Ethical Constraints Research Articles

The Robogut: A Bioreactor Model of the Human Colon for Evaluation of Gut Microbial Community Ecology and Function

The human colon is inhabited by a complex community of microbes. These microbes are integral to host health and physiology. Understanding how and when the microbiome causally influences host health will require microbiome models that can be tightly controlled and manipulated. While in vivo models are unrivalled in their ability to study host-microbial interplay, in vitro models are gaining in popularity as methods to study the ecology and function of the gut microbiota, and benefit from tight controllability and reproducibility, as well as reduced ethical constraints. In this set of protocols, we describe the Robogut, a single-stage bioreactor system designed to replicate the conditions of the distal human colon, to culture whole microbial communities derived from stool and/or colonic biopsy samples, with consideration of methods to create culture medium formulations and to build, run, and sample the bioreactor apparatus. Cleaning and maintenance of the bioreactor system are also described. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Growth medium preparation Support Protocol 1: Preparing medium supplements Basic Protocol 2: Preparing the bioreactor vessels Support Protocol 2: Making acid and base bottles Support Protocol 3: Preparing the effluent bottles Support Protocol 4: Making acid solution Support Protocol 5: Making base solution Basic Protocol 3: Preparing inoculum and inoculating bioreactors Alternate Protocol 1: Preparing inoculum less than 0.5% (w/v) of vessel volume Alternate Protocol 2: Preparing synthetic community aliquots and inoculation via the septum Alternate Protocol 3: Preparing inoculum from a tissue sample Basic Protocol 4: Sampling the bioreactor vessel Basic Protocol 5: Harvesting bioreactor vessel contents at end of experiment Support Protocol 6: Cleaning and sterilizing sampling needles Basic Protocol 6: Cleaning the bioreactor vessel Support Protocol 7: Cleaning bioreactor support bottles.

BBB-on-a-chip with integrated micro-TEER for permeability evaluation of multi-functionalized gold nanorods against Alzheimer’s disease

BackgroundThe lack of predictive models that mimic the blood–brain barrier (BBB) hinders the development of effective drugs for neurodegenerative diseases. Animal models behave differently from humans, are expensive and have ethical constraints. Organ-on-a-chip (OoC) platforms offer several advantages to resembling physiological and pathological conditions in a versatile, reproducible, and animal-free manner. In addition, OoC give us the possibility to incorporate sensors to determine cell culture features such as trans-endothelial electrical resistance (TEER). Here, we developed a BBB-on-a-chip (BBB-oC) platform with a TEER measurement system in close distance to the barrier used for the first time for the evaluation of the permeability performance of targeted gold nanorods for theranostics of Alzheimer’s disease. GNR-PEG-Ang2/D1 is a therapeutic nanosystem previously developed by us consisting of gold nanorods (GNR) functionalized with polyethylene glycol (PEG), angiopep-2 peptide (Ang2) to overcome the BBB and the D1 peptide as beta amyloid fibrillation inhibitor, finally obtaining GNR-PEG-Ang2/D1 which showed to be useful for disaggregation of the amyloid in in vitro and in vivo models. In this work, we evaluated its cytotoxicity, permeability, and some indications of its impact on the brain endothelium by employing an animal-free device based on neurovascular human cells.ResultsIn this work, we fabricated a BBB-oC with human astrocytes, pericytes and endothelial cells and a TEER measuring system (TEER-BBB-oC) integrated at a micrometric distance of the endothelial barrier. The characterization displayed a neurovascular network and the expression of tight junctions in the endothelium. We produced GNR-PEG-Ang2/D1 and determined its non-cytotoxic range (0.05–0.4 nM) for plated cells included in the BBB-oC and confirmed its harmless effect at the highest concentration (0.4 nM) in the microfluidic device. The permeability assays revealed that GNR-PEG-Ang2/D1 cross the BBB and this entry is facilitated by Ang2 peptide. Parallel to the permeability analysis of GNR-PEG-Ang2/D1, an interesting behavior of the TJs expression was observed after its administration probably related to the ligands on the nanoparticle surface.ConclusionsBBB-oC with a novel TEER integrated setup which allow a correct read-out and cell imaging monitoring was proven as a functional and throughput platform to evaluate the brain permeability performance of nanotherapeutics in a physiological environment with human cells, putting forward a viable alternative to animal experimentation.

