Search Results (27,857)

Background: Connexins (Cx) are a family of transmembrane proteins that form gap junctions and connexin hemichannels (HCs), enabling direct intercellular communication within the nervous system. Connexin 43 (Cx43), the principal astrocytic connexin, exhibits a context-dependent dual role: under physiological conditions it maintains tissue homeostasis and metabolic support, whereas under pathological conditions excessive activation of Cx43 hemichannels promotes neuroinflammation, excitotoxicity, blood–brain barrier disruption, and secondary neural tissue damage. Other connexin isoforms also contribute to the pathogenesis of neurological and psychiatric disorders through alterations in neuronal synchronization, glial signaling, and myelin integrity. Objective: To systematize current evidence on the role of key connexin isoforms in acute nervous system injuries—including stroke, traumatic brain injury, spinal cord injury, and peripheral nerve injury—as well as chronic disorders such as neurodegenerative diseases, epilepsy, and psychiatric disorders, with particular emphasis on the functional duality of connexin channels and the therapeutic potential of their selective modulation. Methods: A systematic literature search was conducted in the PubMed, Scopus, and Web of Science databases in accordance with the PRISMA framework and the PRISMA Extension for Scoping Reviews guidelines. The review included data from experimental models, postmortem brain studies, genetic association analyses, and pharmacological intervention studies. The retrieved studies were screened, assessed for eligibility, and integrated using a qualitative narrative synthesis approach. Results: In acute neural injuries, hyperactivation of Cx43 hemichannels amplifies inflammatory signaling, edema formation, and neuronal death, whereas selective HCs inhibitors reduce lesion volume and improve functional outcomes in experimental models. Connexin 36 (Cx36) contributes to cortical spreading depolarization and seizure propagation, while Connexin 32 (Cx32) and Connexin 47 (Cx47) are critically involved in oligodendrocyte function and white-matter demyelination. In PNI, Cx43 upregulation contributes to neuropathic pain, whereas mutations in Cx32 cause hereditary demyelinating neuropathies. In neurodegenerative diseases—including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis—Cx43 hemichannel activity promotes neuroinflammation and pathological protein accumulation, while reduced Cx32/Cx47 expression disrupts metabolic support of axons. In psychiatric disorders such as major depressive disorder, bipolar disorder, and schizophrenia, decreased astrocytic connexin expression (Cx43 and Cx30) has been associated with impaired glial–neuronal communication and cognitive–emotional dysfunction. In epilepsy, increased Cx43/Cx30 expression contributes to neuronal hypersynchronization and blood–brain barrier dysfunction, whereas selective hemichannel blockade suppresses seizure activity. Conclusions: Cx—particularly Cx43—occupies a central position in the molecular mechanisms of secondary neural injury and network dysfunction. The dual functional properties of gap junctions and hemichannels determine their context-dependent effects across neurological and psychiatric diseases. Selective inhibition of pathological HCs activity shows significant neuroprotective and anticonvulsant potential and represents a promising direction for the development of targeted therapeutic strategies. Further studies are required to determine optimal therapeutic time windows, tissue-specific effects, and the long-term safety of Cx modulation. Full article

Background: Bee-derived products are rich in bioactive compounds with antioxidant, anti-inflammatory, antimicrobial, and immunomodulatory properties. Interest is growing in their potential role as adjuncts in supportive nutritional oncology, particularly for preventing and managing treatment-related toxicity symptoms in patients receiving chemotherapy and/or radiotherapy. Methods: A systematic search of human and preclinical studies was conducted in PubMed/MEDLINE, Web of Science, and Scopus from January 2000 to December 2025. Search terms combined bee-related product keywords with oncology-related keywords. Eligible studies included in vitro and in vivo preclinical models as well as clinical studies assessing biological properties, clinical outcomes, safety, and issues of product standardization. Results: Preclinical and clinical studies indicate that beehive products reduce oxidative stress, modulate inflammatory signaling pathways, exhibit antimicrobial activity against wound pathogens, and promote tissue repair. Results are most consistent for oral mucositis and for symptom management in head and neck cancer, where some studies report reduced pain, improved mucosal healing, and better nutritional status. Conclusions: This literature review identifies honey and beehive products as promising functional foods for improving oncological patient care. Further large studies are needed, as the evidence is heterogeneous across sample size, product composition, outcome measures, and therapeutic preparations. Full article

