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Introduction: The safety and therapeutic effects of Gingko biloba extract EGb 761® to treat cognitive decline have been demonstrated in numerous clinical trials. However, trials in Indian populations have been lacking. Methods: This open-label, multicenter, single-arm, phase IV trial enrolled 150 patients aged ≥50 years with major neurocognitive disorder due to Alzheimer's disease, major vascular neurocognitive disorder, or mixed forms of both according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) criteria and a Mini-Mental State Examination (MMSE) score of 12–24. Patients took 120 mg EGb 761® twice daily for 18 weeks. Therapeutic effects were assessed by CERAD constructional praxis and recall of constructional praxis (CERAD CP, CERAD recall of CP), Trail-Making Test (TMT), Behavioral Pathology in Alzheimer's Disease (BEHAVE-AD), Clinical Global Impressions (CGI) scale, and 11-point box scales for tinnitus and vertigo. Safety assessment was based on the occurrence of adverse events as well as changes in clinical, laboratory, and functional parameters. Results: After 18 weeks, significant improvements compared to baseline were found in constructional praxis (CERAD CP, p < 0.0001), memory (CERAD recall of CP, p < 0.0001), speed and executive functioning (TMT A, p < 0.0001; TMT B, p < 0.0001), and behavioral symptoms (BEHAVE-AD, p < 0.0001). Forty-five adverse events were reported in 33 (22.0%) patients in total, including ten presumed adverse drug reactions in 9 (6.0%) patients. Headache and diarrhea of mild-to-moderate severity were the most frequent events. Two serious adverse events, both considered unrelated to the study drug, occurred in 2 (1.3%) patients. Conclusion: This study confirmed the favorable safety profile and suggested therapeutic benefits of EGb 761® in Indian patients with major neurocognitive disorder. [ABSTRACT FROM AUTHOR]

Real-life data from various countries have shown that long-term use of a cannabinoid is possible for the treatment of certain chronic pain conditions, without risk of addiction and with maintenance of an overall benefit on quality of life. The retrospective evaluation presented considers the duration of dronabinol treatment for neuropathic pain in a Center for Pain Evaluation and Treatment (CETD). Between 2016 and 2023 (7 years and 2 months), 165 patients were followed up, 57 % with central pain (DNC) and 43 % with peripheral pain (DNP). Various data were collected once a quarter: analgesic efficacy, adverse events, overall benefit of treatment. Continuation of treatment was considered in the absence of contraindication or treatment-related adverse event, and when the patient requested continuation of treatment without increase in dosage because overall benefit was maintained. The duration of dosage adjustment varied between 1 and 4 months, and daily doses were stable for each patient, ranging from 2.5 to 40 mg. 64 % of patients discontinued treatment within the first 12 months, 44 % within the first 6 months due to inefficacy or intolerance. After 6 months, reasons for discontinuation were never adverse effects or addiction. During the first 2 years, 78 % of patients stopped treatment. At the end of the study, the longest duration of treatment was 7 years and 2 months. Mean duration of treatment was 17 ± 22 during the evaluation. Mean duration of treatment for patient still taking the treatment at the end of evaluation was 41 ± 4 months with DNC (95 % CI: 33–49) and 25 ± 3 months with DNP (95 % CI: 19–31). The proportion of patients receiving treatment for at least 1 year was 68.4 % (39/57) with DNC and 40.8 % (20/49) with DNP, the difference being statistically significant between the 2 groups only at 2 years of treatment (DNC: 39.1 % (27/69) and DNP 17 % (10/59), p = 0.038). The probability of time remaining before a patient stopped treatment was significantly different between the DNC and DNP groups (p = 0.023). With the advent of medical cannabis in France, the real-life data from our study and the literature show that the long-term use of a cannabinoid for the treatment of DN can be envisaged without any major risk, whether addictive or otherwise, and that it can provide a significant and durable benefit in terms of quality of life, justifying its use as a last-line treatment, with a focus on central pain. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, we investigated the effectiveness of the targeted cancer medication CDK4/6 inhibitors, in patients with breast cancer. These medicaments have been used for nearly a decade, but how well they work can vary greatly from one patient to another. By examining the experiences of 86 patients over a period from November 2016 to May 2020, we aimed to understand what factors might predict better or worse outcomes for patients. We discovered that certain characteristics, like the level of the progesterone receptor in the tumor and whether the cancer had spread to multiple locations or the liver, played a significant role in how long patients benefited from treatment without progression. The study also found that management characteristics during treatment could significantly affect patient outcomes. These insights are crucial for developing personalized management strategies that could lead to better outcomes for people with breast cancer. Background: The quest to comprehend the real-world efficacy of CDK4/6 inhibitors (CDKis) in breast cancer continues, as patient responses vary significantly. Methods: This single-center retrospective study evaluated CDKi use outside the trial condition from November 2016 to May 2020. Progression-free survival (PFS), time-to-treatment failure (TTF), short-term and prolonged treatment benefit (≥4 and ≥10 months), as well as prognostic and predictive markers were assessed with Kaplan–Meier and multivariate regression analyses. Results: Out of 86 identified patients, 58 (67.4%) had treatment failure of which 40 (46.5%) were due to progression. Median PFS and TTF were 12 and 8.5 months, respectively. A total of 57 (66.3%) and 42 (48.8%) patients experienced short-term and prolonged treatment benefit. Independent, significant predictors for PFS were progesterone receptor expression (HR: 0.88), multiple metastatic sites (HR: 2.56), and hepatic metastasis (HR: 2.01). Significant predictors for TTF were PR expression (HR: 0.86), multiple sites (HR: 3.29), adverse events (HR: 2.35), and diabetes (HR: 2.88). Aside from tumor biology and adverse events, treatment modifications like pausing and switching of CDKi were predictive for short-term (OR: 6.73) and prolonged (OR: 14.27) therapeutic benefit, respectively. Conclusions: These findings emphasize the importance of tailored treatment strategies, highlighting the role of PR expression, metastatic burden, and therapeutic adjustments in optimizing patient outcomes in real-world breast cancer management. [ABSTRACT FROM AUTHOR]

Background and Objectives: Recent studies suggest that hydrogen gas possesses anti-inflammatory, antioxidant, and anti-apoptotic properties. This study aimed to explore the therapeutic potential of hydrogen gas and assess its safety and tolerability in individuals with chronic obstructive pulmonary disease (COPD). Materials and Methods: Enrolled COPD patients received standard treatments along with additional hydrogen inhalation for 30 min in the morning, afternoon, and evening over a 30-day period. The assessment included changes in the COPD Assessment Test (CAT), the modified Medical Research Council (mMRC) Dyspnea Scale, lung function, sleep quality, inflammation markers, and oxidative stress markers before and after hydrogen inhalation. Results: Six patients participated in this study. Patients 2, 3, 4, 5, and 6 demonstrated improvements in CAT scores following hydrogen gas intervention, with patients 2, 4, 5, and 6 also showing improvements in mMRC scores. Statistically, this study revealed significant improvements in CAT [15.5 (10.5–19.75) vs. 8.5 (3–13.5); p = 0.043] and mMRC scores [2.5 (1–4) vs. 2 (0–3.25); p = 0.046] before and after intervention, respectively. However, no significant differences were observed in lung function, DLCO, sleep quality, and 6 MWT before and after hydrogen therapy. CBC examination showed a significant difference in platelet count before and after treatment [247 (209.75–298.75) vs. 260 (232.75–314.5); p = 0.043], respectively, while other blood tests, inflammation markers, and oxidative stress markers did not exhibit significant differences before and after hydrogen therapy. All patients experienced no obvious side-effects. Conclusions: Adjuvant therapy with hydrogen gas demonstrated symptom improvements in specific COPD patients, and no significant adverse effects were observed in any of the patients. Hydrogen gas may also exert a modulatory effect on platelet count. [ABSTRACT FROM AUTHOR]

