Knockdown of swine leukocyte antigen expression in porcine lung transplants enables graft survival without immunosuppression.

Immune rejection remains the major obstacle to long-term survival of allogeneic lung transplants. The expression of major histocompatibility complex molecules and minor histocompatibility antigens triggers allogeneic immune responses that can lead to allograft rejection. Transplant outcomes therefore depend on long-term immunosuppression, which is associated with severe side effects. To address this problem, we investigated the effect of genetically engineered transplants with permanently down-regulated swine leukocyte antigen (SLA) expression to prevent rejection in a porcine allogeneic lung transplantation (LTx) model. Minipig donor lungs with unmodified SLA expression (control group, n = 7) or with modified SLA expression (treatment group, n = 7) were used to evaluate the effects of SLA knockdown on allograft survival and on the nature and strength of immune responses after terminating an initial 4-week period of immunosuppression after LTx. Genetic engineering to down-regulate SLA expression was achieved during ex vivo lung perfusion by lentiviral transduction of short hairpin RNAs targeting mRNAs encoding ß2-microglobulin and class II transactivator. Whereas all grafts in the control group were rejected within 3 months, five of seven animals in the treatment group maintained graft survival without immunosuppression during the 2-year monitoring period. Compared with controls, SLA-silenced lung recipients had lower donor-specific antibodies and proinflammatory cytokine concentrations in the serum. Together, these data demonstrate a survival benefit of SLA-down-regulated lung transplants in the absence of immunosuppression.

Cardiac Perforation Caused By Pectus Excavatum Metal Bar Stabilizer: A Case Report.

This paper reports the case of a female patient who underwent minimally invasive repair of pectus excavatum (MIRPE) in another service that evolved with bar rotation and cardiac perforation caused by the left stabilizer. The unique and frightening aspect of the case is that despite having the stabilizer inside the ventricle, the patient was oligosymptomatic: occasional chest pain and respiratory discomfort. Preoperative imaging showed rotation of the bar with stabilizers within the thoracic cavity. During surgery, intense ossification was observed around the prosthesis and it was noted that the left stabilizer had perforated the patient's left ventricle. Cardiac repair required a Clamshell incision and cardiopulmonary bypass. This case reinforces the validity of late radiological follow-up after MIRPE in an attempt to avoid this type of event, and the need to reevaluate the use of stabilizers perpendicular to the bar since they are not safe to prevent rotation of these implants.

Standardized generation of human iPSC-derived hematopoietic organoids and macrophages utilizing a benchtop bioreactor platform under fully defined conditions.

BACKGROUND: There is a significant demand for intermediate-scale bioreactors in academic and industrial institutions to produce cells for various applications in drug screening and/or cell therapy. However, the application of these bioreactors in cultivating hiPSC-derived immune cells and other blood cells is noticeably lacking. To address this gap, we have developed a xeno-free and chemically defined intermediate-scale bioreactor platform, which allows for the generation of standardized human iPSC-derived hematopoietic organoids and subsequent continuous production of macrophages (iPSC-Mac). METHODS: We describe a novel method for intermediate-scale immune cell manufacturing, specifically the continuous production of functionally and phenotypically relevant macrophages that are harvested on weekly basis for multiple weeks. RESULTS: The continuous production of standardized human iPSC-derived macrophages (iPSC-Mac) from 3D hematopoietic organoids also termed hemanoids, is demonstrated. The hemanoids exhibit successive stage-specific embryonic development, recapitulating embryonic hematopoiesis. iPSC-Mac were efficiently and continuously produced from three different iPSC lines and exhibited a consistent and reproducible phenotype, as well as classical functionality and the ability to adapt towards pro- and anti-inflammatory activation stages. Single-cell transcriptomic analysis revealed high macrophage purity. Additionally, we show the ability to use the produced iPSC-Mac as a model for testing immunomodulatory drugs, exemplified by dexamethasone. CONCLUSIONS: The novel method demonstrates an easy-to-use intermediate-scale bioreactor platform that produces prime macrophages from human iPSCs. These macrophages are functionally active and require no downstream maturation steps, rendering them highly desirable for both therapeutic and non-therapeutic applications.

Sex-based differences and risk of recurrence in patients with atrial fibrillation undergoing pulmonary vein isolation.