Background: Pre-pectoral direct-to-implant breast reconstruction is increasingly adopted after mastectomy because it avoids pectoralis major dissection, reduces postoperative pain, and eliminates animation deformity. However, reconstruction in patients with large or markedly ptotic breasts remains challenging because of skin envelope management, nipple–areola complex (NAC) viability, and implant stability. This study evaluated batwing skin-reducing mastectomy with immediate pre-pectoral polyurethane-coated implant reconstruction. Methods: We conducted a retrospective single-center study of consecutive patients who underwent batwing skin-reducing mastectomy with immediate pre-pectoral polyurethane-coated implant reconstruction between November 2022 and January 2025. Demographic, oncologic, operative, postoperative, and BREAST-Q data were collected. Primary outcomes included complications, oncologic events, and 12-month patient-reported outcomes. Results: Thirteen patients underwent reconstruction, accounting for 18 breasts, with a mean follow-up of 12.85 months. Mean age was 54.5 ± 9.7 years, mean body mass index was 27.0 ± 3.4 kg/m², and mean Regnault ptosis grade was 3.46 ± 0.52. No seromas or oncologic recurrences were observed. One hematoma and one late infection requiring implant removal occurred. Superficial NAC/central flap epidermolysis developed in four patients and resolved conservatively; no full-thickness NAC necrosis occurred. BREAST-Q scores improved significantly in all domains at 12 months, including satisfaction with breasts, psychosocial well-being, physical well-being, and sexual well-being (all p < 0.05). Conclusions: Batwing skin-reducing mastectomy with immediate pre-pectoral polyurethane implant reconstruction appears safe and reproducible in selected patients with advanced ptosis, with acceptable complication rates and significant improvement in patient-reported outcomes. Full article

Background/Objectives: Inflammatory bowel diseases (IBDs) cause gastrointestinal symptoms that affect patients’ quality of life. IBD improves with physical activity; however, fear of movement is a limiting factor. This study aimed to evaluate the impact of kinesiophobia and assess patients’ knowledge on the role of physical activity and physiotherapists in IBD management. Methods: Participants completed online questionnaires to evaluate demographic and clinical data, lifestyle, physical activity, joint complaints, and physiotherapy preferences. The Tampa Kinesiophobia Scale (TKS) was employed to assess kinesiophobia, and the Godin scale was used to assess regular physical activity. Results: Overall, 356 patients with IBD were analyzed. In total, 51% of the patients reported a decrease in physical activity. Of these, 93% have not consulted a physiotherapist, with 51% expressing a need for it. Meanwhile, 75% of the patients wanted additional information. Higher TKS scores were associated with CD, age, and joint pain. The level of kinesiophobia was high and negatively correlated with the amount of physical activity. Conclusions: Physiotherapists play an important role in patient education and influencing lifestyle in IBD. Their expertise is underutilized, and patients should be sufficiently informed regarding their illness. Integrating education and physiotherapy may reduce kinesiophobia and improve patients’ quality of life. Full article