Background: Ultra‐high dose rate (FLASH) radiation has been reported to efficiently suppress tumor growth while sparing normal tissue; however, the mechanism of the differential tissue sparing effect is still not known. Oxygen has long been known to profoundly impact radiobiological responses, and radiolytic oxygen depletion has been considered to be a possible cause or contributor to the FLASH phenomenon. Purpose: This work investigates the impact of tissue pO2 profiles, oxygen depletion per unit dose (g), and the oxygen concentration yielding half‐maximum radiosensitization (the average of its maximum value and one) (k) in tumor and normal tissue. Methods: We developed a model that considers the dependent relationship between oxygen depletion and change of radiosensitivity by FLASH irradiation. The model assumed that FLASH irradiation depletes intracellular oxygen more rapidly than it diffuses into the cell from the extracellular environment. Cell survival was calculated based on the linear quadratic‐linear model and the radiosensitivity related parameters were adjusted in 1 Gy increments of the administered dose. The model reproduced published experimental data that were obtained with different cell lines and oxygen concentrations, and was used to analyze the impact of parameter uncertainties on the radiobiological responses. This study expands the oxygen depletion analysis of FLASH to normal human tissue and tumor based on clinically determined aggregate and individual patient pO2 profiles. Results: The results show that the pO2 profile is the most essential factor that affects biological response and analyses based on the median pO2 rather than the full pO2 profile can be unreliable and misleading. Additionally, the presence of a small fraction of cells on the threshold of radiobiologic hypoxia substantially alters biological response due to FLASH oxygen depletion. We found that an increment in the k value is generally more protective of tumor than normal tissue due to a higher frequency of lower pO2 values in tumors. Variation in the g value affects the dose at which oxygen depletion impacts response, but does not alter the dose‐dependent response trends, if the g value is identical in both tumor and normal tissue. Conclusions: The therapeutic efficacy of FLASH oxygen depletion is likely patient and tissue‐dependent. For breast cancer, FLASH is beneficial in a minority of cases; however, in a subset of well oxygenated tumors, a therapeutic gain may be realized due to induced normal tissue hypoxia. [ABSTRACT FROM AUTHOR]

Propolis is considered to be one of the most useful products of apitherapy, as the active principles are transmitted directly from the plant to humans, so its use has attracted quite a lot of supporters in human medicine. Due to its complex composition, which includes waxes, resins, balsams, volatile oils, vitamins, minerals, phenolic acids and flavonoids, the therapeutic benefits of propolis and its uses in various diseases are well known. In this paper aspects of the chemical composition of propolis, analysis methods of propolis and the way it can be used as a result of its therapeutic effects are presented.

Background and Objectives: Recent studies suggest that hydrogen gas possesses anti-inflammatory, antioxidant, and anti-apoptotic properties. This study aimed to explore the therapeutic potential of hydrogen gas and assess its safety and tolerability in individuals with chronic obstructive pulmonary disease (COPD). Materials and Methods: Enrolled COPD patients received standard treatments along with additional hydrogen inhalation for 30 min in the morning, afternoon, and evening over a 30-day period. The assessment included changes in the COPD Assessment Test (CAT), the modified Medical Research Council (mMRC) Dyspnea Scale, lung function, sleep quality, inflammation markers, and oxidative stress markers before and after hydrogen inhalation. Results: Six patients participated in this study. Patients 2, 3, 4, 5, and 6 demonstrated improvements in CAT scores following hydrogen gas intervention, with patients 2, 4, 5, and 6 also showing improvements in mMRC scores. Statistically, this study revealed significant improvements in CAT [15.5 (10.5–19.75) vs. 8.5 (3–13.5); p = 0.043] and mMRC scores [2.5 (1–4) vs. 2 (0–3.25); p = 0.046] before and after intervention, respectively. However, no significant differences were observed in lung function, DLCO, sleep quality, and 6 MWT before and after hydrogen therapy. CBC examination showed a significant difference in platelet count before and after treatment [247 (209.75–298.75) vs. 260 (232.75–314.5); p = 0.043], respectively, while other blood tests, inflammation markers, and oxidative stress markers did not exhibit significant differences before and after hydrogen therapy. All patients experienced no obvious side-effects. Conclusions: Adjuvant therapy with hydrogen gas demonstrated symptom improvements in specific COPD patients, and no significant adverse effects were observed in any of the patients. Hydrogen gas may also exert a modulatory effect on platelet count.

Propolis is considered to be one of the most useful products of apitherapy, as the active principles are transmitted directly from the plant to humans, so its use has attracted quite a lot of supporters in human medicine. Due to its complex composition, which includes waxes, resins, balsams, volatile oils, vitamins, minerals, phenolic acids and flavonoids, the therapeutic benefits of propolis and its uses in various diseases are well known. In this paper aspects of the chemical composition of propolis, analysis methods of propolis and the way it can be used as a result of its therapeutic effects are presented. [ABSTRACT FROM AUTHOR]

Estrogens, the sex hormones, have the potential to govern multiple cellular functions, such as proliferation, apoptosis, differentiation, and homeostasis, and to exert numerous beneficial influences for the cardiovascular system, nervous system, and bones in genomic and/or non-genomic ways. Converging evidence indicates that estrogens serve a crucial role in counteracting neurodegeneration and ischemic injury; they are thereby being considered as a potent neuroprotectant for preventing neurological diseases such as Alzheimer’s disease and stroke. The underlying mechanism of neuroprotective effects conferred by estrogens is thought to be complex and multifactorial, and it remains obscure. It is well established that the K+ channels broadly expressed in a variety of neural subtypes determine the essential physiological features of neuronal excitability, and dysfunction of these channels is closely associated with diverse brain deficits, such as ataxia and epilepsy. A growing body of evidence supports a neuroprotective role of K+ channels in malfunctions of nervous tissues, with the channels even being a therapeutic target in clinical trials. As multitarget steroid hormones, estrogens also regulate the activity of distinct K+ channels to generate varying biological actions, and accumulated data delineate that some aspects of estrogen-mediated neuroprotection may arise from the impact on multiple K+ channels, including Kv, BK, KATP, and K2P channels. The response of these K+ channels after acute or chronic exposure to estrogens may oppose pathological abnormality in nervous cells, which serves to extend our understanding of these phenomena.

