Health issues of young adults with hearing loss or deafness: A basis for the development of a chatbot.

BACKGROUND: The loss of hearing and thus communication affects the well-being of millions of people worldwide. Digital tools for coping with everyday life are becoming increasingly important and can have a positive impact on health literacy, especially among young adults. This raises the question of which issues such apps should specifically address in order to meet the needs of young adults with hearing loss or deafness. METHODS: The aim was to identify the health issues of young adults (aged 18-28 years) with hearing loss or deafness in order to derive specific recommendations for a conversational agent (chatbot). A multiple embedded case study design consisting of chat interviews (n = 8) and an online-based expert survey (n = 14) was used. RESULTS: The central phenomenon focuses on "The sense of belonging and feeling well in spite of hearing loss", which is influenced by two main categories: a. the ability to be oneself despite one's vulnerability; b. the desire to be strong despite one's vulnerability. Important health issues include depression, drug use, diet, exercise, isolation due to COVID measures and HIV prophylaxis. CONCLUSION: Written information must be provided in simple and accessible language supported by images and symbols. Conversation agents developed to support people with hearing impairment should be easy to install and self-explanatory to use.

Connected health services: Health professionals' role as seen by parents of a child with inflammatory bowel disease.

Objective: Connected health services will change the scope of health professionals' roles. It is unclear how parents of a child with inflammatory bowel disease perceive the role of health professionals in relation to these services and what their experiences and needs are. The purpose of this study is to highlight parents' experiences with this role. Furthermore, it aims to outline the fundamental needs that parents have regarding this role, in order to promote audience-specific access to these services and derive overarching action measures. Methods: Fourteen parents of children with inflammatory bowel disease from seven different clinics in Switzerland were recruited. Between August 2022 and February 2023, these parents were interviewed in semi-structured interviews. The interviews were analyzed using a structured qualitative content analysis. Results: Five main categories were identified, with few parents having prior experience with the role of health professionals in this area. Parents saw health professionals in the role of gatekeepers, transferers of knowledge and in a supporting function for these services. From the parents' perspective, health professionals should recognize the limitations of these services and use them as a complement to standard treatment. Conclusion: The role of health professionals in relation to connected health services needs to be adapted from the parents' perspective. To meet the needs of parents, health professionals must have access to these services. In addition to health professionals' personal engagement with these services, institutional and policy changes, as well as research on role development from the perspective of other stakeholders are needed.

Parents' experiences of family and daily life after their child's stay in the pediatric intensive care unit: a qualitative descriptive study.

INTRODUCTION: The stay of a critically ill child in a pediatric intensive care unit (PICU) is a significant experience for the family. Thus far, little is known regarding the impact of this stay on parents and their healthy children for whom no continuous aftercare services are offered. This study aimed to capture the post-stay experience and needs of parents after this traumatic event so that they could return to family and everyday life. METHODS: This qualitative descriptive study was conducted in collaboration with four pediatric intensive care units in Switzerland. It included parents whose children had fully recovered after a stay and who did not require continuous medical follow-up. All children were hospitalized in the PICU for at least 48 h. Data were collected through narrative pairs (n = 6) and individual interviews (n = 8). Interviews were audio recorded, transcribed, coded inductively according to Saldaña, and analyzed. RESULTS: The results showed three related phases that influence each other to restore normality in daily life: Trust and inclusion in the treatment process during the stay (1), processing after the stay (2), and returning to everyday life (3). CONCLUSION: Follow-up meetings should be available to all parents whose children have been hospitalized in the PICU. In particular, it should also be available to parents whose children have fully recovered and no longer have any medical disabilities.

Impact of 2-hydroxypropyl-ß-cyclodextrin inclusion complex formation on dopamine receptor-ligand interaction - A case study.

