anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
The comorbidity of chronic pain and depression poses tremendous challenges for the treatment of either one because they exacerbate each other with unknown mechanisms. As the posterior insular cortex (PIC) integrates multiple somatosensory and emotional information and is implicated in either chronic pain or depression, we hypothesize that the PIC and its projections may contribute to the pathophysiology of comorbid chronic pain and depression. We show that PIC neurons were readily activated by mechanical, thermal, aversive, and stressful and appetitive stimulation in naive and neuropathic pain male mice subjected to spared nerve injury (SNI). Optogenetic activation of PIC neurons induced hyperalgesia and conditioned place aversion in naive mice, whereas inhibition of these neurons led to analgesia, conditioned place preference (CPP), and antidepressant effect in both naive and SNI mice. Combining neuronal tracing, optogenetics, and electrophysiological techniques, we found that the monosynaptic glutamatergic projections from the PIC to the basolateral amygdala (BLA) and the ventromedial nucleus (VM) of the thalamus mimicked PIC neurons in pain modulation in naive mice; in SNI mice, both projections were enhanced accompanied by hyperactivity of PIC, BLA, and VM neurons and inhibition of these projections led to analgesia, CPP, and antidepressant-like effect. The present study suggests that potentiation of the PIC→BLA and PIC→VM projections may be important pathophysiological bases for hyperalgesia and depression-like behavior in neuropathic pain and reversing the potentiation may be a promising therapeutic strategy for comorbid chronic pain and depression.
Regular exercise training can lead to several health benefits, reduce mortality risk, and increase life expectancy. On the other hand, a sedentary lifestyle is a known risk factor for chronic diseases and increased mortality. Acute kidney injury (AKI) and chronic kidney disease (CKD) represent a significant global health problem, affecting millions of people worldwide. The progression from AKI to CKD is well-recognized in the literature, and exercise training has emerged as a potential renoprotective strategy. Thus, this article aims to review the main molecular mechanisms underlying the renoprotective actions of exercise training in the context of AKI and CKD, focusing on its antioxidative, anti-inflammatory, anti-apoptotic, anti-fibrotic, and autophagy regulatory effects. For that, bibliographical research was carried out in Medline/PubMed and Scielo databases. Although the pathophysiological mechanisms involved in renal diseases are not fully understood, experimental studies demonstrate that oxidative stress, inflammation, apoptosis, and dysregulation of fibrotic and autophagic processes play central roles in the development of tissue damage. Increasing evidence has suggested that exercise can beneficially modulate these mechanisms, potentially becoming a safe and effective non-pharmacological strategy for kidney health protection and promotion. Thus, the evidence base discussed in this review suggests that an adequate training program emerges as a valuable tool for preserving renal function in experimental animals, mainly through the production of antioxidant enzymes, nitric oxide (NO), irisin, IL-10, and IL-11. Future research can continue to explore these mechanisms to develop specific guidelines for the prescription of exercise training in different populations of patients with kidney diseases.
Purpose: Recent guidelines have recommended minimally invasive surgery (MIS) for unilateral inguinal hernia due to reduced chronic pain. The most performed approaches consist of posterior mesh placement by the transabdominal preperitoneal (TAPP) and totally extraperitoneal (TEP) techniques. However, it remains debatable whether the advantage of those techniques stems from the MIS approach or posterior mesh placement or both. As the transrectus preperitoneal (TREPP) technique is an open option for posterior mesh placement, we conducted a systematic review and meta-analysis comparing TREPP and MIS techniques for groin hernia repair. Material and Methods: Cochrane, Embase, Scopus, Scielo, and PubMed were systematically searched for studies comparing TREPP and MIS techniques for groin hernia repair. Outcomes assessed were recurrence, cumulative surgical site occurrences (SSO), surgical site infection (SSI), and postoperative pain. Results: Twenty-nine studies were screened, and eight were thoroughly reviewed. Three studies were included, of which two compared TREPP with the TEP technique, and one compared TREPP with both TEP and TAPP techniques. We found lower SSI rates for the MIS approaches (0.61% versus 0.33%; risk ratios (RRs) 3.96; 95% confidence interval (CI): 1.04-15.16; P = .04). We did not find statistically significant differences regarding recurrence (2.42% versus 2.51%; RR 1.01; P = .98), postoperative pain (4.2% versus 6.4%; RR 0.61; P = .4), and SSO (4.2% versus 4.0%; RR 0.6; P = .43) between TREPP and MIS techniques. Conclusion: Our systematic review and meta-analysis found a lower SSI for the MIS repair but did not find differences regarding recurrence, SSO, and postoperative pain. More studies are required to provide a more accurate conclusion about this topic.