The challenge of dementia prevention trials and the role of quasi-experimental studies.

Observational studies have shown consistently that modifiable risk factors during life are associated with increased dementia risk in old age but randomized controlled trials (RCTs) on dementia prevention evaluating the treatment of these risk factors did not find consistent effects on cognitive outcomes. The discrepancy in findings is potentially attributable to inherent differences between the two study designs. Although RCTs are the gold standard for establishing causality, designing and conducting an RCT for dementia prevention is complex. Quasi-experimental studies (QESs) may contribute to investigating causality without randomization. QESs use variation in exposure to a risk factor or intervention in an observational setting to deduct causal effects. Design-specific approaches are used to control for confounding, the main caveat of QESs. In this article we address the challenges, opportunities, and limitations of QESs for research into dementia prevention. HIGHLIGHTS: Despite consistent associations between modifiable risk factors and dementia, the mostly neutral effects of randomized controlled trials (RCTs) challenge the causality of these associations. RCTs in the field of dementia prevention are often problematic due to ethical, practical, or financial constraints, and their results may have limited generalizability. Four quasi-experimental study (QES) designs may be suitable to study causality between risk factors and dementia; we critically appraise these study designs for dementia-prevention studies. We describe how specific QES designs can be used to study the effects of risk-factor modification for 12 known risk factors for dementia.

Somatic Cell Reprogramming for Nervous System Diseases: Techniques, Mechanisms, Potential Applications, and Challenges

Nervous system diseases present significant challenges to the neuroscience community due to ethical and practical constraints that limit access to appropriate research materials. Somatic cell reprogramming has been proposed as a novel way to obtain neurons. Various emerging techniques have been used to reprogram mature and differentiated cells into neurons. This review provides an overview of somatic cell reprogramming for neurological research and therapy, focusing on neural reprogramming and generating different neural cell types. We examine the mechanisms involved in reprogramming and the challenges that arise. We herein summarize cell reprogramming strategies to generate neurons, including transcription factors, small molecules, and microRNAs, with a focus on different types of cells.. While reprogramming somatic cells into neurons holds the potential for understanding neurological diseases and developing therapeutic applications, its limitations and risks must be carefully considered. Here, we highlight the potential benefits of somatic cell reprogramming for neurological disease research and therapy. This review contributes to the field by providing a comprehensive overview of the various techniques used to generate neurons by cellular reprogramming and discussing their potential applications.

Evaluation of amniotic fluid treatment effect on placental stem cells immunomodulatory activity

The advent of stem cell therapy in treating various complex diseases has become a major breakthrough in clinics. Mesenchymal stem cells are well known for their pluripotency and their immunomodulation feature, therefore research on mesenchymal stem cells is widely acknowledged. Obtaining viable stem cells with a less invasive extraction method as well as ethical issues is a major challenge in stem cell research. Recently, human placental stem cells are becoming more known as the best source of stem cells due to their ease of extraction, lesser ethical constraints, and presence of mesenchymal stem cells. Naturally derived bioactive compounds to modulate the proliferation, regeneration, cell fate and immunomodulation feature of stem cells are under investigation. In the current in-vitro study, the placenta-derived mesenchymal stem cells were treated with amniotic fluid and were observed for their effects. Our results suggest amniotic fluid treatment enhanced proliferation and induced mesenchymal to the epithelial transition of stem cells. Further, we observed changes in the secretion pattern of cytokines as well as growth factors, which are involved in T-cell suppression. Notable, the of TGFβ (17.4 ± 2.3 ng/ml) and IL-10 (21.7 ± 1.9 pg/ml) with the increase in the concentration of AF whereas the TNFα (8.6 ± 2.1 pg/ml) and IL-6 (12.3 ± 1.6 pg/ml) showed a decline in expression cytokine.Our results suggest amniotic fluid treatment can induce host cell immune suppression; however further validation studies have to be carried out.

