Unintended Adverse Effects Research Articles

Too much of a good thing: how to buffer the unintended adverse effects of empowering leadership?

Too much of a good thing: how to buffer the unintended adverse effects of empowering leadership?

Assessing the effects of sustainable supply chain management practices on operational performance: the role of business regulatory compliance and corporate sustainability culture

PurposeThis study examines the mediating and moderating effects of business regulatory compliance (BRC) on the association between sustainable supply chain management practices (SSCMP) and operational performance (PERFOP), and how corporate sustainability culture (CSC) serves as a boundary condition to BRC.Design/methodology/approachThis research draws data from 245 firms operating in multiple industries in Ghana. Ordinary Least Square (OLS) was employed to test the direct effects, while Hayes Process Macros was employed to test the indirect and conditional effects among the study variables using a structural equation modelling approach.FindingsThe results showed that SSCMP has a direct positive effect on PERFOP. The study further revealed that BRC mediates the relationship between SSCMP and PERFOP. This study found that BRC negatively moderates the association between SSCMP and PERFOP, suggesting that high levels of BRC generate unintended adverse effect on the SSCMP- PERFOP link. However, the results revealed that CSC serves as a boundary condition to BRC.Originality/valueTo the best of our knowledge, this is the first study that emphasizes how the resource-based view and regulatory focus theory interact to explain how different degrees of CSC and BRC impact SSCMP performance outcomes. This study advances research in the sustainability literature, in response to calls for further research in this domain. This study draws decision-makers attention on the need to make sustainability practices an integral part of corporate culture in order to set a business tone that stimulates easy compliance to sustainability requirements.

The combined effect of physical exercise, pranayama, and diet on fatigue in adult cancer patients undergoing chemotherapy: a randomized controlled trial.

Cancer patients undergoing chemotherapy continue to experience significant fatigue, which affects their quality of life. The present study aims to evaluate the combined effect of comprehensive physical exercise, pranayama (regulated breathing practices of yoga), and dietary support intervention on fatigue in cancer patients undergoing chemotherapy. Non-advanced adult cancer patients undergoing chemotherapy (N = 52) were randomized into the intervention group (N = 26) or control group (N = 26). Fatigue assessment was done using the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale (version 4) at baseline and after 3 months. The intervention group participants practiced physical exercise, slow-paced pranayama and supplemented their diet with an intake of 100 g of millet protein powder (MPP), commonly known as "Sattu" in India. The control group received standard medical care. A total of 39 patients (N = 13 in the intervention and N = 26 in the control group) were included in the statistical analysis. Within the intervention group, a statistically significant reduction in fatigue (p = 0.002) with a large effect size (d = 2.1) was observed. There was no statistically significant reduction in fatigue within the control group (p = 0.36). The group comparison showed a statistically significant reduction in post-scores of fatigue (p < 0.0001) in the intervention group as compared to the control group with a moderate effect size (R = 0.1). No unintended adverse effects related to the intervention were observed. The results suggest the potential role of integrated physical exercise, pranayama, and dietary support in reducing fatigue in cancer patients undergoing chemotherapy. Further validation with a larger sample size is required. CTRI/2022/04/041717 [Registered prospectively on 07/04/2022].

Specialty economies of scope in English hospitals: Cost Arguments for colocation

ObjectiveCurrent policy responses to COVID-19 disruption and care backlogs suggest potential changes to the location and structure of hospital healthcare supply. However, few studies investigating the cost effects of hospital reorganisation consider changes in the mix of outputs or test for the existence of economies of scope in hospital healthcare. Attempts to create dedicated hubs to address healthcare demand backlogs could have unintended adverse cost effects where these are provided outside existing hospital arrangements. To evaluate this, we investigate the existence and size of economies of scope in English hospital healthcare. DataWe use cost and activity data from the English NHS, linked to aggregated staff wage information and information taken from hospital financial statements. Cost and activity data was obtained from NHS England's Costing Publications. Wage data was extracted from the NHS's Electronic Staff Record via the NHS England Workforce Statistics Team, and published hospital financial accounts were aggregated and linked together at the organisation level. ResultsGeneral Surgery exhibited positive economies of scope when provided alongside other healthcare, as to a lesser extent did General Medicine and Obstetric/Gynaecology healthcare. There was little evidence for economies of scope in Diagnostic and Pathology services, Orthopaedics, or Emergency Care. Few (2/28) output cross-products (cost complementarities) were statistically significant, but Baumol's wider definition of scope economies demonstrates that scope economies are present in some specialties. ConclusionPolicymakers seeking to maximise the amount of healthcare provided and minimise the costs of doing so may wish to consider retaining General Surgery, General Medicine and Obstetric/Gynaecology healthcare supply alongside the provision of other clinical specialties. There is limited evidence that reconfiguring supply by centralizing other specialty groups into fewer providers would increase costs.