Participants will download the anxiety application to their own handphones, and will complete the programme subsequently in their own time over the course of 2 weeks. The expected duration participants will spend on the anxiety application daily is estimated to be around 5 to 10 minutes, amounting to a total of around 140 minutes (2 hours and 10 minutes) during the 2 weeks intervention. Participants in the anxiety group are asked to complete daily brief exercises. For example, they will practice noticing worry thoughts and journal them down.
The project will use a 2x2 design to assess the efficacy of naltrexone for treating subjects who are both cocaine and alcohol dependent and who will receive either CBT or BRENDA alone or in combination with naltrexone. There will be 300 DSM-IV cocaine-alcohol dependent male and female subjects randomized to one of four groups (75 subjects per group). Subjects will be randomized to either 150mg/day naltrexone or placebo and to receive either CBT (a type of cognitive behavior therapy derived from relapse prevention principles), or a new primary-care basedmodel, BRENDA, comprised of strategies for enhancing motivation and treatment compliance. All subjects will receive one of the four combinations of medication and psychosocial treatment. The length of the study for each subject includes one week of screening/baseline assessments, 12 weeks of double-blind, placebo-controlled naltrexone treatment combined with one of two psychosocial treatments, and a 6-month and 12-month follow-up visit. Following successful completion of detoxification (abstinence from alcohol and cocaine for 7 days), informed consent will be signed, and Week 1 will be devoted to completing screening and baseline measures. In Week 2, subjects will be randomly assigned to medication/ psychosocial treatment combination. Following completion of the 12-week, double-blind treatment trial, subjects will be evaluated at 6-month and 12-months post-treatment visits.
Colorectal cancer (CRC) is a leading cause of cancer mortality worldwide, and cancer-associated fibroblasts (CAFs) play a major role in the tumor microenvironment (TME), which facilitates the progression of CRC. It is critical to understand how CAFs promote the progression of CRC for the development of novel therapeutic approaches. The purpose of this study was to understand how CAF-derived stromal-derived factor-1 (SDF-1) and its interactions with the corresponding C-X-C motif chemokine receptor 4 (CXCR4) promote CRC progression. Our study focused on their roles in promoting tumor cell migration and invasion and their effects on the characteristics of cancer stem cells (CSCs), which ultimately impact patient outcomes. Here, using in vivo approaches and clinical histological samples, we analyzed the influence of secreted SDF-1 on CRC progression, especially in terms of tumor cell behavior and stemness. We demonstrated that CAF-secreted SDF-1 significantly enhanced CRC cell migration and invasion through paracrine signaling. In addition, the overexpression of SDF-1 in CRC cell lines HT29 and HCT-116 triggered these cells to generate autocrine SDF-1 signaling, which further enhanced their CSC characteristics, including those of migration, invasion, and spheroid formation. An immunohistochemical study showed a close relationship between SDF-1 and CXCR4 expression in CRC tissue, and this significantly affected patient outcomes. The administration of AMD3100, an inhibitor of CXCR4, reversed the entire phenomenon. Our results strongly suggest that targeting this signaling axis in CRC is a feasible approach to attenuating tumor progression, and it may, therefore, serve as an alternative treatment method to improve the prognosis of patients with CRC, especially those with advanced, recurrent, or metastatic CRC following standard therapy.