Background: Due to new legal requirements, a patient-relevant benefit for other wound treatment products (sPW) must be demonstrated through clinical studies if reimbursement at the expense of the statutory health insurance is sought in the non-inpatient sector., Method: An interdisciplinary group with expertise in clinical wound care has developed general recommendations for the design of suitable studies. In addition to regulatory documents, previous studies that have already been recognized as proof of benefit in other areas served as a basis., Results: Randomized controlled trials that cover at least the most common types of chronic wounds (arterial, venous, diabetic or pressure sore) are recommended as the best method for gathering evidence. Despite the heterogeneous etiology of chronic wounds, the results should also be transferable to other wound types. The test intervention does not usually consist of the sPW alone, but of a combined wound treatment that follows a treatment plan that is as clearly defined as possible. In the comparison group, all wound treatment options (besides the sPW) must also be available and used according to a similar predefined treatment plan. Depending on the intended purpose and treatment goal, complete wound closure should, if possible, be recorded as the cardinal - although not always as the primary - endpoint. In justified cases, e.g. in the case of intermediate use as part of phase-appropriate wound therapy for chronic wounds, a significant reduction in the wound area can also be considered for benefit assessment. Quality of life (e.g. pain) can also justify a benefit and can therefore be recorded as a primary outcome parameter in clinical trials. The duration of the clinical trial should be adapted to the central endpoints, the medical or nursing goal of wound care and the intended purpose of the sPW. A benefit does not always arise from microbiological, physiological, laboratory or histological parameters or imaging findings., (© 2024. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Duchenne muscular dystrophy (DMD) is an X-linked genetic disease affecting 1 in 5000 young males worldwide annually. Patients experience muscle weakness and loss of ambulation at an early age, with ∼75% reduced life expectancy. Recently developed genetic editing strategies aim to convert severe DMD phenotypes to a milder disease course. Among these, the antisense oligonucleotide (AO)-mediated exon skipping and the adeno-associated viral-delivered clustered regularly interspaced short palindromic repeat (CRISPR) associated protein 9 (adeno-associated viral (AAV)-delivered CRISPR/Cas9) gene editing have shown promising results in restoring dystrophin protein expression and functionality in skeletal and heart muscle in both animals and human cells in vivo and in vitro. However, therapeutic benefits currently remain unclear. The aim of this review is to compare the potential therapeutic benefits, efficacy, safety, and clinical progress of AO-mediated exon skipping and CRISPR/Cas9 gene-editing strategies. Both techniques have demonstrated therapeutic benefit and long-term efficacy in clinical trials. AAV-delivery of CRISPR/Cas9 may potentially correct disease-causing mutations following a single treatment compared to the required continuous AO/PMO-delivery of exon skipping drugs. The latter has the potential to increase the dystrophin expression in skeletal/heart muscle with sustained effects. However, therapeutic challenges including the need for optimised delivery must be overcome in to advance current clinical data.

Advances in technology and improvement of efficacy for many neuromodulation applications have been achieved without understanding the relationship between the stimulation parameters and the neural activity which is generated in the nervous system. It is the neural activity that ultimately drives the therapeutic benefit and the advent of evoked compound action potential recording allows this activity to be directly measured and quantified. Closed-loop control adjusts the stimulation parameters to maintain a predetermined level of neural recruitment and has been shown to provide improved pain relief in individuals with spinal cord stimulators. However, no mechanism that relates more consistent neural recruitment to patient outcomes has been proposed. The authors propose a hypothesis that may explain the difference in efficacy between open- and closed-loop operational modes by considering the relationship between measured neural recruitment with hypothetical dose and side effect response curves. This provides a rational basis for directing clinical research and improving therapeutic systems.

Abstract Background Futile reperfusion (poor functional status despite successful reperfusion) was observed in up to 67% of patients enrolled in recent endovascular treatment (EVT) clinical trials. We investigated the impact of baseline stroke severity on both futile reperfusion and therapeutic benefit of successful EVT. Methods Using a prospective multicenter stroke registry, we identified consecutive ischemic stroke patients with anterior circulation large artery occlusion, who were reperfused successfully by EVT (Thrombolysis in Cerebral Infarction grade 2b–3). The rate of futile reperfusion was assessed across the initial National Institutes of Health Stroke Scale (NIHSS) scores. The frequency of poor outcomes (modified Rankin scale [mRS] 3–6) according to NIHSS scores was compared between patients revascularized successfully by EVT and those who did not receive EVT, after standardizing for age. Results Among 21,591 patients with ischemic stroke, 972 (4.5%) received EVT within 12 h of onset, including 440 who met study eligibility criteria. Futile reperfusion was observed in 226 of the 440 study-eligible patients (51.4%) and was associated with stroke severity: 20.9% in NIHSS scores ≤5, 34.6% in 6–10, 58.9% in 11–20, and 63.8% in > 20 (p 20. Conclusions EVT is more beneficial with increasing stroke severity, although futile reperfusion also increases with higher stroke severity.

Duchenne muscular dystrophy (DMD) is an X‐linked genetic disease affecting 1 in 5000 young males worldwide annually. Patients experience muscle weakness and loss of ambulation at an early age, with ∼75% reduced life expectancy. Recently developed genetic editing strategies aim to convert severe DMD phenotypes to a milder disease course. Among these, the antisense oligonucleotide (AO)‐mediated exon skipping and the adeno‐associated viral‐delivered clustered regularly interspaced short palindromic repeat (CRISPR) associated protein 9 (adeno‐associated viral (AAV)‐delivered CRISPR/Cas9) gene editing have shown promising results in restoring dystrophin protein expression and functionality in skeletal and heart muscle in both animals and human cells in vivo and in vitro. However, therapeutic benefits currently remain unclear. The aim of this review is to compare the potential therapeutic benefits, efficacy, safety, and clinical progress of AO‐mediated exon skipping and CRISPR/Cas9 gene‐editing strategies. Both techniques have demonstrated therapeutic benefit and long‐term efficacy in clinical trials. AAV‐delivery of CRISPR/Cas9 may potentially correct disease‐causing mutations following a single treatment compared to the required continuous AO/PMO‐delivery of exon skipping drugs. The latter has the potential to increase the dystrophin expression in skeletal/heart muscle with sustained effects. However, therapeutic challenges including the need for optimised delivery must be overcome in to advance current clinical data. [ABSTRACT FROM AUTHOR]

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Objective: D-cycloserine (DCS) promotes consolidation of extinction learning. This study extends earlier work by examining whether DCS can enhance cognitive behavioral therapy (CBT) for delusions.Methods: Adults reporting moderate or greater delusions were randomly assigned to receive 50 mg of DCS or placebo prior to 10 weekly CBT sessions. The primary outcome was change in severity of delusions measured with the Psychotic Symptom Rating Scale delusion subscale (PSYRATS-D). Secondary outcomes included persistence of response at 3 and 6 month follow-up and the effects of DCS on memory consolidation and cognitive flexibility. Fifty-eight participants were randomized and 44 completed the trial.Results: The DCS and placebo groups did not differ in change from baseline to end of CBT on PSYRATS-D, nor did DCS improve memory consolidation or cognitive flexibility compared to placebo. However, at the 3 month follow-up visit (week 24), 47% of participants who completed treatment with DCS reported a 20% or greater decrease on PSYRATS-D compared to 15% in the placebo group (p = .04). Change in distress across CBT sessions interacted with treatment group to predict change from baseline to week 24 in PSYRATS-D total score (p = .03) such that response at week 24 was greatest in DCS-treated participants who experienced a decrease in distress during CBT sessions.Conclusions: DCS augmentation of CBT did not improve delusions compared to placebo during treatment; however, DCS was associated with a higher response rate at 3-month follow-up. DCS may produce a delayed therapeutic effect, associated with successful CBT sessions, but this finding requires replication. [ABSTRACT FROM AUTHOR]

