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PurposeJustice, as a relative concept, can be achieved through several methods and practices. Among these, Alternative Dispute Resolution (ADR) stands out as an effective mechanism to resolve disputes, ensuring justice with rigor. In the village of Hulhulia, Bangladesh, ADR has been practiced for nearly 200 years and has proven to be highly beneficial for the community. This study examines the roles, challenges and impacts of ADR in Hulhulia.Design/methodology/approachThis study employs a quantitative approach to collect data from justice-seekers and assess their perceptions. A census survey conducted through structured questionnaire to get the perception of roles, impacts and challenges of ADR from the respondents.FindingsThe present study has found significant associations of the roles and challenges of ADR with impacts on the community. ADR has been instrumental in reducing complexities, ensuring access to justice, fostering peace and harmony and strengthening social capital. These positive outcomes have increased both individual satisfaction and community well-being. Despite facing several challenges, the ADR practices in Hulhulia continue to provide significant benefits to the people, offering a cost-effective and efficient way of resolving disputes. ADR practices in Hulhulia have facilitated the proper execution of justice and strengthen community bonds.Originality/valueThis successful execution demonstrates the potential for recreating this ADR model in other regions to achieve such effectiveness. The study indicates the importance of ADR not only as a tool for justice but also as a method to build inclusive and harmonious communities.

Drug-induced pruritus is a common problem in daily medical practice. Many drugs can cause pruritus after systemic or topical administration, but often the exact mechanism underlying the pathogenesis of itching caused by drugs remains unclear. Therefore, the diagnosis and treatment of drug-induced pruritus are challenging. In the present review, the current knowledge of the most common medications inducing itch with or without skin rash and their underlying mechanisms is summarized. Opioids can cause pruritus, especially if they are administered intrathecally. Some antineoplastic agents can frequently cause intense pruritus due to immune-related cutaneous reactions (immune checkpoint inhibitors) or via triggering hypersensitivity reactions (taxanes) in cancer patients. Recently, it was found that MAS-related G protein-coupled receptor X2 (MRGPRX2), expressed on mast cells in humans, is responsible for drug-induced non-histaminergic pruritus and pseu-doallergic reactions.

Design science research (DSR) is a legitimate research paradigm in the discipline of information systems (IS). One prominent DSR method is Action Design Research (ADR). The purpose of this paper is to evaluate the ADR method based on empirical experiences from a research project. We have found that the ADR method is highly relevant to an applied discipline such as IS. It creates a bridge between the organisational perspective and the technical perspective of the IT artefact. Moreover, the ADR method supports the dual mission of developing theory and producing knowledge that supports IS practitioners. The findings also include empirical evidence pointing towards a lack of prescriptive guidance with respect to the challenges such as: how to identify appropriate evaluation strategies, how to identify the abstraction mechanisms required to move from the specific-and-unique to the generic-and-abstract, and how to formulate design principles. Although we found adequate support at the macro level, the ADR method needs more detailed support for operationalisation in practice. To address this issue, we propose a number of guidelines that either seek to improve the ADR method or support those who apply ADR.

Alternative Dispute Resolution (ADR) has gained popularity as a widely recognized method for resolving disputes globally. In Bangladesh, the Hulhulia Social Development Council (HSDC) has been practicing ADR practices for over 200 years, playing a significant role in fostering peace and harmony. In the village of Hulhulia. HSDC, a democratically elected body comprising 23 members, operates under a legal framework to ensure fairness and transparency in the ADR process. The village is divided into 12 paras (zones), each electing representatives who facilitate the ADR process. The ADR practice in HSDC begins with family-level negotiations, progresses to para representatives, and lastly in HSDC hearings. This method has been remarkably successful, as this process is contributing to reducing the overload of formal justice system, indicating a high level of community satisfaction. ADR in Hulhulia strengthens social bonds, repairs harm to victims and the community, ensures accessibility, and reduces complexity. It also creates peace, harmony, and social capital within the community. However, challenges such as limited logistical support, insufficient skilled manpower, and political interference complicate this process in some way. Despite these challenges, ADR in Hulhulia remains an affordable, efficient, legitimate, and participatory system. Key recommendations to enhance its effectiveness of this process include raising community awareness, updating legal frameworks, and mitigating political influences. The ADR model in Hulhulia exemplifies a useful approach for other rural areas, promoting inclusivity, peace, and community well-being, and highlighting its potential to address disputes effectively while strengthening social bonds.