INTRODUCTION: Studies suggest increased likelihood of atrial fibrillation (AF) recurrence after catheter ablation (CA) in women than in men, indicating that sex may be an independent risk factor for recurrence. Nevertheless, the influence of sex on AF recurrence and underlying mechanisms remains unclear. METHODS: Retrospective, single-centre study including patients undergoing AF CA between 2017 and 2021. Late recurrence (LR) was defined as AF recurrence ≥90 days after ablation, whereas early recurrence (ER) occurred within 90 days. RESULTS: 656 patients (32% women) were included, with a median follow-up period of 26 months. Compared to men, women undergoing CA were older, had higher body mass indexes, and had higher rates of hypertension, thyroid dysfunction, and valvular disease. Women also had increased LR risk after CA (HR 1.76, 95% CI [1.19, 2.59]). A time-split multivariable analysis at one year of follow-up showed no difference in LR risk during the first 12 months after CA (HR 1.19, 95% CI [0.73, 1.94]); however, LR risk increased in women (HR 2.90, 95% CI [1.68, 5.01]) after 12 months. In a sex-stratified analysis, coronary calcium score (CCS) >100 was associated with increased LR risk in men (HR 1.81, 95% CI [1.06, 3.08]), but not in women. Cardiac adipose tissue volume was not associated with increased LR risk. CONCLUSIONS: Fewer women underwent CA than men and LR was more frequent in women, particularly one year after the procedure. CCS was associated with increased LR risk in men.

Comprehensive microRNA expression analysis of pediatric gonadal germ cell tumors: unveiling novel biomarkers and signatures.

microRNAs (miRNAs) are small endogenous noncoding RNAs, and alterations in their expression may contribute to oncogenesis. Discovering a unique miRNA pattern holds the potential for early detection and novel treatment possibilities in cancer. This study aimed to evaluate miRNA expression in pediatric patients with gonadal germ cell tumors (GCTs), focusing on characterizing the miRNA profiles of each histological subtype and identifying a distinct histological miRNA signature for a total of 42 samples of pediatric gonadal GCTs. The analysis revealed distinct miRNA expression profiles for all histological types, regardless of the primary site. We identified specific miRNA expression signatures for each histological type, including 34 miRNAs for dysgerminomas, 13 for embryonal carcinomas, 25 for yolk sac tumors, and one for immature teratoma, compared to healthy controls. Furthermore, we identified 26 miRNAs that were commonly expressed in malignant tumors, with six miRNAs (miR-302a-3p, miR-302b-3p, miR-371a-5p, miR-372-3p, miR-373-3p, and miR-367-3p) showing significant overexpression. Notably, miR-302b-3p exhibited a significant association with all the evaluated clinical features. Our findings suggest that miRNAs have the potential to aid in the diagnosis, prognosis, and management of patients with malignant GCTs.

Qualitative transformations of street-seized ecstasy over a decade: A case study in Rio de Janeiro (Brazil).

The illegal drug market is constantly evolving, with new drugs being created and existing ones being modified. Adulterants are often added to the mix, and the primary substance may be secretly replaced by a new one. Once-known tablets can now be vastly different from what they are sold as, all due to the pursuit of profit and evasion of current drug regulations. These alterations in drug composition pose a threat to society, as their effects are still not well understood. Therefore, it is crucial for police intelligence and public health development to obtain the chemical profiles of illicit drugs. This study presents the chemical fingerprinting of ecstasy tablets seized in the state of Rio de Janeiro (Brazil) between 2012 and 2021. The tablet samples were weighed, extracted, diluted with methanol, and acidified before analysis using gas chromatography high-resolution mass spectrometry and attenuated total reflection Fourier transform infrared spectroscopy. The major constituents found were MDMA and clobenzorex, with fewer occurrences of MDA, MDEA, and 2C-B. The results also indicate that the occurrence of mega-events in the study location impacted the chemical fingerprints of ecstasy. A total of 27 combinations of cutting agents, including caffeine, ephedrine, and anesthetics, were identified. Samples composed of clobenzorex were observed throughout the evaluated period in areas near highways, suggesting that this product is mainly used by truck drivers. These findings can help police intelligence units anticipate the behavior of the illicit market during major events, identify traffic routes, and support public health initiatives.

What Is Behind? Impact of Pelvic Pain on Perceived Stress and Inflammatory Markers in Women with Deep Endometriosis.

