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Endometriosis: Cellular and Molecular Mechanisms Leading to Fibrosis.

Endometriosis is a chronic inflammatory condition affecting women of reproductive age. A relevant feature of endometriosis is the presence of fibrotic tissue inside and around the lesions, thus contributing to the classic endometriosis-related symptoms, pain, and infertility. The molecular mechanisms responsible for the development of fibrosis in endometriosis are not yet defined. The present review aimed to examine the biological mechanisms and signalling pathways involved in fibrogenesis of endometriotic lesions, highlighting the difference between deep infiltrating and ovarian endometriosis. The main cell types involved in the development of fibrosis are platelets, myofibroblasts, macrophages, and sensory nerve fibers. Members of the transforming growth factor (TGF) -β family, as well as the receptor Notch, or the bioactive sphingolipid sphingosine 1-phosphate (S1P), play a role in the development of tissue fibrosis, resulting in their metabolism and/or their signalling pathways altered in endometriotic lesions. It is relevant the knowledge of the molecular mechanisms that guide and support fibrosis in endometriosis, to identify new drug targets and provide new therapeutic approaches to patients.

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Analgesic Efficacy of Pectoral Nerve Blocks in Implant-Based Mammoplasty: A Systematic Review and Meta-Analysis.

To evaluate the analgesic effect of pectoral nerve block in implant-based mammoplasty.

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Motor cortex excitability in chronic low back pain.

Chronic pain is associated with dysfunctional cortical excitability. Research has identified altered intracortical motor cortex excitability in Chronic Lower Back Pain (CLBP). However, research identifying the specific intracortical changes underlying CLBP has been met with inconsistent findings. In the present case-control study, we examined intracortical excitability of the primary motor cortex using transcranial magnetic stimulation (TMS) in individuals with CLBP. Twenty participants with CLBP (M = 54.45 years, SD = 15.89 years) and 18 age- and gender-matched, pain-free controls (M = 53.83, SD = 16.72) were included in this study. TMS was applied to the hand motor area of the right hemisphere and motor evoked potentials (MEPs) were recorded from the first dorsal interosseous muscle of the contralateral hand. Resting motor threshold (rMT) and MEP amplitude were measured using single-pulse stimulation. Short interval intracortical inhibition (SICI) and intracortical facilitation (ICF) were assessed using paired-pulse stimulation. Individuals with CLBP had significantly higher rMT (decreased corticospinal excitability) and lower ICF compared to controls. No significant differences were found in MEP amplitude and SICI. These findings add to the growing body of evidence that CLBP is associated with deficits in intracortical modulation involving glutamatergic mechanisms.

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Integrated Neuroregenerative Techniques for Plasticity of the Injured Spinal Cord.

On the slow path to improving the life expectancy and quality of life of patients post spinal cord injury (SCI), recovery remains controversial. The potential role of the regenerative capacity of the nervous system has led to numerous attempts to stimulate the SCI to re-establish the interrupted sensorimotor loop and to understand its potential in the recovery process. Numerous resources are now available, from pharmacological to biomolecular approaches and from neuromodulation to sensorimotor rehabilitation interventions based on the use of various neural interfaces, exoskeletons, and virtual reality applications. The integration of existing resources seems to be a promising field of research, especially from the perspective of improving living conditions in the short to medium term. Goals such as reducing chronic forms of neuropathic pain, regaining control over certain physiological activities, and enhancing residual abilities are often more urgent than complete functional recovery. In this perspective article, we provide an overview of the latest interventions for the treatment of SCI through broad phases of injury rehabilitation. The underlying intention of this work is to introduce a spinal cord neuroplasticity-based multimodal approach to promote functional recovery and improve quality of life after SCI. Nonetheless, when used separately, biomolecular therapeutic approaches have been shown to have modest outcomes.

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MicroRNAs Dysregulation as Potential Biomarkers for Early Diagnosis of Endometriosis.