The institutional impact of research challenges and constraints on psychology and other social and behavioral sciences

Psychology and other social and behavioral disciplines are severely limited by the extraordinary complexity of the phenomena of study and numerous legal, ethical, and logistical constraints. In this article, we examine the impact of these research challenges on the institutional standing of and support for our disciplines. The immense challenges of human research have contributed to unfavorable stereotypes of the capabilities of social and behavioral scientists and fostered self-censure of our fields. Low consensus for research questions, frameworks, and approaches, and frustration with the limitations of studies have fragmented disciplines such as sociology and anthropology. The numerous obstacles and impediments have led to the subordination of social and behavioral science which has been maintained through policies, practices, ideologies, and stereotypes favoring the natural sciences. Psychologists and other social and behavioral scientists need to recognize the limitations of their research enterprise imposed by the complexity of the study phenomena and stop disparaging their work. Moreover, they need to recognize the potential for conflict and division because of the low consensus in our fields and act collectively to promote social and behavioral science.

ALLERGIC CONTACT CHEILITIS OF BOTH LIPS CAUSED BY WHITE PETROLEUM JELLY

White petroleum jelly is commonly used as a skin protectant for dry skin and dry lips. The active ingredient of white petroleum jelly is "petrolatum". Petroleum jelly very rarely causes hypersensitivity reactions. Even though it is a very rare case, allergic reaction to petroleum jelly is a potential problem of its common use of petroleum jelly for cosmetic and medical purposes. We report a case of a 25years old male patient with allergic contact cheilitis of both lips. The patient presented with complaints of cheilitis of both lips due to the white petroleum jelly application, which was treated with topical and oral steroids. Rechallenge was not done in the interest of the patient and due to ethical constraints. Due to the emerging adverse events related to white petroleum jelly, All health care providers should create awareness about the adverse events related to white petroleum jelly among the public. White petroleum jelly is used worldwide in most of cosmetic products, it should be used with caution. We can use natural cocoa butter kind of products as moisturizers instead of petroleum jelly.

Research Progress on the Osteogenesis-Related Regulatory Mechanisms of Human Umbilical Cord Mesenchymal Stem Cells.

In recent years, research on human umbilical cord mesenchymal stem cells (hUCMSCs) derived from human umbilical cord tissue has accelerated and entered clinical application research. Compared with mesenchymal stem cells (MSCs) from other sources, hUCMSCs can be extracted from different parts of umbilical cord or from the whole umbilical cord. It has the characteristics of less ethical controversy, high differentiation potential, strong proliferation ability, efficient expansion in vitro, avoiding immune rejection and immune privilege, and avoids the limitations of lack of embryonic stem cells, heterogeneity, ethical and moral constraints. hUCMSCs avoid the need for embryonic stem cell sources, heterogeneity, and ethical and moral constraints. Bone defects are very common in clinical practice, but completely effective bone tissue regeneration treatment is challenging. Currently, autologous bone transplantation and allogeneic bone transplantation are main treatment approaches in clinical work, but each has different shortcomings, such as limited sources, invasiveness, immune rejection and insufficient osteogenic ability. Therefore, to solve the bottleneck of bone tissue regeneration and repair, a great amount of research has been carried out to explore the clinical advantages of hUCMSCs as seed cells to promote osteogenesis.However, the regulation of osteogenic differentiation of hUCMSCs is an extremely complex process. Although a large number of studies have demonstrated that the role of hUCMSCs in enhancing local bone regeneration and repair through osteogenic differentiation and transplantation into the body involves multiple signaling pathways, there is no relevant article that summarize the findings. This article discusses the osteogenesis-related regulatory mechanisms of hUCMSCs, summarizes the currently known related mechanisms, and speculates on the possible signals.