Introduction/Objectives: Endometriosis affects 10% of women worldwide. It is noteworthy that this condition is often accompanied by pelvic pain and stress. Endometriosis is a debilitating gynecological condition where tissue similar to the uterine lining grows outside the uterus, often causing significant pain and reproductive issues. We aimed to study the relationship between the intensity of pelvic pain, and stress and inflammatory markers in women with deep endometriosis. Methods: This cross-sectional study analyzed women diagnosed with deep endometriosis through imaging, surgery, and/or biopsy. We assessed pain using the Numerical Rating Scale (NRS). Stress was assessed with the Perceived Stress Scale (PSS-10) questionnaire and the serum cortisol levels. Additionally, we analyzed inflammatory markers, including C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Results: Fifty-two women, with an average age of 37.8 ± 6.9 years, participated in this study. Forty-four percent of these participants demonstrated high levels of stress, as indicated by scores above 26 on the PSS-10. Those categorized with "high stress" on the PSS-10 questionnaire exhibited significantly higher pain levels compared to those with "low stress" (p < 0.05). Furthermore, patients experiencing more-severe pelvic pain (pain score > 7) had notably higher serum cortisol levels. Women with intense pelvic pain (scores above 7 on the NRS) had significantly elevated serum cortisol levels (Cohen's d = 0.72; p = 0.018). Conclusions: A positive association was found between stress levels and the intensity of pelvic pain in women with deep endometriosis, suggesting an interconnection between emotional aspects and biological responses.

Protocol for the establishment of a serine integrase-based platform for functional validation of genetic switch controllers in eukaryotic cells.

Serine integrases (Ints) are a family of site-specific recombinases (SSRs) encoded by some bacteriophages to integrate their genetic material into the genome of a host. Their ability to rearrange DNA sequences in different ways including inversion, excision, or insertion with no help from endogenous molecular machinery, confers important biotechnological value as genetic editing tools with high host plasticity. Despite advances in their use in prokaryotic cells, only a few Ints are currently used as gene editors in eukaryotes, partly due to the functional loss and cytotoxicity presented by some candidates in more complex organisms. To help expand the number of Ints available for the assembly of more complex multifunctional circuits in eukaryotic cells, this protocol describes a platform for the assembly and functional screening of serine-integrase-based genetic switches designed to control gene expression by directional inversions of DNA sequence orientation. The system consists of two sets of plasmids, an effector module and a reporter module, both sets assembled with regulatory components (as promoter and terminator regions) appropriate for expression in mammals, including humans, and plants. The complete method involves plasmid design, DNA delivery, testing and both molecular and phenotypical assessment of results. This platform presents a suitable workflow for the identification and functional validation of new tools for the genetic regulation and reprogramming of organisms with importance in different fields, from medical applications to crop enhancement, as shown by the initial results obtained. This protocol can be completed in 4 weeks for mammalian cells or up to 8 weeks for plant cells, considering cell culture or plant growth time.

Epigenetic processes involved in response to pesticide exposure in human populations: a systematic review and meta-analysis.

In recent decades, the use of pesticides in agriculture has increased dramatically. This has resulted in these substances being widely dispersed in the environment, contaminating both exposed workers and communities living near agricultural areas and via contaminated foodstuffs. In addition to acute poisoning, chronic exposure to pesticides can lead to molecular changes that are becoming better understood. Therefore, the aim of this study was to assess, through a systematic review of the literature, what epigenetic alterations are associated with pesticide exposure. We performed a systematic review and meta-analysis including case-control, cohort and cross-sectional observational epidemiological studies to verify the epigenetic changes, such as DNA methylation, histone modification and differential microRNA expression, in humans who had been exposed to any type of pesticide. Articles published between the years 2005 and 2020 were collected. Two different reviewers performed a blind selection of the studies using the Rayyan QCRI software. Post-completion, the data of selected articles were extracted and analyzed. Most of the 28 articles included evaluated global DNA methylation levels, and the most commonly reported epigenetic modification in response to pesticide exposure was global DNA hypomethylation. Meta-analysis revealed a significant negative correlation between Alu methylation levels and ß-hexachlorocyclohexane, p,p'-dichlorodiphenyldichloroethane and p,p'-dichlorodiphenylethylene levels. In addition, some specific genes were reported to be hypermethylated in promoter regions, such as CDKN2AIGF2, WRAP53α and CDH1, while CDKN2B and H19 were hypomethylated due to pesticide exposure. The expression of microRNAs was also altered in response to pesticides, as miR-223, miR-518d-3p, miR-597, miR-517b and miR-133b that are associated with many human diseases. Therefore, this study provides evidence that pesticide exposure could lead to epigenetic modifications, possibly altering global and gene-specific methylation levels, epigenome-wide methylation and microRNA differential expression.