Tetracyclines have been associated with the development of autoimmune syndromes. The long-term use of minocycline in the treatment of acne has been associated with drug-induced lupus -like syndrome, autoimmune hepatitis and vasculitis. Sporadic cases of serum sickness have presented shortly after minocycline use. Symptoms may be manifested by fever, rash, arthralgia, and malaise. In symptomatic patients, liver function tests, ANA, CBC, and other appropriate tests should be performed to evaluate the patients. Use of all tetracycline-class drugs should be discontinued immediately.
Postoperative delirium (POD) is a common postoperative complication of the elderly caused by a variety of factors. POD is an acute neuropsychiatric disorder characterized by disturbance of attention consciousness and cognitive function fluctuation, and more than 40% of elderly patients have symptoms of hypoactivity POD.The incidence of POD is as high as 17% to 61% in patients with neurocognitive impairment and patients undergoing complex or emergency surgery, which usually occurs between 1 and 3 days after surgery. POD will lead to prolonged hospital stay, functional impairment and even death. How to prevent and treat POD is an urgent clinical problem to be solved at present.

Opiates are commonly used perioperative sedatives and analgesics, which may be associated with the occurrence of postoperative POD in elderly patients and increase the risk of POD. It is not clear whether perioperative use of low doses of opioids could reduces the incidence of POD in elderly patients. In this study, reducing-opioids anesthesia was defined as the use of 1/3 of the conventional opioid dose to observe whether reducing-opioids anesthesia affected the incidence of POD in elderly patients undergoing gastric cancer surgery
Women in experimental branch will receive two sachets. Sachet one contains a total of 5\*10\^8 CFU of Lactobacillus reuteri DSM 16666 \& Lactobacillus reuteri DSM 17938, mixed with maltodextrin for flowability during production. Sachet two contains instant cranberry drink composed of Cranberry extract, xylitol, cranberry aroma, monosodium citrate, zink gluconate, silica.
SH2B1 mutations are associated with obesity, type 2 diabetes, and metabolic dysfunction-associated steatotic liver disease (MASLD) in humans. Global deletion of Sh2b1 results in severe obesity, type 2 diabetes, and MASLD in mice. Neuron-specific restoration of SH2B1 rescues the obesity phenotype of Sh2b1-null mice, indicating that the brain is a main SH2B1 target. However, SH2B1 neurocircuits remain elusive. SH2B1-expressing neurons in the paraventricular hypothalamus (PVHSH2B1) and a PVHSH2B1→dorsal raphe nucleus (DRN) neurocircuit are identified here. PVHSH2B1 axons monosynaptically innervate DRN neurons. Optogenetic stimulation of PVHSH2B1 axonal fibers in the DRN suppresses food intake. Chronic inhibition of PVHSH2B1 neurons causes obesity. In male and female mice, either embryonic-onset or adult-onset deletion of Sh2b1 in PVH neurons causes energy imbalance, obesity, insulin resistance, glucose intolerance, and MASLD. Ablation of Sh2b1 in the DRN-projecting PVHSH2B1 subpopulation also causes energy imbalance, obesity, and metabolic disorders. Conversely, SH2B1 overexpression in either total or DRN-projecting PVHSH2B1 neurons protects against diet-induced obesity. SH2B1 binds to TrkB and enhances brain-derived neurotrophic factor (BDNF) signaling. Ablation of Sh2b1 in PVHSH2B1 neurons induces BDNF resistance in the PVH, contributing to obesity. In conclusion, these results unveil a previously unrecognized PVHSH2B1→DRN neurocircuit through which SH2B1 defends against obesity by enhancing BDNF/TrkB signaling.
Patients receive varlilumab IV over 90 minutes and atezolizumab IV over 30-60 minutes every cycle. Cycles repeat every 21 days for up to 1 year (18 cycles) in the absence of disease progression or unacceptable toxicity. Between cycle 1 and 2, patients also receive SBRT.
INTRODUCTION: Sleep disorders, particularly sleep disordered breathing (SDB), are common in children with Down syndrome (DS). We investigated the relationship between SDB severity and parental psychological wellbeing and their perception of social support.