The octanol-water distribution coefficient (logP), used as a measure of lipophilicity, plays a major role in the drug design and discovery processes. While average logP values remain unchanged in approved oral drugs since 1983, current medicinal chemistry trends towards increasingly lipophilic compounds that require adapted analytical workflows and drug delivery systems. Solubility enhancers like cyclodextrins (CDs), especially 2-hydroxypropyl-ß-CD (2-HP-ß-CD), have been studied in vitro and in vivo investigating their ADMET (adsorption, distribution, metabolism, excretion and toxicity)-related properties. However, data is scarce regarding the applicability of CD inclusion complexes (ICs) in vitro compared to pure compounds. In this study, dopamine receptor (DR) ligands were used as a case study, utilizing a combined in silico/in vitro workflow. Media-dependent solubility and IC stoichiometry were investigated using HPLC. NMR was used to observe IC formation-caused chemical shift deviations while in silico approaches utilizing basin hopping global minimization were used to propose putative IC binding modes. A cell-based in vitro homogeneous time-resolved fluorescence (HTRF) assay was used to quantify ligand binding affinity at the DR subtype 2 (D2R). While all ligands showed increased solubility using 2-HP-ß-CD, they differed regarding IC stoichiometry and receptor binding affinity. This case study shows that IC-formation was ligand-dependent and sometimes altering in vitro binding. Therefore, IC complex formation can't be recommended as a general means of improving compound solubility for in vitro studies as they may alter ligand binding.

Triphenyltin isoselenocyanate: a novel nuclear retinoid X receptor ligand with antiproliferative and cytotoxic properties in cell lines derived from human breast cancer.

Several commercially available triorganotin compounds were previously found to function as agonist ligands for nuclear retinoid X receptor (RXR) molecules. Triphenyltin isoselenocyanate (TPT-NCSe), a novel selenium atom containing a derivative of triorganotin origin, was found to represent a new cognate bioactive ligand for RXRs. TPT-NCSe displayed a concentration- and time-dependent decrease in the cell viability in both human breast carcinoma MCF-7 (estrogen receptor positive) and MDA­MB­231 (triple negative) cell lines. Reactive oxygen species levels generated in response to TPT-NCSe were significantly higher in both carcinoma cell lines treated with TPT-NCSe when compared to mock-treated samples. Treatment with 500 nM TPT-NCSe caused a decrease in SOD1 and increased SOD2 mRNA in MCF-7 cells. The levels of SOD2 mRNA were more increased following the treatment with TPT-NCSe along with 1 µM all-trans retinoic acid (AtRA) in MCF-7 cells. An increased superoxide dismutase SOD1 and SOD2 mRNA levels were also detected in combination treatment of 500 nM TPT-NCSe and 1 µM AtRA in TPT-NCSe-treated MDA-MB-231 cells. The data have also shown that TPT-NCSe induces apoptosis via a caspase cascade triggered by the mitochondrial apoptotic pathway. TPT-NCSe modulates the expression levels of apoptosis­related proteins, Annexin A5, Bcl­2 and BAX family proteins, and finally, it enhances the expression levels of its cognate nuclear receptor subtypes RXRalpha and RXRbeta.

The TiHoCL panel for canine lymphoma: a feasibility study integrating functional genomics and network biology approaches for comparative oncology targeted NGS panel design.

Targeted next-generation sequencing (NGS) enables the identification of genomic variants in cancer patients with high sensitivity at relatively low costs, and has thus opened the era to personalized human oncology. Veterinary medicine tends to adopt new technologies at a slower pace compared to human medicine due to lower funding, nonetheless it embraces technological advancements over time. Hence, it is reasonable to assume that targeted NGS will be incorporated into routine veterinary practice in the foreseeable future. Many animal diseases have well-researched human counterparts and hence, insights gained from the latter might, in principle, be harnessed to elucidate the former. Here, we present the TiHoCL targeted NGS panel as a proof of concept, exemplifying how functional genomics and network approaches can be effectively used to leverage the wealth of information available for human diseases in the development of targeted sequencing panels for veterinary medicine. Specifically, the TiHoCL targeted NGS panel is a molecular tool for characterizing and stratifying canine lymphoma (CL) patients designed based on human non-Hodgkin lymphoma (NHL) research outputs. While various single nucleotide polymorphisms (SNPs) have been associated with high risk of developing NHL, poor prognosis and resistance to treatment in NHL patients, little is known about the genetics of CL. Thus, the ~100 SNPs featured in the TiHoCL targeted NGS panel were selected using functional genomics and network approaches following a literature and database search that shielded ~500 SNPs associated with, in nearly all cases, human hematologic malignancies. The TiHoCL targeted NGS panel underwent technical validation and preliminary functional assessment by sequencing DNA samples isolated from blood of 29 lymphoma dogs using an Ion Torrent™ PGM System achieving good sequencing run metrics. Our design framework holds new possibilities for the design of similar molecular tools applied to other diseases for which limited knowledge is available and will improve drug target discovery and patient care.

