Animal Subjects Research Articles

The nonhuman animal in social studies: Using critical animal studies for empathy

Despite the many contributions of nonhuman animals in history, nonhuman animal representations are seldom crafted with care and accuracy in curricular texts. Because of the anthropocentric vantage point of textbook creation, the nonhuman animal is often portrayed as an object, but as our relationship with the nonhuman world continues to deteriorate, we need now more than ever to consider the agency and subjectivity of nonhuman entities across time and space. In this article, I will use critical contextual analysis as a research method to examine the representation of the horse in a commonly used textbook in middle and high schools in the United States titled World History: Patterns of Interaction to raise larger questions about how to engage with nonhuman animal presence in history with students. Using critical animal studies as a theoretical framework to illuminate the data, the findings reveal that the horse is depicted as agentless and is shown merely as a means for human animals to expand empire and perpetuate social norms. The exploration identifies a gap in the social studies scholarship that neglects the historical contributions of nonhuman animals in curriculum. This article will argue that juxtaposing anthropocentric curricular texts such as the one under investigation with narratives that illuminate nonhuman animal subjectivity is essential for building a more empathetic world and for cultivating a more inclusive historical narrative.

FHL2 in arterial medial calcification in chronic kidney disease.

Arterial medial calcification (AMC) is a common complication in individuals with chronic kidney disease (CKD), which can lead to cardiovascular morbidity and mortality. The progression of AMC is controlled by a key transcription factor called runt-related transcription factor 2 (RUNX2), which induces vascular smooth muscle cells (VSMCs) transdifferentiation into a osteogenic phenotype. However, RUNX2 has not been targeted for therapy due to its essential role in bone development. The objective of our study was to discover a RUNX2 coactivator that is highly expressed in arterial VSMCs as a potential therapy for AMC. We employed transcriptomic analysis of human data and an animal reporter system to pinpoint FHL2 as a potential target. Subsequently, we investigated the mRNA and protein expression patterns of FHL2 in the aortas of both human and animal subjects with CKD. To examine the role of FHL2 in the RUNX2 transcription machinery, we conducted coimmunoprecipitation (Co-IP) and chromatin immunoprecipitation (ChIP) experiments. Next, we manipulated FHL2 expression in cultured VSMCs to examine its impact on high phosphate-induced transdifferentiation. Finally, we employed FHL2 null mice to confirm the role of FHL2 in the development of AMC in vivo. Among all the potential RUNX2 cofactor, FHL2 displays selective expression within the cardiovascular system. In the context of CKD subjects, FHL2 undergoes upregulation and translocation from the cytosol to the nucleus of arterial VSMCs. Once in the nucleus, FHL2 interacts structurally and functionally with RUNX2, acting as a coactivator of RUNX2. Notably, the inhibition of FHL2 expression averts transdifferentiation of VSMCs into an osteogenic phenotype and mitigates aortic calcification in uremic animals, without causing any detrimental effects on the skeletal system. These observations provide evidence that FHL2 is a promising target for treating arterial calcification in patients with CKD.

Characterization of structural, genotoxic, and immunological effects of methyl methanesulfonate (MMS) induced DNA modifications: Implications for inflammation-driven carcinogenesis

Genotoxic DNA damaging agents are the choice of chemicals for studying DNA repair pathways and the associated genome instability. One such preferred laboratory chemical is methyl methanesulfonate (MMS). MMS, an SN2-type alkylating agent known for its ability to alkylate adenine and guanine bases, causes strand breakage. Exploring the outcomes of MMS interaction with DNA and the associated cytotoxicity will pave the way to decipher how the cell confronts methylation-associated stress. This study focuses on an in-depth understanding of the structural instability, induced antigenicity on the DNA molecule, cross-reactive anti-DNA antibodies, and cytotoxic potential of MMS in peripheral lymphocytes and cancer cell lines. The findings are decisive in identifying the hazardous nature of MMS to alter the intricacies of DNA and morphology of the cell. Structural alterations were assessed through UV–Vis, fluorescence, liquid chromatography, and mass spectroscopy (LCMS). The thermal instability of DNA was analyzed using duplex melting temperature profiles. Scanning and transmission electron microscopy revealed gross topographical and morphological changes. MMS-modified DNA exhibited increased antigenicity in animal subjects. MMS was quite toxic for the cancer cell lines (HCT116, A549, and HeLa). This research will offer insights into the potential role of MMS in inflammatory carcinogenesis and its progression.

