Clinical Manifestations of Trauma Exposure in Fibromyalgia: The Role of Anxiety in the Association Between Posttraumatic Stress Symptoms and Fibromyalgia Status.

Little research has investigated how traumatic experiences relate to fibromyalgia (FM). We explored the presence of trauma exposure in a sample of Spanish participants with FM and examined the associations between (a) the number and type of traumatic experiences and posttraumatic stress disorder (PTSD) symptoms and (b) the severity of clinical manifestations in FM, testing for possible mediation models. Participants were 173 FM patients and 53 healthy controls aged 24 to 66 years. Traumatic event type (physical trauma, physical and sexual abuse, psychological trauma), PTSD symptoms, pain intensity, sleep disturbance, anxiety, depression, coping style, and daily functioning were evaluated via self-report. Fibromyalgia patients reported a higher percentage of trauma exposure than controls, more traumatic experiences (mainly emotional and physical trauma), and more PTSD symptoms, Hedges' gs/Cohen's ds = 0.42-0.76. Most FM patients reported having experienced their most distressing traumatic experience and PTSD symptoms before FM diagnosis. PTSD symptom severity was associated with more pain, sleep disturbances, anxiety, depression, coping style, and functional impairment, rs = .23-.33, ps = .025-.008. A multiple mediation analysis showed a significant indirect effect of anxiety in the association between PTSD symptoms and daily functioning. In a subset of FM patients, PTSD symptoms were associated with major clinical symptoms. The results suggest future research should explore the effectiveness of trauma-focused therapy compared to standard cognitive behavioral therapy for these patients.

Catastrophizing, Acceptance, and Coping as Mediators Between Pain and Emotional Distress and Disability in Fibromyalgia.

Catastrophizing, acceptance, and coping have an important predictive value in chronic pain; however, it is not known which of these variables has the greatest contribution in fibromyalgia (FM). This study explored the mediating role of catastrophizing, acceptance, and coping in the relationship between pain and emotional distress/disability in a FM sample. Ninety-two FM patients and 51 healthy participants controls were evaluated on pain- and psychological-related variables. Catastrophizing, acceptance, behavioral coping, and emotional coping were significantly correlated with emotional distress and/or disability. Catastrophizing had a significant effect as a mediator on the relationship between pain and depression/anxiety. The current management of FM could improve by including cognitive techniques aimed at modifying the negative appraisal of pain.

Gender Differences in Patients with Fibromyalgia Undergoing Cognitive-Behavioral Therapy for Insomnia: Preliminary Data.

UNLABELLED: Fibromyalgia (FM) is a chronic musculoskeletal pain syndrome that significantly affects patients' quality of life. Its main symptoms are pain, fatigue, and sleep disturbances. AIM: The aim of this study was to assess the efficacy of cognitive-behavioral therapy for insomnia (CBT-I) in men and women with FM and compare sleep and clinical features between both genders. METHODS: Fifteen women and 13 men were selected to participate in nine weekly CBT-I sessions that involved completing several self-reported questionnaires at pretreatment, post-treatment, and follow-up. Patients were recruited from the Rheumatology Service and Pain Unit of Hospital and a fibromyalgia association. Group psychotherapy was performed at clinical unit of the Faculty of Psychology. RESULTS: Both groups showed significant clinical and statistical improvements in sleep quality and the main symptoms associated with FM (ie, pain intensity, fatigue, anxiety, pain catastrophizing, and pain-related anxiety). Differential treatment responsiveness between sexes was observed. Male group exhibited significant changes at post-treatment in sleep disturbances and pain-related anxiety and catastrophizing. The female group showed post-treatment improvements in sleep latency, general fatigue, and depression, which persisted at follow-up. CONCLUSIONS: Differential responses to treatment between men and women were observed in some sleep- and pain-related variables. Outcomes show the needed to design different treatments for men and women with FM is discussed.

Relationships between physical symptoms, emotional distress, and pain appraisal in fibromyalgia: the moderator effect of alexithymia.