Exposure of the stingless bee Melipona scutellaris to imidacloprid, pyraclostrobin, and glyphosate, alone and in combination, impair its walking activity and fat body morphology and physiology.

The stingless bee Melipona scutellaris performs buzz pollination, effectively pollinating several wild plants and crops with economic relevance. However, most research has focused on honeybees, leaving a significant gap in studies concerning native species, particularly regarding the impacts of pesticide combinations on these pollinators. Thus, this study aimed to evaluate the sublethal effects of imidacloprid (IMD), pyraclostrobin (PYR), and glyphosate (GLY) on the behavior and fat body cell morphology and physiology of M. scutellaris. Foragers were orally exposed to the different pesticides alone and in combination for 48 h. Bees fed with contaminated solution walked less, moved slower, presented morphological changes in the fat body, including vacuolization, altered cell shape and nuclei morphology, and exhibited a higher count of altered oenocytes and trophocytes. In all exposed groups, alone and in combination, the number of cells expressing caspase-3 increased, but the TLR4 number of cells expressing decreased compared to the control groups. The intensity of HSP70 immunolabeling increased compared to the control groups. However, the intensity of the immunolabeling of HSP90 decreased in the IMD, GLY, and I + G (IMD + GLY) groups but increased in I + P-exposed bees (IMD + PYR). Alternatively, exposure to PYR and P + G (PYR + GLY) did not affect the immunolabeling intensity. Our findings demonstrate the hazardous effects and environmental consequences of isolated and combined pesticides on a vital neotropical pollinator. Understanding how pesticides impact the fat body can provide crucial insights into the overall health and survival of native bee populations, which can help develop more environmentally friendly approaches to agricultural practices.

Data-driven coaching to improve statewide outcomes in CABG: before and after interventional study.

BACKGROUND: The impact of quality improvement initiatives program (QIP) on coronary artery bypass grafting surgery (CABG) remains scarce, despite improved outcomes in other surgical areas. This study aims to evaluate the impact of a package of QIP on mortality rates among patients undergoing CABG. MATERIALS AND METHODS: This prospective cohort study utilized data from the multicenter database Registro Paulista de Cirurgia Cardiovascular II (REPLICCAR II), spanning from July 2017 to June 2019. Data from 4018 isolated CABG adult patients were collected and analyzed in three phases: before-implementation, implementation, and after-implementation of the intervention (which comprised QIP training for the hospital team). Propensity Score Matching was used to balance the groups of 2170 patients each for a comparative analysis of the following outcomes: reoperation, deep sternal wound infection/mediastinitis ≤30 days, cerebrovascular accident, acute kidney injury, ventilation time >24 h, length of stay <6 days, length of stay >14 days, morbidity and mortality, and operative mortality. A multiple regression model was constructed to predict mortality outcomes. RESULTS: Following implementation, there was a significant reduction of operative mortality (61.7%, P =0.046), as well as deep sternal wound infection/mediastinitis ( P <0.001), sepsis ( P =0.002), ventilation time in hours ( P <0.001), prolonged ventilation time ( P =0.009), postoperative peak blood glucose ( P <0.001), total length of hospital stay ( P <0.001). Additionally, there was a greater use of arterial grafts, including internal thoracic ( P <0.001) and radial ( P =0.038), along with a higher rate of skeletonized dissection of the internal thoracic artery. CONCLUSIONS: QIP was associated with a 61.7% reduction in operative mortality following CABG. Although not all complications exhibited a decline, the reduction in mortality suggests a possible decrease in failure to rescue during the after-implementation period.

Harvesting the Power of Green Synthesis: Gold Nanoparticles Tailored for Prostate Cancer Therapy.

