Neuropsychological and biopsychosocial evolution, therapeutic adherence and unmet care needs during paediatric transplantation: study protocol of a mixed-methods design (observational cohort study and focus groups) - the TransplantKIDS mental health project.

The present article describes the protocol of a mixed-methods study (an observational cohort design and focus groups), aimed to examine neuropsychological functioning and other biopsychosocial outcomes, therapeutic adherence and unmet care needs in paediatric population undergoing solid organ or allogeneic hematopoietic transplant during the pre- and post-transplant phases. Following a multi-method/multi-source approach, neuropsychological domains will be comprehensively measured with objective tests (SDMT, K-CPT 2/CPT 3, TAVECI/TAVEC, WISC-V/WAIS-IV Vocabulary and Digit Span subtests, Verbal Fluency tests, Stroop, ROCF, and TONI-4); ecological executive functioning, affective and behavioral domains, pain intensity/interference, sleep quality and therapeutic adherence will be assessed through questionnaires (parent/legal guardians-reported: BRIEF-2 and BASC-3; and self-reported: BASC-3, BPI, PROMIS, AIQ and SMAQ); and blood levels of prescribed drugs will be taken from each patient's medical history. These outcomes will be measured at pre-transplant and at 4-weeks and 6-months post-transplant phases. The estimated sample size was 60 patients (any type of transplant, solid organ, or hematopoietic) from La Paz University Hospital (Madrid, Spain). Finally, three focus group sessions will be organized with patients, parents/guardians, and transplant clinicians (n = 15, with 5 participants per group), in order to qualitatively identify unmet care needs during the pre-, and post-transplant stages of the process. The study protocol was registered at ClinicalTrials.gov (NCT05441436).

Optimizing Pain Intensity Assessment in Clinical Trials: How Many Ratings are Needed to Best Balance the Need for Validity and to Minimize Assessment Burden?

Pain intensity is the most commonly used outcome domain in pain clinical trials. To minimize the chances of type II error (ie, concluding that a treatment does not have beneficial effects, when in fact it does), the measure of pain intensity used should be sensitive to changes produced by effective pain treatments. Here we sought to identify the combination of pain intensity ratings that would balance the need for reliability and validity against the need to minimize assessment burden. We conducted secondary analyses using data from a completed 4-arm clinical trial of psychological pain treatments (N = 164 adults). Current, worst, least, and average pain intensity in the past 24 hours were assessed 4 times before and after treatment using 0 to 10 numerical rating scale-11. We created a variety of composite scores using these ratings and evaluated their reliability (Cronbach's alphas) and validity (ie, associations with a gold standard score created by averaging 16 ratings and sensitivity for detecting between-group differences in treatment efficacy). We found that for each measure, reliability increased as the number of ratings used to create the measures increased and that ratings from 3 or more days were needed to have adequately strong associations with the gold standard. Regarding sensitivity, the findings suggest that composite scores made up of ratings from 4 days are needed to maximize the chances of detecting treatment effects, especially with smaller sample sizes. In conclusion, using data from 3 or 4 days of assessment may be the best practice. PERSPECTIVE: Composite scores made up of at least 3 days of pain ratings appear to be needed to maximize reliability and validity while minimizing the assessment burden. TRIAL REGISTRATION: clinicaltrials.gov NCT01800604.

Improving the Access of Highly Sensitized Patients to Kidney Transplantation From Deceased Donors: The Spanish PATHI Program With Allocation Based on the Virtual Crossmatch.