Alexithymia is a personality construct that is frequently identified in fibromyalgia (FM). Previous studies have explored the relationship between alexithymia and emotional distress in this disease. Yet, the additional link with factors of pain appraisal is unknown. This study examined the moderating effect of alexithymia in the relationship between emotional distress and pain appraisal in 97 FM women. A control group of 100 healthy women also participated in the study. All participants completed several self-reports about pain experience, sleep quality, impairment, emotional distress, pain appraisal, and alexithymia. FM women showed significantly more difficulty in identifying and describing feelings, but less externally oriented thinking than healthy women. In the clinical group, difficulty in identifying feelings and difficulty in describing feelings significantly correlated with lower sleep quality, higher anxiety and depression, and increased pain catastrophizing and fear of pain. Difficulty in describing feelings significantly correlated with higher pain experience and vigilance to pain. Externally oriented thinking was not correlated with any of the clinical variables. Difficulty in identifying feelings moderated the relationship between anxiety and pain catastrophizing, and difficulty in describing feelings moderated the relationship between anxiety and fear of pain. Implications of the findings for the optimization of care of FM patients are discussed.

Microwave-assisted synthesis of potent PDE7 inhibitors containing a thienopyrimidin-4-amine scaffold.

A series of novel thienopyrimidin-4-amines have been synthesized and evaluated as phosphodiesterase (PDE) inhibitors. A rationale for the observed selectivity against PDE7 has been obtained from molecular modelling studies on the most active compounds.

Cognitive-behavioral therapy for insomnia and sleep hygiene in fibromyalgia: a randomized controlled trial.

Sleep disturbances play an important role in the exacerbation of pain and other troubling symptoms reported by patients with fibromyalgia (FM). The objective of this trial was to analyze the efficacy of a cognitive-behavioral therapy for insomnia (CBT-I) versus a sleep hygiene (SH) education program at improving sleep and other clinical manifestations in FM. Sixty-four FM women with insomnia were randomly assigned to the CBT-I or the SH groups, and 59 completed the treatments (30 in the CBT-I group and 29 in the SH group). Participants completed several self-report questionnaires at pre-, post-treatment and follow-ups. The CBT-I group reported significant improvements at post-treatment in several sleep variables, fatigue, daily functioning, pain catastrophizing, anxiety and depression. The SH group only improved significantly in subjective sleep quality. Patients in the CBT-I group showed significantly greater changes than those in the SH group in most outcome measures. The findings underscore the usefulness of CBT-I in the multidisciplinary management of FM.

Fibromyalgia: gender differences and sleep-disordered breathing.

OBJECTIVES: The prevalence of fibromyalgia (FM) is much lower in men than in women. Therefore, current knowledge about this chronic pain syndrome emerged mainly from research on women. The aim of the present study was to compare clinical symptoms and sleep parameters between male and female FM patients. METHODS: Forty FM patients (18 men and 22 women) aged 48.00±8.45 years were evaluated with questionnaires on pain, sleep, fatigue, depression, anxiety and functional impact, and polysomnography (PSG). RESULTS: 61% of male FM patients had an apnea-hypopnea index (AHI) greater than 15, compared to 31.8% of women, and a desaturation index (DI) above five, which was twice more prevalent in men than in women. In addition, males had poorer sleep quality (16.05±2.92% vs. 13.08±3.88%; p=0.01) and slow wave sleep (SWS) (stage 3 duration: 9.02±7.84% vs. 14.44±7.32%; p=0.03) than women. No differences were found between the two groups in the level of pain, emotional distress, or daily functioning. However, pain in men, fatigue in women, and functional impact in both sexes seemed to be related to worse sleep quality. Also in women, alterations in total sleep time (TST) and rapid eye movement (REM) sleep features appeared to be related to emotional status. CONCLUSIONS: Alterations in sleep respiratory patterns were more highly prevalent in male than in female FM patients. More so in male FM patients, the alterations in sleep patterns, non-refreshing sleep, and other FM-related symptoms observed in this population might be part of a primary sleep-disordered breathing.

Synthesis and evaluation of quinazoline derivatives as phosphodiesterase 7 inhibitors.

The latest scientific findings concerning PDE7 and PDE4 inhibition suggest that selective small-molecule inhibitors of both enzymes could provide a novel approach to treat a variety of immunological diseases. In this context, we describe a new series of quinazoline derivatives from quinazolin-4-thiones which include a substituted biphenyl fragment. Some of these compounds show inhibitory potencies at sub-micromolar levels against the catalytic domain of PDE7.

Frailty assessment to individualize treatment in older patients with lymphoma.

