False-Profile Radiograph Sourcil-Edge and Bone-Edge Measurements Correlate to Different Weightbearing Regions of the Acetabulum: A 3-Dimensional Analysis.

BACKGROUND: The acetabular sourcil is commonly interpreted as a reliable radiographic representation of the weightbearing dome of the acetabulum, despite limited modern data. Assessment of weightbearing acetabular coverage has been described using both the sourcil edge and bone edge as anatomic landmarks, leading to confusion and potential misguidance in surgical decision-making and thus compromised patient outcomes. PURPOSE/HYPOTHESIS: The purpose of this study was to characterize the 3-dimensional (3D) anatomic correlates of the sourcil-edge and bone-edge radiographic measurements on false-profile radiographs. It was hypothesized that the sourcil edge would represent anterolateral coverage and the bone edge would represent anterior coverage. STUDY DESIGN: Descriptive laboratory study. METHODS: A total of 80 hips were grouped by large or small differences between bone-edge and sourcil-edge anterior center-edge angles, based on upper and lower quartiles of discrepancy. Three-dimensional surface mesh models and digitally reconstructed radiographs were generated from hip computed tomography scans. Sourcil-edge and bone-edge anterior center-edge angles were identified on digitally reconstructed radiographs and registered to the 3D models with fiducial markers. Intersections of bone-edge and sourcil-edge projection lines with the acetabular rim were obtained from the 3D models. RESULTS: The bone-edge and sourcil-edge projections intersected the acetabular rim at clockface means of 2:05 ± 0:22 and 1:12 ± 0:25, respectively. The 3D models consistently demonstrated that, in both large- and small-discrepancy groups, the sourcil edge corresponded to the acetabular area just posterior to the anterior inferior iliac spine (AIIS) projection, and the bone edge corresponded to the weightbearing region inferior to the AIIS. Additionally, in large-discrepancy hips, the bone edge corresponded to more prominent acetabular coverage in the region inferomedial to the AIIS when compared with the small-discrepancy hips. CONCLUSION: On false-profile radiographs, the sourcil edge corresponds to superior femoral head coverage, and the bone edge corresponds to anterosuperior coverage. Radiographs with a large discrepancy between sourcil-edge and bone-edge measurements demonstrate acetabular rim prominence in the region of the AIIS. CLINICAL RELEVANCE: Characterizing the anatomic weightbearing regions of the acetabulum represented on false-profile radiographs facilitates improved clinical and intraoperative decision-making in hip preservation surgery, including acetabuloplasty and periacetabular osteotomy.

The Role of Cannabinoid-1 Receptor Ligands in the Ovalbumin-Induced Mouse Model of Allergic Asthma: Is It Related to Transient Receptor Potential Vanilloid-1 Channels?

Objectives: The aim of this study was to investigate the role of cannabinoid (CB1) receptors on airway inflammation and hypersensitivity in allergic asthma and the potential interactions with TRPV1 channels. Materials and Methods: BALB/c mice were sensitized and provoked with ovalbumin to create a model of allergic asthma. CB1 selective agonist arachidonoyl 2'-chloroethylamide (ACEA) was administered intraperitoneally at doses of 0.5, 3, and 5 mg/kg. Receptor antagonism studies were performed utilizing selective CB1 antagonists AM251 at a dose of 3 mg/kg. TRPV1 channel was selectively blocked by capsazepine at a dose of 2.5 mg/kg. Penh values were recorded in vivo by a whole-body plethysmograph under methacholine challenge. Inflammatory cell count was performed in bronchoalveolar lavage fluid (BALF). Serum levels of proinflammatory cytokines were measured by Enzyme-Linked ImmunoSorbent Assay (ELISA). Inflammation in the lung tissue was scored histopathologically. Statistical significance was determined using one-way analysis of variance or Kruskal-Wallis test and expressed as p<0.05. Results: In sensitized animals, provocation with inhaled ovalbumin increased Penh values, serum interleukin (IL)-4, IL-5, IL-13 levels, eosinophil, neutrophil, lymphocyte, macrophage counts in BALF, and inflammation in the lung tissue. ACEA applications did not significantly alter Penh values, BALF inflammatory cell levels, and histological changes related to inflammation in the lung tissue according to the disease group; however, only at a dose of 5 mg/kg, it reduced the levels of the inflammatory cytokine IL-4. AM251 decreased Penh values, eosinophil and neutrophil migration in BALF, and inflammation score of lung tissue compared with the disease group. Although BALF inflammatory cell levels and Penh values were higher in the AM251+ACEA group than in the AM251 group, the differences were insignificant. In the CPZ+ACEA group, Penh values were significantly higher, and serum IL-4 and IL-13 levels and BALF eosinophil counts were lower than that in the CPZ group. Conclusions: This study demonstrated an important role of the CB1 receptors in allergic asthma. CB1 antagonism reduced airway hyperresponsiveness and inflammation and showed immunomodulatory effects. The effect of the CB1 agonist ACEA on asthma does not appear to be related to TRPV1 channels.