The dextran sodium sulfate (DSS) colitis model is the most widely used experimental model of inflammatory bowel disease (IBD) due to its simplicity and versatility, with over 7000 PubMed entries in the last decade and an exponential rise in recent years. Since its initial description in 1985, DSS colitis has been extensively evaluated across species, most notably in mice and rats, and has yielded substantial insights into IBD pathogenesis. However, the model’s multifactorial nature poses a dual challenge: it offers an opportunity but complicates study design, interpretation, and translational relevance. This complexity is worsened by inconsistent reporting, which hampers reproducibility and comparability across studies. The broad use of the DSS-induced colitis model yields numerous insights about the model, which help better understand its complexity, characteristics and limitations. Although DSS colitis is induced locally, inflammation in the colon and gut barrier destruction may also affect other organs (such as the liver and brain) and their metabolism and molecular responses, which, in turn, may interfere with colitis-underlying mechanisms and drug response, and may influence the interpretation of results. These intrinsic (intra-experimental) characteristics of the DSS model are summarised in the paper (colitis, gut–brain axis, gut–liver axis). In addition, the DSS model is heavily influenced by numerous extrinsic (inter-experimental) factors (environmental, microbiological, genetic), which may further complicate the colitis model, the study outcomes, and data interpretation, and these are also discussed in the paper. As science advances and new data accumulate, understanding the intricate interplay among internal mechanisms, external factors, and technical variables becomes increasingly essential for the accurate interpretation of DSS outcomes. This review synthesises the complexity and interdependence of factors shaping the DSS model, emphasising the need for meticulous reporting and consideration of methodological nuances to enhance reproducibility, interpretation, and translational value in DSS colitis research. In addition, the review provides practical guidance through a “traps and tricks” subsection and checklist table designed to provide a framework and practical recommendations to better understand, apply, and interpret DSS model results in the context of broader systemic and methodological considerations. Full article

Introduction: Tuberculous aneurysm of the thoracic aorta (TBAA) is an extremely rare but potentially fatal manifestation of tuberculosis (TB). Clinical presentation may include hemoptysis in the absence of parenchymal lung abnormalities. Case report: We presented a 62-year-old male with cough, chest pain, and minimal hemoptysis. Diagnostic evaluation confirmed an aneurysm of the descending thoracic aorta at a site previously treated with endovascular repair, with no imaging findings suggestive of pulmonary TB. Bronchoscopy revealed blood in the main bronchi without an identifiable endobronchial source. The diagnosis of TB was established by polymerase chain reaction (PCR) testing of bronchial aspirate obtained during bronchoscopy. Emergency surgical intervention was recommended because of an impending aortic rupture, but the patient declined surgery. Standard antituberculous therapy was initiated, and the patient subsequently developed drug-induced liver injury, prompting temporary cessation of treatment. The clinical course was later complicated by the development of an aortoesophageal fistula (AEF), with significant implications for prognosis. Conclusions: Early recognition of TBAA, along with a multidisciplinary approach that integrates advanced diagnostic modalities, timely vascular intervention, and carefully managed antituberculous therapy, is essential to reduce mortality and optimize treatment outcomes. Full article

Background/Objective: This study evaluated the analgesic and anti-inflammatory effects of ambroxol in an experimental model of endometriosis. Methods: Ambroxol was administered at doses of 10, 50, and 100 mg/kg (Abx 10, Abx 50, and Abx 100) by daily gavage for 21 days. A medroxyprogesterone-treated group (Progesterone) was included as a positive control. Pain was assessed using validated behavioral tests, including the Rat Grimace Scale (RGS), the von Frey test, and the rotarod test. Additionally, interleukin-1β (IL-1β) levels and total leukocyte counts were measured in peritoneal lavage fluid. The volumetric reduction in endometriotic implants was evaluated by ultrasonography, while histopathological analysis characterized inflammatory infiltrate and epithelial layer integrity using a standardized scoring system. Results: All ambroxol doses reduced spontaneous pain manifestations throughout the treatment. The mechanical withdrawal threshold significantly increased from the second week onward, and motor quality improved over the course of the study. A significant reduction in IL-1β levels compared with the negative control (Control(−)) was observed on day 21. Abx 50 and Abx 100 significantly reduced implant volumes (48.2% and 56.2%, respectively) and promoted marked disruption of the endometriotic epithelial layer. When compared with Progesterone, higher doses—particularly 100 mg/kg—demonstrated comparable efficacy. Conclusions: Taken together, these pleiotropic effects support the potential for drug repurposing in endometriosis. Full article