The overlap of disordered eating, autism and ADHD: future research priorities as identified by adults with lived experience.

The focus of mental health research in emerging fields should be driven by the priorities of people with relevant lived experience. Autism and ADHD are childhood-onset neurodevelopmental conditions that are associated with a range of health inequalities, including increased risk for eating disorders. The evidence base for how best to support neurodivergent individuals who experience disordered eating is still in its infancy, but research suggests that existing clinical approaches are not currently fit for purpose. In this Personal View, through community consultation with autistic people and people with ADHD who have experienced disordered eating, we present a comprehensive ranked list of research topics that people with lived experience prioritise. These priorities could be clustered into two areas: improving outcomes and identifying causal mechanisms. Within the theme of improving disordered eating outcomes, priorities are the improvement of treatment, the need for neurodiversity training in clinical services, and the identification and minimisation of unintended adverse effects of psychological intervention. Within the theme of identifying causal mechanisms, priorities are the identification of risk factors and a better understanding of the effect of autistic or ADHD neurocognitive profiles as potential contributors to eating disorder vulnerability. The final top ten research priorities are contextualised in terms of how they compare to the existing literature on the overlap between autism or ADHD and eating disorders, and concrete suggestions are made for how to implement these research priorities as testable hypotheses. Research informed by these priorities will build necessary understanding of the reasons behind the increased risk for eating disorders in neurodivergent people, and how to best support people who are affected by disordered eating to live positive and fulfilling lives.

Improving consumer understanding of pesticide toxicity labels: experimental evidence

Consumers often inadvertently misperceive the health hazards associated with over-the-counter pesticides under the current textual labeling policy, potentially leading to improper use. We conducted an incentivized framed field experiment with eye tracking to evaluate the effectiveness of the current pesticide labels that convey risk using signal words (Caution, Warning, Danger) compared to two visually focused label alternatives: traffic light colors and skull intensity symbols. A total of 166 participants were randomly assigned to one of three label formats and asked to rank toxicity levels and make purchasing decisions within multiple price lists. Results show that signal words fail to adequately communicate toxicity levels. Specifically, participants’ correct assessment of toxicity level dramatically improves from 54% under the existing signal word label to 95% under the traffic light and 83% under the skull intensity symbol labels. We also find that participants are more likely to choose the less toxic alternatives under the new labels, suggesting the current labeling system may affect choice and have unintended adverse effects on human health.

A Single-Dose mRNA Vaccine Employing Porous Silica Nanoparticles Induces Robust Immune Responses Against the Zika Virus.

Recently, lipid nanoparticles (LNPs)-based mRNA delivery has been approved by the FDA for SARS-CoV-2 vaccines. However, there are still considerable points for improvement in LNPs. Especially, local administration of LNPs-formulated mRNA can cause off-target translation of mRNA in distal organs which can induce unintended adverse effects. With the hypothesis that large and rigid nanoparticles can be applied to enhance retention of nanoparticles at the injection site, a polyethyleneimine (PEI)-coated porous silica nanoparticles (PPSNs)-based mRNA delivery platform is designed. PPSNs not only facilitate localized translation of mRNA at the site of injection but also prolonged protein expression. It is further demonstrated that the development of a highly efficacious Zika virus (ZIKV) vaccine using mRNA encoding full-length ZIKV pre-membrane (prM) and envelope (E) protein delivered by PPSNs. The ZIKV prME mRNA-loaded PPSNs vaccine elicits robust immune responses, including high levels of neutralizing antibodies and ZIKV E-specific T cell responses in C57BL/6 mice. Moreover, a single injection of prME-PPSNs vaccine provided complete protection against the ZIKV challenge in mice.