Structural and clinical characterization of CYP11B2 inhibition by dexfadrostat phosphate.

Aldosterone synthase (CYP11B2) represents a promising drug target because its genetic dysregulation is causally associated with cardiovascular disease, its autonomous activity leads to primary aldosteronism, and its deficiency leads to salt wasting syndromes. The serendipitous discovery that the dextro-rotatory stereoisomer of the racemic aromatase (CYP19A1) inhibitor CGS16949A mediates potent CYP11B2 inhibition led to the purification and clinical development of dexfadrostat phosphate. To characterize the pharmacophore of dexfadrostat phosphate, structure-based enzyme coordination with CYP11B2, CYP11B1 and CYP19A1 was combined with steroid turnover upon in vitro and clinical treatment. Dexfadrostat, but not its 5S-enantiomer (5S-fadrozole), precisely coordinates with the catalytic heme moiety in the space of the CYP11B2 substrate binding pocket forming a tight and stable complex. Conversely, neither rigid nor flexible docking led to a plausible coordination geometry for dexfadrostat in steroid 11ß-hydroxylase (CYP11B1 - orthologue to CYP11B2) or in CYP19A1. The inhibitory preference of dexfadrostat was confirmed in vitro using an adrenal cortex-derived cell line. Dexfadrostat phosphate treatment of healthy subjects in the context of a clinical phase 1 study led to a dose-dependent decrease in urinary aldosterone secretion, accompanied by an increase in urinary corticosterone and deoxycorticosterone metabolites. Increased urinary corticosterone metabolites are indicative of CYP11B2 (18-oxidase) inhibition with clinical features reminiscent of patients with inborn corticosterone methyloxidase type II deficiency. An off-target effect on CYP19A1 was not observed as indicated by no clinical changes in testosterone and estradiol levels. Therefore, dexfadrostat exhibits the ideal structural features for binding and catalytic inhibition of CYP11B2 but not CYP11B1. Clinically, treatment with dexfadrostat phosphate leads to suppression of aldosterone levels by inhibiting predominantly one or both final CYP11B2-mediated reactions.

Digital Health for Migrants, Ethnic and Cultural Minorities and the Role of Participatory Development: A Scoping Review.

Digital health interventions (DHIs) are increasingly used to address the health of migrants and ethnic minorities, some of whom have reduced access to health services and worse health outcomes than majority populations. This study aims to give an overview of digital health interventions developed for ethnic or cultural minority and migrant populations, the health problems they address, their effectiveness at the individual level and the degree of participation of target populations during development. We used the methodological approach of the scoping review outlined by Tricco. We found a total of 2248 studies, of which 57 were included, mostly using mobile health technologies, followed by websites, informational videos, text messages and telehealth. Most interventions focused on illness self-management, mental health and wellbeing, followed by pregnancy and overall lifestyle habits. About half did not involve the target population in development and only a minority involved them consistently. The studies we found indicate that the increased involvement of the target population in the development of digital health tools leads to a greater acceptance of their use.

Identification of Novel ß-Tubulin Inhibitors Using a Combined In Silico/In Vitro Approach.

Due to their potential as leads for various therapeutic applications, including as antimitotic and antiparasitic agents, the development of tubulin inhibitors offers promise for drug discovery. In this study, an in silico pharmacophore-based virtual screening approach targeting the colchicine binding site of ß-tubulin was employed. Several structure- and ligand-based models for known tubulin inhibitors were generated. Compound databases were virtually screened against the models, and prioritized hits from the SPECS compound library were tested in an in vitro tubulin polymerization inhibition assay for their experimental validation. Out of the 41 SPECS compounds tested, 11 were active tubulin polymerization inhibitors, leading to a prospective true positive hit rate of 26.8%. Two novel inhibitors displayed IC50 values in the range of colchicine. The most potent of which was a novel acetamide-bridged benzodiazepine/benzimidazole derivative with an IC50 = 2.9 µM. The screening workflow led to the identification of diverse inhibitors active at the tubulin colchicine binding site. Thus, the pharmacophore models show promise as valuable tools for the discovery of compounds and as potential leads for the development of cancer therapeutic agents.

Virtual screening and biological evaluation to identify pharmaceuticals potentially causing hypertension and hypokalemia by inhibiting steroid 11ß-hydroxylase.