Biosynthetic gold nanoparticles (bAuNPs) present a promising avenue for enhancing bio-compatibility and offering an economically and environmentally responsible alternative to traditional production methods, achieved through a reduction in the use of hazardous chemicals. While the potential of bAuNPs as anticancer agents has been explored, there is a limited body of research focusing on the crucial physicochemical conditions influencing bAuNP production. In this study, we aim to identify the optimal growth phase of Pseudomonas aeruginosa cultures that maximizes the redox potential and coordinates the formation of bAuNPs with increased efficiency. The investigation employs 2,6-dichlorophenolindophenol (DCIP) as a redox indicator. Simultaneously, we explore the impact of temperature, pH, and incubation duration on the biosynthesis of bAuNPs, with a specific emphasis on their potential application as antitumor agents. Characterization of the resulting bAuNPs is conducted using ATR-FT-IR, TEM, and UV-Vis spectroscopy. To gain insights into the anticancer potential of bAuNPs, an experimental model is employed, utilizing both non-neoplastic (HPEpiC) and neoplastic (PC3) epithelial cell lines. Notably, P. aeruginosa cultures at 9 h/OD600 = 1, combined with biosynthesis at pH 9.0 for 24 h at 58 °C, produce bAuNPs that exhibit smaller, more spherical, and less aggregated characteristics. Crucially, these nanoparticles demonstrate negligible effects on HPEpiC cells while significantly impacting PC3 cells, resulting in reduced viability, migration, and lower IL-6 levels. This research lays the groundwork for the development of more specialized, economical, and ecologically friendly treatment modalities.

Development, characterization, and biological study of bioglass coatings 45S5 and BioK on zirconia implant surfaces.

Zirconia implants are gaining attention as a viable alternative to titanium implants due to their comparable osseointegration development, improved soft tissue adaptation, and enhanced aesthetics. An encouraging avenue for improving zirconia implant properties involves the potential application of bioactive coatings to their surfaces. These coatings have shown potential for inducing hydroxyapatite formation, crucial for bone proliferation, and improving implant mechanical properties. This study aimed to evaluate the effect of coating zirconia implants with two bioactive glasses, 45S5 and BioK, on osteogenesis in vitro and osseointegration in vivo. Zirconia samples and implants were prepared using Zpex zirconia powder and blocks, respectively. The samples were divided into three groups: polished zirconia (ZRC), zirconia coated with 45S5 bioglass (Z + 45S5), and zirconia coated with BioK glass (Z + BK). Coatings were applied using a brush and sintered at 1200°C. Chemical analysis of the coatings was carried out using x-ray diffraction and Fourier Transform Infrared Spectroscopy. Surface topography and roughness were characterized using scanning electron microscopy and a roughness meter. In vitro experiments used mesenchymal cells from Wistar rat femurs, and the coated zirconia implants were found to promote cell viability, protein synthesis, alkaline phosphatase activity, and mineralization, indicating enhanced osteogenesis. In vivo experiments with 18 rats showed positive results for bone formation and osseointegration through histological and histomorphometric analysis and a push-out test. The findings indicate that bioactive glass coatings have the potential to improve cell differentiation, bone formation, and osseointegration in zirconia implants.

Preparing Collared Peccary (Pecari tajacu Linnaeus, 1758) for Reintroduction into the Wild: A Screening for Parasites and Hemopathogens of a Captive Population.

The reintroduction of captive animals to the wild helps restore endangered species, but it risks pathogen transmission, harming wild populations. Such transmission can impact the genetic diversity and long-term viability of these populations. This study assessed parasite diversity and load in captive Pecari tajacu, a species native to the Americas and culturally significant to Brazilian indigenous culture, prior to reintroduction. Samples from 24 peccaries were analyzed for ectoparasites, hemopathogens, and stool parasites with direct and molecular analysis. Findings showed that various parasites were present. Two peccaries (8.3%) were infested by the adult tick Amblyomma sculptum. Six (25.0%) tested positive for Trypanosoma evansi, four (16.7%) for hemobacteria of the family Anaplasmataceae, twelve (50.0%) for hemotropic Mycoplasma, and seven (29.2%) for Leishmania braziliensis. Stool samples indicated multiple parasites, with sixteen (66.7%) peccaries infected by Strongylida order parasites, Spiruridae in three (12.5%), and Ascaris suum in one (4.2%) animal. Cysts of Balantidium sp. were found in twenty (83.3%), Entamoeba polecki in five (20.8%), and Iodamoeba bütschlii in two (8.3%) peccaries. To our current knowledge, this is the first global report of Leishmania braziliensis, Iodamoeba bütschlii, and Entamoeba polecki in P. tajacu, irrespective of the environment, including both captivity and wild conditions. Some of these parasites are common in domestic animals, and others are zoonotic, indicating potential interspecies pathogen transmission.

Challenges in measuring sleep quality among women with endometriosis: A comparison of two questionnaires.