More hard words: Learning emotion and mental state adjectives from linguistic context

ABSTRACT How do young children learn the meanings of adjectives that label emotions and mental states, like happy or confident? The concepts behind these words seem easy to grasp, and yet the properties they denote are abstract and lack reliable visual correlates, much as with verbs such as think or know. There is robust evidence that the linguistic context in which mental state verbs appear supports their acquisition. Using a two-pronged approach, we explore whether the same is true for these adjectives. First, we present a comprehensive study of adjectives in child-directed speech (CDS) in CHILDES corpora, revealing that these adjectives have a unique distributional profile based on the semantics of co-occurring words, and the syntactic complements with which they appear, distinguishing them from other adjective types. Second, we present a word learning study with adults using a version of the Human Simulation Paradigm manipulating key variables from the corpus study (subject animacy and syntactic complements), while holding other features (morphosyntactic form and syntactic position of the adjective) constant. Participants’ guesses demonstrate that they recruit these cues to constrain the meaning of novel adjectives to one corresponding to an emotion or mental state. By presenting a thorough comparison of adjective types across key linguistic contexts and providing evidence that such contexts constrain adjective meaning, we systematically extend syntactic bootstrapping to the adjectival domain in a way that goes well beyond previous work, and paints a vibrant picture of what supports the acquisition of adjectives.

ANIMAL INTERFACES AND (NON)HUMAN PERSONAS

This article explores the phenomenon of animal interfaces from a critical digital culture and media perspective. It focuses specifically on the shared boundary between the animal and technology, considering how such interfaces shape animal subjectivity and persona. By tracking various case studies of dog-technology interfaces – including, space dogs, dog photography and bionic dogs – it explores the possibility of a possible ‘cydog’ persona. I argue that dogs interfacing technology represent a possible animal persona that uniquely captures the intricacies of animal being. The cydog is an additional concept to help think through nonhuman persona that are irreducible and subjective, yet remained enframed by human actions. Guided by theorists Donna Haraway, Joanna Zylinska and Akira Lippit, I argue that interfaces play a key role in cydog encounters, creating increasingly complicated interactions that simultaneously mask anthropocentric pursuit and unmask nonhuman personas.

129 Neuroimaging Analysis of Bilateral Thalamic Delivery for Gene Therapy

INTRODUCTION: Axonal transport from the thalamus (an integrative hub for the entire cortex) has been shown to facilitate widespread gene/protein delivery. Here, we report our neuroimaging experience with bilateral thalamic convection-enhanced delivery of adeno-associated virus (AAV) vectors for GM2 gangliosidoses. METHODS: Magnetic resonance imaging (MRI) of eight pediatric patients who underwent bilateral thalamic HEXA/HEXB delivery were retrospectively reviewed. Quantitative three-dimensional volumetric analyses of MRI thalamic signals were used to establish volume of distribution (Vd) versus volume of infusion (Vi). The distance of cannula placement within the thalamus was calculated and validated using the numbers used in the intraoperative ROSA robotic software. Backflow and leakage into surrounding structures were also analyzed. RESULTS: Fourteen thalamic injection volumes were considered in the final analysis. Calculated volume of thalamic infusate signal was up to 43.8% (mean = 21.3±13.3) of the thalamic volume. The Vd/Vi ratio ranged from 0.4-2.7 (mean = 1.9±0.7), depending on infusate volume. Diffusate shape was round to slightly ellipsoid in all patients. Backflow and leakage were encountered in 14.3% and 12.5%, respectively, of thalamic injections. CONCLUSIONS: This study provides the first in-human quantitative MRI data for intrathalamic infusion. The ideal location for the cannula tip was determined to be between the mediodorsal and lateral dorsal nuclei and the ideal trajectory keeps all of the cannula steps within the thalamic boundaries. We also compare these data to published NHP and our own NHP and sheep data. Overall, the Vd/Vi ratios are lower in human subjects (∼2) than in animal subjects (∼3). We hypothesize that this may be due in part to species specific differences in displacement of extracellular fluid versus infusion volume.