Background: Surgical palatal techniques are established alternatives to continuous positive airway pressure (CPAP) in selective patients with obstructive sleep apnea (OSA) with retropalatal airway collapse. Anterior palatoplasty (AP) stiffens and advances the soft palate, whereas radiofrequency-assisted uvulopalatoplasty (RF-UPP) uses thermal ablation to reduce palatal tissue. This study aimed to compare the 6-month efficacy and morbidity of AP vs. RF-UPP in treating mild-to-moderate OSA. Materials and Methods: We conducted a single-center retrospective cohort study (March 2023–March 2025) of 86 adults (mean age ~42 years; 69.8% male) with mild-moderate OSA (apnea–hypopnea index [AHI] 5–30) due to palatal obstruction; 43 patients underwent AP and 43 patients underwent RF-UPP. Polysomnographic AHI, Epworth sleepiness scale (ESS), snoring severity (0–10 visual analog scale, VAS) and sleep-related quality of life (functional outcomes of sleep questionnaire, FOSQ) were analyzed at baseline and 6 months postoperatively. Postoperative pain (0–10 VAS), recovery time, and bleeding events were also assessed. Results: Baseline characteristics were similar between groups (AHI ~22 vs. 21 events/h; ESS ~11 vs. 10; snoring VAS ~8.4 vs. 8.2 in AP vs. RF-UPP, all p > 0.1). At 6 months, the AP group achieved a greater mean AHI reduction than the RF-UPP group (−13.5 ± 7.5 vs. −8.0 ± 7.2, p < 0.001), with post-treatment AHI averaging 8.5 ± 6.0 vs. 13.2 ± 6.5 events/h (AP vs. RF-UPP). AP yielded a higher surgical success rate (34/43 (79.1%) vs. 23/43 (53.5%), p = 0.012), meeting the criteria of ≥50% AHI reduction to <15; p = 0.01. Subjective outcomes improved in both groups, but AP showed greater mean reductions in ESS (−5.5 vs. −3.1 points, p = 0.001) and snoring VAS (−5.7 vs. −3.1, p = 0.002). The improvements in ESS, snoring VAS, and FOSQ scores were observed in both groups, with significantly greater gains after AP. Postoperative pain and time to resumption of normal diet were higher in the AP group. No major complications occurred in either group. Conclusions: Anterior palatoplasty demonstrated superior efficacy to RF-UPP in mild-moderate OSA at the expense of increased postoperative pain and a longer recovery period. AP may offer a greater therapeutic benefit in appropriately selected patients with palatal obstruction. Full article

Background/Objectives: Catheter-related bladder discomfort (CRBD) is a common complication that patients with Foley catheters may experience following surgery. Previous studies have suggested that nefopam can reduce the incidence and severity of CRBD; however, dose-dependent effects (20 mg vs. 40 mg) have not been directly compared. Therefore, this study aimed to evaluate the dose-dependent effects of nefopam on CRBD, determine its effective dose, and assess the incidence of associated side effects. Methods: Electronic medical records of patients aged 18–70 years with American Society of Anesthesiologists physical status I–III who underwent elective transurethral ureteroscopic lithotripsy under general anesthesia from August 2016 to December 2022 were reviewed. Patients were categorized into three groups: premedication with intravenous nefopam 20 mg (group N20), premedication with nefopam 40 mg (group N40), or no premedication (control, group C). Results: The incidence rates of CRBD were 85.7% in group C, 81.3% in group N20, and 51.4% in group N40, showing a significant difference among the groups (p = 0.003, Pearson’s chi-squared test). Postoperative NRS was significantly different among the groups (p < 0.001, one-way ANOVA). In post hoc analysis, both group N20 and group N40 showed significantly lower scores compared to group C (p = 0.002, p = 0.001 respectively). The severity of CRBD also decreased in a dose-dependent manner, which was considered significant. No significant differences were observed among the groups in terms of intraoperative hemodynamic stability or postoperative nausea and vomiting. Conclusions: The administration of nefopam 40 mg significantly reduced the incidence and severity of CRBD compared with no premedication. Full article