Endometriosis is a benign chronic disease in women that is characterized by the presence of active foci of the endometrium or endometrial tissue occurring outside of the uterus. The disease causes disabling symptoms such as pelvic pain and infertility, which negatively affect a patient's quality of life. In addition, endometriosis imposes an immense financial burden on the healthcare system. At present, laparoscopy is the gold standard for diagnosing the disease because other non-invasive diagnostic tests have less accuracy. In addition, other diagnostic tests have low accuracy. Therefore, there is an urgent need for the development of a highly sensitive, more specific, and non-invasive test for the early diagnosis of endometriosis. Numerous researchers have suggested miRNAs as potential biomarkers for endometriosis diagnosis due to their specificity and stability. However, the greatest prognostic force is the determination of several miRNAs, the expression of which varies in a given disease. Despite the identification of several miRNAs, the studies are investigatory in nature, and there is no consensus on them. In the present review, we first provide an introduction to the dysregulation of miRNAs in patients with endometriosis and the potential use of miRNAs as biomarkers in the detection of endometriosis. Then we will describe the role of the mir-200 family in endometriosis. Several studies have shown that the expression of the mir-200 family changes in endometriosis patients, suggesting that they could be used as a diagnostic biomarker and therapeutic target for endometriosis.

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Combinations of Cannabidiol and Δ-Tetrahydrocannabinol in Reducing Chemotherapeutic Induced Neuropathic Pain.

Neuropathic pain is a condition that impacts a substantial portion of the population and is expected to affect a larger percentage in the future. This type of pain is poorly managed by current therapies, including opioids and NSAIDS, and novel approaches are needed. We used a cisplatin-induced model of neuropathic pain in mice to assess the effects of the cannabinoids THC and CBD alone or in varying ratios as anti-nociceptive agents. In addition to testing pure compounds, we also tested extracts containing high THC or CBD at the same ratios. We found that pure CBD had little impact on mechanical hypersensitivity, whereas THC reduced mechanical hypersensitivity in both male and female mice (as has been reported in the literature). Interestingly, we found that high CBD cannabis extract, at the same CBD dose as pure CBD, was able to reduce mechanical hypersensitivity, although not to the same level as high THC extract. These data suggest that, at least for CBD-dominant cannabis extracts, there is an increase in the anti-nociceptive activity that may be attributed to other constitutes of the plant. We also found that high THC extract or pure THC is the most efficacious treatment for reducing neuropathic pain in this model.

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Cancer Patients First Treated with Chemotherapy: Are They More Likely to Receive Surgery in the Pandemic?

Due to the ramping down of cancer surgery in early pandemic, many newly diagnosed patients received other treatments first. We aimed to quantify the pandemic-related shift in rate of surgery following chemotherapy. This is a retrospective population-based cohort study involving adults diagnosed with cancer between 3 January 2016 and 7 November 2020 in Ontario, Canada who received chemotherapy as first treatment within 6-months of diagnosis. Competing-risks regression models with interaction effects were used to quantify the association between COVID-19 period (receiving a cancer diagnosis before or on/after 15 March 2020) and receipt of surgical reSection 9-months after first chemotherapy. Among 51,653 patients, 8.5% ( = 19,558) of them ultimately underwent surgery 9-months after chemotherapy initiation. Receipt of surgery was higher during the pandemic than before (sHR 1.07, 95% CI 1.02-1.13). Material deprivation was independently associated with lower receipt of surgery (least vs. most deprived quintile: sHR 1.11, 95% CI 1.04-1.17), but did not change with the pandemic. The surgical rate increase was most pronounced for breast cancer (sHR 1.13, 95% CI 1.06-1.20). These pandemic-related shifts in cancer treatment requires further evaluations to understand the long-term consequences. Persistent material deprivation-related inequity in cancer surgical access needs to be addressed.

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Sex Differences in Oxycodone/Naloxone vs. Tapentadol in Chronic Non-Cancer Pain: An Observational Real-World Study.