Albino Wistar Rats: Advantages and Limitations in Biomedical Research

Abstract Albino Wistar rats refer to a strain of the Wistar rats which is part of the Norway rat species; it is a popular animal model in many areas of research specifically in neuroscience, pharmacology, and toxicology among others. These rats are particularly valuable due to their high level of genetic homogeneity, ease of handling, and reproducible results which have kept them in the list of requirements for researchers who want to minimize extraneous variables in their studies. One can bet on the fact that the Albino Wistar rats are inbred, and therefore, even their genetic disposition is normalized. Wistar rats originated from the United States of America in the 19th century. In several generations of breeding, this rat strain was used to establish desired characteristics, which resulted in greatly reduced genetic variability. Thus, throughout the whole process of the research, one can be sure that the results of the study will not have any relation to the genetic differences of the participants. In addition, Albino Wistar rats are a kind of animal that is inoffensive and takes well to experimental environment. This ensures that the animals do not have to be subdued or fought before getting a sample and the process does not have to stress the animals or the researcher. Furthermore, they have a shorter gestation period, approximately 21 days, and a short existence of approximately 2 years. Such features make Albino Wistar rats suitable to be used by researchers who would wish to get a fast result or those who have a small budget. It should also be pointed out, although, that there are some drawbacks in employing Albino Wistar rats as animal subjects as well. The following is the major drawback; they are prone to certain diseases for example infections and some types of tumors. It means that the studied population may have higher sensitivity to disease and its manifestations, which may influence the results of studies, when disease processes or potential treatments are examined. The other limitation is that Albino Wistar rat has a relatively shorter life span than any other strain of rats. Reduced life expectancy can also reduce the possibilities of research, especially in trials concerned with aging or late outcomes of interventions. Experimentalists must put these aspects into consideration when choosing their sample and the type of animals to use. Nevertheless, despite these drawbacks, Wistar rats still can be considered valuable source for the researchers taking into account all the mentioned advantages. Because of their high reproducibility, ease of handling, genetic uniformity, and ability to adapt to the laboratory conditions, they provide a perfect model for dissecting complex biological functions and generating new models for diseases affecting mankind. Due to the advancement in scientific knowledge and technology, the researchers may 1 day overcome the said-named limitations associated with the use of Albino Wistar rats as animal models.

Astragalus polysaccharides ameliorates experimental colitis by regulating memory B cells metabolism

It is well-established that the reduced Memory B cells (MBCs) play an important role in the pathogenesis of ulcerative colitis (UC), rendering them a potential therapeutic target for UC intervention. Astragalus polysaccharide (APS), a primary active constituent derived from the classic traditional Chinese medicine Astragalus membranaceus (AM), has been used for centuries in the treatment of UC in both human and animal subjects due to its renowned immunomodulatory properties. However, it is unknown whether APS can regulate MBCs to alleviate experimental colitis. In the present investigation, the murine colitis was successfully induced using dextran sulphate sodium (DSS) and subsequently treated with APS for a duration of 7 days. APS exhibited significant efficacy in reducing the disease activity index (DAI), colonic weight index, the index of colonic weight/colonic length. Furthermore, APS mitigated colonic pathological injuries, restored the colonic length, elevated the immunoglobulin A (IgA), transforming growth factor-β1 (TGF-β1) and interleukin (IL)-10 levels, while concurrently suppressing IgG, IgM, IL-6, tumor necrosis factor alpha (TNF-α) levels. Crucially, the quantities of MBCs, IgA+MBCs and forkhead box P3 (Foxp3+) MBCs were notably increased along with a concurrent decrease in IgG1+MBCs, IG2a+MBCs, IgG2b+MBCs after APS administration in colitis mice. Additionally, the Mitotracker red expressions of MBCs and their subgroups demonstrated a significantly up-regulation. Meanwhile, the transcriptomics analysis identified mitochondrial metabolism as the predominant and pivotal mechanism underlying APS-mediated mitigation of DSS-induced colitis. Key differentially expressed genes, including B-cell linker (BLNK), aldehyde dehydrogenase 1A1 (ALDH1A1), B-cell lymphoma 6 (BCL-6), B-lymphocyte-induced maturation protein 1 (Blimp-1), paired box gene 5 (PAX5), purinergic 2 × 7 receptor (P2X7R), B Cell activation factor (BAFF), B Cell activation factor receptor (BAFFR), CD40, nuclear factor kappa-B (NF-κB), IL-6 and so on were implicated in this process. These mRNA expressions were validated through quantitative polymerase chain reaction (qPCR) and immunohistochemistry. These findings revealed that APS effectively restored MBCs and their balance to ameliorate DSS-induced colitis, which was potentially realized via promoting mitochondrial metabolism to maintain MBCs activation.