Molecular Engineering of Electrosprayed Hydrogel Microspheres to Achieve Synergistic Anti-Tumor Chemo-Immunotherapy with ACEA Cargo.

Molecular engineering of drug delivering platforms to provide collaborative biological effects with loaded drugs is of great medical significance. Herein, cannabinoid receptor 1 (CB1)- and reactive oxygen species (ROS)-targeting electrosprayed microspheres (MSs) are fabricated by loading with the CB1 agonist arachidonoyl 2'-chloroethylamide (ACEA) and producing ROS in a photoresponsive manner. The synergistic anti-tumor effects of ACEA and ROS released from the MSs are assessed. ACEA inhibits epidermal growth factor receptor signaling and altered tumor microenvironment (TME) by activating CB1 to induce tumor cell death. The MSs are composed of glycidyl methacrylate-conjugated xanthan gum (XGMA) and Fe3+, which form dual molecular networks based on a Fe3+-(COO-)3 network and a C═C addition reaction network. Interestingly, the Fe3+-(COO-)3 network can be disassembled instantly under the conditions of lactate sodium and ultraviolet exposure, and the disassembly is accompanied by massive ROS production, which directly injures tumor cells. Meanwhile, the transition of dual networks to a single network boosts the ACEA release. Together, the activities of the ACEA and MSs promote immunogenic tumor cell death and create a tumor-suppressive TME by increasing M1-like tumor-associated macrophages and CD8+ T cells. In summation, this study demonstrates strong prospects of improving anti-tumor effects of drug delivering platforms through molecular design.

The effects of leptin and cannabinoid CB1 receptor agonist/antagonist in cerebral tissues of epileptic rats

SUMMARY OBJECTIVE: In this study, the effects of leptin, cannabinoid-1 (CB1) receptor agonist ACEA and antagonist AM251, and the interactions between leptin and CB1 receptor agonist/antagonist on oxidant and antioxidant enzymes in the cerebrum, cerebellum, and pedunculus cerebri tissue samples were investigated in the penicillin-induced epileptic model. METHODS: Male Wistar albino rats (n=56) were included in this study. In anesthetized animals, 500 IU penicillin-G potassium was injected into the cortex to induce epileptiform activity. Leptin (1 μg), ACEA (7.5 μg), AM251 (0.25 μg), and the combinations of the leptin+ACEA and leptin+AM251 were administered intracerebroventricularly (i.c.v.) after penicillin injections. Malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) levels were measured in the cerebral tissue samples and plasma with the ELISA method. RESULTS: MDA levels increased, while SOD and GPx levels decreased after penicillin injection in the cerebrum and cerebellum. The efficacy of penicillin on SOD, MDA and GPx levels was further enhanced after leptin or AM251 injections. Whereas, ACEA decreased the MDA levels and increased GPx levels compared with the penicillin group. Administration of AM251+leptin did not change any oxidation parameter compared with the AM251. Furthermore, co-administration of ACEA and leptin significantly increased oxidative stress compared with the ACEA-treated group by increasing MDA and decreasing GPx levels. CONCLUSION: It was concluded that leptin reversed the effect of ACEA on oxidative stress. Co-administration of AM251 and leptin did not change oxidative stress compared with the AM251-treated group suggesting AM251 and leptin affect oxidative stress using the same pathways.

How are experiences and acceptability of child maltreatment related to resilience and posttraumatic growth: a cross cultural study.

Background: Post-traumatic growth (PTG) and resilience, regarded as positive psychological change following a traumatic experience, are under-researched across cultures in people exposed to child maltreatment (CM).Objective: We investigated how experiences and the perceived acceptability of CM are related to resilience and PTG in countries with different cultures, living standards, and gross national income.Method: A total of 478 adults from Cameroon (n = 111), Canada (n = 137), Japan (n = 108), and Germany (n = 122) completed an online survey with self-reported questionnaires, including the Brief Resilience Scale and the Post Traumatic Growth Inventory-Short Form.Results: Across countries, self-reported male gender and age were positively associated with resilience, while experiences of physical abuse and emotional maltreatment were negatively associated with resilience. Experiences of emotional maltreatment were positively associated with PTG. Higher levels of PTG and resilience were found amongst Cameroonian participants as compared to other countries.Conclusion: Our results suggest that positive changes following CM can vary significantly across cultures and that experiences of specific CM subtypes, but not the perceived acceptability of CM, may be important for a deeper understanding of how individuals overcome trauma and develop salutogenic outcomes. Our findings may inform CM intervention programmes for an enhanced cultural sensitivity.

Across the four countries (Canada, Cameroon, Germany, Japan), more experiences of physical abuse and emotional maltreatment were associated with lower resilience; more experiences of emotional maltreatment were associated with greater post-traumatic growth.Higher levels of post-traumatic growth and resilience were found in Cameroon as compared to other countries.Positive changes following child maltreatment vary across cultures and experiences of specific child maltreatment subtypes, but the perceived acceptability of child maltreatment did not exert an influence on salutogenic post-traumatic outcomes.

Childhood maltreatment history and trauma-specific predictors of parenting stress in new fathers.