BACKGROUND: In 2015, the Spanish National Transplant Organization developed a prioritization system (Program for Access to Transplantation for Highly Sensitized Patients [PATHI]) to increase transplant options for patients with calculated panel-reactive antibodies (cPRAs) ≥98%, based on virtual crossmatch. We describe the experience with the implementation of PATHI and assess its efficacy. METHODS: PATHI registry was used to collect characteristics of donors and patients between June 15, 2015, and March 1, 2018. One-year graft and patient survival and acute rejection were also measured. A Cox model was used to identify factors related to patient death and graft loss and logistical regression for those associated with rejection. RESULTS: One thousand eighty-nine patients were included, and 272 (25%) were transplanted. Transplant rate by cPRA was 54.9%, 40.5%, and 12.8% in patients with cPRA98%, cPRA99%, and cPRA100%, respectively. One-year patient survival was 92.5%. Recipient age ≥60, time under dialysis >7 y, and delayed graft function were mortality risk factors. One-year graft survival was 88.7%. The factor related to graft loss was delayed graft function. The rejection rate was 22%. Factors related to rejection were sex, older recipients, and posttransplant donor-specific antibodies. CONCLUSIONS: A prioritization approach increases transplant options for highly sensitized patients with appropriate short-term postransplant outcomes. Along with other programs, PATHI may inspire other countries to adopt strategies to meet transplant needs of these patients.

ANF therapy® for pain management, feasibility, satisfaction, perceived symptom reduction and side effects: a real-world multisite observational study.

[Purpose] Non-invasive and drug-free interventions for pain are being developed. One of them is ANF (which stands for "Amino Neuro Frequency") Therapy®, which consists in the application of carbonized metal devices on a patient's skin. We aimed to: 1) test perceived changes in pain intensity after ANF application, 2) record frequency and severity of side effects, 3) assess clinician and patient satisfaction, 4) explore effects on swelling and range of motion (ROM). [Participants and Methods] In this real-world multisite observational study, N=113 physical therapists in 45 countries, applied ANF to N=1,054 patients (Mage=45.2, 56.2% female) with pain complaints. Demographic data, pain intensity (NRS-11), effects of ANF on swelling and ROM, clinician and patient satisfaction and side effects were collected. [Results] Main pain locations were: low back (14.9%), knee (12.4%), neck (10%), and shoulder (9.6%). Pre-treatment pain intensity was high (Mean=7.6, SD=1.9). It significantly decreased post-treatment (Mean=3.1, SD=2.0), t(1053)=7.25, with a large effect size (Cohen's d=2.2). Swelling decreased and ROM increased. Average satisfaction with ANF was 92/100. Patients often experienced mild side effects (42.3%): dry mouth, headache and fatigue. [Conclusion] Results show large effect sizes, high satisfaction, and mild and short-term side effects. This is very promising but should be interpreted with caution considering the study limitations.

Protocol for a multi-phase, multi-center, real-world, hybrid effectiveness-implementation study of a digital intervention for pediatric chronic pain co-designed with patients (Digital SPA).

Background: Children and adolescents with chronic pain are a vulnerable population who often lack the resources to manage their condition. Due to high personal, social, and economic consequences, proper management in its early stages is key to reducing disability. The aim of this project is to co-develop a digital intervention for pediatric chronic pain (Digital SPA) with end-users and to evaluate its effectiveness and implementation outcomes in Spain. Methods: (Phase 1) Focus groups with patients, parents, and clinicians (n = 5-6 each) will inform about unmet pain care needs and provide a starting point for co-designing the intervention. (Phase 2) Content creation and usability testing will be based on the results of Phase 1, and the theory-driven development will follow the latest available evidence. The intervention will use validated psychological techniques focused on improving functioning by teaching pain coping skills. (Phase 3) Hybrid effectiveness-implementation trial. Participants (n = 195) will be adolescents aged 12-17 years old with chronic pain and one of their parents. Assessments include physical function, pain, sleep, anxiety, mood, satisfaction and adherence to the treatment, and number of visits to the emergency room. A qualitative framework analysis will be conducted with data from Phase 1. Effects of the intervention will be evaluated using linear multilevel modeling. The Consolidated Framework for Implementation Research (CFIR) and Behavioral Interventions Using Technology (BIT) frameworks will be used to evaluate implementation. Discussion: This study is expected to produce a co-created evidence-based digital intervention for pediatric chronic pain and a roadmap for successful implementation. Trial registration number TRN and date of registration: ClinicalTrials.gov (registered on 26 June 2023: https://clinicaltrials.gov/study/NCT05917626). Contributions to the literature The implementation of digital health interventions has two major gaps: (1) adherence to treatment is suboptimal, and (2) the process of making the interventions available to the end-user in a sustainable way is often unsuccessful.In this study, we expect that assessing users' needs and co-designing an intervention with them will improve adherence.Documenting the implementation process from the project inception and integrating the results into an implementation framework will allow for replication and extension in different contexts.This study will increase the knowledge about implementation in a vulnerable population: adolescents with chronic pain without access to in-person multidisciplinary pain care.