Development of a polystyrene-based microplastic model for bioaccumulation and biodistribution study using radiotracing and nuclear analysis method

The investigation of micro or nano plastics behavior in the environment is essential to minimize the hazards of such pollutants on humans. While the conventional method requires sophisticated procedures and a lot of animal subjects, the nuclear technique confers a sensitive, accurate, and real-time method using radiolabeled micro or nano plastics as a tracer. In this study, polystyrene sulfonate-based microplastic (PSM) was developed with a size of around 3.6 μm, followed by radiolabeling with iodine-131 (131I) or zinc-65 (65Zn) for microplastic radiotracer model. After a stability study in seawater, phosphate buffer saline (PBS), and human serum albumin (HSA) for fifteen days, PSM-131I remained stable (>90 %), except in HSA (50–60 % after day-9), while PSM-65Zn was unstable (<50 %).

A Political and ethical landscape of brain organoid research

Human cerebral organoids (hCOs), produced in labs through directed cell culture of embryonic or induced pluripotent stem cells, closely replicate the 3-dimensional architecture of the human brain on a micro scale. This technology has been used to model neurological disease and shows promise to complement or supplant animal subjects in preclinical therapeutic investigation. However, attention must be paid by researchers and institutions to the various ethical concerns associated with hCO development. Human-animal chimeras produced through the grafting of hCOs have shown integration of neurological function, calling into question the moral status of both the animal chimeras and the organoid itself. Sensationalist reporting on such acts may also prompt public backlash, potentially jeopardizing hCO research and the promised benefits thereof. Moreover, concerns arise over privacy and consent for past and prospective donors of stem cells used to produce organoids. Genetic information may be considered privileged to the public domain and disrupted trust can reduce the supply of willing donors. Though hCOs are believed thus far to lack the capacity for consciousness and cognitive function, consideration must be given to their potential status as moral agents with further development or enhancement. Boundaries concerning organoids adhered to by researchers have been largely voluntary and informal to this point. By edict or by the power of the purse, governmental regulatory agencies ought to formalize necessary guidelines to ensure compliance with ethical principles and the adequate representation of all affected stakeholders in future decisions.

Factors Causing Overpassivisation of Unaccusative Verbs by Japanese Learners of English

It has been reported that second language (L2) learners of English including Japanese learners of English (JLEs) overpassivise unaccusative verbs although it is a kind of intransitive verbs. In order to account for the phenomenon, several assumptions have been proposed. However, so far, it is unclear which assumption is the most effective for explaining the overpassivisation of unaccusatives. Thus, this study tries to examine which of the three factors, animacy of subjects, existence of conceptualizable agents, or telicity of verbs, the most strongly affects overpassivisation of unaccusative verbs by JLEs. In this study, we conducted two experiments to examine this question. Study 1 was conducted with 100 university JLEs to compare the effect of animacy of subjects with that of the existence of conceptualizable agents. As a result, it was found that the animacy of subjects more strongly affected the overpassivisation of unaccusatives than the existence of conceptualizable agents. We conducted Study 2 with 101 university JLEs to examine which of the two factors, the existence of conceptualizable agents or the degree of telicity, is more influential. The results showed that the former was influential, but the latter was less so on the overpassivisation of unaccusatives. From the results of the two experiments, we concluded that the animacy of subject is the strongest influential factor among the three. On the other hand, the telicity of verbs hardly influences any errors.

Antihypertensive Property of Celery: A Narrative Review on Current Knowledge.