Several drugs were found after their market approval to unexpectedly inhibit adrenal 11ß-hydroxylase (CYP11B1)-dependent cortisol synthesis. Known side-effects of CYP11B1 inhibition include hypertension and hypokalemia, due to a feedback activation of adrenal steroidogenesis, leading to supraphysiological concentrations of 11-deoxycortisol and 11-deoxycorticosterone that can activate the mineralocorticoid receptor. This results in potassium excretion and sodium and water retention, ultimately causing hypertension. With the risk known but usually not addressed in preclinical evaluation, this study aimed to identify drugs and drug candidates inhibiting CYP11B1. Two conceptually different virtual screening methods were combined, a pharmacophore based and an induced fit docking approach. Cell-free and cell-based CYP11B1 activity measurements revealed several inhibitors with IC50 values in the nanomolar range. Inhibitors include retinoic acid metabolism blocking agents (RAMBAs), azole antifungals, α2-adrenoceptor ligands, and a farnesyltransferase inhibitor. The active compounds share a nitrogen atom embedded in an aromatic ring system. Structure activity analysis identified the free electron pair of the nitrogen atom as a prerequisite for the drug-enzyme interaction, with its pKa value as an indicator of inhibitory potency. Another important parameter is drug lipophilicity, exemplified by etomidate. Changing its ethyl ester moiety to a more hydrophilic carboxylic acid group dramatically decreased the inhibitory potential, most likely due to less efficient cellular uptake. The presented work successfully combined different in silico and in vitro methods to identify several previously unknown CYP11B1 inhibitors. This workflow facilitates the identification of compounds that inhibit CYP11B1 and therefore pose a risk for inducing hypertension and hypokalemia.

Novel thiazolopyridine derivatives of diflapolin as dual sEH/FLAP inhibitors with improved solubility.

Inflammatory responses are orchestrated by a plethora of lipid mediators, and perturbations of their biosynthesis or degradation hinder resolution and lead to uncontrolled inflammation, which contributes to diverse pathologies. Small molecules that induce a switch from pro-inflammatory to anti-inflammatory lipid mediators are considered valuable for the treatment of chronic inflammatory diseases. Commonly used non-steroidal anti-inflammatory drugs (NSAIDs) are afflicted with side effects caused by the inhibition of beneficial prostanoid formation and redirection of arachidonic acid (AA) into alternative pathways. Multi-target inhibitors like diflapolin, the first dual inhibitor of soluble epoxide hydrolase (sEH) and 5-lipoxygenase-activating protein (FLAP), promise improved efficacy and safety but are confronted by poor solubility and bioavailability. Four series of derivatives bearing isomeric thiazolopyridines as bioisosteric replacement of the benzothiazole core and two series additionally containing mono- or diaza-isosteres of the phenylene spacer were designed and synthesized to improve solubility. The combination of thiazolo[5,4-b]pyridine, a pyridinylen spacer and a 3,5-Cl2-substituted terminal phenyl ring (46a) enhances solubility and FLAP antagonism, while preserving sEH inhibition. Moreover, the thiazolo[4,5-c]pyridine derivative 41b, although being a less potent sEH/FLAP inhibitor, additionally decreases thromboxane production in activated human peripheral blood mononuclear cells. We conclude that the introduction of nitrogen, depending on the position, not only enhances solubility and FLAP antagonism (46a), but also represents a valid strategy to expand the scope of application towards inhibition of thromboxane biosynthesis.

Dopamine Receptor Ligand Selectivity-An In Silico/In Vitro Insight.

Different dopamine receptor (DR) subtypes are involved in pathophysiological conditions such as Parkinson's Disease (PD), schizophrenia and depression. While many DR-targeting drugs have been approved by the U.S. Food and Drug Administration (FDA), only a very small number are truly selective for one of the DR subtypes. Additionally, most of them show promiscuous activity at related G-protein coupled receptors, thus suffering from diverse side-effect profiles. Multiple studies have shown that combined in silico/in vitro approaches are a valuable contribution to drug discovery processes. They can also be applied to divulge the mechanisms behind ligand selectivity. In this study, novel DR ligands were investigated in vitro to assess binding affinities at different DR subtypes. Thus, nine D2R/D3R-selective ligands (micro- to nanomolar binding affinities, D3R-selective profile) were successfully identified. The most promising ligand exerted nanomolar D3R activity (Ki = 2.3 nM) with 263.7-fold D2R/D3R selectivity. Subsequently, ligand selectivity was rationalized in silico based on ligand interaction with a secondary binding pocket, supporting the selectivity data determined in vitro. The developed workflow and identified ligands could aid in the further understanding of the structural motifs responsible for DR subtype selectivity, thus benefitting drug development in D2R/D3R-associated pathologies such as PD.