Adverse drug reactions (ADRs), which are the phenotypic manifestations of clinical drug toxicity in humans, are a major concern in precision clinical medicine. A comprehensive evaluation of ADRs is helpful for unbiased supervision of marketed drugs and for discovering new drugs with high success rates. In current practice, drug safety evaluation is often oversimplified to the occurrence or nonoccurrence of ADRs. Given the limitations of current qualitative methods, there is an urgent need for a quantitative evaluation model to improve pharmacovigilance and the accurate assessment of drug safety. In this study, we developed a mathematical model, namely the Adverse Drug Reaction Classification System (ADReCS) severity-grading model, for the quantitative characterization of ADR severity, a crucial feature for evaluating the impact of ADRs on human health. The model was constructed by mining millions of real-world historical adverse drug event reports. A new parameter called Severity_score was introduced to measure the severity of ADRs, and upper and lower score boundaries were determined for 5 severity grades. The ADReCS severity-grading model exhibited excellent consistency (99.22%) with the expert-grading system, the Common Terminology Criteria for Adverse Events. Hence, we graded the severity of 6277 standard ADRs for 129,407 drug-ADR pairs. Moreover, we calculated the occurrence rates of 6272 distinct ADRs for 127,763 drug-ADR pairs in large patient populations by mining real-world medication prescriptions. With the quantitative features, we demonstrated example applications in systematically elucidating ADR mechanisms and thereby discovered a list of drugs with improper dosages. In summary, this study represents the first comprehensive determination of both ADR severity grades and ADR frequencies. This endeavor establishes a strong foundation for future artificial intelligence applications in discovering new drugs with high efficacy and low toxicity. It also heralds a paradigm shift in clinical toxicity research, moving from qualitative description to quantitative evaluation.

Design research (DR) positions information technology artifacts at the core of the Information Systems discipline. However, dominant DR thinking takes a technological view of the IT artifact, paying scant attention to its shaping by the organizational context. Consequently, existing DR methods focus on building the artifact and relegate evaluation to a subsequent and separate phase. They value technological rigor at the cost of organizational relevance, and fail to recognize that the artifact emerges from interaction with the organizational context even when its initial design is guided by the researchers' intent. We propose action design research (ADR) as a new DR method to address this problem. ADR reflects the premise that IT artifacts are ensembles shaped by the organizational context during development and use. The method conceptualizes the research process as containing the inseparable and inherently interwoven activities of building the IT artifact, intervening in the organization, and evaluating it concurrently. The essay describes the stages of ADR and associated principles that encapsulate its underlying beliefs and values. We illustrate ADR through a case of competence management at Volvo IT.

Fentanyl is a synthetic opioid analgesic widely used in perioperative medicine due to its high analgesic potency and short duration of action. Previous studies suggest that the analgesic and anesthetic effects of fentanyl may be associated with endogenous catecholamine levels. This study aimed to evaluate the relationship between fentanyl's analgesic potency and anesthesia duration and endogenous levels of adrenaline (ADR) and noradrenaline (NDR) in rats, as well as changes in oxidative stress and inflammation markers including malondialdehyde (MDA), total glutathione (tGSH), and interleukin-6 (IL-6). Three groups of six rats each were formed: an intact group receiving fentanyl, an intact group treated with metyrosine, and an adrenalectomized group receiving fentanyl. Fentanyl was administered at doses of 2, 15, 30, and 75 µg/kg, and anesthesia duration was recorded following intraperitoneal injection. Analgesic activity was assessed by measuring pain threshold using the paw pressure method, and immobility in the supine position was evaluated as an observational parameter. ADR, NDR, MDA, tGSH, and IL-6 levels were biochemically measured in blood and tissue samples. Fentanyl produced analgesic effects in all experimental groups. However, no distinct anesthetic effect sufficient for surgical procedures was observed. Although the durations of immobility in the supine position were recorded, these observations were not evaluated as a direct measure of anesthetic duration. Different doses of fentanyl did not lead to significant alterations in oxidative stress parameters, antioxidant capacity, or anti-inflammatory cytokine levels across the groups. In conclusion, although the analgesic effect of fentanyl increased in a dose-dependent manner, it was found to be independent of serum ADR and NDR levels. High-dose fentanyl (75 µg/kg) did not induce anesthesia and did not significantly affect oxidative stress markers (MDA, tGSH) or IL-6 levels. The increase in MDA and the decrease in tGSH observed in the absence of adrenal hormones support their indirect antioxidant role. Overall, the findings indicate that fentanyl modulates catecholamine responses depending on dose and hormonal status, while its analgesic effect appears to be primarily mediated through µ-opioid receptor activation.