[Suicidal attempt in a school-aged patient and related factors: a case report]. / Intento de suicidio en paciente escolar y factores relacionados: reporte de caso.

Background: Suicide is a public health problem, which has increased in recent years, becoming a serious cause of mortality, mostly in low- and middle-income countries. Suicidal behavior is infrequent before adolescent years, various related factors have been described. The purpose of this work is to describe the case of a patient in school age who attempted suicide and the identified factors that might have contributed. Clinical case: Nine-year-old male attempted suicide by hanging in the bathroom, endangering his life. He received emergency attention and hospitalized in intensive care. During his hospitalization, the mental health service approached him. Amongst the factors previously associated with suicidal intent during school age and identifiable in the patient are family disintegration, symptoms of major depression episodes, reading-related learning difficulties and attention deficit hyperactivity disorder. The patient received treatment and follow up consultation, without showing any suicidal behavior up to this date. The patient is currently 13 years old. Conclusions: It must be recognized that children of school age can present suicidal behavior. It is important to acknowledge the factors associated with this kind of behavior, to reduce risks and provide an opportune attention and handling.

Introducción: el suicidio es un problema de salud pública que se ha incrementado en los últimos años, convirtiéndose en una grave causa de mortalidad principalmente en países de ingresos bajos y medios. Las conductas suicidas son poco frecuentes antes de la adolescencia, por lo que se han descrito diversos factores relacionados. El propósito de este trabajo es describir el caso de un paciente en edad escolar que intentó suicidarse y las causas identificadas que pudieron influir. Caso clínico: paciente masculino de nueve años puso su vida en riesgo al intentar suicidarse por ahorcamiento en el cuarto de baño. Recibió atención de urgencia y estuvo en la terapia intensiva. Durante su hospitalización fue abordado por el servicio de salud mental. Entre los factores que han sido previamente asociados al intento suicida en la edad escolar que pudieron identificarse en el paciente se encuentran: desintegración familiar, síntomas de episodio depresivo grave, dificultad en el aprendizaje para la lectura y un trastorno por déficit de atención con hiperactividad. El paciente recibió tratamiento y seguimiento, hasta el día de hoy no ha vuelto a presentar comportamientos suicidas. Actualmente tiene trece años. Conclusiones: se debe reconocer que los niños en edad escolar pueden presentar comportamientos suicidas, y es importante conocer los factores asociados a este tipo de conductas. Esto, con la finalidad de poder reducir el riesgo, así como otorgar atención y manejo de forma oportuna.

NS1-Specific Antibody Response Facilitates the Identification of Children With Dengue and Zika in Hyperendemic Areas.

BACKGROUND: Infections by dengue virus (DENV) and Zika virus (ZIKV) have some similar symptoms and a cross-reactive immune response, although with different risk populations and outcomes. Here, we evaluated the virological characteristics and the nonstructural protein 1 (NS1)-specific antibody responses to DENV and ZIKV in children suspected of dengue in different epidemiological moments in Colombia. METHODS: Viral RNA, circulating NS1 and IgM/IgG specific for DENV and ZIKV were performed by reverse transcription-quantitative polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA) in 301 children suspected of dengue enrolled in a hospital setting during the ZIKV epidemic and a primary healthcare setting during a DENV epidemic. For the detection of DENV and ZIKV-specific IgM, an NS1-based ELISA was validated using characterized pediatric samples. Clinical and laboratory parameters were also evaluated. RESULTS: DENV RNA or NS1 antigen was detected in the plasma of 62% of children, and in none, the ZIKV RNA was found. NS1-based ELISA for DENV and ZIKV IgM showed a sensitivity/specificity of 90/84% and 73/98%, respectively. Of 114 children without detectable viremia or antigenemia, 30.7%, 17.5%, 22% and 30% were IgM-DENV+, IgM-ZIKV+, IgM-DENV+ZIKV+ and IgM-DENV-ZIKV-, respectively. The ZIKV/DENV IgM-NS1 ratio allows the identification of the infecting ortho flavivirus in 88% of the children with IgM-DENV+ZIKV+, confirming a high predominance of DENV infections in the 2 pediatric settings. CONCLUSION: Overall, 88% of the children with clinical suspicion of dengue had an identifiable ortho flaviviral infection, with 80% caused by DENV, 7% by ZIKV and 0.7% classified as recent infections or coinfection, demonstrating active viral cocirculation in the pediatric population of southern Colombia. The IgM-NS1 detection improved the identification of ortho flaviviral infections in children without viremia or antigenemia, suggesting it is a helpful complementary tool for medical personnel in tropical regions with high viral cocirculation and different clinical scenes.