PURPOSE: A study analyzing the application of a protocol of comprehensive geriatric assessment (CGA) in older patients with lymphoma was carried out to allow frailty-based patient classification and individualized treatment. METHODS: Lymphoma patients older than 70 years referred to the Geriatric Clinic at a tertiary hospital between May 2016 and March 2021 were included. The assessment protocol included comorbidity, polypharmacy, nutritional, functional, and mental status, geriatric syndromes, and life expectancy. CGA enabled patient classification into four groups (Type I to Type IV) based on frailty assessment instrument scoring and clinical, functional, and mental status. Variables were compared using parametric and non-parametric statistical tests and Kaplan-Meier survival curves. RESULTS: Ninety-three patients (55.9% women) were included. Median age was 81.1 years (± 5.7). 23 patients (24.7%) were classified as robust (type I), 30 (32.3%) as pre-frail (type II) with potentially reversable deficits, 38 (40.9%) as frail (type III), and 2 (2.2%) as requiring palliative care (type IV). Patients received oncospecific treatment with modifications carried out in 64.5% of cases based on CGA results. Differences in overall survival (p = 0.002), response to treatment (p < 0.001) and likelihood of increased frailty (p = 0.024) were observed, with type III-IV patients showing significantly worse outcomes. CONCLUSION: Performance of standardized, systematic CGA by geriatricians permits older lymphoma patients to be classified according to frailty, with significant differences in terms of clinical outcomes across groups. We propose incorporating CGA performed by geriatricians as part of the multidisciplinary care team to optimize therapeutic strategy for these patients.

Understanding the relationship between attachment style, pain appraisal and illness behavior in women.

Insecure attachment has been hypothesized to be an important factor for understanding the experience of pain. Considering the Attachment-Diathesis Model of Chronic Pain developed by Meredith, Ownsworth, and Strong (2008), this cross-sectional study examines the relationship between attachment style, pain appraisal, and illness behavior. Two hundred healthy women recruited from community contexts completed a battery of self-report measures including the Short-form McGill Pain Questionnaire, Pain Catastrophizing Scale, Pain Anxiety Symptoms Scale-20, Pain Vigilance and Awareness Questionnaire, Illness Attitude Scales, Beck Anxiety Inventory, Beck Depression Inventory, and the Experiences in Close Relationships Questionnaire-Revised. The results showed that attachment anxiety was significantly correlated with pain catastrophizing, pain-related fear, depression, and illness behavior. However, attachment anxiety and avoidance were not associated with pain intensity. Attachment anxiety moderated the relationship between pain catastrophizing and illness behavior, and between pain hypervigilance and illness behavior. Pain catastrophizing and pain-related fear partially mediated the effect of attachment anxiety on illness behavior. The findings highlight potential contributions of attachment style and pain appraisal for explaining illness behavior. This study supports earlier reports and suggests the usefulness of assessing attachment style for early identification of people who might exhibit a high risk of dysfunctional responses to pain. Our findings also suggest that increasing people's insight about their attachment style and modifying some associated dysfunctional responses may be important in the treatment of chronic pain.

Effect of Cognitive-Behavioral Therapy on Nocturnal Autonomic Activity in Patients with Fibromyalgia: A Preliminary Study.

Objective: fibromyalgia is a complex chronic pain syndrome characterized by widespread musculoskeletal pain, insomnia and autonomic alterations. Cognitive-behavioral therapy (CBT) is regarded as a promising treatment in fibromyalgia, but its impact on autonomic function remains uncertain. In this research, we studied the effect of CBT on autonomic functions in fibromyalgia. Methods: Twenty-five participants underwent overnight polysomnographic recordings before and after CBT programs focused on pain (CBT-P) or a hybrid modality focused on pain and insomnia (CBT-C). Sleep quality, daily pain, depression and anxiety were assessed by self-reported questionnaires. We analyzed heart rate variability (HRV) using high-frequency power (HF) as a marker for parasympathetic activity, and low-frequency power (LF) and the LF/HF ratio as relative sympathetic markers during wakefulness and at each sleep stage. Results: After treatment, 14 patients (/25, 58.0%) reported improvement in their sleep: 6 in the CBT-P condition (/12, 50%), and 8 in the CBT-C condition (/13, 61.5%). We found that, regardless of the type of CBT, patients who reported improvement in sleep quality (n = 14, 58%) had an increase in HF during stages N2 (p < 0.05) and N3 (p < 0.05). These changes were related to improvement in sleep quality (N2, r = −0.43, p = 0.033) but not to pain, depression or anxiety. Conclusions: This study showed an improvement in parasympathetic cardiac control during non-rapid-eye-movement sleep following CBT in fibromyalgia participants who reported better sleep after this therapy. CBT may have a cardio-protective effect and HRV could be used as a sleep monitoring tool in fibromyalgia.