For new fathers, parenting stress is a risk factor for impaired early parenting and child maltreatment perpetration. Predictors of parenting stress, including fathers' own experiences of trauma, could be useful intervention targets to support new fathers. We aim to examine associations between new fathers' own histories of child maltreatment, and their perinatal mental health, relationships, and parenting stress. We recruited 298 first-time fathers for a survey that measured child maltreatment history, trauma sequelae including posttraumatic stress disorder (PTSD), major depressive disorder (MDD), interpersonal reactivity, substance use, anger expression, coparenting quality, and parenting stress. On the Parenting Stress Index (PSI) (from 36 to 180), bivariate analysis demonstrated that new fathers who experienced child maltreatment (n = 94) had significantly higher parenting stress (x̅ = 85.3, σ = 18.7) than those who did not (n = 204; x̅ = 76.0, σ = 16.6; P < .000). Hierarchical linear regression modeling indicated that a child maltreatment history, PTSD, and MDD were significantly associated with parenting stress. The strongest predictors of parenting stress were coparenting quality and complex trauma sequelae-interpersonal reactivity and anger expression. Interventions to reduce fathers' parenting stress by targeting known mental health and relationship sequelae of maltreatment are promising avenues to breaking intergenerational transmission of child maltreatment and psychiatric vulnerability.

Para nuevos papás, el estrés de crianza es un factor de riesgo para la deficiente crianza temprana y para cometer maltrato infantil. Los factores de predicción del estrés de crianza, incluyendo las propias experiencias de trauma de los papás, pueden ser útiles metas de intervención para apoyar a los nuevos papás. Nos propusimos examinar las asociaciones entre las propias historias de maltrato de los nuevos papás, y su salud mental perinatal, relaciones y estrés de crianza. Reclutamos 298 papás primerizos para una encuesta que medía la historia de maltrato infantil, la secuela de trauma incluyendo el trastorno de estrés postraumático (PTSD), el trastorno depresivo serio (MDD), la reactividad interpersonal, el uso de sustancias, la expresión de ira, la calidad de la crianza compartida, así como el estrés de crianza. En el Índice de Estrés de Crianza (de 36-180), los análisis bivariantes demostraron que los nuevos papás que habían experimentado maltrato infantil (N = 94) tenían significativamente un mayor estrés de crianza (x̅ = 85.3, σ = 18.7) que aquellos que no habían tenido tal experiencia (N = 204; x̅ = 76.0, σ = 16.6; P<.000). El modelo de regresión lineal jerárquica indicó que una historia de maltrato infantil, PTSD y MDD estaban significativamente asociados con el estrés de crianza. Los más fuertes factores de predicción del estrés de crianza fueron la calidad de la crianza compartida y la compleja secuela de trauma-la reactividad interpersonal y la expresión de la ira. Las intervenciones para reducir el estrés de crianza de los papás por medio del enfoque en la salud mental conocida y las secuelas en la relación del maltrato son una vía prometedora para romper la transmisión intergeneracional del maltrato infantil y la vulnerabilidad siquiátrica.

Pour les nouveaux pères le stress de parentage est un facteur de risque pour le parentage précoce compromis et la perpétration de maltraitance de l'enfant. Les prédicteurs de stress de parentage, y compris les propres expériences de trauma des pères, pourraient être des cicles d'intervention utiles afin de soutenir les nouveaux pères. Nous nous sommes donné pour but d'examiner les liens entre le propre passé de maltraitance de l'enfant des nouveaux pères et leur santé mentale périnatale, leurs relations et le stress de parentage. Nous avons recruté 298 nouveaux pères (pères pour la première fois) pour un sondage mesurant l'histoire de la maltraitance de l'enfant, les séquelles de trauma y compris les troubles de stress post-traumatique (TSPT), les troubles dépressifs majeurs (MDD en anglais), la réactivité interpersonnelle, la toxicomanie, l'expression de colère et la qualité du co-parentage ainsi que le stress parental. Pour l'Index de Stress de Parentage (de 36-180), une analyse bivariée a montré que les nouveaux pères qui avaient fait l'expérience de maltraitance de l'enfance (N = 94) avaient un stress de parentage bien plus élevé (x̅ = 85,3, σ = 18,7) que ceux n'en ayant pas fait l'expérience (N = 204; x̅ = 76,0, σ = 16,6; P<,000). Un modèle de régression linéaire hiérarchique a indiqué qu'un passé de maltraitance de l'enfant, le TSPT et le MDD étaient fortement liés au stress de parentage. Les facteurs de prédiction les plus forts de stress de parentage étaient la qualité du co-parentage et les séquelles de trauma complexes - réactivité interpersonnelle et l'expression de la colère. Les interventions pour réduire le stress de parentage des pères en ciblant la santé mentale connue et les séquelles de maltraitance sont un chemin prometteur pour casser la transmission intergénérationnelle de la maltraitance de l'enfant et la vulnérabilité psychiatrique.