Using animal models to identify clinical risk factors in the older population due to alcohol use and misuse.

The number of people over the age of 65 years old is increasing and understanding health risks associated with the aged population is important. Recent research has revealed that alcohol (ethanol) consumption levels in older demographics remains elevated and often occurs in a dangerous binge pattern. Given ethical constraints on investigating high level or binge pattern alcohol consumption in humans, animal models are often used to study the effects of ethanol. The current review highlights ongoing work revealing that aged rats are often more sensitive to the effects of acute ethanol compared to younger rats. Specifically, aged rats are more sensitive to the motor impairing, hypnotic, hypothermic, and often the cognitive effects of ethanol compared to younger rats. In addition, the development of ethanol tolerance following chronic exposure may have a different temporal pattern in aged rats compared to younger rats. However, the neurobiological mechanisms that cause the increased sensitivity to ethanol in aged animals have yet to be identified. Furthermore, the differential age effects of ethanol highlight clinical risk factors for alcohol misuse in the older human population. Future work is needed to determine underlying CNS mechanisms producing altered effects of ethanol in aged subjects and also the development of educational material concerning ethanol's effects across ages for health care providers working with the aged population.

Influence of prenatal cannabinoid exposure on early development and beyond.

Public perception surrounding whether cannabis use is harmful during pregnancy often diverges greatly from the recommendations of doctors and healthcare providers. In contrast to the medical guidance of abstinence before, during, and after pregnancy, many women of reproductive age believe cannabis use during pregnancy is associated with little potential harm. Legalization and social cues support public perceptions that cannabis use during pregnancy is safe. Moreover, pregnant women may consider cannabis to be a safe alternative for treating pregnancy related ailments, including morning sickness. Compounding the problem is a lack of medical and federal guidance on safe, low, or high-risk levels of cannabis use. These issues mirror the continuing debate surrounding alcohol use and health, in particular, whether there are safe or lower risk levels of alcohol consumption during pregnancy. Clinical studies to date suffer from several limitations. First, most human studies are correlative in nature, meaning that causal associations cannot be made between in utero cannabis exposure and health and behavioral outcomes later in life. Due to obvious ethical constraints, it is not possible to randomly assign pregnant mothers to cannabis or other drug exposure conditions-a requirement needed to establish causality. In addition, clinical studies often lack quantitative information on maternal exposure (i.e., dose, frequency, and duration), include a small number of individuals, lack replication of outcome measures across cohorts, rely on self-report to establish maternal drug use, and suffer from unmeasured or residual confounding factors. Causal associations between maternal cannabis exposure and offspring outcomes are possible in preclinical cohorts but there is a large amount of heterogeneity across study designs and developmental differences between rodents and humans may limit translatability. In this review, we summarize research from human and preclinical models to provide insight into potential risks associated with prenatal cannabinoid exposure (PCE). Finally, we highlight gaps in knowledge likely to contribute to the growing divide between medical guidance and public attitudes regarding cannabis use during pregnancy.

Bombyx mori as a model for Niallia circulans pathogenicity.

Increasing incidences of resistance to antibiotics by pathogenic bacteria is a worldwide concern and isolation of antibiotic-resistant strains of Niallia circulans (formerly known as Bacillus circulans), an opportunistic human pathogen, has been reported. Due to their lack of ethical constraints as well as their cost-effective rearing, invertebrates have been commonly used to study infection by bacteria pathogenic to humans. In this study, we demonstrate that a foodborne strain of N. circulans kills larvae of the silkworm, Bombyx mori within 48 h after hemolymph injection. The infected larvae turned black with an increase in the phenoloxidase (PO) activity in the hemolymph. Midgut injection of N. circulans resulted in the killing of larvae within 96 h. A significant increase in bacterial load was observed in the hemolymph 12 h after infection. The viable hemocyte number decreased to 48% within 12 h of injection. RT-qPCR analysis revealed that upon hemolymph infection with N. circulans the expression of the antimicrobial peptide (AMP) genes, Bmdefensin-B and Bmgloverin-3, were upregulated 2.5- and 1.8-fold, respectively, whereas 1.6-fold upregulation was observed for BmToll-2 in the larval fat body. Therapeutic effects of antibiotics like tetracycline, imipenem, ceftriaxone, ampicillin, and clindamycin were observed against N. circulans in the Bombyx larvae with varying efficacies. Results from this study suggest that larvae of B. mori can be used as infection models for screening therapeutics that are effective against N. circulans.

