Search

Objective: Malignant pleural mesothelioma is a fatal disease and a clinical challenge, as few effective treatment modalities are available. Previous evidence links the gut microbiome to the host immunoreactivity to tumors. We thus evaluated the impact of a novel microbiome modulator compound (MMC) on the gut microbiota composition, tumor immune microenvironment, and cancer control in a model of malignant pleural mesothelioma. Methods: Age- and weight-matched immunocompetent (n = 23) or athymic BALB/c mice (n = 15) were randomly assigned to MMC or no treatment (control) groups. MMC (31 ppm) was administered through the drinking water 14 days before AB12 malignant mesothelioma cell inoculation into the pleural cavity. The impact of MMC on tumor growth, animal survival, tumor-infiltrating leucocytes, gut microbiome, and fecal metabolome was evaluated and compared with those of control animals. Results: The MMC delayed tumor growth and significantly prolonged the survival of immunocompetent animals (P = .0015) but not that of athymic mice. The improved tumor control in immunocompetent mice correlated with increased infiltration of CD3+CD8+GRZB+ cytotoxic T lymphocytes in tumors. Gut microbiota analyses indicated an enrichment in producers of short chain fatty acids in MMC-treated animals. Finally, we observed a positive correlation between the level of fecal short chain fatty acids and abundance of tumor-infiltrating cytotoxic T cells in malignant pleural mesothelioma. Conclusions: MMC administration boosts antitumor immunity, which correlates with a change in gut microbiome and metabolome. MMC may represent a valuable treatment option to combine with immunotherapy in patients with cancer.

Introduction The efficacy and of current antidepressants is insufficient. Esketamine, a new antidepressant administered by nasal route, is available since 2019 in the management of resistant characterized depressive episodes. Objectives To evaluate the response profile of patients to Esketamine in our institution specialized in mental health. Methods We included all patients treated with Esketamine in our institution from November 2019 to September 2021.We collected efficacy and tolerability data using the computerized and paper patient record, prescribing support software, and nursing staff. Results Since 2019, we treated 11 patients with Esketamine in combination with an antidepressant as indicated in the MA. Two patients from the 11 were found resistant, three discontinued due to adverse events, four relapsed after an initial clinical response, and two were still ongoing at the end of the study. Conclusions Despite an initial and rapid response, our study does not highlight any long-term efficacy of Esketamine in resistant depressive disorder. This highlight the fact that its use in the acute phase of depression or earlier in the management strategy could be a good alternative because of its rapid onset of action. Esketamine was initiated as a last line therapy, which may represent a bias in the evaluation of the molecule, as the later the depression is treated, the lower the response rate. The place of Esketamine in the therapeutic strategy is not yet well determined due to a lack of hindsight, and the question of pharmacological tolerance and dependence on the molecule arises. Disclosure No significant relationships.

Background: Shamanism is a spiritual tradition in which trance practitioners deliberately modify their state of consciousness to seemingly interact with an invisible world to resolve their community members' problems. This review aims to provide a multidisciplinary overview of scientific research on shamanic trance., Methods: The search was performed using PubMed and Google Scholar databases. Twenty-seven articles were found to be eligible, and their data were classified into four dimensions, namely, a) phenomenology, b) psychology, c) neuro-physiological functions, and d) clinical applications., Results: These studies suggest that these trances are non-pathological, different from normal states of consciousness in terms of phenomenology and neurophysiology, and influenced by multiple personal and environmental variables. Furthermore, while trances may offer therapeutic potential, their scope should be approached cautiously, underscoring the need for rigorous studies to assess the effectiveness of shamanic approaches for complementary therapies., Conclusion: Overall, shamanic trance and its potential benefits remain an intriguing and multifaceted area of scientific study, offering insights into the intersections of consciousness, spirituality, and possibly therapy., (© 2024. The Author(s).)

