / Imprinting

The review is presented about contribution of glucocorticoids and stress to programming / imprinting phenomena. After their definition, possible mechanisms of such phenomena are described, including the role of glucocorticoids in ontopathogenic model, as well as the ways of diminishing adverse effects of these hormones. It is outlined that health professionals should participate in educational campaigns for decreasing adverse actions of stress and glucocorticoids, especially in perinatal period. Moreover, DOHaD concept should be introduced to the contents of university courses in biomedical sciences.

Missing the mark -- new methods needed to detect and address high-risk pesticide residues in the global food supply

The primary metric used by regulators to track whether pesticide residues in food pose worrisome risks is the percent of samples tested in a given year that contain residues above applicable tolerances in the US and Maximum Residue Limits (MRLs) in most other countries. The Dietary Risk Index (DRI) system is used to determine the degree to which current policies governing allowed pesticide residue levels in food are keeping high-risk residues out of the global food supply. Residue data generated by the US Pesticide Data Program (PDP) and UK-Food Standards Agency (FSA) are utilized. Over the last 10 years 2449 samples of food have contained violative residues over applicable tolerances or MRLs. Of these, about 60% posed low or very-low dietary risks relative to acceptable dietary intake levels set by regulators. Conversely, only about 4% of high- and very-high risk samples tested by the US-PDP contained residues above the applicable tolerance. Accordingly, current US and UK policies are failing to flag most high-risk samples and are triggering more intense scrutiny and/or adverse regulatory actions in the case of many samples posing low or very-low risks. Recommendations are offered to enhance the ability to track and incrementally reduce pesticide dietary risks.

Trends in Malpractice Payments and Adverse Actions against Pharmacists in the United States between 1990-2022

Background: We evaluated malpractice payments and adverse actions against pharmacists in the United States. Malpractice is defined as professional negligence by act or omission. Adverse actions are actions administered by the board of registration in a health profession against a provider. The purpose of the study is to analyze the trends in malpractice payments and adverse actions for pharmacists during the period 1990-2022. Methods: This is a retrospective study that utilizes the National Practitioner Data Bank (NPDB) data analysis tool for the period 1990-2022. This information was exported to a data visualization tool and trends were studied. Results: During the period of the study there were 2480 malpractice payments and 44,204 adverse action reports made against pharmacists. In the current study we found that there has been a 19.56% decline in the number of malpractice payments against pharmacists in the last 5 years from 46 in 2018 to 37 in 2022. Similarly, adverse action reports also show a downward trend from 2016 to 2022. Conclusion: Pharmacy profession implements multiple processes to protect patients from medication errors. As the volume of prescriptions increases in the US, there is an increased risk of error and subsequent litigation against pharmacists. Even though malpractice payments and adverse actions against pharmacists have continued to decline, the probability of an adverse action remains high for practicing pharmacists. As the role of pharmacist continues to evolve there is a need to keep up with the changes in the healthcare market.

The Effects of Curcumin on Mechanical Functions and Cardiac Contractility in Isolated Rat Hearts.

Curcumin is a bioactive compound that has well-known pharmacological activities. Numerous studies have shown that curcumin provides potential cardiovascular benefits through a variety of mechanisms.The present study aims to discuss different concentrations of curcumin's impact on mechanical functions and cardiac contractility in isolated perfused rat hearts. The hearts were isolated under sodium thiopental (50 mg/kg) anesthesia and perfused with a modified Krebs-Henseleit solution (mK-Hs). After stabilization, curcumin was applied in concentrations of 0.1, 1, and 10 µM. In isolated rat hearts, indexes of + dP / dt max, LVDP, MAP, and LVEDP were evaluated for cardiac contractility and ventricular function. All curcumin concentrations reduced +dP/dtmax and LVDP. Ten µM curcumin also significantly decreased heart rate. Curcumin (1 and 10 µM) increased LVEDP and reduced MAP amplitude with a concomitant increase in MAP duration. Curcumin at all concentrations did not affect dMAPdtmax and dMAPdtmin. Our results might suggest that curcumin at higher concentrations (≥ 1 µM) increases LVEDP with a negative chronotropic effect and decreases MAP amplitude with an increase in MAP duration. There is sufficient evidence from this study that Curcumin possesses an adverse inotropic action. Different disease models should support the pathophysiological role of Curcumin on cardiac contraction.