OBJECTIVE: This study aimed to underscore the issues associated with the dichotomization of categories in sleep questionnaires among women diagnosed with endometriosis and sleep disturbances, as well as their potential impact on the validity of the research findings. BACKGROUND: A range of questionnaires is employed across settings from primary care to research to classify sleep disturbances. Insomnia Severity Index (ISI) and the Pittsburgh Sleep Quality Index (PSQI) are two frequently utilized instruments for evaluating sleep. Nonetheless, these tools may produce divergent outcomes when applied to the same population. METHODS: To evaluate the sleep quality of patients with deep endometriosis (DE), two self-administered questionnaires were utilized: ISI and PSQI. Patients rated their average pelvic pain over the preceding four weeks on a numeric rating scale (NRS) ranging from 0 to 10. Patients with an ISI score >14 or PSQI >5 were classified as poor sleepers, while the others as good sleepers. RESULTS: Among the 161 patients who completed both sleep questionnaires, 129 (80 %) rated their subjective sleep quality as good. However, when the scores from the sleep questionnaires were analyzed, only 17 (11 %) patients were classified as good sleepers by the PSQI, whereas the ISI classified 83 (52 %) patients as good sleepers. When comparing the standardized scores, moderate to good reliability was found (intraclass correlation coefficient, 0.76; 95 % confidence interval, 0.69-0.82). CONCLUSION: Both questionnaires yield consistent scores that seem comparable in women with DE; however, the cutoff values seem inadequate for this population. Therefore, we can probably rely on both questionnaire scores, yet their recommended cutoff values should be approached with caution.

When and how to discuss about palliative care and advance care planning with cancer patients: A mixed-methods study.

OBJECTIVES: To identify the patients who are most likely to participate in discussions about palliative care (PC) and advance care planning (ACP), and to determine their preferred timing and approach of discussion. METHODS: The study included women aged 18-75 years diagnosed with breast cancer. In the quantitative phase, sociodemographic and clinical characteristics, knowledge, decision-making, and stigmas were evaluated. The qualitative phase included questions about patients' understanding, timing, and method of discussing PC and ACP, which were analyzed by Bardin's content analysis. RESULTS: In Phase 1, a total of 115 participants were included, with 53.04% completing both phases and 46.96% declining further participation. Those who completed both phases exhibited higher rates of marriage and educational attainment, while those who declined Phase 2 had a higher prevalence of advanced-stage cancer and palliative treatment. Completion of both phases was associated with a greater knowledge of reality and increased awareness of PC and ACP. Furthermore, the qualitative analysis revealed 5 convergent themes: timing, demystification, patient empowerment, misconception elimination, and open communication. These themes informed the development of a conceptual model that provides a framework for discussing PC and ACP with patients at different stages of cancer diagnosis and treatment, highlighting appropriate and inappropriate approaches and timing. SIGNIFICANCE OF RESULTS: Early discussion is beneficial, but withholding information or infringing on autonomy should be avoided. The study reveals that married and highly educated individuals tend to be more receptive to these discussions. However, patients with late-stage cancer tend to decline participation. Patients value open communication, demystification of PC, and empowering discussions that eliminate misunderstandings. Efforts should be made to reach patients with limited familiarity, particularly those with late-stage cancer, to increase their receptiveness to enable well-informed decision-making.

Mindfulness intervention effect on endometriosis-related pain dimensions and its mediator role on stress and vitality: a path analysis approach.

Endometriosis-related pain is supposedly mainly responsible for generating psychological stress and deteriorating the quality of life. However, the interaction between these factors has not been investigated, considering its multidimensional nature and through the path of effects of psychosocial approaches. The present study aims to investigate the effect of a brief mindfulness-based intervention (bMBI) on pain dimensions and its mediator role on psychological stress and QoL-Vitality improvement. A secondary analysis of a pilot randomized controlled trial using a series of parallel and serial mediators was carried out. The results showed that bMBI improves the sensory (B = -6.09 [-9.81, -2.52], ß = -0.42) and affective (B = -3.40 [-5.02, -1.80], ß = -0.47) pain. The bMBI effect on psychological stress reduction was mediated by these changes in sensory (B = -2.81 [-6.06, -0.41], ß = -0.21) and affective (B = -1.97 [-5.07, -0.17], ß = -0.15) pain. Serial sensory pain and psychological stress reduction (B = 2.27 [0.11, 5.81], ß = -0.09) mediated the bMBI effect on quality of life vitality. Meditation training promotes additional improvement in affective and sensory pain characteristics through which psychological stress is reduced. The sensory pain dimension must be positively impacted in combination with psychological stress for the bMBI improves women's vitality. Adding a psychosocial intervention like meditation training to the standard treatment plan may be required for some women to achieve the needed changes to restore well-being.