SCF 3 -substituted internal alkynes undergo regio- and stereoselective hydrohalogenation to provide the corresponding β-halo-α-SCF 3 -alkenes. The regioselectivity is ensured by the strong polarization of the C≡C triple bond in SCF 3 -alkynes, while the stereoselectivity is governed by the strength of the proton donor and/or by the solvent polarity. The potential of β-iodo-α-SCF 3 -alkenes was illustrated in several cross-coupling, protodeiodination, and cyanation reactions.

Background: Understanding cancer symptom cluster through network analyses is a new approach in oncology, revealing interconnected and influential relationships among reported symptoms. We aimed to assess these relationships using network analysis in posttreatment breast cancer patients, focusing on the five dimensions of cancer-related fatigue (CRF), and on other common difficulties encountered by oncological patients (i.e., pain, anxiety, depression, sleep difficulties, cognitive impairments, and emotion regulation and mental adaptation difficulties)., Method: This study involved a complementary analysis of data from two interventional studies. Participants completed questionnaires before and after the intervention, with baseline scores being used in this article. Partial correlation network analysis modeled the relationships between symptoms in five distinct networks, each of them including one specific dimension of CRF. The core symptom in each network was identified based on the highest centrality indices., Results: Depression emerged as the core symptom in all networks, strongly associated with all fatigue dimensions (partial correlations ranging from 0.183 to 0.269) except mental fatigue. These findings indicate robust connections between symptoms, as variations in depression scores directly or indirectly influence fatigue and other symptoms within the cluster., Conclusion: Our results support the multidimensional aspect of CRF, and its links with other common symptoms. To effectively reduce patient CRF, interventions should address not only fatigue but also the closely related symptoms from the cluster, such as depression, given its centrality in the cluster., Trial Registration: ClinicalTrials.gov (NCT03144154 and NCT04873661). Retrospectively registered on May 1, 2017 and April 29, 2021, respectively., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

A photocatalyzed formal (3+2) cycloaddition has been developed to construct original polysubstituted α-SCF 3 cyclopentanones in a regio- and diastereoselective manner. This building block approach leverages trifluoromethylthio alkynes and branched/linear aldehydes, as readily available reaction partners, in consecutive hydrogen atom transfers and C-C bond formations. Difluoromethylthio alkynes are also compatible substrates. Furthermore, the potential for telescoped reaction starting from alcohols instead of aldehydes was demonstrated, as well as process automatization and scale-up under continuous microflow conditions. This prompted density functional theory (DFT) calculations to support a radical-mediated cascade process., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Trance states include various practices characterized by a modulation of consciousness, but with their own specific characteristics and induction techniques. They have been very seldom scientifically studied, and their phenomenological similarities and differences are poorly documented. This paper will focus on two types of Western trances developed after the leaders were trained in traditional shamanic communities: the auto-induced cognitive trance (AICT) and the Mahorikatan ® trance (MT). Twenty-five AICT and 26 MT participants who were able to self-induce the trance state completed questionnaires about their trance practice (e.g. context of the first trance episode, frequency of practice, and consequences on personal life) and the phenomenological characteristics (i.e. emotional, physical, and cognitive) of the trance episodes they experienced. These characteristics were compared to explore similarities and differences between the two trance states. AICT and MT are characterized by the expression of different emotions, modification of various perceptions, a feeling of unicity (i.e. being completely oneself), and an expansion of consciousness. AICT participants commonly reported body movements, vocalizations, as well as increased creativity, visions of entities and/or places, and feeling of interaction with the environment. MT participants commonly reported a feeling of body dissolution. Most participants in both groups reported positive effects of their trance practice on their personal life. These results helped characterize AICT and MT, as well as their similarities and differences. Further studies should continue to explore the characteristics of such trance states, as well as their potential clinical applications., Competing Interests: C.S. is the founder of the TranceScience Research Institute (Paris, France) and developed the AICT technique. P.L. is the founder of The Call of Souls Project Foundation (Plainevaux, Belgium) and developed the MT dance. The other authors declare no conflict of interest related to this work., (© The Author(s) 2024. Published by Oxford University Press.)