Nurse Practitioner Scope of Practice and Patient Harm: Evidence from Medical Malpractice Cases and Adverse Action Reports

Nurse Practitioner Scope of Practice and Patient Harm: Evidence from Medical Malpractice Cases and Adverse Action Reports

Encouraging probiotics for the prevention and treatment of immune-related adverse events in novel immunotherapies against malignant glioma.

Among the malignant tumors in the central nervous system (CNS), glioma is the most challenging tumor to the public society, which accounts for the majority of intracranial malignant tumors with impaired brain function. In general, conventional therapies are still unable to provide an effective cure. However, novel immunotherapies have changed the treatment scene giving patients a greater potential to attain long term survival, improved quality of life. Having shown favorable results in solid tumors, those therapies are now at a cancer research hotspot, which could even shrink the growth of glioma cells without causing severe complications. However, it is important to recognize that the therapy may be occasionally associated with noteworthy adverse action called immune-related adverse events (IRAEs) which have emerged as a potential limitation of the therapy. Multiple classes of mediators have been developed to enhance the ability of immune system to target malignant tumors including glioma but may also be associated with the IRAEs. In addition, it is probable that it would take long time after the therapy to exhibit severe immune-related disorders. Gut microbiota could play an integral role in optimal immune development and/or appropriate function for the cancer therapy, which is a vital component of the multidirectional communication between immune system, brain, and gut, also known as gut-brain-immune axis. Here, we show the potential effects of the gut-brain-immune axis based on an "engram theory" for the innovative treatment of IRAEs.

Mandatory reporting and the retaliation factor

Despite state and federal immunity protections, mandated reporters (MRs) of child maltreatment often experience retaliation from alleged perpetrators, employers, or other entities. Existing research demonstrates a correlation between experiencing retaliation and failing to report incidents of future maltreatment. Retaliation may include adverse employment actions, releasing the MRs’ identity, civil lawsuits, board complaints, and harassment. This study examines the impact of experienced/witnessed retaliation, fear of retaliation, and professional training on MRs’ willingness to report maltreatment, accept maltreatment cases, and testify in court. A self-administered survey sampled 619 MRs from varying professions throughout the United States and found (27.1%) experienced retaliation, though (14.9%) of those did not indicate retaliation type experienced. The most common forms included harassment (73.8%) and releasing the MRs’ identity (30.4%). Experienced retaliation resulted in MRs being less willing to report maltreatment and testify in court. Witnessed retaliation resulted in MRs being less likely to report abuse and accept certain maltreatment cases.

Public Service in Times of Politicized Crisis: How Combatting COVID-19 Reveals Threats to Merit Principles

Throughout the COVID-19 pandemic, politicization of public health policy has loomed over the governmental response in the United States. The scope of politicization is underscored by instances of political pressures faced by public employees across state and local government. Observation of such instances prompts questions regarding the implications of highly politicized crisis on public personnel systems. Using systematic qualitative content analysis of data from syndicated news articles, this study identifies publicized instances of adverse personnel actions experienced by public employees during the first six months of the COVID-19 pandemic. Following the identification of publicized instances, this study also explores legislative trends focusing on public personnel systems during highly politicized emergency conditions. Results outline the positional roles subject to adverse actions, along with traits of legislative activity changing public personnel systems in the states identified. Implications of the study and considerations for future research are then discussed.

Hydroxypropyl chitosan nail lacquer of ciclopirox-PLGA nanocapsules for augmented in vitro nail plate absorption and onychomycosis treatment