Opioid analgesics are essential in the management of severe and chronic pain; however, their prolonged use is limited by the onset of analgesic tolerance and opioid-induced hyperalgesia (OIH). Recent studies increasingly implicate both synaptic functional and structural plasticity within nociceptive pathways as crucial mechanisms in OIH and tolerance. This review integrates current mechanistic understanding of how opioids alter synaptic transmission throughout the dorsal root ganglia (DRG), spinal dorsal horn, and supraspinal nociceptive networks. Peripherally, μ-opioid receptor (MOR) activation on TRPV1-positive nociceptors initiates presynaptic long-term potentiation (LTP), forming an early substrate for central sensitization. In the spinal dorsal horn, chronic opioid exposure drives NMDAR-dependent LTP, TRPC-mediated calcium influx, and actin cytoskeleton remodeling, leading to persistent increases in synaptic strength and excitatory connectivity. In supraspinal regions—including the ventral hippocampus, prefrontal cortex, and amygdala—opioids promote experience-dependent plasticity and predictive coding, which link environmental cues to reduced analgesic effectiveness. In addition to synaptic functional plasticity, opioid-induced synaptic structural plasticity within nociceptive pathways has been shown to underlie the long-term nature of opioid analgesic tolerance. Collectively, these data define a distributed network of opioid-responsive synapses whose pathological potentiation underpins the development of tolerance and hyperalgesia. Elucidating these mechanisms underlying OIH and tolerance paves the way for targeted therapeutic strategies that maintain analgesic efficacy while minimizing adverse synaptic remodeling and negative outcomes. Full article

Brain metastases remain a major problem for cancer patients, impacting their treatment and survival. The pathogenesis of brain metastases is largely unknown. Recent reports indicate that the adhesion molecule protocadherin γ C3 (PCDHGC3) is differentially expressed in various cancer cells and endothelial cells of the blood–brain barrier (BBB), suggesting its involvement in the development of brain metastases. Therefore, we generated a PCDHGC3 knockout (KO) in the triple-negative breast cancer cell line HCC1806 and the malignant melanoma cell line A2058. Control and KO cells were compared using cell proliferation, adhesion and invasion assays, gene expression analyses and matrix metalloproteinase (MMP) activity assays. While the PCDHGC3 KO mutation led to increased proliferation in HCC1806 cells, with no difference observed in A2058, it significantly increased adhesion to in vitro BBB models as well as invasion in both HCC1806 and A2058 KO cell lines. Although changes in mRNA expression of genes involved in metastasis, angiogenesis and cell adhesion were found in PCDHGC3 KO breast cancer and melanoma cells, the number of genes with significantly increased mRNA expression was higher in A2058 KO cells than in HCC1806 KO cells. While the mRNA expression of MMP1 and 2 was increased in A2058 KO cells, no significant changes were found in HCC1806 KO cells. However, increased MMP activity in the cell culture medium was detected in HCC1806 KO cells, while A2058 KO cells showed lower MMP-activity compared to control. These findings provide insights into the role of PCDHGC3 in cancer cell extravasation during metastatic process and identify potential therapeutic targets for further investigation. Full article

Background: Meralgia paresthetica is a neuropathic pain syndrome caused by compression of the lateral femoral cutaneous nerve (LFCN). While often self-limited, a subset of patients develops persistent symptoms requiring interventional management. Ultrasound guidance has improved accuracy and safety in peripheral nerve blocks, but evidence from Internal Medicine-led procedures remains limited. Methods: We performed a retrospective, observational case series including all patients aged ≥17 years who underwent ultrasound-guided LFCN blocks at Virgen del Rocío University Hospital between 2016 and 2024. Demographic data, comorbidities, procedural details, complications, and clinical outcomes were collected. Symptomatic response and recurrence were assessed descriptively. Results: Eleven patients were included (10 women; median age 56 years). The most frequent comorbidities were obesity (45.5%) and type 2 diabetes mellitus (18.2%). Clinical improvement following LFCN block was achieved in 10 of 11 patients (91%). Three patients (27%) experienced recurrence, with a median time to recurrence of 24 months; two underwent a second successful block, and one showed spontaneous resolution. No major complications occurred, and only one patient developed a mild, self-limited local reaction. Conclusions: Ultrasound-guided LFCN block is a safe, well-tolerated, and highly effective intervention for patients with persistent meralgia paresthetica. Outcomes achieved by an Internal Medicine specialist appear consistent with previously published reports from anesthesiology settings, underscoring the value of point-of-care ultrasound as a practical and precise tool for managing neuropathic pain within Internal Medicine settings. Full article