Physicians' perception about predictors of opioid abuse in patients with chronic non-cancer pain: a Delphi study.

Background: Opioids are being prescribed widely, and increasingly, for the treatment of chronic non-cancer pain (CNCP). However, several side effects are associated with mid- and long-term opioid use and, for certain patients, with the risk of problematic opioid use. The aim of this study is to know the perception of the physicians about which variables could be associated with increased risk of patients with CNCP developing a problem of abuse or misuse of the prescribed opioid medication. Methods: Twenty-nine physicians with experience in CNCP pain management and opioids prescription participated in a two-round Delphi study focused on the risk factors for opioid misuse and abuse. Results: The variables that reached consensus regarding their relationship with the increased risk of suffering a problem of opioid abuse or misuse were: (1) Experiencing pain on a daily basis, (2) previous use of high-dose opioids, (3) generalized anxiety, (4) hopelessness, (5) benzodiazepine intake, (6) use of opioids for reasons other than pain, (7) family problems, family instability or family breakdown, and (8) having access to several opioid prescribers. The only variable that reached consensus regarding it not being associated to a possible risk of abuse or misuse was having mild pain intensity (0-4 on a NRS-11). Conclusions: This study provides useful information that could help make decisions about the use of opioids for CNCP treatment and prevent future difficulties. Prospective studies testing the relationship of the variables that reached consensus with the risk of opioid misuse and abuse are warranted. Significance: This study shows the variables of CNCP that the professional must take into account in order to avoid possible problems when prescribing opioids.

Spent coffee grounds and its antioxidant dietary fiber promote different colonic microbiome signatures: Benefits for subjects with chronodisruption.

Chronodisruption, commonly displayed by people living with obesity (PLO), is linked to colonic microbiota dysbiosis, and may increase the risk of many chronic non-communicable diseases, whereas dietary interventions-called chrononutrition may mitigate it. We evaluated the in vitro effects of spent coffee grounds (SCG), and their antioxidant dietary fiber (SCG-DF) on the colonic microbiota of an obese donor displaying dysbiosis and chronodisruption. Basal microbiota pattern was associated with an increased risk of non-communicable chronic diseases. Both samples decrease species richness and increase microbiota diversity (p < 0.05; Chao and Shannon index, respectively), positively enhancing Firmicutes/Bacteroidetes index (SCG, p < 0.04; SCG-DF, p < 0.02). SCG and SCG-DF modulated the microbiota, but SCG-DF induced greater changes, significantly increasing. p_Actonobacterias (SCG p < 0.04; SCG-DF, p < 0.02), and reducing g_Alistipes; s_putredinis, g_Prevotella;s_copri. The highest increase was displayed by p_Proteobacteria (f_Desulfovibrionaceae and f_Alcanigenaceae, p < 0.05), while g_Haemophilus; s_parainfluenzae decreased (p < 0.05). However, neither SCG nor SCG-DF modulated g_Alistipes (evening-type colonic microbial marker) beneficially. SCG and SCG-DF reduced (p < 0.05) g_Lachnospira, a microbial evening-type marker, among other microbial populations, of an obese donor displaying chronodisruption and dysbiosis. SCG and SCG-DF displayed a prebiotic effect with the potential to mitigate diseases linked to chronodisruption.

A regional scale study of parasites in Percichthys trucha, an endemic fish of southern South America: insights on diversity and distribution from two decades of field surveys.