Onychomycosis accounts for 90% of nail infections worldwide. Topical therapy provides localized effects with minimal adverse systemic actions, yet its effectiveness is limited by minimal drug permeation through the keratinized nail plate. Ciclopirox (CIX) is a FDA-approved broad-spectrum antimycotic agent. However, the complete cure with its nail lacquer (8% w/v) may continue for one year with a high cost. Therefore, poly lactide-co-glycolide (PLGA) nanocapsules (NCs) of CIX were prepared by nanoprecipitation and optimized through a 23 factorial design to be incorporated into hydroxypropyl chitosan (HPCH) based nail lacquer. Nail hydration, in vitro nail absorption, minimum inhibitory concentration (MIC), inhibition zones and ex vivo fungal growth on nail fragments were evaluated. The optimized NCs of CIX based on 100 mg PLGA 2 A and lipoid S75 showed a mean diameter of 174.77 ± 7.90 nm, entrapment efficiency (EE%) of 90.57 ± 0.98%, zeta potential (ZP) of −52.27 ± 0.40 mV and a prolonged drug release. Nail lacquer of the optimized NCs exhibited a higher stability than NCs dispersion. Compared to CIX solution (1% w/v), the respective decrease in MIC for NCs and their lacquer was four- and eight-fold. The lacquer superiority was confirmed by the enhancement in the nail hydration and absorption by 4 and 2.60 times, respectively, relative to CIX solution and the minimal ex vivo fungal growth. Therefore, HPCH nail lacquer of (1% w/v) CIX-PLGA-NCs can be represented as a potential topical delivery system for enhanced in vitro nail absorption and therapeutic efficacy against onychomycosis at a low dose.

Discrimination by Another Name Is Still Unlawful

Most employers know that they cannot lawfully fire union supporters. To do so is a clear unfair labor practice under the National Labor Relations Act. Well‐versed labor practitioners know, however, that while union advocates cannot suffer from adverse actions due to their sympathies, they also do not enjoy special treatment. Employers can lawfully terminate pro‐union employees so long as the fact that the employee favors a union does not play a role in the decision.

Human access and deterministic processes play a major role in structuring planktonic and sedimentary bacterial and eukaryotic communities in lakes.

Lakes provide habitat for a diverse array of species and offer a wide range of ecosystem services for humanity. However, they are highly vulnerable as they are not only impacted by adverse actions directly affecting them, but also those on the surrounding environment. Improving knowledge on the processes responsible for community assembly in different biotic components will aid in the protection and restoration of lakes. Studies to date suggested a combination of deterministic (where biotic/abiotic factors act on fitness differences amongst taxa) and stochastic (where dispersal plays a larger factor in community assembly) processes are responsible for structuring biotic communities, but there is no consensus on the relative roles these processes play, and data is lacking for lakes. In the present study, we sampled different biotic components in 34 lakes located on the South Island of New Zealand. To obtain a holistic view of assembly processes in lakes we used metabarcoding to investigate bacteria in the sediment and surface waters, and eukaryotes in the sediment and two different size fractions of the water column. Physicochemical parameters were collected in parallel. Results showed that deterministic processes dominated the assembly of lake communities although the relative importance of variable and homogeneous selection differed among the biotic components. Variable selection was more important in the sediment (SSbact and SSeuks) and for the bacterioplankton (Pbact) while the assembly of the eukaryotic plankton (SPeuks, LPeuks) was driven more by homogeneous selection. The ease of human access to the lakes had a significant effect on lake communities. In particular, clade III of SAR11 and Daphnia pulex were only present in lakes with public access. This study provides insights into the distribution patterns of different biotic components and highlights the value in understanding the drivers of different biological communities within lakes.

Myasthenia gravis during treatment with anti-PD-1 - succesfull treatment using pirydostygminum – case report and literature review

Background: Against limited effectiveness of known oncological treatment such as chemio-and radiotherapy or surgery, new ways of treatment, such as for example immunotherapy has developed. Usage of immune checkpoint inhibitors (ICPIs), resulting in overactivation of immune system, may significantly raise efficacy of oncological treatment, but simultaneously predispose to occurrence various autoimmunological health complications. Adverse actions of the therapy may affect multiple organs and systems, with the presented example of immune-related neurological complication, myasthenia gravis. This relatively rare condition may be severe, life-threatening illness. Case report: We present a case of 66-year-old male patient diagnosted with a large tumor histopathologically assessed as squamous cell carcinoma. Due to ineffectiveness of implemented chemio- and radiotherapy, he was qualified for anti-PD1 immunotherapy with nivolumab. General treatment tolerance was very good with positive antineoplastic effect. Autoimmune hypothyroidism has emerged, therefore levothyroxine therapy has been implemented. After about a year of using immunotherapy, significant weakness and decrease in muscle strength has appeared, subsequently, immunotheraphy-related myasthenia gravis was raised. Improvement in the patient's condition was achieved after initiating pyridostigmine treatment. Cessation of antineoplastic treatment wasn’t necessary, what is unusual. Conclusions: Undeniably myastenia gravis may determine serious, life-threatening adverse effect of immunotherapy. Usually requires withdrawal of applied antioncological treatment, and should be treated with immunomodulators, immunosuppressants or intravenous immunoglobulins or plasmaphaeresis, however – as we present- in some cases may be properly cured only with pyridostygmine.