Levels and trends of perfluoroalkyl acids (PFAAs) in water (2013-2020) and fish from selected riverine basins in Spain.

The aim of the present study was to assess the presence of perfluoroalkyl acids (PFAAs), namely perfluoroalkane sulfonates and perfluoroalkyl carboxylic acids, in Spanish river basins in order to: identify potential spatiotemporal variations; evaluate the effectiveness of the measures implemented for the reduction/elimination of these pollutants; verify the fulfillment of the Environmental Quality Standards (EQSs) in the European Union. PFOS and PFOA were determined in 116 water samples from four sites in the Duero basin, the largest in the Iberian Peninsula, collected seasonally from 2013 to 2020. In addition, 30 fish sample composites from the sample banks of Duero, Tagus, Ebro, Eastern Cantabrian and Catalonian basins were analyzed for 15 PFAAs. Median PFOS and PFOA concentrations were 0.72 and 0.42 ng/L, ranging from values below the limit of quantification (LOQ) to 81 and 22 ng/L, respectively. During the studied period, 51% of water samples were above the EQS of 0.65 ng/L for PFOS. In the case of fish, the PFOS range was

Temporal preparation and inhibitory deficit in fibromyalgia syndrome.

Cognitive deficits in fibromyalgia may be specifically related to controlled processes, such as those measured by working memory or executive function tasks. This hypothesis was tested here by measuring controlled temporal preparation (temporal orienting) during a response inhibition (go no-go) task. Temporal orienting effects (faster reaction times for targets appearing at temporally attended vs. unattended moments) and response inhibition were impaired in fibromyalgia compared to the control group. It is concluded that frontal networks underlying attentional control (temporal orienting and response inhibition) can be a dysfunctional neurocognitive mechanism in fibromyalgia.

Predictors of the pain perception and self-efficacy for pain control in patients with fibromyalgia.

OBJECTIVE: This study analyzes the role of a number of cognitive-affective dimensions in the experience and coping of pain in patients with fibromyalgia (FM). Specifically, it was examined whether anxiety, depression, pain catastrophizing and pain-related anxiety predict the pain perception and the self-efficacy expectations in these patients. METHOD: Seventy-four fibromyalgia patients were asked to complete a questionnaire survey including the Chronic Pain Self-Efficacy Scale, the Hospital Anxiety and Depression Scale, the Pain Anxiety Symptoms Scale-20, the Pain Catastrophizing Scale, and the Short-form McGill Pain Questionnaire. RESULTS: Some relevant correlation and predicting patterns were identified. Physiological anxiety was the best predictor of the sensorial dimension of pain. Pain fear was a significant predictor of the pain intensity. Helplessness was the best predictor of the affective dimension of pain, whereas depression was a significant predicting variable of the self-efficacy expectations. CONCLUSIONS: This study shows the relevance of the pain-related anxiety in the pain perception, and of the depression in the self-efficacy expectations in FM patients. Clinical applications of the findings and further research lines in this area are discussed.

Psychopathology as a Moderator of the Relationship Between Physical Symptoms and Impairment in Fibromyalgia Patients.

BACKGROUND: Fibromyalgia (FM) is a chronic pain syndrome that is accompanied by notable psychological distress. However, little research has been done on how the psychopathological profile of FM patients may influence their functional status. METHOD: Using the Symptom Checklist-90-Revised the study examined the psychopathological dimensions of 181 women with FM, and the role of psychopathology as a moderator of the relationship between physical symptoms and impairment of functioning. RESULTS: FM patients exhibited T-scores above the cutoff point ≥60) in all dimensions, and 76.2% were identified as "clinical cases". Somatization was a significant predictor of pain intensity, somatization and obsession-compulsion contributed significantly to predicting poor sleep quality, while somatization, depression and anxiety were significant predictors of impairment. Psychopathology was a statistically significant moderator that increased the impact of poor sleep quality on impairment. CONCLUSIONS: The dysfunctional psychological style is key in the impairment associated with FM. The evaluation of psychopathological profiles can allow the early identification of the patients who are most vulnerable to impaired functioning due to the presence of possible psychopathology, as well facilitating therapeutic adaptations.