The current conservation status of Percichthys trucha (Creole perch) is Least Concern, although the population trend is considered to be decreasing. We conducted an extensive survey of parasite fauna in this species over two decades in its distribution range in Argentina. Fish were collected using gill and trawl nets. Parasites were collected, identified, and counted to calculate prevalence and mean intensity. The present work reports the parasite species infecting P. trucha, using data from our own survey and from previously published records. This information enables us to evaluate infection and distribution patterns, assess the role of P. trucha as host, determine the specificity of the parasites, and evaluate the threat represented by introduced, invasive parasites. The data set consists of a total of 453 host-parasite-locality records, of which only 15 are exclusively bibliographic. We found 44 parasite taxa: 19 digeneans, 4 monogeneans, 5 cestodes, 8 nematodes, 4 acanthocephalans, 3 crustaceans, and 1 mollusk. The most represented families were Diplostomidae, Heterophyidae, and Dactylogyridae. This study increases the number of parasite species known from 25 to 44. It can be concluded that this parasite fauna is characterized by high diversity, particularly of digeneans, and most of the parasites reproduce within this host, a pattern which is related to the top position of this fish species in the trophic webs. Six parasite species (Allocreadium patagonicum, Homalometron papilliferum, Acanthostomoides apophalliformis, Duplaccessorius andinus, Pseudodelphys limnicola, and Hysterothylacium patagonense) exhibit high host specificity (only matures in Creole perches) and are widely distributed, which could now be considered as "biogeographical core helminth fauna." Some P. trucha populations are affected by the invasion of alien fishes like Cyprinus carpio and pathogenic parasites like Lernaea cyprinacea and Schizocotyle acheilognathi. Our findings emphasize the need for further research.

A Two-Step Single Plex PCR Method for Evaluating Key Colonic Microbiota Markers in Young Mexicans with Autism Spectrum Disorders: Protocol and Pilot Epidemiological Application.

Many neurological disorders have a distinctive colonic microbiome (CM) signature. Particularly, children with autism spectrum disorders (ASD) exhibit a very dissimilar CM when compared to neurotypical (NT) ones, mostly at the species level. Thus far, knowledge on this matter comes from high-throughput (yet very expensive and time-consuming) analytical platforms, such as massive high-throughput sequencing of bacterial 16S rRNA. Here, pure (260/280 nm, ~1.85) stool DNA samples (200 ng.µL-1) from 48 participants [39 ASD, 9 NT; 3-13 y] were used to amplify four candidate differential CM markers [Bacteroides fragilis (BF), Faecalibacterium prausnitzii (FP), Desulfovibrio vulgaris (DV), Akkermansia muciniphila (AM)], using micro-organism-specific oligonucleotide primers [265 bp (BF), 198 bp (FP), 196 bp (DV), 327 bp (AM)] and a standardized two-step [low (step 1: °Tm-5 °C) to high (stage 2: °Tm-0 °C) astringent annealing] PCR protocol (2S-PCR). The method was sensitive enough to differentiate all CM biomarkers in the studied stool donors [↑ abundance: NT (BF, FP, AM), ASD (DV)], and phylogenetic analysis confirmed the primers' specificity.

Unique Immune Blood Markers Between Severe Dengue and Sepsis in Children.

BACKGROUND: Pediatric dengue and sepsis share clinical and pathophysiologic aspects. Multiple inflammatory and regulatory cytokines, decoy receptors and vascular permeability factors have been implicated in the pathogenesis of both diseases. The differential pattern and dynamic of these soluble factors, and the relationship with clinical severity between pediatric dengue and sepsis could offer new diagnosis and therapeutic strategies. METHODS: We evaluated the concentration levels of 11 soluble factors with proinflammatory, regulatory and vascular permeability involvement, in plasma from children with dengue or sepsis, both clinically ranging from mild to severe, in the early, late and convalescence phases of the disease. RESULTS: During early acute infection, children with sepsis exhibited specific higher concentration levels of IL-6, vascular endothelial growth factor (VEGF), and its soluble decoy receptor II (sVEGFR2) and lower concentration levels of IL-10 and the soluble tumor necrosis factor receptor 2 (sTNFR2), in comparison with children with severe dengue. In addition, the circulating amounts of soluble ST2, and VEGF/sVEGFR2 were widely associated with clinical and laboratory indicators of dengue severity, whereas secondary dengue virus infections were characterized by an enhanced cytokine response, relative to primary infections. In severe forms of dengue, or sepsis, the kinetics and the cytokines response during the late and convalescence phases of the disease also differentiate. CONCLUSIONS: Dengue virus infection and septic processes in children are characterized by cytokine responses of a specific magnitude, pattern and kinetics, which are implicated in the pathophysiology and clinical outcome of these diseases.