Impedance Mismatch: On the peculiar problems arising in mental cohabitation under ethical and moral constraints in reforming reason - personal confession(s)

Impedance Mismatch: On the peculiar problems arising in mental cohabitation under ethical and moral constraints in reforming reason - personal confession(s)

To Score or Not to Score: Factors Influencing Performance and Feasibility of Automatic Content Scoring of Text Responses

AbstractIn this article, we systematize the factors influencing performance and feasibility of automatic content scoring methods for short text responses. We argue that performance (i.e., how well an automatic system agrees with human judgments) mainly depends on the linguistic variance seen in the responses and that this variance is indirectly influenced by other factors such as target population or input modality. Extending previous work, we distinguish conceptual, realization, and nonconformity variance, which are differentially impacted by the various factors. While conceptual variance relates to different concepts embedded in the text responses, realization variance refers to their diverse manifestation through natural language. Nonconformity variance is added by aberrant response behavior. Furthermore, besides its performance, the feasibility of using an automatic scoring system depends on external factors, such as ethical or computational constraints, which influence whether a system with a given performance is accepted by stakeholders. Our work provides (i) a framework for assessment practitioners to decide a priori whether automatic content scoring can be successfully applied in a given setup as well as (ii) new empirical findings and the integration of empirical findings from the literature on factors that influence automatic systems' performance.

How should we promote transient diversity in science?

Diversity of practice is widely recognized as crucial to scientific progress. If all scientists perform the same tests in their research, they might miss important insights that other tests would yield. If all scientists adhere to the same theories, they might fail to explore other options which, in turn, might be superior. But the mechanisms that lead to this sort of diversity can also generate epistemic harms when scientific communities fail to reach swift consensus on successful theories. In this paper, we draw on extant literature using network models to investigate diversity in science. We evaluate different mechanisms from the modeling literature that can promote transient diversity of practice, keeping in mind ethical and practical constraints posed by real epistemic communities. We ask: what are the best ways to promote an appropriate amount of diversity of practice in scientific communities?

An integrated ancient Chinese philosophical perspective on corporate governance

Although the concept of corporate governance began with the emergence of corporations, the concept of governance can be traced back to ancient China. Currently, discussions of this topic focus mainly on the differences between approaches to and theories about corporate governance and examine their effectiveness, an integrated view that draws on Chinese theories and cultures is missing. This paper attempts to address the gaps by conceptually synthesizing insights from ancient Chinese philosophies to construct an integrated framework; it further defines the legal and ethical constraints while incorporating both an ancient Chinese (i.e., Eastern) philosophical perspective and Western governance elements and both national-level and firm-level variables. Drawing on institutional theory (Scott, 1995, 2004, 2008a, 2008b) and considering the interaction of legal and ethical constraints, a model — the ethical-legal model — constructs and categorizes corporate governance approaches into four types driven by different types of institutions and compares how these approaches are related to different governance perspectives (agent, stewardship and stakeholder). An autonomous (Wu Wei) governance approach is trigged when the cognitive institution is formed as a result of high levels of both legal and ethical constraints and drives autonomous corporate governance with a shift in focus from compliance to commitments

Research on the Evaluation System of Scientific Research Ethics Based on AHP-Fuzzy Comprehensive Evaluation

Scientific research ethics is the value concept and code of conduct to be followed in scientific research, technological development and other scientific and technological activities. However, in recent years, some researchers have ignored ethical constraints in scientific research activities, resulting in more prominent ethical issues in scientific research. This study takes China Southern Power Grid Corporation as an example, based on ISO9000 standards, uses AHP-fuzzy comprehensive evaluation theory to establish a scientific research ethics evaluation system, aiming at improving the timeliness and targeting of scientific research ethics management.