Intercultural communication in long-term care: The perspective of relatives from Switzerland.

INTRODUCTION: Due to globalization and the resulting diversity intercultural communication is increasingly coming to the fore. In addition, long-term care is mainly staffed with caregivers who have a migration background, which makes successful intercultural communication all the more important. Therefore, the aim of the present study was to define recommendations by interviewing relatives which can be used to promote intercultural communication in long-term care with regard to relationship building. METHOD: A qualitative explorative content analysis, which follows the content-structuring method with an inductive approach. The semi-structured guided individual interviews were conducted with relatives (n = 14) of residents from two retirement centers in Switzerland. RESULTS: Four categories were defined: "Perceive communication as a need", "Consider the desire for recognition of relatives", "Promote readiness of caregivers", and "Know opportunities and challenges in intercultural communication". CONCLUSION: Intercultural communication means being aware of the significance of culture and one's own origins in order to recognize the peculiarities of the counterpart and to interact sensitively with them. Relatives want to be actively involved when nurses reach their limits in communication and interaction. Relatives want safe care that is based on empathy. When nurses show concern towards others in a person-centered way and are aware of where they come from, this can promote trust and contribute significantly to supporting communication and interaction between cultures.

Resources and resilience factors: How advanced practice nurses can promote resilience in hearing and visually impaired people - A grounded theory perspective from Switzerland.

BACKGROUND: There is an increase in hearing and visual impairments worldwide. Those affected have a reduced ability to participate in social contacts, mobility, and access to information. Until now, there have been no recommendations for Advanced Practice Nurses (APNs) in Switzerland to support this group of people in the autonomous organization of everyday life in their own homes. OBJECTIVE: The aim of the study was to understand how people integrate their dual hearing and visual impairments into everyday life to derive recommendations for APNs to support individuals to manage their daily lives. METHODS: Following the constructivist approach of grounded theory, guided interviews and a questionnaire survey with hearing and visually impaired persons (n = 46) over 70 years of age on independent daily living were conducted (concurrent embedded strategy). In addition, demographic data on age, gender, living situation, and use of assistive devices were analyzed. FINDINGS: Based on the results, a communication-based dynamic resilience model (CoRes) was developed. This article represents the third phase of the three-stage-model. Integration of altered hearing depends on resources and risk factors. CONCLUSIONS: Advanced practice nurses can use recommendations from this research to actively help individuals and their families build resilience.

A qualitative study of the sources of chronic obstructive pulmonary disease-related emotional distress.

OBJECTIVE: The aim of this study is to identify the sources of illness-related emotional distress from the perspective of individuals living with mild to severe chronic obstructive pulmonary disease (COPD). METHODS: A qualitative study design with purposive sampling was applied at a Swiss University Hospital. Eleven interviews were conducted with individuals who suffered from COPD. To analyze data, framework analysis was used, guided by the recently presented model of illness-related emotional distress. RESULTS: Six main sources for COPD-related emotional distress were identified: physical symptoms, treatment, restricted mobility, restricted social participation, unpredictability of disease course and COPD as stigmatizing disease. Additionally, life events, multimorbidity and living situation were found to be sources of non-COPD-related distress. Negative emotions ranged from anger, sadness, and frustration to desperation giving rise to the desire to die. Although most patients experience emotional distress regardless of the severity of COPD, the sources of distress appear to have an individual manifestation. DISCUSSION: There is a need for a careful assessment of emotional distress among patients with COPD at all stages of the disease to provide patient-tailored interventions.

Combination of In Silico and In Vitro Screening to Identify Novel Glutamate Carboxypeptidase II Inhibitors.