Modulation of adipogenesis and lipogenesis by indomethacin and pantoprazole

Endocrine disruptors are suggested to act as potential “obesogens” by interacting with various metabolic processes in adipose tissue. Besides industrial chemicals that are blamed for acting as endocrine disruptors as well as obesogens, pharmaceuticals can also cause obesogenic effects as unintended adverse effects. However, limited studies evaluated the obesogenic adverse effects of pharmaceuticals. Based on this information, the present study aimed to investigate the possible in vitro adipogenic/lipogenic potential of indomethacin and pantoprazole that are prescribed during pregnancy. Their effects on lipid accumulation, adiponectin level, glycerol-3-phosphate dehydrogenase (G3PDH) activity, and expression of adipogenic genes and proteins were investigated in 3 T3-L1 cell line. The range of concentrations of the pharmaceuticals was selected according to their Cmax values. Lipid accumulation was increased dependently with indomethacin dose and with pantoprazole at its highest concentration. Both pharmaceuticals also increased adiponectin levels, which was thought to play a role in stimulating the adipogenesis pathway. Moreover, both pharmaceuticals altered the gene and/or protein expression of some adipogenic/lipogenic transcriptional factors, which may lead to disruption of metabolic pathways during the fetal period. In conclusion, indomethacin and pantoprazole may have obesogenic effects through different mechanisms and their potential to cause obesity should be investigated by further in vivo and epidemiological studies.

Are real-time volunteer apps really helping visually impaired people? A social justice perspective

While digital technologies have undoubtedly enhanced the quality of life for individuals with visual impairment, their influence on social justice remains underexplored. Drawing upon intergroup contact theory, this study employs a mixed-methods approach, utilizing both surveys and interviews, to examine the impact of real-time volunteer apps on social justice from the perspectives of both visually impaired people (VIP) and non-impaired people (NIP). Our results reveal unintended adverse effects associated with the use of real-time volunteer apps. Despite enhancing perceived social connection, these apps paradoxically increase VIP's prejudice vulnerability, which is potentially attributed to the social contrast effect. Meanwhile, app usage increases NIP's stereotyping and reduces their social acceptance of VIP groups, as these apps fail to create equal status contact between NIP and VIP. This research illuminates the complex dynamics of how information technology (IT) affects social justice for VIP and highlights the overlooked downside of IT. It advances our understanding of intergroup contact theory by providing empirical evidence on contact effects when equal status conditions are lacking and serves as a reminder to app designers and developers of the crucial role of social influence in app design, particularly in the development of apps intended for minority groups.

Heavy metal poisoning caused by Chinese folk remedies in psoriasis patients: a retrospective analysis

Psoriasis, characterized as a chronic relapsing disease with a protracted course, often drives patients to seek relief through Chinese folk remedies (CFR). Nonetheless, the complex compositions of these remedies frequently result in unintended adverse effects, notably various types of heavy metal poisoning. Our study involved an exhaustive collection and analysis of clinical data from psoriasis patients who developed heavy metal poisoning due to CFR usage, admitted to Beijing Chao-Yang Hospital from January 2011 to October 2023. Our analysis identified 44 cases of mercury poisoning, 17 of lead poisoning, 21 of arsenic poisoning, and 4 instances of mixed heavy metal poisoning. The folk remedies used ranged from fumigation and inhalation to skin application and oral administration. Distinct pathogenic characteristics were observed in each poisoning type. After treatment with metal chelating agents, all patients experienced a reduction in heavy metal levels in their bodies, accompanied by varying degrees of symptom alleviation. This study underscores the vital necessity of opting for formal, medically approved treatments for psoriasis, thereby avoiding the hazardous consequences of unregulated folk remedies that may lead to severe heavy metal poisoning.