The ventilatory depressant actions but not the antinociceptive effects of morphine are blunted in rats receiving intravenous infusion of L-cysteine ethyl ester

This study demonstrates that intravenous infusion of the cell-penetrant thiol ester, L-cysteine ethyl ester (L-CYSee), to adult male Sprague-Dawley rats elicited (a) minor alterations in frequency of breathing, expiratory time, tidal volume, minute ventilation, or expiratory drive but pronounced changes in inspiratory time, end-inspiratory and expiratory pauses, peak inspiratory and expiratory flows, EF50, relaxation time, apneic pause, inspiratory drive and non-eupneic breathing index, (b) minimal changes in arterial blood-gas (ABG) chemistry (pH, pCO2, pO2, SO2) and Alveolar-arterial (A-a) gradient (index of alveolar gas exchange), and (c) minimal changes in antinociception (tail-flick latency). Subsequent injection of morphine (10 mg/kg, IV) elicited markedly smaller effects on the above parameters, ABG chemistry, and A-a gradient in rats receiving L-CYSee, whereas morphine antinociception was not impaired. Infusions of L-cysteine or L-serine ethyl ester (oxygen rather than sulfur moiety), did not affect morphine actions on ABG chemistry or A-a gradient. L-CYSee (250 μmol/kg, IV) injection elicited dramatic changes in ventilatory parameters given 15 min after injection of morphine in rats receiving L-CYSee. Our findings suggest that (a) L-CYSee acts in neurons that drive ventilation, (b) L-CYSee reversal of the adverse actions of morphine on ventilation, ABG chemistry and A-a gradient may be via modulation of intracellular signaling pathways activated by morphine rather than by direct antagonism of opioid receptors since morphine antinociception was not diminished by L-CYSee, and (c) the thiol moiety of L-CYSee is vital to efficacy, (d) intracellular conversion of L-CYSee to an S-nitrosylated form may be part of its mechanism of action.

The NLRB Is Not the Only Concern

The NLRB Is Not the Only Concern

Patient‑centered care and "people-first language" as tools to prevent stigmatization of patients with obesity.

Obesity is a global health problem with serious consequences, such as diabetes, dyslipidemia, cardiovascular disease, infertility, and certain cancers. Excess body weight, mainly due to its manifestation in an individual's appearance, also affects the psychological condition. Therefore, health care providers need to make an effort to diagnose and comprehensively treat obesity. The obesity treatment should be systemic and carried out by a multidisciplinary therapeutic team consisting of a doctor, nurse, dietitian, psychologist or physiotherapist, and surgeon. The first-line therapy of obesity includes lifestyle modification and increased physical activity. Pharmacological treatment is recommended in all adult patients with a body mass index (BMI) exceeding 30 kg/m2 or those with a BMI greater than or equal to 27 kg/m2 with at least 1 obesity‑related comorbidity. Bariatric surgery should be considered in adults with a BMI of 40 kg/m2 or greater, or those with a BMI greater than or equal to 35 kg/m2 with at least 1 obesity‑related disease. The holistic model of obesity treatment also includes psychological therapy. The European Association for the Study of Obesity recommends psychological assistance for all individuals with previous treatment failure. Adverse or harmful actions toward people with obesity, ascribing negative traits and behaviors to them, and their marginalization in the public space are referred to as stigmatization of obesity. This phenomenon is associated with reduced compassion and willingness to help, and a feeling of dislike or even anger toward this group of patients. The consequences of stigmatization are worse mental health, poorer physical health, avoidance of health care, and the maintenance or increase of excess body weight. Therefore, talking about obesity using the principles of "people-first language," as well as implementing a patient‑centered care model are important.