Les usages du cannabis, en médecine et dans les traditions populaires, sont divers et anciens, ils ont été freinés depuis un siècle par la prohibition. Nous assistons depuis une trentaine d'années à un renouveau des pratiques sociales – production, distribution, usages – liées au cannabis. La découverte du système endocannabinoïde introduit un élément nouveau en faveur de l'utilisation médicale de cette plante. Les indications des cannabinoïdes en psychiatrie sont potentiellement nombreuses et demandent à être discutées. Il en va de même pour les mécanismes à l'œuvre qui restent à identifier, notamment via les états modifiés de la conscience, ceci afin d'analyser leur effet thérapeutique. The uses of cannabis in medicine and folk traditions are numerous, diverse and ancient. Their development has been inhibited by prohibition. We have been witnessing the last thirty years a number of very important transformations related to cannabis production, distribution and use. The recent discovery of the endocannabinoid system introduces new therapeutic perspectives supporting medical use of cannabis and derivative products. In the field of psychiatry there are a number of indications that need to be discussed concerning the mechanisms of their therapeutic effects. The interest of intoxication (e.g. altered states of consciousness or states of nonordinary reality) as a therapeutic tool is a central issue to be analyzed. [ABSTRACT FROM AUTHOR]

Récemment, le concept de « pleine conscience incarnée » (embodiment) a été proposé comme dénominateur commun aux approches bouddhistes et occidentales de la pleine conscience (Khoury, Dionne & Grégoire, 2018). Cet article vise à approfondir et élargir cette notion de pleine conscience incarnée afin de démontrer que celle-ci implique nécessairement une prise en compte des aspects interpersonnels et sociaux, souvent négligés dans la théorie, la pratique et la recherche. Des études récentes menées sur les effets interpersonnels de la pleine conscience sont d'abord exposées et des avenues sont ensuite proposées afin de stimuler le développement de ce domaine de recherche. The concept of " embodied mindfulness " (Khoury, Dionne, & Grégoire, 2018; Khoury et al., 2017) was recently introduced and discussed according to both Eastern and Western conceptualizations and operationalization of mindfulness. Our previous papers (Khoury et al., 2018; Khoury et al., 2017) proposed embodiment as a common process that integrates mindfulness across the Buddhist traditions and western schools of thoughts. Moreover, it grounded the notion of " embodied mindfulness " in Buddhist philosophy and neurobiology, namely in the integration of top-down and bottom-up processes. This new notion allowed a common understanding of the mechanisms of change of different Western mindfulness practices, namely Western mindfulness meditation and Langerian mindfulness. It also proposed consciousness as an interaction between the mind, the body, and the outside world. This article aims to deepen and broaden the notion of " embodied mindfulness " by taking into account the interpersonal and social contexts, which are often neglected in the theory, practice and research pertaining to mindfulness. In order to investigate the social dimension of mindfulness, we conducted a thorough qualitative review of theoretical and empirical papers pertaining to the interpersonal, familial, relational, and social aspects of mindfulness and thus, according to both mindfulness-meditation and Langerian mindfulness approaches. Empirical research addressing the interpersonal and social effects of mindfulness in both approaches is presented and discussed. Additionally, we reviewed the state of research in conceptualizing, operationalizing, and measuring the interpersonal/social dimension of mindfulness in both the meditative and Langerian approaches. The results of interpersonal mindfulness are presented and discussed according to the different contexts. In the family context, both correlational and experimental studies have suggested positive effects of mindfulness on relationships between couples (e.g., increase of satisfaction and reduction of reactivity) and on the emotional, social, and behavioral adjustments of children of parents with higher mindfulness disposition or following mindfulness training. The positive outcomes on children were found across different developmental stages (e.g., childhood, early, and late adolescence) and included lower aggressiveness and externalizing behaviors, and more positive interactions with parents and peers, therefore higher self-regulation. The results were also found among both nonclinical and clinical populations, including children with neurodevelopmental disorders such as Attention Deficit and Hyperactivity Disorder and Autism Spectrum Disorder. In psychotherapy context, qualitative and correlational studies suggested that dispositional mindfulness is correlated with an increase in therapeutic alliance and presence, therefore, an increase in therapeutic effectiveness. In addition, an experimental study showed better clinical outcomes among patients seen by therapists practicing meditation than therapists who were in the control group. On the social level, both correlational and experimental studies have suggested positive effects of mindfulness on prosocial behaviors, empathy, altruism, compassion, and reduction in discrimination. These results were obtained in both the meditative and Langerian approaches. According to current research, interpersonal mindfulness, even though globally defined, was only measured in parenting and teaching contexts. Therefore, the need of having a contextually independent measure of interpersonal mindfulness is very high. In light of the empirical results, we believe that the notion of " embodied mindfulness " would benefit from being extended to include more explicitly its interpersonal dimension. Integrating both intrapersonal and interpersonal/social dimensions in conceptualizing and measuring mindfulness can broaden our understanding of mindfulness and its applications and carry important implications in devising new mindfulness-based interventions, which should consider both the intrapersonal and interpersonal dimensions of mindfulness. [ABSTRACT FROM AUTHOR]

Cet article, qui ne prétend pas constituer une revue exhaustive de la littérature, a pour but de (re)sensibiliser le lecteur aux bienfaits de l'animal de compagnie sur la santé médico-psychologique et sociale. Alors que les bienfaits physiques et locomoteurs d'avoir un animal de compagnie sont évidents, les autres relais, sociaux, cardiovasculaires, endocriniens et immunitaires sont, eux, moins bien connus. Chez les sujets avec ou sans pathologie cardiovasculaire, des liens ont été établis selon lesquels le fait d'être propriétaire d'un animal de compagnie a des effets sur l'hypertension, l'hyperlipidémie, l'activité physique, l'obésité, le système nerveux autonome, la réactivité cardiovasculaire et le taux de survie chez les sujets avec ou sans pathologie cardiovasculaire établie. Les relais par lesquels le bien-être physique est amélioré chez son propriétaire par l'animal sont essentiellement d'ordre cardiovasculaire, locomoteur et immunitaire. Le bien-être psychologique, lui, transite surtout par les relais sociaux. Il s'avère toutefois que la plupart des travaux sont essentiellement centrés sur des propriétaires de chiens, et qu'une lacune existe dans la littérature scientifique quant aux propriétaires de chats et de ce que l'on appelle les « NAC », à savoir les Nouveaux Animaux de Compagnie. Pet ownership seems to be medico-psychologically helpful and is thought to make a positive contribution to health, health behaviors and the general well-being of young and older people. For many years, researchers have hypothesized about the influence pets may have on their owners' health, specifically in regard to loneliness, stress, and anxiety. However, such information was anecdotal until the early 1980s, when scientific research demonstrated increased one-year survival rate for pet-owning cardiac patients. Subsequent research has expanded to explore the neuroendocrine pathways that may account for the positive physical and psychosocial health benefits of pet ownership. The widespread ownership of pets among people of various ages and the effort and money spent on behalf of pets suggests that a majority of owners derive a significant benefit from their companionship. People's histories with pets are likely to influence their pattern of ownership, the benefits they derive from ownership, their perceptions of the pet's role and the degree to which the pet influences the person's sense of well-being. This article, which does not claim to be an exhaustive review of the literature, aims to (re) sensitize the reader to the benefits of pet ownership and the human – companion animal interaction on medico-psychological health. Pet ownership, or just being in the presence of a companion animal, is associated with health benefits, including improvements in mental, social, and physiologic health status. While the physical and musculoskeletal benefits of having a pet are obvious, the other relays, social, cardiovascular and immune, are less well known. Even if dog ownership appears to facilitate walking behavior, only a minority of older dog owners walks their dogs. There are links between pet's ownership, and hypertension, hyperlipidemia, physical activity, obesity, autonomic function, heart rate variability, cardiovascular reactivity, enhanced secretion of S-IgA, stress-related parameters such as cortisol, improvement of immune system functioning, pain management and survival in people with and without established cardiovascular disease. Positive relationships show measurably higher oxytocin with lower cortisol and alpha-amylase levels. Psychological well-being, for its part, passes mainly through social relays. The psychological benefits of companion animals are most likely to be through reduction in depression, anxiety, social isolation, self-reported fear and anxiety, reported loneliness, and through enhanced empathy, improved learning, increased trustworthiness of and trust toward other persons. These benefits, however, are probably linked to the degree of bonding of the owner with the animal. It appears, however, that most of the existing work is focused primarily on dog owners, and that a gap exists in the scientific literature about cat owners and the so-called "NACs", namely New Pets. [ABSTRACT FROM AUTHOR]