Economic and environmental implications of carbon capture in an olive pruning tree biomass biorefinery

This study explores the integration of bioenergy with carbon capture and storage (BECCS) in a biorefinery system that converts olive tree prunings into bioethanol and antioxidants. With a capacity to process 1,500 tons of prunings daily, the biorefinery yields an annual production of around 12,000 tons of antioxidants (purity >60 %) and 78,000 tons of bioethanol. Utilizing a holistic approach involving process simulations and life cycle assessment, our analysis covers technical, economic, and environmental dimensions across two scenarios differing in design and heating source: natural gas or a BECCS system using olive prunings. Our findings reveal the potential for BECCS to drastically reduce the carbon footprint, potentially achieving net-negative emissions (−84.37 kg CO2eq per 1.00 kg of bioethanol and 0.15 kg antioxidants produced). However, these environmental gains are counterbalanced by economic and environmental challenges, with investment and operating costs nearly doubling and leading to complex environmental trade-offs related to eutrophication (+75 %), increased water consumption (+45 %), and expanded land use (+80 %). Nevertheless, the premium nature of carbon-negative products, coupled with growing awareness and supportive policy frameworks, may overcome these economic barriers. This study highlights the importance of holistic evaluation when integrating CCS into biorefineries facilitating informed decision-making to address unintended adverse effects and promoting sustainability.

Understanding the Unintended Effects of Human-Machine Moderation in Addressing Harassment within Online Communities

ABSTRACT We set out to explore the unintended effects of human-machine moderation in mitigating harassment within online communities. We examine communities that use a block-list type bot to prevent harassment from the source of harassment. Drawing from social categorization and selective exposure theories, we theorize that employing a machine alongside humans for community moderation will create unintended adverse effects. Specifically, within the moderated focal community, we hypothesize an emboldening effect characterized by an increase in harassment among community members directed at their outgroup members. Additionally, we expect a disengaging effect, that is, a downward trend in the focal community’s membership. Finally, in neighboring communities that share the same topic of discussion, we expect a spillover effect, that is, an increase in harassment. Employing Detoxify, a Bidirectional Encoder Representations from Transformers (BERT)-based model, we evaluate harassment scores in the focal community by analyzing 4 million Reddit comments across various communities. These scores serve as inputs for Bayesian Structural Time Series analysis, revealing evidence for both disengaging and spillover effects. For the emboldening effect, we use community-specific keywords in a predefined computer-assisted document classification approach, Keyword Assisted Topic Model (keyATM), to identify the target of harassment. We use mean comparison and regression discontinuity to assess the change in the level of harassment targeting outgroup members before and after the human-machine moderation implementation.

Assessing the Impact of Agents with Antiviral Activities on Transmembrane Ionic Currents: Exploring Possible Unintended Actions

As the need for effective antiviral treatment intensifies, such as with the coronavirus disease 19 (COVID-19) infection, it is crucial to understand that while the mechanisms of action of these drugs or compounds seem apparent, they might also interact with unexplored targets, such as cell membrane ion channels in diverse cell types. In this review paper, we demonstrate that many different drugs or compounds, in addition to their known interference with viral infections, may also directly influence various types of ionic currents on the surface membrane of the host cell. These agents include artemisinin, cannabidiol, memantine, mitoxantrone, molnupiravir, remdesivir, SM-102, and sorafenib. If achievable at low concentrations, these regulatory effects on ion channels are highly likely to synergize with the identified initial mechanisms of viral replication interference. Additionally, the immediate regulatory impact of these agents on the ion-channel function may potentially result in unintended adverse effects, including changes in cardiac electrical activity and the prolongation of the QTc interval. Therefore, it is essential for patients receiving these related agents to exercise additional caution to prevent unnecessary complications.

Russo–Ukrainian war: Limits of Western economic sanctions

AbstractThe potency of economic sanctions imposed on nations depends on demand and supply adjustment possibilities. Adverse GDP impacts will be maximal when import, export, production, distribution and finance are inflexible (universal non-substitution). This paper elaborates these conditions, and quantifies the maximum GDP loss that Western sanctions could have inflicted on Russia in 2022–2023. It reports the World Bank's predictions, contrasts them with results and draws inferences about the efficiency of Russia's workably competitive markets. The paper shows that Russia's economic system exhibits moderate universal substitutability and is less vulnerable to punitive discipline than Western policymakers suppose. The likelihood that the Kremlin will restore Ukraine's territorial integrity, ceteris paribus, is correspondingly low. The authors also observe that unintended adverse side effects from sanctions and counter-sanctions were excessive because policymakers chose to maximize GDP-damage to Russia instead of optimizing Western and third-party net benefits. Given moderate substitutability, Western policymakers can switch to smart net benefit maximizing sanctions that enhance Western and third-party welfare without significantly bolstering Russia's military industrial productivity and war-waging capabilities by retaining embargoes on weapons, technology and critical components, while selectively softening other restrictions. Smart sanctions might facilitate a negotiated settlement of the Russo–Ukrainian war.