The lesbian, gay, bisexual, transgender, and queer(LGBTQ +) community is a marginalized minority group who continues to face and experience significant discrimination, prejudice, stigma, oppression, and abuse in various societal domains including health care. The older adult LGBTQ + community is an especially vulnerable group as they have unique minority stressors attributed to intersectional identities of age, ableism, ethnicity, and employment, among other factors. It is critical for health care providers to recognize and mitigate disproportionate care by engaging in strategies that promote inclusion and affirmation of their sexual orientation and gender identity. The biopsychosocial, cultural, and spiritual framework is a useful tool to care for this community in a holistic and compassionate way., Competing Interests: Disclosure We do not have any financial disclosures., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: Treatment for cleft lip and/or palate (CL/P) in the United Kingdom is administered on a standardised pathway from diagnosis to early adulthood, with options to be re-referred in later life. At age 16, patients become responsible for their treatment decisions. Evidence from the wider health literature indicates this transition can be challenging and that this population may require additional support. The present study explored young people's experiences of transition to adult care in the context of CL/P services, with the aim of identifying support needs and informing future service delivery., Design: Individual semi-structured interviews were conducted with 15 individuals with CL/P (aged 17-25 years) to explore transition experiences. Interviews lasted an average of 69 min and data were analysed using reflexive thematic analysis., Results: Four themes, with subthemes, were identified: 1) Readiness for Transition covered feelings of preparedness and how health professionals approached transition; 2) Making Decisions as an Adult described concerns and considerations when making treatment decisions; 3) Finding and Using Support, reflected the roles of caregivers and peers in developing self-advocacy; and 4) Reflections on Transition Care offered insight into how care could be improved., Conclusion: Individuals born with CL/P may experience challenges in becoming responsible for their own care and treatment decisions. The findings of this study indicate that a dedicated transition protocol may be beneficial, such that adolescents are prepared to confidently access and manage their care into adulthood. Opportunities for improvements in transition planning and provision are discussed., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Repeated exposure to substances of abuse results in an increase in some behavioral responses. This phenomenon, called behavioral sensitization (BS), is well described in preclinical models. However, its existence in humans is still a matter of debate. After a review of preclinical evidence of BS and its mechanisms in animal models, we reviewed the evidence supporting the existence of BS in humans, despite the limited research available in this regard. We focused our review on opioids and psychostimulants, since they share the ability to promote addictive behaviors. Further, they induce BS despite their distinct sedative and stimulant properties. Moreover, we proposed future research perspectives in this review to address the remaining unsolved questions, especially regarding BS in humans using a harm reduction approach., Competing Interests: Declaration of Competing Interest Unrelated to the present work, FV has served in Advisory Boards for ACCORD Healthcare, Camurus AB, and has congress fees paid by ACCORD Healthcare, Camurus AB, Recordati., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The over-prescription of opioid analgesics is a growing problem in the field of addiction, which has reached epidemic-like proportions in North America. Over the past decade, oxycodone has gained attention as the leading opioid responsible for the North America opioid crisis. Oxycodone is the most incriminated drug in the early years of the epidemic of opioid use disorder in USA (roughly 1999-2016). The number of preclinical articles on oxycodone is rapidly increasing. Several publications have already compared oxycodone with other opioids, focusing mainly on their analgesic properties. The aim of this review is to focus on the genomic and epigenetic regulatory features of oxycodone compared with other opioid agonists. Our aim is to initiate a discussion of perceptible differences in the pharmacological response observed with these various opioids, particularly after repeated administration in preclinical models commonly used to study drug dependence potential., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Marie and Noble.)