Glutamate carboxypeptidase II (GCPII) is a metalloprotease implicated in neurological diseases and prostate oncology. While several classes of potent GCPII-specific inhibitors exist, the development of novel active scaffolds with different pharmacological profiles remains a challenge. Virtual screening followed by in vitro testing is an effective means for the discovery of novel active compounds. Structure- and ligand-based pharmacophore models were created based on a dataset of known GCPII-selective ligands. These models were used in a virtual screening of the SPECS compound library (∼209.000 compounds). Fifty top-scoring virtual hits were further experimentally tested for their ability to inhibit GCPII enzymatic activity in vitro. Six hits were found to have moderate to high inhibitory potency with the best virtual hit, a modified xanthene, inhibiting GCPII with an IC50 value of 353 ± 24 nM. The identification of this novel inhibitory scaffold illustrates the applicability of pharmacophore-based modeling for the discovery of GCPII-specific inhibitors.

Highly potent and selective 5-lipoxygenase inhibition by new, simple heteroaryl-substituted catechols for treatment of inflammation.

5-Lipoxygenase (LO) catalyzes the first steps in the formation of pro-inflammatory leukotrienes (LT) that are pivotal lipid mediators contributing to allergic reactions and inflammatory disorders. Based on its key role in LT biosynthesis, 5-LO is an attractive drug target, demanding for effective and selective inhibitors with efficacy in vivo, which however, are still rare. Encouraged by the recent identification of the catechol 4-(3,4-dihydroxyphenyl)dibenzofuran 1 as 5-LO inhibitor, simple structural modifications were made to yield even more effective and selective catechol derivatives. Within this new series, the two most potent compounds 3,4-dihydroxy-3'-phenoxybiphenyl (6b) and 2-(3,4-dihydroxyphenyl)benzo[b]thiophene (6d) potently inhibited human 5-LO in cell-free (IC506b and 6d = 20 nM) and cell-based assays (IC506b = 70 nM, 6d = 60 nM). Inhibition of 5-LO was reversible, unaffected by exogenously added substrate arachidonic acid, and not primarily mediated via radical scavenging and antioxidant activities. Functional 5-LO mutants expressed in HEK293 cells were still prone to inhibition by 6b and 6d, and docking simulations revealed distinct binding of the catechol moiety to 5-LO at an allosteric site. Analysis of 5-LO nuclear membrane translocation and intracellular Ca2+ mobilization revealed that these 5-LO-activating events are hardly affected by the catechols. Importantly, the high inhibitory potency of 6b and 6d was confirmed in human blood and in a murine zymosan-induced peritonitis model in vivo. Our results enclose these novel catechol derivatives as highly potent, novel type inhibitors of 5-LO with high selectivity and with marked effectiveness under pathophysiological conditions.

Ableism, Human Rights, and the COVID-19 Pandemic: Healthcare-Related Barriers Experienced by Deaf People in Aotearoa New Zealand.

The COVID-19 pandemic significantly affected global healthcare access and exacerbated pre-pandemic structural barriers. Literature on disabled people's experiences accessing healthcare is limited, with even less framing healthcare access as a human rights issue. This study documents and critically analyses Deaf people's healthcare access experiences in Aotearoa New Zealand during the COVID-19 pandemic. Eleven self-identified Deaf individuals participated in semi-structured videoconferencing interviews. Discourse analysis was applied to participant narratives with discourses juxtaposed against a human rights analysis. Barriers influencing healthcare access included: (1) the inability of healthcare providers to communicate appropriately, including a rigid adherence to face mask use; (2) cultural insensitivity and limited awareness of Deaf people's unique needs; and (3) the impact of ableist assumptions and healthcare delaying care. Barriers to healthcare access represent consecutive breaches of rights guaranteed under the United Nations Convention on the Rights of Persons with Disabilities (CRPD). Such breaches delay appropriate healthcare access and risk creating future compounding effects. Action is required to address identified breaches: (1) The CRPD should also underpin all health policy and practice development, inclusive of pandemic and disaster management responsiveness. (2) Health professionals and support staff should be trained, and demonstrate competency, in Deaf cultural awareness and sensitivity.

Synthesis and structure-activity relationships for some novel diflapolin derivatives with benzimidazole subunit.

A series of derivatives of the potent dual soluble epoxide hydrolase (sEH)/5-lipoxygenase-activating protein (FLAP) inhibitor diflapolin was designed, synthesised, and characterised. These novel compounds, which contain a benzimidazole subunit were evaluated for their inhibitory activity against sEH and FLAP. Molecular modelling tools were applied to analyse structure-activity relationships (SAR) on both targets and to predict solubility and gastrointestinal (GI) absorption. The most promising dual inhibitors of these series are 5a, 6b, and 6c.