Challenging the status quo: a framework for mechanistic and human-relevant cardiovascular safety screening.

Traditional approaches to preclinical drug safety assessment have generally protected human patients from unintended adverse effects. However, these assessments typically occur too late to make changes in the formulation or in phase 1 and beyond, are highly dependent on animal studies and have the potential to lead to the termination of useful drugs due to liabilities in animals that are not applicable in patients. Collectively, these elements come at great detriment to both patients and the drug development sector. This phenomenon is particularly problematic in the area of cardiovascular safety assessment where preclinical attrition is high. We believe that a more efficient and translational approach can be defined. A multi-tiered assessment that leverages our understanding of human cardiovascular biology, applies human cell-based in vitro characterizations of cardiovascular responses to insult, and incorporates computational models of pharmacokinetic relationships would enable earlier and more translational identification of human-relevant liabilities. While this will take time to develop, the ultimate goal would be to implement such assays both in the lead selection phase as well as through regulatory phases.

Comparing the Efficiency of Infrazygomatic Crest (IZC) Screws and Conventional Method for Anterior Retraction in Patients Undergoing Fixed Orthodontic Treatment for Class 2 Malocclusion: A Prospective Clinical Study.

Introduction In orthodontic treatment for class 2 malocclusion, conventional approaches involve extracting the upper first premolars and using methods like en masse retraction and extra-oral or intra-oral distalization. However, these often result in unintended forces and adverse effects. Contemporary techniques, such as maxillary arch distalization with mini-implants like infrazygomatic crest (IZC) implants, offer superior outcomes. IZC implants provide a safe, flexible, and effective site for implant placement, achieving a remarkable 93.7% success rate. Power arms enable precise control, allowing orthodontists to apply controlled forces for optimal tooth movement. This study aims to compare cephalometric parameters pre and post treatment using IZC/buccal shelf (BS) screws and conventional retraction, assessing the efficiency of IZC screws in maintaining arch length during teeth retraction. Methods In a split-mouth study at Yenepoya Dental College, 40 orthodontic patients aged 18-35 were divided into control (premolar extraction, anterior retraction) and study (third molar removal, IZC screw distalization) groups. The control group used a nitinol spring/E chain for retraction, while the study group employed IZC screw-assisted en masse distalization. Regular reviews and adjustments occurred, with radiographs and study models assessed after six months for cephalometric parameters and arch length. Results A significant difference was found in U1-SN (degree), L1-Apog (in mm), L1-NB (degree), and L1-NB (in mm) of pretreatment records, whereas all other measurements showed statistically similar values between conventional and IZC groups. Improvement was higher with the conventional group when compared with IZC groups in these measurements due to the extraction of the first premolars rather than third molar extraction and distalization. However, the IZC group also showed statistically significant improvement in cephalometric parameters such as U1-SN (degree), L1-Apog (in mm), L1-NB (degree), and L1-NB (in mm). Conclusion The statistical analysis of radiographic and cast measurements in both the maxilla and mandible demonstrated a significant efficiency of IZC screws in teeth retraction while preserving arch length compared to conventional methods. Nevertheless, to strengthen the findings of our study, additional clinical investigations on IZC screws are warranted.

Languaging psychopathology: neurobiology and metaphor.