Improving prediction of COVID-19 mortality using machine learning in the Spanish SEMI-COVID-19 registry.

COVID-19 is responsible for high mortality, but robust machine learning-based predictors of mortality are lacking. To generate a model for predicting mortality in patients hospitalized with COVID-19 using Gradient Boosting Decision Trees (GBDT). The Spanish SEMI-COVID-19 registry includes 24,514 pseudo-anonymized cases of patients hospitalized with COVID-19 from 1 February 2020 to 5 December 2021. This registry was used as a GBDT machine learning model, employing the CatBoost and BorutaShap classifier to select the most relevant indicators and generate a mortality prediction model by risk level, ranging from 0 to 1. The model was validated by separating patients according to admission date, using the period 1 February to 31 December 2020 (first and second waves, pre-vaccination period) for training, and 1 January to 30 November 2021 (vaccination period) for the test group. An ensemble of ten models with different random seeds was constructed, separating 80% of the patients for training and 20% from the end of the training period for cross-validation. The area under the receiver operating characteristics curve (AUC) was used as a performance metric. Clinical and laboratory data from 23,983 patients were analyzed. CatBoost mortality prediction models achieved an AUC performance of 84.76 (standard deviation 0.45) for patients in the test group (potentially vaccinated patients not included in model training) using 16 features. The performance of the 16-parameter GBDT model for predicting COVID-19 hospital mortality, although requiring a relatively large number of predictors, shows a high predictive capacity.

Mediating Role of Treatment Perceptions in the Relationship Between Individual Characteristics and Engagement With a Digital Psychological Intervention for Pediatric Chronic Pain: Secondary Data Analysis.

BACKGROUND: Engagement predicts benefits from self-managed treatments. However, engagement is an important concern in digital interventions, with over 50% of patients being nonadherent to interventions in chronic conditions such as chronic pain. Little is known about the individual characteristics that contribute to engagement with a digital self-management treatment. OBJECTIVE: This study tested the mediating role of treatment perceptions (difficulty and helpfulness) in the association between individual baseline characteristics (treatment expectancies and readiness to change) and treatment engagement (online and offline) with a digital psychological intervention for adolescents with chronic pain. METHODS: A secondary data analysis of a single-arm trial of Web-based Management of Adolescent Pain, a self-guided internet intervention developed for the management of chronic pain in adolescents, was conducted. Survey data were collected at baseline (T1), midtreatment (ie, 4 weeks after the treatment started; T2), and post treatment (T3). Online engagement was assessed using back-end information on the number of days adolescents accessed the treatment website, while the offline engagement was assessed with the reported frequency of use of skills (ie, pain management strategies) learned at the end of the treatment. Four parallel multiple mediator linear regression models, using ordinary least square regression incorporating the variables were tested. RESULTS: In total, 85 adolescents with chronic pain (12-17 years old, 77% female) participated. Several mediation models were significant in predicting online engagement. A significant indirect effect was found for the path expectancies-helpfulness-online engagement (effect 0.125; SE 0.098; 95% CI 0.013-0.389) and for the path precontemplation-helpfulness-online engagement (effect -1.027; SE 0.650; 95% CI -2.518 to -0.054). Fourteen percent of the variance of online engagement was explained by the model including expectancies as a predictor (F3=3.521; P<.05), whereas 15% was explained by the model where readiness to change was the predictor (F3=3.934; P<.05). Offline engagement was partially explained in the model including readiness to change as the predictor but with marginal significance (F3=2.719; R2=0.111; P=.05). CONCLUSIONS: Treatment perception, specifically, perceived helpfulness, was a mediator of the pathway between both treatment expectancies and readiness to change and online engagement with a digital psychological intervention for chronic pain. Assessing these variables at baseline and midtreatment may help to determine the risk of nonadherence. Further work is needed to confirm these mediation pathways in larger samples. TRIAL REGISTRATION: ClinicalTrials.gov NCT04043962; https://clinicaltrials.gov/ct2/show/NCT04043962.