The electrophysiological and behavioral evaluation of the peptide hemopressin and cannabinoid CB1 receptor agonist and antagonist in pentylenetetrazol model of epilepsy in rats.

This study endeavoured to assess the effect of hemopressin (Hp), a nano peptide obtained from the alpha chain of hemoglobin, on chronic epileptic activity and its potential correlation with cannabinoid receptor type 1 (CB1). Male Wistar albino rats (230-260 g) were used. The kindling process was conducted by administering a sub-convulsant dose of pentylenetetrazol (PTZ) (35 mg/kg, i.p) three times a week for a maximum of 10 weeks. Tripolar electrodes and external cannula guides for intracerebroventricular (i.c.v) injections were surgically implanted in the skulls of kindled rats. On the day of the experiment, doses of Hp, AM-251, and ACEA were administered prior to the PTZ injections. Electroencephalography recordings and behavioural observations were conducted simultaneously for 30 min after the PTZ injection. The administration of Hp (0.6 µg, i.c.v) resulted in a decrease in epileptic activity. The CB1 receptor agonist ACEA (7.5 µg, i.c.v) showed an anticonvulsant effect, but the CB1 receptor antagonist AM-251 (0.5 µg, i.c.v) displayed a proconvulsant effect. The co-administration of Hp (0.6 µg, i.c.v) and ACEA (7.5 µg, i.c.v) and of Hp (0.6 µg, i.c.v) and AM-251 (0.5 µg, i.c.v) produced an anticonvulsant effect. However, when AM-251 was administered prior to Hp, it produced a proconvulsant impact that overrode Hp's intended anticonvulsant effect. Interestingly, the co-administration of Hp (0.03 µg) + AM-251 (0.125 µg) unexpectedly exhibited an anticonvulsant effect. Electrophysiological and behavioural evaluations demonstrated the anticonvulsant effect of Hp in the present model, highlighting the possibility that Hp may act as an agonist for the CB1 receptor.

The Cannabinoid Ligand Arachidonyl-2'-Chloroethylamide (ACEA) Ameliorates Depressive and Overactive Bladder Symptoms in a Corticosterone-Induced Female Wistar Rat Model.

There is growing need to increase the knowledge on the cannabinoid ligands in the treatment of overactive bladder. Among potential candidates, arachidonyl-2'-chloroethylamide (ACEA), a selective cannabinoid CB1 receptor agonist is proposed. The aim of this paper was to determine if ACEA, a selective cannabinoid CB1 receptor agonist, could reverse the effects of corticosterone (CORT), characteristic of depressive and bladder overactivity potential. The animals (48 female rats) were divided into four groups: I-control, II-received CORT, III-received ACEA, and IV-received the combination of CORT and ACEA. The conscious cystometry, forced swim test (FST), and locomotor activity measurements were performed 3 days after the last dose of ACEA, followed by ELISA measurements. In group IV, ACEA restored urodynamic parameters that were altered by CORT. CORT prolonged the immobility time in FST and the values were lowered by ACEA. ACEA normalized the expression of c-Fos in all the analyzed central micturition centers (group IV vs. group II). ACEA restored the CORT-induced changes in the biomarkers in urine (BDNF, NGF), bladder detrusor (VAChT, Rho kinase), bladder urothelium (CGRP, ATP, CRF, OCT-3, TRPV1), and hippocampus (TNF-α, IL-1ß and Il-6, CRF, IL-10, BDNF, NGF). In conclusion, ACEA was proven to reverse CORT-induced changes in both cystometric and biochemical parameters that are determinants of OAB/depression, which represents an example of an existing link between OAB and depression via cannabinoid receptors.

Inhibition of the Human Neuronal Sodium Channel Nav1.9 by Arachidonyl-2-Chloroethylamide, An Analogue of Anandamide in a hNav1.9/rNav1.4 Chimera, An Experimental and in Silico Study.

Cannabinoids regulate analgesia, which has aroused much interest in identifying new pharmacological therapies in the management of refractory pain. Voltage-gated Na+ channels (Navs) play an important role in inflammatory and neuropathic pain. In particular, Nav1.9 is involved in nociception and the understanding of its pharmacology has lagged behind because it is difficult to express in heterologous systems. Here, we utilized the chimeric channel hNav1.9_C4, that comprises the extracellular and transmembrane domains of hNav1.9, co-expressed with the ß1 subunit on CHO-K1 cells to characterize the electrophysiological effects of ACEA, a synthetic surrogate of the endogenous cannabinoid anandamide. ACEA induced a tonic block, decelerated the fast inactivation, markedly shifted steady-state inactivation in the hyperpolarized direction, decreasing the window current and showed use-dependent block, with a high affinity for the inactivated state (ki = 0.84 µM). Thus, we argue that ACEA possess a local anaesthetic-like profile. To provide a mechanistic understanding of its mode of action at the molecular level, we combined induced fit docking with Monte Carlo simulations and electrostatic complementarity. In agreement with the experimental evidence, our computer simulations revealed that ACEA binds Tyr1599 of the local anaesthetics binding site of the hNav1.9, contacting residues that bind cannabinol (CBD) in the NavMs channel. ACEA adopted a conformation remarkably similar to the crystallographic conformation of anandamide on a non-homologous protein, obstructing the Na+ permeation pathway below the selectivity filter to occupy a highly conserved binding pocket at the intracellular side. These results describe a mechanism of action, possibly involved in cannabinoid analgesia.