Explanatory models of the mind inform our working assumptions about mental illness with direct implications for clinical practice. Neurobiological models assert that the mind can be understood in terms of genetics, chemistry, and neuronal circuits. Growing evidence suggests that clinical deployment of neurobiological models of illness may have unintended adverse effects on patient attitudes, public perception, provider empathy, and the effectiveness of psychiatric treatment. New approaches are needed to find a better language for describing (let alone explaining) the experience of mental illness. To address this gap, we draw upon interdisciplinary sources and semiotic theory to characterize the role of metaphor in the conceptualization and communication of psychopathology. We examine the metaphors recruited by contemporary neurobiological models and metaphor's role in facilitating descriptive clarity or evocative creativity, depending on intention and context. These multiple roles reveal the implications of metaphorical reasoning in clinical practice, including cognitive flexibility, personalized communication, and uncertainty tolerance. With this analysis, we propose a clinical approach that embraces the meta-process of ongoing novel metaphor generation and co-elaboration, or languaging metaphors of psychopathology. Our goal is to bring attention to the value of employing ever-evolving, shapeable metaphorical depictions of psychiatric illness: metaphors that enable a capacity for change in individuals and society, reduce stigma, and nurture recovery.

Closing the clean cooking gap: Which policies and institutional qualities matter?

Access to clean energy is vital for fostering economic development and promoting shared prosperity. Yet, billions of people in the developing world continue to lack access to clean cooking fuels and technologies, creating a growing clean cooking gap. Achieving universal access to clean cooking requires integrated policies and quality institutions. However, attempts to examine the policies and institutional qualities that matter are missing. We take up this task and study the role of public policies and institutional qualities in closing the clean cooking gap using a generalized method of moment and a dynamic panel threshold model for 65 developing countries covering the period between 2005 and 2022. Our result confirms that economic management policies and policies for social inclusion and equity were critical to closing the clean cooking gap. Also, structural policies, except for a few dimensions, were found to minimize the clean cooking gap. However, we find an unintended adverse effect of a strict public sector management and institution on the clean cooking gap. Our study recommends the need for targeted interventions involving subsidies, tax incentives, and credit guarantees carried out under a flexible regulatory framework.

Predicting gene expression changes upon epigenomic drug treatment

Background Tumors are characterized by global changes in epigenetic modifications such as DNA methylation and histone modifications that are functionally linked to tumor progression. Accordingly, several drugs targeting the epigenome have been proposed for cancer therapy, notably, histone deacetylase inhibitors (HDACi) such as vorinostat and DNA methyltransferase inhibitors (DNMTi) such as zebularine. However, a fundamental challenge with such approaches is the lack of genomic specificity, i.e., the transcriptional changes at different genomic loci can be highly variable, thus making it difficult to predict the consequences on the global transcriptome and drug response. For instance, treatment with DNMTi may upregulate the expression of not only a tumor suppressor but also an oncogene, leading to unintended adverse effect. Methods Given the pre-treatment transcriptome and epigenomic profile of a sample, we assessed the extent of predictability of locus-specific changes in gene expression upon treatment with HDACi using machine learning. Results We found that in two cell lines (HCT116 treated with Largazole at eight doses and RH4 treated with Entinostat at 1µM) where the appropriate data (pre-treatment transcriptome and epigenome as well as post-treatment transcriptome) is available, our model distinguished the post-treatment up versus downregulated genes with high accuracy (up to ROC of 0.89). Furthermore, a model trained on one cell line is applicable to another cell line suggesting generalizability of the model. Conclusions Here we present a first assessment of the predictability of genome-wide transcriptomic changes upon treatment with HDACi. Lack of appropriate omics data from clinical trials of epigenetic drugs currently hampers the assessment of applicability of our approach in clinical setting.

Development of a 3D Perfused In Vitro System to Assess Proangiogenic Properties of Compounds.

Perturbation of angiogenesis is associated with a variety of diseases and pro- as well as antiangiogenic therapies are being actively explored. Additionally, unintended adverse drug effects on angiogenesis might lead to promotion of tumor progression and cardiovascular complications. Several tri-dimensional microfluidic vessel-on-chip systems have been described that allow a more accurate investigation of vascular physiology and pathology, compared to the two-dimensional static culture of endothelial cells. The OrganoPlate® angiogenesis-on-chip system has been demonstrated to be amenable to high-throughput screening for the antiangiogenic properties of molecules. We set out to adapt this system for high-throughput screening of molecules with proangiogenic properties. Our technical advancement of the OrganoPlate® angiogenesis-on-chip assay expands its applicability in the early screening of both anti- as well as proangiogenic properties of compounds for therapeutic modulation of angiogenesis as well as the identification of angiogenesis-associated drug-induced vascular toxicities.