The incidence of hypertension is increasing significantly on a global scale, and it is considered the leading cause of heart disease and death. Despite the availability of hypotensive drugs, they have many side effects that decrease adherence to treatments and lead to uncontrolled blood pressure. Studies have revealed that celery contains bioactive compounds that oppose hypotensive effect. A thorough literature review was conducted using Scopus, PubMed, and Google Scholar databases. To identify relevant studies on the topic, our search strategy employed keywords such as "celery," "Apium gravenols L," "hypertension," "high blood pressure," "apigenin," "antihypertensive," and "hypotensive." The search was limited to articles published between January 2013 and December 2023. The inclusion criteria were original research articles that involved both animal and human subjects, published in English, and reported results applicable to the subject of this review. Review articles or articles in the form of theses or books were excluded. The available evidence revealed that celery enhances blood pressure parameters. Clinical trials clarified that celery possesses its effect through many bioactive compounds, specifically 3-n-butylphthalide and apigenin. Based on animal and human studies, celery seems to elicit blood pressure regulation mainly by the vasodilatory, diuretic, and calcium channel-blocking properties. Furthermore, celery seed extract seems to exert a bradycardia effect. The current literature review showed a considerable number of studies on the hypertensive models, which confirmed that celery and its extracts are effective hypotensive agents. Some limitations in comparing published data should be considered, including differences in doses, extracts, species of celery, and administration form.

Effect of low-intensity laser therapy on levels of biomarkers during orthodontic tooth movement – A systematic review

This systematic review aimed to explore the association between low-intensity laser therapy (LILT) and various biomarkers, elucidating the potential of this therapeutic modality to expedite orthodontic tooth movement (OTM). A systematic literature search was conducted using electronic databases including PubMed, Central of the Cochrane Library, and Google Scholar databases. Randomized controlled trials (RCTs) and non-randomized controlled clinical trials (nRCTs) using LILT as an adjunct to the standard orthodontic procedures in human and animal subjects as participants were included in the study. The quality of the human and animal studies was assessed using the Revised Cochrane risk of bias tool and Systematic Review Centre for Laboratory Animal Experimentation’s (SYRCLE’s) risk of bias tool respectively. Animal studies revealed increased receptor activator of nuclear factor-kappa B (RANK)/RANK ligand (RANKL), matrix metalloproteinase-9 (MMP-9), and collagen type I expression. Human studies showed elevated interleukin-1-beta (IL-1β), interleukin-16 (IL-16) and RANKL levels, suggesting LILT influences biomarkers associated with bone resorption and connective tissue rearrangement. A high risk of bias was observed in all animal studies and 5 out of 6 human studies. The systematic review concluded that LILT emerges as a promising technique for enhancing orthodontic tooth movement, influencing key biomarkers linked to osteoclastic activity and collagen synthesis. However, the high risk of bias in animal and human studies emphasizes the need for further research to validate findings and optimize laser parameters for clinical benefits.

A comprehensive review on potential drug-drug interactions of proton pump inhibitors with antidiabetic drugs metformin and DPP-4 inhibitors.

A drug interaction is a condition in which two or more drugs are taken at the same time. Type 2 diabetes mellitusis a significant contributor to polypharmacy. Proton pump inhibitors (PPIs) are often prescribed in combination with metformin or DPP-4 inhibitors (sitagliptin, saxagliptin, linagliptin, and alogliptin) or a combined dose of metformin and DPP-4 inhibitor to treat gastritis in diabetic patients. This review article mainly focused on evaluating the potential drug-drug interactions (DDIs) between PPIs (i.e. esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole) with metformin and PPIs with DPP-4 inhibitors. The findings demonstrated the existence of pharmacokinetic and pharmacodynamic DDIs between the aforementioned PPIs with metformin and DPP-4 inhibitors, which could impact the biological activities (i.e., hypoglycemia) of these drugs. Moreover, this review suggested that esomeprazole could be the best drug in the PPI group to be prescribed simultaneously with metformin and DPP-4 inhibitors, as most of the antidiabetic drugs of this study did not show any interaction with esomeprazole. The findings of this study also revealed that both antidiabetic drugs and PPIs could have positive interactions as PPIs have the potential to lessen the gastrointestinal side effects of metformin and DPP-4 inhibitors. To achieve the greatest therapeutic impact with the fewest side effects, careful dose control of these drugs is required. So, more extensive research on both human and animal subjects are needed to ascertain the veracity of this hypothesis.

Age and sex-based impacts of maternal iron deficiency on offspring's cognitive function and anemia: A systematic review.