Background: Evidence has accumulated demonstrating the existence of opioid receptor heteromers, and recent data suggest that targeting these heteromers could reduce opioid side effects while retaining therapeutic effects. Indeed, CYM51010 characterized as a MOR (mu opioid receptor)/DOR (delta opioid receptor) heteromer-preferring agonist promoted antinociception comparable with morphine but with less tolerance. In the perspective of developing these new classes of pharmacological agents, data on their putative side effects are mandatory., Methods: Therefore, in this study, we investigated the effects of CYM51010 in different models related to drug addiction in mice, including behavioral sensitization, conditioned place preference and withdrawal., Results: We found that, like morphine, CYM51010 promoted acute locomotor activity as well as psychomotor sensitization and rewarding effect. However, it induced less physical dependence than morphine. We also investigated the ability of CYM51010 to modulate some morphine-induced behavior. Whereas CYM51010 was unable to block morphine-induced physical dependence, it blocked reinstatement of an extinguished morphine induced-conditioned place preference., Conclusions: Altogether, our results reveal that targeting MOR-DOR heteromers could represent a promising strategy to block morphine reward., (© The Author(s) 2023. Published by Oxford University Press on behalf of CINP.)

Regioselective ring opening of cyclic sulfamidates was achieved by means of nucleophilic polyfluorinated alkoxides to access achiral and chiral β- and γ-OR F amines and α-amino esters. Subsequent transformations provide free amines ready for incorporation into bioactive substances through amide bond formation or nucleophilic aromatic substitution.

Background: Burn injuries affect more than 60,000 children every year in the UK, with many experiencing scarring as a result. Scarring can be highly variable, and research is required to explore the factors that may influence variability, as well as the psychosocial impact of these injuries on children and their caregivers. A multicentre burns cohort study is being planned to investigate genetic determinants of scarring and long-term psychosocial outcomes. Public involvement (PI) is an essential element of the design and feasibility stages of this planning. As part of this work, this study aimed to gain an in-depth understanding of parents' attitudes towards participation in burns research, specifically a longitudinal cohort study of children with small burns (<10% total body surface area [TBSA])., Methods: In total, 16 parents of children with burns took part in semi-structured interviews regarding their experiences of taking part in research and their attitudes towards the potential future cohort study. Interviews were audio-recorded, transcribed verbatim and analysed using Reflexive Thematic Analysis., Results: Four themes were identified: 'Acknowledging trauma'; 'Aligning research with experience'; 'Research as a reciprocal relationship'; and 'Contributing to change'., Discussion: These four themes represent factors that parents suggested were important for acceptability, relevance, recruitment and retention of participants into a longitudinal multicentre cohort study of children with a burn injury and their caregivers., Conclusion: The findings of this study will be incorporated into the design of such a study, as well as having wide reaching relevance for research in the field of paediatric burn injuries., Lay Summary: Background to this subject More than 60,000 children experience a burn injury every year in the UK and many of these injuries lead to scarring. We know that the extent of this scarring can vary, and we know that some children and their parents/caregivers manage well but others struggle with the challenges they face after having a burn. Researchers would like to carry out research on these topics, including asking participants to take part in research over several years to find out how genetics might influence scarring, as well as their psychological experiences over this time. Before they conduct this study, it is very important that researchers understand parents' attitudes towards this kind of research. The current study aimed to find out parents' opinions and ask what issues were important to them when taking part in burns research. Details of how the work was conducted Parents of children who had experienced a scald (a type of burn injury) were asked to take part in a research interview. In total, 16 parents took part in this study. We recorded these interviews and analysed them, looking for patterns and shared experiences in participants' interviews. What we did and did not learn from this study We found four themes in the interview data: 'Acknowledging trauma', 'Aligning research with experience', 'Research as a reciprocal relationship', and 'Contributing to change'. Overall, these themes suggest that parents were mostly supportive of a 'burns cohort study', but they have also highlighted some important considerations for this research and other future burns research studies., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Increasingly available open medical and health datasets encourage data-driven research with a promise of improving patient care through knowledge discovery and algorithm development. Among efficient approaches to such high-dimensional problems are a number of machine learning methods, which are applied in this paper to pressure ulcer prediction in modular critical care data. An inherent property of many health-related datasets is a high number of irregularly sampled time-variant and scarcely populated features, often exceeding the number of observations. Although machine learning methods are known to work well under such circumstances, many choices regarding model and data processing exist. In particular, this paper address both theoretical and practical aspects related to the application of six classification models to pressure ulcers, while utilizing one of the largest available Medical Information Mart for Intensive Care (MIMIC-IV) databases. Random forest, with an accuracy of 96%, is the best-performing approach among the considered machine learning algorithms.