When not teaming up puts parents at risk: Coparenting and parental burnout in dual-parent heterosexual families in Switzerland.

Parental burnout refers to loss of energy and pleasure in the parental role. It is predictive of psychopathological outcomes in parents and dysfunctional parenting behaviors. Support of parental duties is central to alleviation of parental burden and prevention of burnout. Coparenting is the concept related to interparental mutual support in rearing a child. However, the links between coparenting and parental burnout have yet to be assessed. We thus aimed in this study to assess which dimensions of coparenting are linked with parental burnout. A total of 306 participants from the French-speaking part of Switzerland (120 fathers, 186 mothers) completed online questionnaires about parental burnout, their coparental relationship, and sociodemographic characteristics. We performed hierarchical regressions, entering sociodemographic characteristics in a first block and coparenting dimensions in a second block. Results showed that (i) a higher number of children and having younger children are linked to higher burnout; (ii) coparenting exposure to conflict is related to higher burnout, whereas endorsement of the partner's parenting is related to lower burnout; and (iii) no interaction effect occurs between sociodemographic characteristics and coparenting variables. Coparenting thus significantly contributes to the occurrence of burnout syndrome. Working on the coparental relationship preventively in parental educational programs or at a relational systemic level in therapy may help prevent burnout. Treating one parent only may not be sufficient to alleviate burnout, as negative coparenting could counter the effect of individual therapy.

Anti-cancer effects of selective cannabinoid agonists in pancreatic and breast cancer cells.

OBJECTIVE: Cancer ranks first among the causes of morbidity and mortality all over the world, and it is expected to continue to be the main cause of death in the coming years. Therefore, new molecular targets and therapeutic strategies are urgently needed. In many cases, some reports show increased levels of endocannabinoids and their receptors in cancer, a condition often associated with tumour aggressiveness. Recent studies have suggested that cannabinoid-1/2 receptors contribute to tumour growth in a variety of cancers, including pancreatic, colon, prostate, and breast cancer. Understanding how cannabinoids can regulate key cellular processes involved in tumorigenesis, such as: cell proliferation and cell death, is crucial to improving existing and new therapeutic approaches for the cancer patients. The present study was aimed to characterize the in-vitro effect of L-759633 (a selective CB2 receptor agonist), ACPA (a selective CB1 receptor agonist) and ACEA (a selective CB1 receptor agonist) on the cell proliferation, clonogenicity, and apoptosis in pancreatic (PANC1) and breast (MDA-MB-231) cancer cells. METHODS: The viability and/or proliferation of cells were detected by MTS assay. A clonogenic survival assay was used to detect the ability of a single cell to grow into a colony. Apoptosis was determined with Annexin V staining (Annexin V-FITC/PI test) and by analyzing the expression of Bcl-2-associated X protein (Bax) and B-cell lymphoma 2 (Bcl-2). RESULTS: We found that selective CB1/2 agonists suppressed cell proliferation, clonogenicity and induced proapoptotic function in human PANC1 pancreatic and MDA-MB-231 breast cancer cells. Based on our findings, these agonists led to the inhibition of both cell viability and clonogenic growth in a dose dependent manner. CB1/2 agonists were observed to induce intrinsic apoptotic pathway by upregulating Bax, while downregulating Bcl-2 expression levels. CONCLUSION: Our data suggests that CB1/2 agonists have the therapeutic potential through the inhibition of survival of human PANC1 pancreatic and MDA-MB-231 breast cancer cells and also might be linked with further cellular mechanisms for the prevention (Fig. 5, Ref. 49).

Digressions on the fascist state of mind. Psychoanalytic perspectives on narcissism and 'social-ism'.

This paper explores some features of the theoretical and clinical problem of narcissism in the light of Bion's model of the mind, with particular reference to the distinction between narcissism and 'social-ism'. This model is compared and contrasted to Jung's speculations on the relationship between adaptation and individuation as a process implying a sense of guilt. Jung's highlighting of the element of guilt is directly connected to his subjective experience depicted in the Red Book in the episode of the 'Murder of the hero'. Aspects of pathological narcissism are also explored in the paper, through briefly analysing some passages of Pasolini's movie Salò or the 120 days of Sodom.

Cet article étudie quelques caractéristiques du problème théorique et clinique du narcissisme, à la lumière du modèle de l'esprit de Bion, en faisant particulièrement référence à la distinction entre narcissisme et 'social-isme'. Ce modèle est comparé et mis en contraste avec les spéculations de Jung concernant la relation entre adaptation et individuation, en tant que processus impliquant un sentiment de culpabilité. L'accent que met Jung sur l'élément de culpabilité est directement relié à son expérience subjective décrite dans le Livre Rouge dans l'épisode du « Meurtre du héros¼. L'article explore également des aspects du narcissisme pathologique, en analysant brièvement des passages du film de Pasolini « Salo, ou les 120 journées de Sodome ¼.