Iron deficiency is a recognized global health concern, particularly impactful during pregnancy where the mother serves as the primary source of iron for the developing fetus. Adequate maternal iron levels are crucial for fetal growth and cognitive development. This review investigates the correlation between maternal iron deficiency and cognitive impairment and anemia in offspring, considering age and gender differentials. PubMed, ScienceDirect, and Google Scholar databases were queried using keywords "maternal," "iron," "gender/sex," and "cognition." The review included studies on human and animal subjects where maternal iron deficiency was the exposure and offspring cognitive function and anemia were outcomes. Out of 1139 articles screened, fourteen met inclusion criteria. Twelve studies highlighted cognitive deficits in offspring of iron-deficient mothers, with females generally exhibiting milder impairment compared to males. Additionally, two studies noted increased anemia prevalence in offspring of iron-deficient mothers, particularly affecting males and younger individuals. The findings suggest that male offspring are at higher risk of both anemia and cognitive dysfunction during youth, while females face increased risks in adulthood. Thus, maternal iron deficiency elevates the likelihood of anemia and cognitive impairments in offspring, underscoring the importance of addressing maternal iron status for optimal child health.

The Interaction between Stress and Inflammatory Bowel Disease in Pediatric and Adult Patients.

Background: Inflammatory bowel diseases (IBDs) have seen an exponential increase in incidence, particularly among pediatric patients. Psychological stress is a significant risk factor influencing the disease course. This review assesses the interaction between stress and disease progression, focusing on articles that quantified inflammatory markers in IBD patients exposed to varying degrees of psychological stress. Methods: A systematic narrative literature review was conducted, focusing on the interaction between IBD and stress among adult and pediatric patients, as well as animal subjects. The research involved searching PubMed, Scopus, Medline, and Cochrane Library databases from 2000 to December 2023. Results: The interplay between the intestinal immunity response, the nervous system, and psychological disorders, known as the gut-brain axis, plays a major role in IBD pathophysiology. Various types of stressors alter gut mucosal integrity through different pathways, increasing gut mucosa permeability and promoting bacterial translocation. A denser microbial load in the gut wall emphasizes cytokine production, worsening the disease course. The risk of developing depression and anxiety is higher in IBD patients compared with the general population, and stress is a significant trigger for inducing acute flares of the disease. Conclusions: Further large studies should be conducted to assess the relationship between stressors, psychological disorders, and their impact on the course of IBD. Clinicians involved in the medical care of IBD patients should aim to implement stress reduction practices in addition to pharmacological therapies.

Ethical Challenges in Mariculture: Adopting a Feminist Blue Humanities Approach

As mariculture—the cultivation of aquatic organisms in marine environment—intensifies to meet the demands of sustainable blue growth and national policies, novel ethical challenges will arise. In the context of ethics, primary concerns over aquaculture and mariculture tend to stay within differing value-based perspectives focused on benefits to human and non-human subjects, specifically animal welfare and animal rights. Nonetheless, the burgeoning field of feminist blue humanities provides ethical considerations that extend beyond animal subjects (including humans), often because of its concerns with new materialist, posthumanist, and other relations-based theories. This article examines feminist blue humanities and the contributions it may bring to understanding contemporary and future ethical challenges posed by mariculture and its intensification, especially the cultivation of low-trophic organisms. By offering an overview of feminist blue humanities, this article explores some of its particularities by drawing out three major ethical concerns facing contemporary mariculture, specifically material reconfigurations, radical alteration of the lives of low-trophic species through industrialization and increases in maricultural waste products.

Abstract WP28: A Multiscale, Anatomically, and Neurochemically Realistic In Silico Toolbox for the Simulation of Cerebrovascular Ischemia