Whole-body MRI for juvenile idiopathic arthritis.

In addition to addressing important questions related to disease pathogenesis, timely diagnosis, and adequate management, paediatric rheumatology research should address unmet patient needs. The aim is to improve patient outcomes and minimisation of long-term irreversible damage—aspects that are particularly relevant for diseases with childhood onset. Evidence-based recommendations and patient-driven research agendas are scarce in paediatric rheumatology due to the challenges posed by ethical constraints, complex considerations about children's participation in research, and, often, the absence of developmentally appropriate outcomes.

Novel selenium and/or copper substituted hydroxyapatite-gelatin-chitosan-eggshell membrane nanocomposite scaffolds for bone tissue engineering applications.

Limitations with the majority of bone therapeutic treatments include low availability, ethical constraints and low biological compatibility. Although a number of choice materials have been exploited successfully, there has always been scope for improvement as well as development of the next-generation of materials. Herein, scaffolds - developed from gelatin, chitosan and eggshell membranes - were crosslinked using tannic acid, and further infused with selenium and/or copper substituted hydroxyapatite nanoparticles to generate a novel nanocomposite substrate. FESEM images of the nanocomposite scaffolds revealed the presence of interconnected pores, mostly spread over the whole surface of the scaffold, alongside XRD and FTIR profiling that detailed the formation of hydroxyapatite as a sole phase. Moreover, physical characterisation of the nanocomposite confirmed that the hydroxyapatite particulates and the eggshell membrane fibres were uniformly distributed and contributed to the surface roughness of the scaffold. Biocompatibility and cytotoxicity of the novel constructs were assessed using the mouse-derived osteoblastic cell line, MC3T3-E1, and standard cell culture assays. Metabolic activity assessment (i.e. MTS assay), LDH-release profiles and Live/Dead staining demonstrated good cell adhesion, viability, and proliferation rates. Accordingly, this work summarises the successful development of a novel construct which may be exploited as a clinical/therapeutic treatment for bone repair as well as a possible translational application as a novel biomaterial for the drug development pipeline.

Data Privacy in Healthcare: In the Era of Artificial Intelligence

Data Privacy has increasingly become a matter of concern in the era of large public digital respositories of data. This is particularly true in healthcare where data can be misused if traced back to patients, and brings with itself a myriad of possibilities. Bring custodians of data, as well as being at the helm of disigning studies and products that can potentially benefit products, healthcare professionals often find themselves unsure about ethical and legal constraints that undelie data sharing. In this review we touch upon the concerns, leal frameworks as well as some common practices in these respects.

The transformative potential of virtual, augmented and mixed reality in colorectal surgery: opportunities and challenges.

In the past three decades, colorectal surgery has embraced a series of technological advancements focusing on precision preoperative planning, the adoption of minimally invasive laparoscopic, robotic, and endoscopic surgical techniques, and the formulation of personalized, patient-centric care. The main evidence-based drivers for such utilities are, reduction in postoperative pain and operative trauma, improvements in disease specific outcomes, the enhancement of patients’ healthcare journey, and the safeguarding of intermediate and long-term quality of life measures1,2. Incorporation of these developments into mainstream clinical practice has presented several challenges. These include, the concerns related to patient safety, standardization of operative approach, as well as ensuring cost efficiencies and cost containment relating to surgical-care3,4. Furthermore, there are ethical, technical, and financial constraints associated with minimally invasive surgical (MIS) training, which has impacted a significant section of the existing workforce as well as new generations of surgeons5-8.