Quercetin and Its Fermented Extract as a Potential Inhibitor of Bisphenol A-Exposed HT-29 Colon Cancer Cells' Viability.

Bisphenol A (BPA) promotes colon cancer by altering the physiological functions of hormones. Quercetin (Q) can regulate signaling pathways through hormone receptors, inhibiting cancer cells. The antiproliferative effects of Q and its fermented extract (FEQ, obtained by Q gastrointestinal digestion and in vitro colonic fermentation) were analyzed in HT-29 cells exposed to BPA. Polyphenols were quantified in FEQ by HPLC and their antioxidant capacity by DPPH and ORAC. Q and 3,4-dihydroxyphenylacetic acid (DOPAC) were quantified in FEQ. Q and FEQ exhibited antioxidant capacity. Cell viability with Q+BPA and FEQ+BPA was 60% and 50%, respectively; less than 20% of dead cells were associated with the necrosis process (LDH). Treatments with Q and Q+BPA induced cell cycle arrest in the G0/G1 phase, and FEQ and FEQ+BPA in the S phase. Compared with other treatments, Q positively modulated ESR2 and GPR30 genes. Using a gene microarray of the p53 pathway, Q, Q+BPA, FEQ and FEQ+BPA positively modulated genes involved in apoptosis and cell cycle arrest; bisphenol inhibited the expression of pro-apoptotic and cell cycle repressor genes. In silico analyses demonstrated the binding affinity of Q > BPA > DOPAC molecules for ERα and ERß. Further studies are needed to understand the role of disruptors in colon cancer.

Does pain catastrophizing and distress intolerance mediate the relationship between PTSD and prescribed opioid misuse in people with chronic noncancer pain?

OBJECTIVE: There is an ongoing debate on the use of long-term high-dose medically prescribed opioid analgesics for patients with chronic noncancer pain. Such use is elevated when there is comorbid pain and PTSD, which is quite prevalent. Therefore, it is relevant to investigate the psychological variables that may explain opioid misuse in this population. The purpose of this study was to examine the interaction effect of PTSD severity, distress intolerance, and pain catastrophizing on prescribed opioid misuse in chronic noncancer pain patients. METHOD: A total of 168 participants (M age = 60 years, 74% women) were assessed regarding opioid medication, pain intensity, traumatic psychological events, PTSD, distress intolerance, pain catastrophizing, and current opioid misuse. RESULTS: Groups were formed according to the level of PTSD severity (no symptoms, moderate symptoms, and severe symptoms). Significant differences were found between the groups in pain intensity, catastrophizing, distress intolerance, and opioid misuse. The severe-symptoms group had the highest scores on all variables. There were no between-group differences in the prescribed medication. Mediation analysis showed that the relationship between PTSD severity and opioid misuse was completely and independently mediated by distress intolerance and pain catastrophizing. CONCLUSIONS: Distress intciolerance and pain catastrophizing may be theoretically and clinically relevant constructs in understanding the motivation for opioid misuse in people with concurrent chronic noncancer pain and PTSD. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

A Mobile Application to Help Self-Manage Pain Severity, Anxiety, and Depressive Symptoms in Patients with Fibromyalgia Syndrome: A Pilot Study.