Circulating microRNAs as potential biomarkers in triple-negative breast cancer: a translational research study of the NACATRINE trial.

Liquid biopsy is increasingly vital in monitoring neoadjuvant breast cancer treatment. This study collected plasma samples at three time points from participants in the Neoadjuvant Carboplatin in Triple Negative Breast Cancer (NACATRINE), analyzing miRNA expression with NanoString's nCounter® Human v3 miRNA assay. In the carboplatin arm, four ct-miRNAs exhibited dynamic changes linked to pathologic complete response, with a combined area under the curve of 0.811. Similarly, the non-carboplatin arm featured four ct-miRNAs with an area under the curve of 0.843. These findings underscore the potential of ct-miRNAs as personalized tools in breast cancer treatment, assisting in predicting treatment response and assessing the risk of relapse. Integrating ct-miRNA analysis into clinical practice can optimize decisions and enhance patient outcomes.

Mindfulness-Based Intervention Effect on the Psychophysiological Marker of Self-Regulation in Women With Endometriosis-Related Chronic Pain.

Endometriosis is a gynecological disease that involves a broad biopsychosocial compromise with the potential to create a negative vicious cycle. Despite the complexity of factors influencing women's improvement, most interventions investigated target just the peripheral nociceptive sources of endometriosis-related pain. An alternative is intervening in self-regulation, which can potentially influence multiple domains of the illness experience. The present study examines the effect of a brief Mindfulness-Based Intervention (bMBI) on attention and autonomic nervous system regulation in women with endometriosis-related pain. Also, explore the interaction between these self-regulation domains and the affective pain dimension. An exploratory analysis of the secondary outcomes of a pilot randomized controlled trial was performed. The vagally-mediated Heart Rate Variability (vmHRV) at rest, cognitive stress, and recovery was employed to measure autonomic regulation. The Flanker and Stroop tasks were used to estimate the attention domains. Results showed that bMBI (n = 26) significantly improved Flanker accuracy and Flanker and Stroop reaction time compared to the control group (n = 28). bMBI significantly increased vmHRV at rest and recovery after cognitive stress. Attention mediated the bMBI effect on affective pain improvement. Results suggest that bMBI improves self-regulation domains with the potential to develop a broad biopsychosocial benefit in the endometriosis context. PERSPECTIVE: This article demonstrates the positive impact of a brief Mindfulness-Based Intervention on attention and parasympathetic regulation in women suffering from endometriosis-related pain. This mindfulness-induced self-regulation improvement can benefit affective pain and potentially multiple psychophysiological processes relevant to endometriosis.

Gene expression alterations predict the pathological complete response in triple-negative breast cancer exploratory analysis of the NACATRINE trial.

This exploratory analysis of the Neoadjuvant Carboplatin in Triple Negative Breast Cancer (NACATRINE) study aimed to identify the biomarkers of pathological complete response (pCR) in patients with triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy (NAC) within the context of a clinical trial. The NACATRINE trial is a phase II, single-center, randomized, open-label clinical trial that investigated the addition of carboplatin to sequential anthracycline- and taxane-based NAC for TNBC. We evaluated the gene expression in untreated samples to investigate its association with pCR, overall survival (OS), and disease-free survival (DFS). RNA was extracted from the tissue biopsy, and the nCounter Breast Cancer panel was used to analyze gene expression. Of the 66 patients included in the gene expression profiling analysis, 24 (36.4%) achieved pCR and 42 (63.6%) had residual disease. In unsupervised hierarchical clustering analyses, differentially expressed genes between patients with and without pCR were identified irrespective of the treatment (24 genes), carboplatin (37 genes), and non-carboplatin (27 genes) arms. In receiver operating characteristic (ROC) curve analysis, 10 genes in the carboplatin arm (area under the ROC curve [AUC], 0.936) and three genes in the non-carboplatin arm (AUC, 0.939) were considered to be potential pCR-associated biomarkers. We identified genes that were associated with improvements in OS and DFS in addition to being related to pCR. We successfully identified gene expression signatures associated with pCR in pretreatment samples of patients with TNBC treated with NAC. Further investigation of these biomarkers is warranted.