Introduction: Despite therapeutic advances, roughly half of acute ischemic stroke (AIS) patients fail to achieve independence. Multiscale tools permitting nano- to macroscalar representations of the hemodynamic, electrical, and neurochemical disturbance in AIS are thus demanded. The vastness of potential scenarios evolving in individual patients renders full investigation into all possible courses of disease unattainable in human or animal subjects. Digital phantoms have proliferated in the precision medicine era, yet such frameworks remain immature in neuroscience. Here, we introduce a realistic simulation toolbox governed by a vast parameter space to model AIS. Methods: A numerical implementation of a 4-compartment (neuronal, astrocytic, extracellular, and capillary) model (www.cellml.org) was modified to simulate evolution of AIS, including the dynamic interplay of &gt;80 neurochemical processes related to cellular energetics and tuned with hemodynamic (e.g. CBF) aberrations relevant to the neurovascular unit. Two different ischemic conditions are simulated to illustrate use of the framework: i. ~50% CBF reduction; ii. ~80% CBF reduction. Results: As seen in Fig. 1, while a 50% reduction in CBF reduces glucose concentration ([GLC]) in extracellular, glial, and neuronal spaces, ATP concentrations are maintained (with glial levels dropping slightly in order that glial cells can offer support to neuronal function), and sodium concentrations ([Na+]) in both cell spaces remain constant. By comparison, an 80% CBF reduction yields falling [ATP], such that Na homeostasis is disturbed and dynamic alterations in [Na+] in the cellular compartments can be observed, leading to time-dependent cytotoxicity. Conclusion: We present a digital model and generalized framework for modeling the evolution of hemodynamic, thermal, ionic, and other disturbances in AIS, conceived as a multifaceted tool for hypothesis building and testing pathologic scenarios

Comprehensive metabolic investigation of dopamine reuptake inhibitor HDMP-28 in equine liver microsomes and Cunninghamella elegans for doping control.

A dopamine reuptake inhibitor is a type of medication or substance that works by blocking the reuptake of dopamine in the brain. Dopamine reuptake inhibitors offer multiple effects, including increased alertness, improved mood, and therapeutic potential for conditions like depression, ADHD, and Parkinson's disease. HDMP-28, or methylnaphthidate, is a potent synthetic stimulant from the phenyltropane class. It surpasses methylphenidate in both dopamine reuptake inhibition and half-life. As a dopamine reuptake inhibitor, it boosts dopamine levels by hindering reuptake into nerve cells, resulting in heightened stimulation and increased energy. In order to comprehensively address both the tangible and potential repercussions of the unauthorized utilization of the aforementioned substance in sports, it is imperative to establish analytical methodologies for the identification of the parent drug and its primary metabolites. Additionally, a comprehensive analysis of the metabolic characteristics of HDMP-28 in both human and animal subjects has yet to be published. This study explores the metabolic conversion of HDMP-28 mediated by equine liver microsomes and Cunninghamella elegans. An extraction and detection method was developed, optimized, and validated for doping assessment in equine urine and plasma. Liquid chromatography-high-resolution mass spectrometry was employed to determine metabolite structures. The study identified 31 (22 phase I and 9 phase II) metabolites of HDMP-28, including hydroxylated, hydrogenated, and hydrolyzed analogs. Glucuronic acid-conjugated metabolites were also detected. This manuscript describes metabolites based on the in vitro studies, which might not be the same in vivo. These findings aid in the detection and understanding of the illicit use of HDMP-28 in equestrian sports.

How Do Molecular Systems Engineering Scientists Frame the Ethics of Their Research?

Background There are intense discussions about the ethical and societal implications of biomedical engineering, but little data to suggest how scientists think about the ethics of their work. The aim of this study is to describe how scientists frame the ethics of their research, with a focus on the field of molecular systems engineering. Methods Semi-structured qualitative interviews were conducted during 2021–2022, as part of a larger study. This analysis includes a broad question about how participants view ethics as related to their work, with follow up probes about the topics they consider most important. Interviews were transcribed, inductively coded by two researchers to consensus, and analyzed thematically. Results Twenty-four scientists participated in the study. Interviewees hold positions as professors, principal investigators, and senior staff researchers in universities or research institutes in the United States and Europe. Among those scientists who reported reflecting on ethical considerations in their work, many equated ethics with research ethics topics (e.g., safety, replicability), or with regulation and guidelines. Participants expressed the view that ethical issues are primarily relevant for clinical trials of bioengineered products, or for those working with animal or human subjects. Scientists described their research as “too early” or “not examining anything living” with regard to ethical reflection. Finally, many felt that ethics is seen as territory for experts and therefore beyond scientists’ competencies. Conclusions Molecular systems engineering scientists currently focus on regulatory aspects as the framework for their ethical analyses. They describe using a framework to define when life arises, as a means to determine when further ethical engagement is warranted. Further research is needed to investigate how scientists relate to the ethics of their scientific work, and build consensus around concepts of life, autonomous behavior, and physiological relevance of bioengineered systems.