Treatment for individuals with fibromyalgia syndrome (FMS) is complex and is not always accessible to those who could benefit. The aim of this study was to conduct a preliminary evaluation of a mobile-app-delivered, cognitive behavioral treatment (CBT)-based intervention in helping adults self-manage fibromyalgia symptoms. A total of 100 adults with FMS (M [SD] age = 49.81, [9.99] years; 94% women) were given access to the digital treatment program and downloaded the app. Pain severity, anxiety symptoms, depression symptoms, fatigue, and sleep quality were assessed at pre-treatment, post-treatment, and 3-month follow-up. Fifty-three of the potential participants completed the 47-day treatment. Data showed significant improvements in pain severity (p = 0.007, d = 0.43), anxiety (p = 0.011, d = 0.40) and depressive symptoms (p = 0.001, d = 0.50) from pre-treatment to post-treatment. The effect sizes associated with app use are consistent with improvements seen in previously published clinical trials of CBT for FMS. Improvements were generally maintained, although there was some decrease in the outcomes from post-treatment to the 3-month follow-up. Most participants reported that they were very satisfied with the app. The use of the app was associated with similar levels of improvements found with in-person CBT treatment for FMS. Research to evaluate the effectiveness of the app in a controlled trial is warranted.

Fermentation Extract of Naringenin Increases the Expression of Estrogenic Receptor ß and Modulates Genes Related to the p53 Signalling Pathway, miR-200c and miR-141 in Human Colon Cancer Cells Exposed to BPA.

The estrogenic receptor beta (ERß) protects against carcinogenesis by stimulating apoptosis. Bisphenol A (BPA) is related to promoting cancer, and naringenin has chemoprotective activities both can bind to ERß. Naringenin in the colon is metabolized by the microbiota. Cancer involves genetic and epigenetic mechanisms, including miRNAs. The objective of the present study was to evaluate the co-exposure effect of colonic in vitro fermented extract of naringenin (FEN) and BPA, to elucidate molecular effects in HT-29 colon cancer cell line. For this, we quantified genes related to the p53 signaling pathway as well as ERß, miR-200c, and miR-141. As an important result, naringenin (IC50 250 µM) and FEN (IC50 37%) promoted intrinsic pathways of apoptosis through phosphatase and tensin homolog (PTEN) (+2.70, +1.72-fold, respectively) and CASP9 (+3.99, +2.03-fold, respectively) expression. BPA decreased the expression of PTEN (-3.46-fold) gene regulated by miR-200. We suggest that once co-exposed, cells undergo a greater stress forcing them to mediate other extrinsic apoptosis mechanisms associated with death domain FASL. In turn, these findings are related to the increase of ERß (5.3-fold with naringenin and 13.67-fold with FEN) gene expression, important in the inhibition of carcinogenic development.

Effect of drying method on the production of in vitro short-chain fatty acids and histone deacetylase mediation of cocoa pod husk.

We evaluated the effect of cocoa pod husk (CPH) processing (microwave [MW], forced-air drying [FAD], and FAD plus extrusion [FAD-E]), and in vitro gastrointestinal digestion on the in vitro human colonic fermentation metabolism, in vitro bioactivity on human HT-29 colon cancer cell, and the in silico mechanism of selected compounds. CPH as a substrate for human colonic microbiota significantly decrease local pH (MW -0.7, FAD -0.2, and FAD-E -0.3, 24 h) and modifies their metabolic activity (short-chain fatty acids [SCFAs] production). FAD-E generated the highest butyric (7.6 mM/L, 4 h) and FAD the highest acetic and propionic acid levels (71.4 and 36.7 mM/L, 24 h). The in vitro colonic fermented FAD-E sample (FE/FAD-E) caused HT-29 colorectal cancer cells death by inducing damage on membrane integrity and inhibiting (up to 92%) histone-deacetylase (HDAC) activity. In silico results showed that chlorogenic acid, (-)-epicatechin, and (+)-catechin, followed by butyric and propionic acids, are highly involved in the HDAC6 inhibitory activity. The results highlight the potential human health postbiotic benefits of CPH consumption, mediated by colonic microbiota-derived metabolites. PRACTICAL APPLICATION: The enormous amount of CPH (10 tons/1 ton of dry beans) generated by the cocoa industry can be used as a removable source of bioactive compounds with physicochemical functionality and health bioactivity. However, their potential applications and health benefits are insufficiently explored. CPH represents a serious disposal problem; practical and innovative ideas to use this highly available and affordable material are urgent. Research exploring their potential applications can increase the sustainability of the cocoa agro-industry. This paper highlights the value addition that can be achieved with this valuable industrial co-product, generating new functional products and ingredients.