Fibromyalgia as a Heterogeneous Condition: Subgroups of Patients Based on Physical Symptoms and Cognitive-Affective Variables Related to Pain.

Fibromyalgia (FM) is a chronic syndrome characterized by heterogeneous clinical manifestations, and knowing this variability can help to develop tailored treatments. To understand better the heterogeneity of FM the present cross-sectional study analyzed the role of several physical symptoms (pain, fatigue and poor sleep quality) and cognitive-affective variables related to pain (pain catastrophizing, pain vigilance, self-efficacy in pain management, and pain acceptance) in the configuration of clinical profiles. A sample of 161 women with FM fulfilled an interview and several self-report measures to explore physical symptoms, cognitive-affective variables, disability and psychopathology. To establish FM groups a hierarchical cluster analysis was performed. The findings revealed three clusters that differed in the grouping variables, Wilks' λ = .17, F(14, 304) = 31.50, p < .001, ηp2 = .59. Group 1 (n = 72) was characterized by high physical and psychological affectation, Group 2 (n = 19) by low physical affectation and high pain self-efficacy, and Group 3 (n = 70) by moderate physical affectation and low pain catastrophizing. The external validation of the clusters was confirmed, Wilks' λ = .72, F(4, 314) = 14.09, p < .001, ηp2 = .15, showing Group 1 the highest levels of FM impact and psychopathological distress. Considering the distinctive clinical characteristics of each subgroup therapeutic strategies addressed to the specific needs of each group were suggested. Assessing FM profiles may be key for a better understanding and approach of this syndrome.

Combined cognitive-behavioral therapy for fibromyalgia: Effects on polysomnographic parameters and perceived sleep quality.

Background/Objective: Cognitive-behavioral therapy (CBT) is one of the first-line treatments in the management of fibromyalgia (FM) and it has been applied with considerable success to treat the psychological processes associated with pain and insomnia. We hypothesized that treating sleep and pain jointly with new combined modalities of CBT may offer greater sleep-related benefits to patients. Method: Thirty-nine female patients with FM and insomnia were randomly allocated to receive CBT centered on pain (CBT-P) or combined CBT focused on pain and insomnia (CBT-C). Participants were assessed at baseline and post-treatment with the Pittsburgh Sleep Quality Index and an ambulatory polysomnography.Results: Participants who received CBT-P showed increases in time in bed and total sleep time and decreases in light sleep, but there was no improvement in perceived sleep quality. Participants who received combined CBT-C showed more meaningful improvements related to refreshing sleep (i.e., higher sleep efficiency and less time awake and longer time in Stage 4 sleep), and these changes were concordant with a significant improvement in self-perceived sleep quality. Conclusions: This study suggests that new CBT-C approaches can improve insomnia-related clinical aspects.

Antecedentes/Objetivo: La terapia cognitivo-conductual (TCC) es un tratamiento de primera línea para abordar la fibromialgia (FM) que se ha aplicado con cierto éxito para el tratamiento del dolor y el insomnio. Se hipotetiza que intervenir sobre el sueño y el dolor con una modalidad combinada de TCC (TCC-C) puede mejorar el sueño de estos pacientes. Método: Treinta y nueve mujeres con FM e insomnio fueron aleatorizadas para recibir TCC centrada en dolor (TCC-D) o TCC-C. Se evaluaron al inicio y en el post-tratamiento con el Índice de Calidad del Sueño de Pittsburgh y polisomnografía ambulatoria. Resultados: Las participantes en la TCC-D mostraron aumentos del tiempo en cama y del tiempo total de sueño, y un descenso del sueño ligero, pero no hubo una mejora en la calidad del sueño percibida. Las participantes en la TCC-C mostraron mejoras significativas relacionadas con el sueño reparador (mayor eficiencia del sueño, menos tiempo de vigilia y más tiempo en fase 4 del sueño), y estos cambios fueron congruentes con una mejora en la calidad del sueño percibida. Conclusiones: Este estudio sugiere que nuevos enfoques TCC-C en FM pueden mejorar aspectos clínicos relacionados con el insomnio.