Background: The impact of randomised controlled trials (RCTs) depends heavily on the presentation of the findings. Objective: Classically, RCT findings are presented in the form of absolute risk reduction (ARR), number needed to treat (NNT) to prevent one adverse outcome, and relative risk reduction (RRR) or hazard ratio (the most favourable means for drug marketing). However, the estimation of average survival gain (i.e. outcome postponement between a trial intervention and comparator) is an alternative and informative means of presenting the findings of RCTs. Study selection: Recent cardiovascular RCTs evaluating ezetimibe added to simvastatin, evolocumab, canakinumab, ticagrelor, rivaroxaban, ivabradine, LCZ 696 (sacubitril/valsartan), and transfemoral aortic valve replacement are analysed and discussed. Findings: The average survival gains ranged between 4.9 days on a composite end point with ticagrelor versus clopidogrel in randomised patients with acute coronary syndrome and 117 days of life expectancy obtained with TAVR versus standard therapy in patients with severe aortic stenosis deemed ineligible for surgery. Conclusions: Using outcome postponement as an additional measure of treatment effect is likely to be more easily understood than hazard ratio or RRR by both patients and physicians and could help when evaluating drugs. [ABSTRACT FROM AUTHOR]

In a society dominated by technological progress, sexuality, as a need of the human being, requires particular attention and to deserve a careful look is precisely the interaction between sexuality and robotics. The latter, was born as a field of research and interdisciplinary practice which, thanks to or because of its developments on human-machine interactions, offers possibilities and raises questions in the field of sexual health. The triumph of sex dolls, as satisfactory tools for sexual purposes, has stimulated the reflection of numerous scientists to produce a sexual tool that came ever closer to the imaginary of the human being: the sex robot. The sex robot, in fact, recalls the characteristics of the human being in a more sophisticated way: it is able to entertain conversations, to experience emotions and has a pre-programmed personality. The sex robot even has the ability to simulate sexual movements and positions and to imitate an orgasm. This sexual product, therefore, was developed specifically for sexual purposes. The "march" of sex robots in real life is becoming increasingly accentuated to the point that, according to some scientists, humans, in a few decades, will find themselves having more sexual relations with sex robots than with their fellow humans in the flesh. Faced with this unceasing technological evolution, the scientific community is questioning the relationship between sex robots and human beings, focusing on the ethical aspects related to the latter. It follows that the appearance of these sexual products in the cybernetic industry has divided the scientific community, and not, into two ethical orientations. The first, considers sex robots to be potential, rather than deficient, tools for solving problems, such as pedophilia and prostitution; the second, on the other hand, considers the sex robots products capable of generating negatively significant social changes, such as an increase in deviant sexual behavior, the robotization of consent and the alienation of the human being. The position of those who consider sex robots as simple products for the exclusive use of a few people has also emerged in the scientific community. In addition, health professionals and the whole community are wondering about the use of sex robots in the therapeutic field. In fact, although the efficacy of other sexual products, such as sex toys, has been widely proven in the treatment of orgasm problems, on the effectiveness of sex robots as a therapeutic tool, however, there is little documentation. The undoubted efficacy of sex robots in sexual therapy seems to have fueled a general skepticism by psychotherapists and physicians, who are relatively open to the use of sex robots in the treatment of sexual dysfunctions and whose attitudes are influenced by ethical considerations regarding their use. The skepticism towards these sexual products does not depend exclusively on a technophobic vision or on an excessive moralism but arises from the need to exploit the potential of this sexual product by protecting public health and reducing related risks. The ethical evaluation by physicians and psychotherapists depends on several factors, such as gender, age, reasons behind the use of these sexual products, past experiences and the different training of health professionals. In other words, female psychotherapists and physicians present more ethical concerns than their male colleagues. Furthermore, younger therapists more easily accept the application of technology in the therapeutic field than their older colleagues. Sex robots, even, are rated negatively when used as a consumer product rather than as a therapeutic tool. The critical attitude of psychotherapists and doctors also depends on the negative association of sex robots with emotional dependence and pornography. Different sexual health professionals, namely psychotherapists and physicians, evaluate the use of sexual robots in clinical practice differently: the former, in fact, tend to be more critical than the latter. However, in clinical and therapeutic settings, the use of sex robots seems to increase in several fields of intervention, such as in the treatment of erectile dysfunction, premature ejaculation and anxiety related to the first sexual relationship or, even, with socially isolated people, sex offenders and, above all, with people suffering from dementia, autism and physical disability. According to Döring and Poeschl (2018), the technological advancement of sexual products provides opportunities for the creation of health promotion projects and, therefore, the sex industry and engineers should jointly engage with other expert figures, such as health professionals, in perfecting robots that have a positive impact on people's sexual well-being. The aim of this work is to highlight the relationship between technology and sexuality, focusing attention on the risks and benefits deriving from the use of sex robots and emphasizing the attitudes of health professionals towards the use of sex robots in the therapeutic field. [ABSTRACT FROM AUTHOR]