El presente trabajo explora algunos rasgos del problema teórico y clínico del narcisismo a la luz del modelo de la mente de Bion, con particular referencia a la distinción entre narcisismo y 'social-ismo'. Este modelo es comparado y contrastado con la especulación de Jung sobre la relación entre adaptación e individuación como un proceso que implica un sentimiento de culpa. La acentuación de Jung del elemento de culpa está directamente conectada con su experiencia subjetiva ilustrada en el Libro Rojo, en el episodio de la 'Muerte del héroe'. Se exploran también aspectos del narcisismo patológico, a través de un breve análisis de algunos pasajes de la película de Pasolini: Saló o los 120 días de Sodoma.

Este artigo explora algumas características do problema teórico e clínico do narcisismo à luz do modelo mental de Bion, com particular referência à distinção entre narcisismo e "socialismo". Esse modelo é comparado e contrastado com as especulações de Jung sobre a relação entre adaptação e individuação como um processo que implica um sentimento de culpa. O destaque de Jung sobre o elemento de culpa está diretamente ligado à sua experiência subjetiva descrita no Livro Vermelho no episódio do 'Assassinato do herói'. Aspectos do narcisismo patológico também são explorados no artigo, analisando brevemente algumas passagens do filme Salò de Pasolini ou os 120 dias de Sodoma.

Synthetic cannabinoids reduce the inflammatory activity of microglia and subsequently improve neuronal survival in vitro.

Microglia are resident immune cells of the brain that survey the microenvironment, provide trophic support to neurons, and clear debris to maintain homeostasis and healthy brain function. Microglia are also drivers of neuroinflammation in several neurodegenerative diseases. Microglia produce endocannabinoids and express both cannabinoid receptor subtypes suggesting that this system is a target to suppress neuroinflammation. We tested whether cannabinoid type 1 (CB1) or type 2 (CB2) receptors could be targeted selectively or in combination to dampen the pro-inflammatory behavior of microglia, and whether this would have functional relevance to decrease secondary neuronal damage. We determined that components of the endocannabinoid system were altered when microglia are treated with lipopolysaccharide and interferon-gamma and shift to a pro-inflammatory phenotype. Furthermore, pro-inflammatory microglia released cytotoxic factors that induced cell death in cultured STHdhQ7/Q7 neurons. Treatment with synthetic cannabinoids that were selective for CB1 receptors (ACEA) or CB2 receptors (HU-308) dampened the release of nitric oxide (NO) and pro-inflammatory cytokines and decreased levels of mRNA for several pro-inflammatory markers. A nonselective agonist (CP 55,940) exhibited similar influence over NO release but to a lesser extent relative to ACEA or HU-308. All three classes of synthetic cannabinoids ultimately reduced the secondary damage to the cultured neurons. The mechanism for the observed neuroprotective effects appeared to be related to cannabinoid-mediated suppression of MAPK signaling in microglia. Taken together, the data indicate that activation of CB1 or CB2 receptors interfered with the pro-inflammatory activity of microglia in a manner that also reduced secondary damage to neurons.

Dual action of the cannabinoid receptor 1 ligand arachidonyl-2'-chloroethylamide on calcitonin gene-related peptide release.

BACKGROUND: Based on the current understanding of the role of neuropeptide signalling in migraine, we explored the therapeutic potential of a specific cannabinoid agonist. The aim of the present study was to examine the effect of the synthetic endocannabinoid (eCB) analogue, arachidonyl-2'-chloroethylamide (ACEA), on calcitonin gene-related peptide (CGRP) release in the dura and trigeminal ganglion (TG), as cannabinoids are known to activate Gi/o-coupled cannabinoid receptors type 1 (CB1), resulting in neuronal inhibition. METHODS: The experiments were performed using the hemi-skull model and dissected TGs from male Sprague-Dawley rats. CGRP release was induced by either 60 mM K+ (for depolarization-induced stimulation) or 100 nM capsaicin (for transient receptor potential vanilloid 1 (TRPV1) -induced stimulation) and measured using an enzyme-linked immunosorbent assay. The analysis of CGRP release data was combined with immunohistochemistry in order to study the cellular localization of CB1, cannabinoid receptor type 2 (CB2), CGRP and receptor activity modifying protein 1 (RAMP1), a subunit of the functional CGRP receptor, in the TG. RESULTS: CB1 was predominantly expressed in neuronal somas in which colocalization with CGRP was observed. Furthermore, CB1 exhibited colocalization with RAMP1 in neuronal Aδ-fibres but was not clearly expressed in the CGRP-immunoreactive C-fibres. CB2 was mainly expressed in satellite glial cells and did not show substantial colocalization with either CGRP or RAMP1. Without stimulation, 140 nM ACEA per se caused a significant increase in CGRP release in the dura but not TG, compared to vehicle. Furthermore, 140 nM ACEA did not significantly modify neither K+- nor capsaicin-induced CGRP release. However, when the TRPV1 blocker AMG9810 (1 mM) was coapplied with ACEA, K+-induced CGRP release was significantly attenuated in the TG and dura. CONCLUSIONS: Results from the present study indicate that ACEA per se does not exhibit antimigraine potential due to its dual agonistic properties, resulting in activation of both CB1 and TRPV1, and thereby inhibition and stimulation of CGRP release, respectively.