Human embryonic stem (hES) cells are highly sensitive to apoptotic stimuli such as DNA damage, which allows for the rapid elimination of mutated cells during development. However, the mechanisms that maintain hES cells in the primed apoptotic state are not completely known. Key activators of apoptosis, the BH3-only proteins, are present at low levels in most cell types. In contrast, hES cells have constitutive high levels of the BH3-only protein, NOXA. We examined the importance of NOXA for enabling apoptosis in hES cells. hES cells deleted for NOXA showed remarkable protection against multiple apoptotic stimuli. NOXA was constitutively localized to the mitochondria, where it interacted with MCL1. Strikingly, inhibition of MCL1 in NOXA knockout cells was sufficient to sensitize these cells to DNA damage-induced cell death. Our study demonstrates that an essential function of constitutive high levels of NOXA in hES cells is to effectively antagonize MCL1 to permit rapid apoptosis., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: A symptom cluster is very common among oncological patients: cancer-related fatigue (CRF), emotional distress, sleep difficulties, pain, and cognitive difficulties. Clinical applications of interventions based on non-ordinary states of consciousness, mostly hypnosis and meditation, are starting to be investigated in oncology settings. They revealed encouraging results in terms of improvements of these symptoms. However, these studies often focused on breast cancer patients, with methodological limitations (e.g., small sample size, no control group, and no follow-up). Another non-ordinary state of consciousness may also have therapeutic applications in oncology: self-induced cognitive trance (SICT). It seems to differ from hypnosis and meditation, as it involves the body more directly. Thus, investigating its clinical applications, along with hypnosis and meditation interventions, could improve available therapeutic options in oncology. This article details the study protocol of a preference-based longitudinal controlled superiority trial aiming to assess the effectiveness of 3 group interventions (hypnosis, meditation, and SICT) to improve oncological patients' quality of life, and more specifically CRF, emotional distress, sleep, pain, and cognitive difficulties (primary outcomes)., Methods and Analysis: A power analysis required a total sample of 160 patients. Main inclusion criteria are: cancer diagnosis, active treatments completed for less than a year, no practice of hypnosis, meditation, or SICT, and presence of at least one of these four symptoms: fatigue, sleep difficulties, depression, or anxiety. Each participant will choose the intervention in which they want to participate (hypnosis, mindful self-compassion meditation, SICT, or no intervention-control group). To test the effectiveness of the interventions, data will be collected by questionnaires and neurobiological measures and directly from the medical record at four time points: before inclusion in the study (baseline); immediately after the intervention; and at 3- and 12-month follow-up. The longitudinal data in each group will then be measured., Discussion: In addition to standard cancer therapies, there is a growing interest from patients in complementary approaches, such as hypnosis, meditation, and SICT. The results of this study will be useful to increase knowledge about short- and long-term effectiveness of 3 group interventions for CRF, emotional distress, sleep, pain, and cognitive difficulties in patients with different cancers., Clinical Trial Registration: ClinicalTrials.gov/ (NCT04873661). Retrospectively registered on the 29th of April 2021. url: https://clinicaltrials.gov/ct2/show/NCT04873661., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Grégoire, Marie, Sombrun, Faymonville, Kotsou, van Nitsen, de Ribaucourt, Jerusalem, Laureys, Vanhaudenhuyse and Gosseries.)