Purpose: In recent years, second-look transurethral resection of bladder tumors (TURBT) has been recommended for patients with stage T1 bladder cancer after the initial TURBT for restaging and deciding the subsequent treatment. However, we believe that second-look TURBT has therapeutic benefits, such as low incidence of recurrence and progression. Therefore, we compare the differences in long-term outcome between patients who did and did not accept second-look TURBT for stage T1 bladder cancer. Methods: We assessed 504 patients diagnosed with urothelial carcinoma who underwent initial TURBT between January 2012 and December 2016 at a single medical center; of these patients, 177 were diagnosed with T1 bladder cancer during the initial TURBT, and we excluded no muscle from the specimen in the initial TURBT. The patients were categorized into groups 1 and 2 based on the acceptance of second-look TURBT, which was performed within 4–14 weeks after the initial TURBT. Group 1 underwent second-look TURBT, but group 2 did not. Both groups were followed-up for recurrence-free survival (RFS) and progression-free survival (PFS), and the risk factors for recurrence and progression were analyzed. Results: In total, 93 (52.5%) patients in group 1 underwent second-look TURBT, and 84 (47.5%) in group 2 did not. The 2-year RFS rates were 74.6% and 60.0% and the PFS rates were 91.2% and 87.5% in groups 1 and 2, respectively. Conclusion: This study demonstrated higher recurrence-free and progression-free survival rates for patients who underwent second-look TURBT. This result emphasizes the importance of second-look TURBT in stage T1 bladder cancer not only for restaging but also for therapeutic benefit. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Inflammatory bowel disease (IBD) is a chronic, recurrent, and remitting inflammatory disease resulting from immune dysregulation in the gut. As a clinically frequent disease, it can affect individuals throughout their lives, with multiple complications. Glucagon-like peptide 2 (GLP-2) is a potent epithelium-specific intestinal growth factor. However, native GLP-2 has a relatively short half-life in human circulation because of extensive renal clearance and rapid degradation by the proteolytic enzyme dipeptidyl peptidase-IV (DPP-IV). Previously, We prepared a recombinant GLP-2 variant (GLP-2②), which has increased half-life and activity as compared to the [Gly2]GLP-2 monomer. The aim of the present study was to investigate the protective potential of GLP-2② in IBD models. LPS-induced in vitro model and dextran sulfate sodium (DSS)-induced in vivo model were used to study the anti-inflammatory and therapeutic effect of GLP-2②. We found that treated with GLP-2② showed a significantly reduction in the secretion of inflammatory cytokines. Furthermore, GLP-2② alleviated symptoms of DSS-induced colitis. GLP-2② treated mice displayed an increase in body weight, lower colitis scores, and fewer mucosal damage compared with GLP-2 treated mice. MPO activities, protein expression of NLRP3 and COX2 in the colon tissues were significantly reduced in GLP-2② groups. Importantly, the ameliorative effect of GLP-2② was related to anti-apoptosis effect in colon tissues. These findings demonstrated that GLP-2② may offer a superior therapeutic benefit over [Gly2]GLP-2 monomer for treatment of IBD. [ABSTRACT FROM AUTHOR]

The success or failure of a therapeutic approach, medical or psychological, are influenced by many factors. Among them we can mention the patient’s insufficient knowledge about the disease, preconceptions of patient or caregiver’s fear of stigmatization, the issue regarding duration and side effects of treatment, cost of medicines and so on. Last but not least, the therapist’s ability to communicate accordingly to the beneficiaries’ comprehension and barriers encountered in the communication between actors directly involved in the therapeutic process (patient caregiver, psychologist, and doctor) can change the opportunity to obtain a suitable therapeutic benefit yet from beginning. Materials and methods: In order to assess the concordance between the messages sent by doctors and how they are received by patients and caregivers, we have applied a different questionnaire for the three categories of respondents mentioned above. These three distinct sets of questions were completed during 100 psychiatric consultations, in ambulatory regimen. Results: Comparative analysis of the questionnaire results has shown major differences between the information that doctors thought they had sent and what was actually received by patients and caregivers. Paradoxically, the more medical explanations were elaborated and detailed, the less volume of adequate information was taken home by beneficiaries. Conclusions: It is necessary for each of us to have a self-assessment of how we communicate with patients and which is the real benefit that we offer through our words. It is also mandatory to adapt the „language of medicine” to the common people understanding abilities (without medical training).

Résumé Objectif L’objectif de cette étude est de mettre en exergue les effets de l’utilisation de lieux d’échanges virtuels sur l’adaptation psychologique des patientes à la pathologie cancéreuse et notamment au cancer du sein. Méthode Pour ce faire, une revue de littérature a été effectuée. Les bases de données Cairn, Wiley Online Library, Taylor and Francis, ScienceDirect, Journal of Medical Internet Research (JMIR), Communication organisation, PubMed Central NCBI, APA PsycNET, Cross Ref, Oxford Journals, Persee, et Link Springer ont été explorés. Nous avons inclus toutes les études quantitatives et qualitatives portant sur l’utilisation de technologies ou de ressources en ligne en lien avec le cancer et plus particulièrement le cancer du sein. Résultats Cinquante-deux articles ont alors été sélectionnés. Quarante incluaient exclusivement des femmes atteintes du cancer du sein, et 12 incluaient différents types de cancer (sein, prostate, reins, poumon, sang…). La plupart des études ont rapporté des résultats significatifs en termes d’adaptation psychologique : une amélioration du bien-être émotionnel, psychologique et général ; une diminution de l’anxiété et du stress ; un meilleur optimisme ; une meilleure qualité de vie, ainsi qu’une meilleure participation à la santé. Conclusion Les résultats suggèrent une relation positive entre les lieux d’échanges pour les patientes et les résultats concernant la gestion de leur vécu par rapport à la maladie. Objectives We want to know the effects of virtual exchanges places, on psychological adaptation of women patients to cancer pathology, and especially breast cancer. Patients and methods A literature review was made. Databases Cairn, Wiley Online Library, Taylor and Francis, ScienceDirect Journal of Medical Internet Research (JMIR), Communication organisation, PubMed Central NCBI, APA PsycNET, EBSCOST, Cross Ref, Oxford Journals, Persee, and Link Springer were explored. We included all quantitative and qualitative studies on the use of technologies and online resources related to cancer, especially breast cancer. Results Fifty-two articles were selected. Forty only included women with breast cancer and 12 included different types of cancer (breast, prostate, kidney, leukemia…). Most of the studies have reported significant results in terms of psychological adaptation: improved emotional, psychological and general well-being; a decrease in anxiety and stress; a greater optimism; a better quality of life and a better participation in health. Conclusions Results suggest a positive relationship between spaces of exchange for women patients and outcomes related to their experiences in relation to the disease. [ABSTRACT FROM AUTHOR]

For most cancers, chemotherapeutic options are rapidly expanding, providing the oncologist with substantial choices. Therefore, there is a growing need to select the best systemic therapy, for any individual, that effectively halts tumor progression with minimal toxicity. Having the capability to predict benefit and to anticipate toxicity would be ideal, but remains elusive at this time. An alternative approach is an adaptive approach that involves close observation for treatment response and emergence of resistance. Currently, response to systemic therapy is estimated using radiographic tests. Unfortunately, radiographic estimates of response are imperfect and radiographic signs of response can be delayed. This is particularly problematic for targeted agents, as tumor shrinkage is often not apparent with these drugs. As a result, patients are exposed to prolonged courses of toxic drugs that may ultimately be found to be ineffective. A biomarker-based adaptive strategy that involves the serial analysis of the metabolome is attractive. The metabolome changes rapidly with changes in physiology. Changes in the circulating metabolome associated with various antineoplastic agents have been described, but further work will be required to understand what changes signify clinical benefit. We present an investigative approach for the discovery and validation of metabolomic response biomarkers, which consists of serial analysis of the metabolome and linkage of changes in the metabolome to measurable therapeutic benefit. Potential pitfalls in the development of metabolomic biomarkers of response and loss of response are reviewed. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) have been extensively used in both preclinical and clinical studies for a variety of diseases and injury. Accumulating evidence indicates that paracrine function through their secretomes is considered one of the primary attributes for MSC-mediated repair and regeneration. Secretomes from MSCs include both soluble factors and factors released within extracellular vesicles (EVs). Within EVs there are selective subsets of proteins, lipids, and nucleic acids that can modulate recipient cells and disease microenvironments. In this review, we summarize the current understanding of MSC-derived secretomes at molecular and therapeutic levels, focusing on their potential as novel cell-free therapies. [ABSTRACT FROM AUTHOR]