The Impact of CB1 Receptor on Inflammation in Skeletal Muscle Cells.

BACKGROUND: Various factors trigger the inflammatory response and cytokine activation in skeletal muscle. Inflamed muscle will exhibit significant levels of inflammation and cytokine activity. Interleukin-6 (IL-6), a pro-inflammatory cytokine, exerts pleiotropic effects on skeletal muscle. Endocannabinoid produced by all cell types binds to a class of G protein-coupled receptors, in particular cannabinoid CB1 receptors, to induce skeletal muscle actions. OBJECTIVE: The purpose of this research was to discover whether activation of cannabinoid CB1 receptors in L6 skeletal muscle cells may promote IL-6 gene expression. MATERIALS AND METHODS: L6 skeletal muscle cells were cultured in 25 cm2 flasks and quantitative reverse transcription-polymerase chain reaction (probe-based) utilised to quantify IL-6 gene expression levels among different treatment settings. RESULTS: Arachidonyl-2'-chloroethylamide (ACEA) 10 nM, a persistent selective CB1 receptor agonist, promotes IL-6 gene expression in a time-dependent manner. Rimonabant 100 nM, a selective cannabinoid CB1 receptor antagonist, blocks the impact of ACEA. However, insulin does not change IL-6 gene expression. CONCLUSION: For the first time, a unique link between ACEA and IL-6 up-regulation has been established; IL-6 up-regulation generated by ACEA is mediated in skeletal muscle through cannabinoid CB1 receptor activation. As a result, cannabinoid CB1 receptors may be useful pharmaceutical targets in the treatment of inflammation and related disorders in skeletal muscle tissues.

Involvement of the endocannabinoid system in the inhibition of Sindbis virus replication: a preliminary study.

BACKGROUND: Sindbis virus (Alphaviridae) is a plus-strand RNA virus that is dependent on the host cell for replication. Cannabinoid (CB) receptors are found on most human cells, including virally infected cells. Activation of cannabinoid receptors has been shown to alter normal cellular physiology. This study aimed to assess how agonist (ACEA) or antagonists/inverse agonist (AM251) of the cannabinoid receptors would alter the cellular environment and impact Sindbis virus replication. METHODS: Human hepatoma (Huh7) cells were used as our model for viral replication. Cells were infected with Sindbis virus (SINV) and then treated with CB agonist (ACEA) (10 µM) or antagonist/inverse agonist (AM-251) (10 µM) and virus replication was monitored. A double subgenomic Sindbis virus containing a green fluorescent protein (GFP) reporter gene inserted into a 3' subgenomic promoter was utilized for these assays to quickly measure viral replication. GFP fluorescent cells were analyzed using flow cytometry to measure the percentage of cells expressing the viral reporter and also quantify the levels of GFP fluorescence. RESULT: Treatment of SINV-infected Huh7 cells with CB1 receptor antagonist/inverse agonist (AM251, 10 µM) resulted in a significant decrease in viral replication, while infected cells treated with a CB1 receptor agonist (ACEA, 10 µM) resulted in a significant increase of viral infection. The data indicates that activation of CB1 receptor by cannabinoids significantly influences the ability of Sindbis virus to replicate in the host cell. CONCLUSION: Blocking CB1 receptor activity with 10 µM AM251 reduced viral replication, but activating the CB1 receptor with 10 µM ACEA resulted in an increase in viral infection. These results indicate cannabinoids may significantly impact a virus replicating in human liver cells. Future confirmation with other viruses and cell lines will be performed to better understand the impact of cannabinoids on viral infections.

Cannabinoid receptor-1 has an effect on CD200 under rotenone and alpha-synuclein induced stress.

Decades after identifying cannabinoids and their beneficial effects on Parkinson's disease (PD), many gaps are still missing. Although, CB2-dependent actions have been shown as underlying positive effects of cannabinoid treatment, in recent years, another receptor of cannabinoids, CB1, emerged as a valuable player in cannabinoid-induced neuroprotection. Remarkably, the effects of CB1 are mainly related to immune cells in the CNS, microglia, and astrocytes. However, oxidative stress, α-syn accumulation, and immune disbalance are essential aspects of both neurons and glial cells. Therefore, in this study, we investigated the effects of the CB1 on both α-syn and rotenone-treated SH-SY5Y and C8-D1A cells. ACEA and AM-251 were used as CB1 agonists and antagonists. Cell viability, IL-1ß, IL-6, TNF-α levels, and CD200 expressions were determined in culture mediums. Our results demonstrated that preformed fibril form (pFF) of α-syn did not cause any significant change in SH-SY5Y cells compared to C8-D1A cells. Rotenone significantly increased the expression of IL-1ß, IL-6, and TNF-α levels in both cells. pFF α-syn and rotenone treatment caused a decrease in CD200 expression. Surprisingly both ACEA and AM-251 alleviated rotenone-induced increase in cytokine levels in both cell lines. Although ACEA prevented pFF α-syn induced increase in cytokine levels and decrease in CD200 expression in C8-D1A cells, AM-251 failed to affect CD200 expression levels. Additionally, ACEA + AM-251 abolished the protective effects of both ACEA and AM-251 against rotenone and α-syn insults in both cell lines. The current study suggests that cannabinoid receptor agonism alleviates rotenone and α-syn-dependent inflammation in neurons and astrocytes.