Importance of homoeopathic posology in relation to pharmacovigilance: A review

Pharmacovigilance is the pharmacological science relating to the detection, assessment, understanding and prevention of adverse effects, particularly long term and short term side effects of medicines. It is the science of collecting, monitoring, researching, assessing and evaluating information from healthcare providers and patients on the adverse effects of medications, with a view to identify new information about hazards associated with medicines and preventing harm to patients. The results confirm effectiveness of the drug in clinical practice. Present study helps to know the risk and benefits of drug as there is a belief that medicines are diluted in Homoeopathy and it will not produce any unwanted aggravation. Doses are responsible for cure as it depends upon susceptibility, potency, and repetition of doses. Hahnemann did much experimental research through clinical trial and concluded to minimize the quantity of dose for best results. Homoeopathy therapeutic dose is capable of only producing a slight temporary aggravation or intensification of already existing symptoms, never of producing new symptoms. Clinicians must aware of distinction between Homoeopathic aggravation and Adverse drug reaction and serve public health accordingly without any harm.Methodology: An intense literature search was made using electronic data bases, hand searching, journals, web pages, reviewing bibliography resources, available publications, Major scientific databases namely Pubmed, Science Direct and Springer were searched. The search words used were Pharmacovigilance, Safety of AYUSH drugs, Adverse Drug action, Posology, Doses in Homoeopathy.Results: Thirty studies were included in the review. Most of research is carried on placebo control studies and Homoeopathic aggravations. Some studies concluded the presence of adverse events but their effects are very transient. Studies revealed that dose depends upon susceptibility of patient. Apart from drug adverse events studies showed light on different things like study of drug in different potencies and their effectiveness in different doses and these also should be validated scientifically and accepted by scientific fraternity. Conclusion: Considering the importance of dose and there effect which may produce aggravation or adverse events which may be serious or transient, future research should focus on pharmacovigilance to aware clinicians on its risks and advise their patients accordingly.

Reflection and Development on Traditional Doctrines of Administrative Law–Administrative Penalty, Adverse Action of Punitive and Non-punitive Nature

Reflection and Development on Traditional Doctrines of Administrative Law–Administrative Penalty, Adverse Action of Punitive and Non-punitive Nature

Syntaxin interacts with arachidonic acid to prevent diabetes mellitus

Syntaxin regulates pancreatic β cell mass and participates in insulin secretion by regulating insulin exocytosis. In addition, syntaxin 4 reduces IFNγ and TNF-α signaling via NF-ĸB in islet β-cells that facilitates plasma glucose sensing and appropriate insulin secretion. Arachidonic acid (AA) has potent anti-inflammatory actions and prevents the cytotoxic actions of alloxan and streptozotocin (STZ) against pancreatic β cells and thus, prevents the development of type 1 diabetes mellitus (induced by alloxan and STZ) and by virtue of its anti-inflammatory actions protects against the development of type 2 diabetes mellitus (DM) induced by STZ in experimental animals that are models of type 1 and type 2 DM in humans. AA has been shown to interact with syntaxin and thus, potentiate exocytosis. AA enhances cell membrane fluidity, increases the expression of GLUT and insulin receptors, and brings about its anti-inflammatory actions at least in part by enhancing the formation of its metabolite lipoxin A4 (LXA4). Prostaglandin E2 (PGE2), the pro-inflammatory metabolite of AA, activates ventromedial hypothalamus (VMH) neurons of the hypothalamus and inhibits insulin secretion leading to reduced glucose tolerance and decreases insulin sensitivity in the skeletal muscle and liver. This adverse action of PGE2 on insulin release and action can be attributed to its (PGE2) pro-inflammatory action and inhibitory action on vagal tone (vagus nerve and its principal neurotransmitter acetylcholine has potent anti-inflammatory actions). High fat diet fed animals have hypothalamic inflammation due to chronic elevation of PGE2. Patients with type 2 DM show low plasma concentrations of AA and LXA4 and elevated levels of PGE2. Administration of AA enhances LXA4 formation without altering or reducing PGE2 levels and thus, tilts the balance more towards anti-inflammatory events. These results suggest that administration of AA is useful in the prevention and management of DM by enhancing the action of syntaxin, increasing cell membrane fluidity, and reducing VMH inflammation. Docosahexaenoic acid (DHA) has actions like AA: it increases cell membrane fluidity; has anti-inflammatory actions by enhancing the formation of its anti-inflammatory metabolites resolvins, protectins and maresins; interacts with syntaxin and enhance exocytosis in general and of insulin. But the DHA content of cell membrane is lower compared to AA and its content in brain is significant. Hence, it is likely DHA is important in neurotransmitters secretion and regulating hypothalamic inflammation. It is likely that a combination of AA and DHA can prevent DM.