Phenotypic Characteristics and Copy Number Variants in a Cohort of Colombian Patients with VACTERL Association.

VACTERL association (OMIM 192350) is a heterogeneous clinical condition characterized by congenital structural defects that include at least 3 of the following features: vertebral abnormalities, anal atresia, heart defects, tracheoesophageal fistula, renal malformations, and limb defects. The nonrandom occurrence of these malformations and some familial cases suggest a possible association with genetic factors such as chromosomal alterations, gene mutations, and inherited syndromes such as Fanconi anemia (FA). In this study, the clinical phenotype and its relationship with the presence of chromosomal abnormalities and FA were evaluated in 18 patients with VACTERL association. For this, a G-banded karyotype, array-comparative genomic hybridization, and chromosomal fragility test for FA were performed. All patients (10 female and 8 male) showed a broad clinical spectrum: 13 (72.2%) had vertebral abnormalities, 8 (44.4%) had anal atresia, 14 (77.8%) had heart defects, 8 (44.4%) had esophageal atresia, 10 (55.6%) had renal abnormalities, and 10 (55.6%) had limb defects. Chromosomal abnormalities and FA were ruled out. In 2 cases, the finding of microalterations, namely del(15)(q11.2) and dup(17)(q12), explained the phenotype; in 8 cases, copy number variations were classified as variants of unknown significance and as not yet described in VACTERL. These variants comprise genes related to important cellular functions and embryonic development.

Immunodeficiency in a Patient with 22q11.2 Distal Deletion Syndrome and a p.Ala7dup Variant in the MAPK1 Gene.

The genetic basis for sporadic immunodeficiency in patients with 22q11.2 distal deletion syndrome is unknown. We report an adult with a type 1 (D-F) 22q11.2 distal deletion syndrome and recurrent severe infections due to herpes zoster virus, presenting mild T cell lymphopenia and diminished frequency of naive CD4+ T cells, but increased frequencies of central, effector, and terminally differentiated memory T cells. Antigen-specific CD4+ and CD8+ T cells to influenza, rotavirus, and SEB were conserved in the patient, but responses to tetanus toxoid were temporarily undetectable. Exomic sequencing identified the c.20_22dupCGG (NM_002745.4) variant in the remaining MAPK1 gene of the patient, which adds 1 alanine to the polyalanine amino-terminal tract of the protein (p.Ala7dup). The mother, unlike the father, was heterozygote for the variant. Western blot analysis with the patient's activated PBMCs showed a 91% reduction in the MAPK1 protein. Further studies will be necessary to determine whether or not the variant present in the remaining MAPK1 gene of the patient is pathogenic.

PLGA Nanoparticles for the Intraperitoneal Administration of CBD in the Treatment of Ovarian Cancer: In Vitro and In Ovo Assessment.

The intraperitoneal administration of chemotherapeutics has emerged as a potential route in ovarian cancer treatment. Nanoparticles as carriers for these agents could be interesting by increasing the retention of chemotherapeutics within the peritoneal cavity. Moreover, nanoparticles could be internalised by cancer cells and let the drug release near the biological target, which could increase the anticancer efficacy. Cannabidiol (CBD), the main nonpsychotropic cannabinoid, appears as a potential anticancer drug. The aim of this work was to develop polymer nanoparticles as CBD carriers capable of being internalised by ovarian cancer cells. The drug-loaded nanoparticles (CBD-NPs) exhibited a spherical shape, a particle size around 240 nm and a negative zeta potential (-16.6 ± 1.2 mV). The encapsulation efficiency was high, with values above 95%. A controlled CBD release for 96 h was achieved. Nanoparticle internalisation in SKOV-3 epithelial ovarian cancer cells mainly occurred between 2 and 4 h of incubation. CBD antiproliferative activity in ovarian cancer cells was preserved after encapsulation. In fact, CBD-NPs showed a lower IC50 values than CBD in solution. Both CBD in solution and CBD-NPs induced the expression of PARP, indicating the onset of apoptosis. In SKOV-3-derived tumours formed in the chick embryo model, a slightly higher-although not statistically significant-tumour growth inhibition was observed with CBD-NPs compared to CBD in solution. To sum up, poly-lactic-co-glycolic acid (PLGA) nanoparticles could be a good strategy to deliver CBD intraperitoneally for ovarian cancer treatment.