For most cancers, chemotherapeutic options are rapidly expanding, providing the oncologist with substantial choices. Therefore, there is a growing need to select the best systemic therapy, for any individual, that effectively halts tumor progression with minimal toxicity. Having the capability to predict benefit and to anticipate toxicity would be ideal, but remains elusive at this time. An alternative approach is an adaptive approach that involves close observation for treatment response and emergence of resistance. Currently, response to systemic therapy is estimated using radiographic tests. Unfortunately, radiographic estimates of response are imperfect and radiographic signs of response can be delayed. This is particularly problematic for targeted agents, as tumor shrinkage is often not apparent with these drugs. As a result, patients are exposed to prolonged courses of toxic drugs that may ultimately be found to be ineffective. A biomarker-based adaptive strategy that involves the serial analysis of the metabolome is attractive. The metabolome changes rapidly with changes in physiology. Changes in the circulating metabolome associated with various antineoplastic agents have been described, but further work will be required to understand what changes signify clinical benefit. We present an investigative approach for the discovery and validation of metabolomic response biomarkers, which consists of serial analysis of the metabolome and linkage of changes in the metabolome to measurable therapeutic benefit. Potential pitfalls in the development of metabolomic biomarkers of response and loss of response are reviewed.

Résumé Nous rendons ici hommage à Moreau (de Tours) pour son travail sur le haschisch et les essais thérapeutiques avant-gardistes qu’il a menés. Le cannabis est connu pour ses utilisations à visée thérapeutique depuis au moins 6000 ans avant notre ère. Nous examinons les données ethnobotaniques, biologiques et cliniques qui font état de ces usages. L’identification récente des premiers cannabinoïdes et de leurs mécanismes d’action via les récepteurs CB1 et CB2 a été à l’origine de la découverte d’un système endocannabinoïde complexe qui intervient dans de nombreux domaines de la vie : la régulation de la douleur et des mécanismes inflammatoires, la motricité et la spasticité, l’anxiété, le comportement alimentaire et les défenses immunitaires. La découverte de ce système endocannabinoïde ouvre de nouvelles perspectives thérapeutiques, mais il représente aussi des défis scientifiques et cliniques complexes liés à ses interactions avec d’autres systèmes de neurotransmission endogène. We pay tribute to Moreau (de Tours) for his work on haschish and the early clinical trials he has been conducting. Cannabis is known for its therapeutic properties for at least 6000 years. We examine the ethnobotanical, biological and clinical data which support such uses. The recent identification of the first cannabinoids and their mechanisms of action via CB1 and CB2 receptors have led to the discovery of a complex endocannabinoid system involved in many areas of life: the regulation of pain and inflammatory processes, motor spasticity, anxiety, eating behavior, immune systems. The discovery of the endocannabinoid system opens new therapeutic perspectives, but also presents complex scientific and clinical management challenges related to their interactions with other endogenous neurotransmission systems. [ABSTRACT FROM AUTHOR]

Objectives Brain imaging is now used to inform hypotheses relating not just to brain function but also the actions of drugs for depression. It can identify the relevant functional neuroanatomy of drug action and its relation to hot and cold cognition. Patients Patients with acute major depression or in recovery from same, in comparison with healthy controls. Results In the case of drugs for depression, we are limited by our understanding of the neurocognitive mechanisms involved. However, it has already been possible to show improved memory for positive descriptors for a range of drugs for depression and these are aligned in both healthy controls and patients. Brain imaging has shown corresponding early effects of drug treatment on how the amygdala responds to negative emotional stimuli. Study of cold cognition, while less developed, has attracted interest from the development of vortioxetine. Imaging studies in recovered patients and controls suggest cognitive enhancing effects of vortioxetine, which may be relevant to recovery from depression. Conclusions The challenge is to develop a coherent neurocognitive theory of depression that can explain or give context to the observed patterns of symptoms and their response to treatment. Brain imaging will play an important part in this programme of work. [ABSTRACT FROM AUTHOR]

Background: Flavonoidal class phytochemicals are the best examples of secondary metabolite found in different natural sources, including 'fruits, grains, vegetables, broccoli, tea, berries, wine, strawberries, apples, grapes, lettuce, and citrus fruit. Natural products are a rich source of flavonoidal compounds present in our diet source., Objective: Flavonoidal class chemicals can be subcategorized into chalcones, isoflavone, flavonols, catechin, flavones, flavanones, and anthocyanidin with respect to their basic chemical structures. Psoralea corylifolia L. belongs to the family Fabaceae and is an herbal medicine used in traditional Chinese Medicine for the treatment of inflammatory disorders, bacterial infections, and cancerous disorders., Methods: In the present work, scientific data have been collected from different databases and analyzed in order to find the therapeutic potential of corylin in medicine. Different scientific databases such as Google, Scopus, PubMed, Science Direct, etc., have been searched to collect the needed scientific information on corylin. Scientific information on corylin has been collected in the present work in order to know the pharmacological activities and medicinal uses of corylin in the scientific fields. However, analytical techniques data of corylin have also been collected and analyzed for standardization of Psoralea corylifolia and other medicinal plants., Results: Scientific data analysis of research works revealed the medicinal importance of Psoralea corylifolia and its important phytoconstituents corylin in medicine. Scientific data analysis revealed that corylin is a flavonoidal class phytochemical found in the nuts of Psoralea corylifolia L. Biological importance of corylin in bone differentiation, bone growth, and osteoporosis has been proven in this scientific research work. The anti-inflammatory, anti-oxidant, and antitumor activity of corylin has been also described in this medical literature. The biological importance of corylin in hyperlipidemia, insulin resistance, atherosclerosis, hepatocellular carcinoma, and neurodisorders have also been presented in this work., Conclusion: Scientific data analysis revealed the biological importance and therapeutic potential of corylin in the field of medicine., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Résumé: Le traitement au long cours des troubles de l’humeur conduit à une diminution marquée de la mortalité, notamment par suicide, de ces patients dont le risque suicidaire est majeur. Les données s’accumulent depuis 40ans pour proposer que le lithium bénéficie d’un effet suicide, lui conférant une place à part dans l’arsenal thérapeutique. En effet, le lithium présente un effet préventif des conduites suicidaires dans le trouble bipolaire comme dans le trouble unipolaire. Cet effet semble indépendant de son efficacité thymorégulatrice et supérieur à ce qui est observé avec les anticonvulsivants. Les mécanismes d’action du lithium continuent d’être étudiés tant ils sont complexes. Les pistes se multiplient pour envisager que le lithium agisse sur différents traits de vulnérabilité suicidaire ou qu’il puisse corriger des anomalies cérébrales associées au suicide. Les travaux scientifiques, de la molécule à l’épidémiologie, concourent à proposer le lithium en première ligne pour lutter contre le risque suicidaire des patients souffrant de troubles thymiques. Il est alors envisageable de recourir au lithium dans une perspective dimensionnelle, pour traiter le risque suicidaire, l’impulsivité et l’agressivité, et ce, indépendamment du traitement thymorégulateur choisi pour le patient. [Copyright &y& Elsevier]