PurposeAction design research (ADR) has become widely accepted as a prominent research method within information systems when managing design-oriented research projects. One purpose of the ADR method is to provide methodological guidance for the building of IT artefacts. However, several scholars have reported a lack of guidance of method support at the micro level. This article aims to complement the macro level of the ADR method by integrating prescriptive method support at the micro level.Design/methodology/approachA qualitative approach including direct content analysis. An empirical ADR project was analysed in order to identify method support that could be integrated into the ADR method.FindingsMethod support at the micro level was identified for all the stages of the ADR method. The method support consists of procedural support, guiding concepts, and various techniques for the documentation of project tasks stated in the ADR method.Research limitations/implicationsThe contribution to theory consists of aspects concerning the integration of macro and micro levels: relationships between normative and prescriptive support, continuous focus shifts, and method completeness.Practical implicationsThe contribution to practice consists of explicit suggestions for method support that could be integrated into the ADR method.Originality/valueThis study extends previously provided knowledge by offering empirical evidence concerning theoretical constructions consisting of explicit relationships between ADR tasks and integrated method support, and elaboration on the integration of macro and micro levels.

Background: Multidrug resistance (MDR) can develop in cancer cells after treatment with anticancer drugs, mainly due to the overexpression of the ATP-binding cassette (ABC) transporters. We analyzed the ability of two pungent-tasting alkaloids—capsaicin and piperine from Capsicum frutescens and Piper nigrum, respectively—to reverse multidrug resistance in the cancer cell lines Caco-2 and CEM/ADR 5000, which overexpress P-glycoprotein (P-gp) and other ABC transporters. Methods: The MTT assay was first used to determine the cytotoxicity of doxorubicin, the alkaloids, and digitonin alone, and then their combinations. Furthermore, rhodamine (Rho) 123 and calcein-AM were used to detect the effects of alkaloids on the activity of P-gp. Results: Capsaicin and piperine synergistically enhanced the cytotoxicity of doxorubicin in Caco-2 and CEM/ADR 5000 cells. Furthermore, capsaicin and piperine increased the intracellular accumulation of the fluorescent P-glycoprotein (P-gp) substrates rhodamine and calcein and inhibited their efflux from the MDR cell lines. Conclusion: Our study has demonstrated that capsaicin and piperine are P-gp substrates and have potential chemosensitizing activity, which might be interesting for the development of novel modulators of multidrug resistance.

Human Cytochrome P450 (CYP) enzymes constitute a superfamily of membrane-bound hemoproteins that are responsible for the metabolism of a wide variety of clinically, physiologically, and toxicologically important compounds. These heme-thiolate monooxygenases play a pivotal role in the detoxification of xenobiotics, participating in the metabolism of many structurally diverge compounds. This short-review is intended to provide a summary on the major roles of CYPs in Phase I xenobiotic metabolism. The manuscript is focused on eight main topics that include the most relevant aspects of past and current CYP research. Initially, (I) a general overview of the main aspects of absorption, distribution, metabolism, and excretion (ADME) of xenobiotics are presented. This is followed by (II) a background overview on major achievements in the past of the CYP research field. (III) Classification and nomenclature of CYPs is briefly reviewed, followed by (IV) a summary description on CYP’s location and function in mammals. Subsequently, (V) the physiological relevance of CYP as the cornerstone of Phase I xenobiotic metabolism is highlighted, followed by (VI) reviewing both genetic determinants and (VI) nongenetic factors in CYP function and activity. The last topic of the review (VIII) is focused on the current challenges of the CYP research field.