A South-to-South Cultural Adaptation of an Evidence-Based Parenting Program for Families in the Philippines.

Rates of child maltreatment are higher in low- and middle-income countries due to risk factors such as social inequities, economic adversity, and sociocultural norms. Given the evidence showing the effectiveness of parenting interventions to prevent child maltreatment, this study embarked on a cultural adaptation of an evidence-based parenting program with the eventual goal of integrating it within a nationwide conditional cash transfer program for low-income Filipino parents with children aged 2-6 years. We document the systematic adaptation of the Parenting for Lifelong Health for Young Children program that was developed and tested in South Africa, for low-resource Filipino families using the heuristic framework for the cultural adaptation of interventions. We underscore the merits of conducting a multistage top-down and bottom-up process that uses a participatory approach among cultural insiders and outsiders to develop a parenting intervention that reflects the contextual realities and cultural values of end users. The adapted program, Masayang Pamilya Para sa Batang Pilipino, is the product of a delicate and deliberate effort to balance Filipino childrearing goals and values with the scientific evidence on components of parenting interventions known to promote positive parenting and prevent child maltreatment.

Los índices de maltrato infantil son más altos en los países de ingresos medios y bajos debido a factores de riesgo, como las desigualdades sociales, las dificultades económicas y las normas socioculturales. Teniendo en cuenta los datos que demuestran la eficacia de las intervenciones en la crianza para prevenir el maltrato infantil, este estudio inició una adaptación cultural de un programa de crianza factual con el objetivo principal de integrarlo dentro de un programa de transferencia condicional de dinero en efectivo a nivel nacional para padres filipinos de bajos recursos con niños de entre dos y seis años. Documentamos la adaptación sistemática del programa "Crianza para una buena salud durante toda la vida" (Parenting for Lifelong Health, PLH) orientado a niños pequeños que se desarrolló y se probó en Sudáfrica, para familias filipinas de bajos recursos utilizado el marco heurístico para las adaptaciones culturales de las intervenciones. Subrayamos los méritos de llevar a cabo un proceso multietapa descendente y ascendente que emplea un método participativo entre personas conocedoras de las culturas y personas ajenas a ella para desarrollar una intervención en la crianza que refleje las realidades contextuales y los valores culturales de los usuarios finales. El programa adaptado, Masayang Pamilya Para sa Batang Pilipino, es el producto de un esfuerzo comprometido y deliberado de equilibrar los objetivos y los valores de la crianza de los niños filipinos con las pruebas científicas sobre los componentes de las intervenciones en la crianza que promueven la crianza positiva y previenen el maltrato infantil.

Childhood maltreatment and social functioning in psychotic disorders: a systematic review protocol.

Background: Childhood maltreatment (CM) is thought to play a key role in the etiology and course of psychotic disorders (PD). In addition, CM is related to neurobiological and clinical characteristics that can lead to poor social functioning. However, the extent to which CM and social functioning are directly associated in individuals with PD, is unclear. Therefore, we aim to systematically review the literature to provide an estimate on the strength of the association between CM and different domains of social functioning in PD and to summarize potential moderators and mediators of this association.Methods and analysis: To identify relevant studies, we will systematically search the following databases: Pubmed (Medline), PsycInfo, Embase, Web of Science (Core Collection), and Pilots (trauma), manually search reference lists and contact experts in the field. Studies will be included if they investigate and report on the association between CM (exposure) and social functioning (outcome) in adults with PD. Two independent reviewers will screen titles, abstracts and full texts according to eligibility criteria, perform data extraction and assess study quality according to a modified version of the Newcastle-Ottawa Scale.Analysis: Effect estimates will be pooled in a meta-analysis. Heterogeneity and publication bias will be assessed and the effects of potential moderators (genetic factors, type of diagnosis, duration of illness, type of CM and age at the time of CM exposure) will be analyzed using meta-regressions. Candidate moderators and mediators (neurocognition, cognitive schemas, comorbidities, stress sensitivity, attachment) will be also examined qualitatively.Ethics and dissemination: Because this review will make use of already published data, ethical approval will not be sought. This work has the potential to inform upcoming investigations on the association between the exposure to CM in PD and social functioning. PROSPERO registration number CRD42020175244.

The first systematic review (and meta-analysis) of the association between CM and different domains of social functioning in individuals with PD.Evidence on both moderators and mediators of the association is summarized.