Despite the large body of research on sex differences in pain, there is a lack of translation to real-world pain management. Our aim was to analyse the sex differences in the analgesic response to oxycodone/naloxone (OXN) and tapentadol (TAP), in comparison with other opioids (OPO) commonly prescribed for chronic non-cancer pain (CNCP). An observational and cross-sectional study was conducted on ambulatory CNCP patients ( = 571). Sociodemographic, clinical (pain intensity, relief, and quality of life), safety (adverse events (AEs), adverse drug reactions), hospital frequentations and pharmacological (morphine equivalent daily dose (MEDD)) variables were collected. Multiple linear regressions were carried out to assess the association between sex and outcomes. Sex differences were observed, with lower female tolerability and higher hospital frequentation, especially in the OXN group (OR AEs report = 2.8 [1.8-4.4], < 0.001). Here, females showed higher hospital use (23% hospital admission, 30% prescription change, < 0.05), requiring a higher MEDD (127 ± 103 mg/day, < 0.05), compared to OXN men. Regardless of the opioid group, CNCP women were significantly older than men (three years), with significantly higher benzodiazepine use (OR = 1.6 [1.1-2.3]), more constipation (OR = 1.34 [0.93-1.90]) and headache (OR = 1.45 [0.99-2.13]) AEs, than men who were more likely to refer sexual dysfunction (OR = 2.77 [1.53-5.01]), and loss of libido (OR = 1.93 [1.22-3.04]). Sex-differences were found related to poorer female drug tolerability and higher hospital resources, even worst in OXN female users. Other differences related to older female ages and benzodiazepine prescription, need to be further analysed from a gender perspective.

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Predictors of Functional Recovery among Musculoskeletal Oncology Patients Undergoing Lower Extremity Endoprosthetic Reconstruction.

Functional outcomes are important for oncology patients undergoing lower extremity reconstruction. The objective of the current study was to describe patient reported function after surgery and identify predictors of postoperative function in musculoskeletal oncology patients undergoing lower extremity endoprosthetic reconstruction.

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A Retrospective Comparison of Three Patient-Controlled Analgesic Strategies: Intravenous Opioid Analgesia Plus Abdominal Wall Nerve Blocks versus Epidural Analgesia versus Intravenous Opioid Analgesia Alone in Open Liver Surgery.

: Adequate pain control is of crucial importance to patient recovery and satisfaction following abdominal surgeries. The optimal analgesia regimen remains controversial in liver resections. : Three groups of patients undergoing open hepatectomies were retrospectively analyzed, reviewing intravenous patient-controlled analgesia (IV-PCA) versus IV-PCA in addition to bilateral rectus sheath and subcostal transversus abdominis plane nerve blocks (IV-PCA + NBs) versus patient-controlled thoracic epidural analgesia (TEA). Patient-reported pain scores and clinical data were extracted and correlated with the method of analgesia. Outcomes included total morphine consumption and numerical rating scale (NRS) at rest and on movement over the first three postoperative days, time to remove the nasogastric tube and urinary catheter, time to commence on fluid and soft diet, and length of hospital stay. : The TEA group required less morphine over the first three postoperative days than IV-PCA and IV-PCA + NBs groups (9.21 ± 4.91 mg, 83.53 ± 49.51 mg, and 64.17 ± 31.96 mg, respectively, < 0.001). Even though no statistical difference was demonstrated in NRS scores on the first three postoperative days at rest and on movement, the IV-PCA group showed delayed removal of urinary catheter (removal on postoperative day 4.93 ± 5.08, 3.87 ± 1.31, and 3.70 ± 1.30, respectively) and prolonged length of hospital stay (discharged on postoperative day 12.71 ± 7.26, 11.79 ± 5.71, and 10.02 ± 4.52, respectively) as compared to IV-PCA + NBs and TEA groups. : For postoperative pain management, it is expected that the TEA group required the least amount of opioid; however, IV-PCA + NBs and TEA demonstrated comparable postoperative outcomes, namely, the time to remove nasogastric tube/urinary catheter, to start the diet, and the length of hospital stay. IV-PCA with NBs could thus be a reliable analgesic modality for patients undergoing open liver resections.

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