Résumé: En dépit d’une diminution progressive de prescription au cours des vingt dernières années au profit d’autres thymorégulateurs anticonvulsivants ou antipsychotiques atypiques, le lithium demeure clairement le « Gold Standard » dans la prise en charge des troubles bipolaires. En termes d’efficacité d’une part, les sels de lithium ont fait la preuve dans les méta-analyses récentes d’une efficacité supérieure aux autres thymorégulateurs, notamment sur la réduction du risque suicidaire. En termes de rapport bénéfice-risque d’autre part, le lithium montre une réduction globale de la mortalité toutes causes confondues et un allongement de l’espérance de vie des patients bipolaires. Principal frein à la prescription, le risque d’insuffisance rénale terminale a été largement surévalué dans les anciennes études ; de prévalence faible (0,5 % d’insuffisance rénale terminale après 30ans d’exposition contre 0,25 % dans la population générale), il n’existe qu’à partir de 20 à 30ans d’utilisation chronique du lithium, généralement chez des patients surdosés, mal surveillés, et présentant souvent d’autres facteurs de vulnérabilité rénale. La surveillance du traitement est simple : elle comprend la fonction rénale, le dosage plasmatique de lithium, la TSH, la calcémie et la PTH. À la lumière de ces données récentes, les cliniciens doivent privilégier le choix du lithium en première intention chez les patients bipolaires, que ce soit en monothérapie ou en combinaison avec d’autres thymorégulateurs. En effet, le risque iatrogénique grave lié au lithium est extrêmement faible. Ce risque doit être mis en balance avec le risque suicidaire considérable dans cette maladie – environ un patient bipolaire sur dix meurt par suicide. Dans ce contexte, la diminution de prescription de lithium constitue une perte de chance avérée pour un nombre important de patients bipolaires. [Copyright &y& Elsevier]

Résumé: La pharmacologie dans les troubles bipolaires chez l’enfant et l’adolescent bénéficie d’un intérêt croissant mais peu d’études concernent le lithium. L’efficacité du lithium en monothérapie est modérée, avec des taux de réponse de l’ordre de 35 à 63 %. Le bénéfice des combinaisons thérapeutiques (association au divalproate de sodium, à la carbamazépine ou à la rispéridone) est net avec des taux de réponse atteignant 70 à 90 %. Le taux de rechute sous lithium en monothérapie est élevé (37 à 56 %) mais peu étudié. Si le profil de tolérance du lithium est rassurant, les effets secondaires rapportés semblent plus fréquents que chez l’adulte, et l’on ne dispose d’aucune donnée à long terme. Enfin, la lisibilité de tous ces résultats souffre d’une limite majeure liée à l’hétérogénéité clinique avec l’usage extensif du diagnostic de bipolarité chez l’enfant prépubère. Les études futures bénéficieront du cadre diagnostique distinguant les diagnostics de « Dysrégulation Émotionnelle Sévère » (ou « Temper Dysregulation Disorder with Dysphoria » dans le DSM-5) chez l’enfant et de trouble bipolaire de type I chez l’adolescent. [Copyright &y& Elsevier]

Résumé: L’efficacité du lithium dans la prise en charge du trouble bipolaire est largement reconnue depuis de nombreuses années. Il est toujours proposé comme traitement de première intention par la plupart des sociétés scientifiques à travers leurs recommandations thérapeutiques (« guidelines »). Le lithium est indiqué dans le traitement aigu de la crise maniaque, dans le traitement de l’épisode dépressif et dans la prévention des récidives maniaque et dépressive. Les preuves scientifiques sont particulièrement solides pour le traitement de la manie et la prévention des récidives. Les données d’efficacité dans le traitement aigu de la dépression sont moins convaincantes. Le but de cet article est de faire le point sur les données scientifiques démontrant l’intérêt du lithium dans la prise en charge du trouble bipolaire. [Copyright &y& Elsevier]

The increased prevalence of hypertensive patients with type 2 diabetes mellitus (T2DM) is evident worldwide, leading to a higher risk of cardiovascular disease onset, which is substantially associated with disabilities and mortality in the clinic. In order to achieve the satisfyingly clinical outcomes and prognosis, the comprehensive therapies have been conducted with a beneficial effect on both blood pressure and glucose homeostasis, and clinical trials reveal that some kind of antihypertensive drugs such as angiotensin converting enzyme inhibitors (ACE-I) may, at least in part, meet the dual requirement during the disease management. As a nonselective β-blocker, carvedilol is employed for treating many cardiovascular diseases in clinical practice, including hypertension, angina pectoris and heart failure, and also exhibit the effectiveness for glycemic control and insulin resistance. Apart from alleviating sympathetic nervous system activity, several causes, such as lowering oxygen reactive species, may contribute to the effects of carvedilol on controlling plasma glucose levels, suggesting a feature of this drug having multiple targets. Interestingly, numerous distinct K+ channels expressed in pancreatic β-cells and peripheral insulin-sensitive tissues, which play a sentential role in glucose metabolism, are subjected to extensive modulation of carvdilol, establishing a linkage between K+ channels and drug's effects on the control of glucose. A variety of evidence shows that the impact of carvedilol on different K+ channels, including Kv, K Ach , K ATP and K 2 P , can lead to positive influences for glucose homeostasis, contributing to its clinical beneficial effectiveness in treatment of hypertensive patients with T2DM. This review focus on the control of plasma glucose conferred by carvedilol modulation on K+ channels, providing the novel mechanistic explanation for drug's actions. [Display omitted] [ABSTRACT FROM AUTHOR]

Estrogens, the sex hormones, have the potential to govern multiple cellular functions, such as proliferation, apoptosis, differentiation, and homeostasis, and to exert numerous beneficial influences for the cardiovascular system, nervous system, and bones in genomic and/or non-genomic ways. Converging evidence indicates that estrogens serve a crucial role in counteracting neurodegeneration and ischemic injury; they are thereby being considered as a potent neuroprotectant for preventing neurological diseases such as Alzheimer's disease and stroke. The underlying mechanism of neuroprotective effects conferred by estrogens is thought to be complex and multifactorial, and it remains obscure. It is well established that the K + channels broadly expressed in a variety of neural subtypes determine the essential physiological features of neuronal excitability, and dysfunction of these channels is closely associated with diverse brain deficits, such as ataxia and epilepsy. A growing body of evidence supports a neuroprotective role of K + channels in malfunctions of nervous tissues, with the channels even being a therapeutic target in clinical trials. As multitarget steroid hormones, estrogens also regulate the activity of distinct K + channels to generate varying biological actions, and accumulated data delineate that some aspects of estrogen-mediated neuroprotection may arise from the impact on multiple K + channels, including Kv, BK, K ATP , and K 2P channels. The response of these K + channels after acute or chronic exposure to estrogens may oppose pathological abnormality in nervous cells, which serves to extend our understanding of these phenomena., Competing Interests: The author declares 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 Li.)