METHODS: 44 children with DS (3-19 years) underwent overnight polysomnography and were categorised into three groups: primary snoring, Mild and Moderate/Severe obstructive sleep apnoea (OSA). Parents completed questionnaires about their child's behaviour (Child Behavior Checklist), sleep symptoms (Pediatric Sleep Survey Instrument) and SDB-related quality of life (OSA-18), together with the DUKE-UNC Functional Social Support (DUKE) and Psychological General Well-Being Index (PGWBI) questionnaires for themselves. 34 children completed a follow-up study after 2 years.
RESULTS: There were no significant differences between SDB severity groups for parental perceived social support or psychological wellbeing. Total scores on the DUKE were below average and PGWBI scores were indicative of moderate psychological distress in all three groups. Reduced perceived levels of social support were significantly correlated with externalising child behaviour and sleep disturbance. Diminished parental psychological wellbeing was also significantly correlated with increased sleep disturbances and reduced quality of life in children. At follow-up there were no significant changes in any questionnaire outcome, however parents of children with improved SDB severity had improved PGWBI vitality scores.
CONCLUSION: The degree of parent-reported sleep disturbance in children with DS was linked to suboptimal perceived parental social support and poor psychological wellbeing. Our results emphasise the need for enhanced awareness of the detrimental effects of sleep problems in children with DS on parental wellbeing.
During the performance of spinal anesthesia using isobaric 0.5% bupivacaine 12 mg, an intravenous infusion of 502 ml of Normal Saline will be initiated. The infusion will be administered over 5 -10 minutes. The study drug will be prepared by an independent assistant.
The supervised exercise program included: continues endurance training on cycle ergometers (6 sessions a week). Every session included warm up (\<50% target intensity 2 min, gradually increasing load 1-10 w/min up to target intensity within 5 - 10 min); exercise phase (100% of the target intensity (30-50% watts or 30-50% HRmax), starting with \>5 minutes and gradually prolonged up to 30 min); cool down with gradual reduction of the load within 3 minutes); additional aerobic exercises performed sitting and/or standing (30 minutes, 5 days/week); respiratory muscle training (7 days/week, for 15 minutes) using ball trainer.
Irradiation will take place during DIBH induced by the MANIV (Bellavista 1000, IMTMedical®) with SL mode. Oxygen will be added (FiO2 60%) to safely and easily prolong the DIBH duration up to 30 seconds to allow the complete delivery of a treatment beam \[13\]. Prior to treatment, a radio-opaque fiducial will be implanted in the tumor by an interventional radiologist, to facilitate the tumor position monitoring from onboard imaging. Residual tumor baseline shift and motion will thus be measured during beam delivery, and used to recompute the optimal safety margins that ensure an adequate dose coverage of at least 90% of tumors, according to literature recommendations \[24\]. We will also compare these safety margins computed under MANIV condition with those routinely applied in free-breathing condition to estimate the gain in terms of margin reduction.
The Model Care approach was implemented in 7 practices, where PCPs were trained to address major risk factors for CM, including maternal depression, alcohol/substance abuse, intimate partner violence, food insecurity, harsh punishment and major stress. We taught how they can be briefly assessed and initially addressed. The initial training consisted of one 4-hour in-person session. Use of the Parent Screening Questionnaire (PSQ) was discussed, as was the importance of applying it universally during regular checkups. PCPs SEEK Parent Handouts on each targeted problem. We held 1-hour booster sessions every 6 months over the subsequent 2.5 years.
Viral hemorrhagic septicemia virus (VHSV) poses a significant threat to the aquaculture industry, prompting the need for effective preventive measures. Here, we developed an inactivated VHSV and revealed the molecular mechanisms underlying the host's protective response against VHSV. The vaccine was created by treating VHSV with 0.05 % formalin at 16 °C for 48 h, which was determined to be the most effective inactivation method. Compared with nonvaccinated fish, vaccinated fish exhibited a remarkable increase in survival rate (99 %) and elevated levels of serum neutralizing antibodies, indicating strong immunization. To investigate the gene changes induced by vaccination, RNA sequencing was performed on spleen samples from control and vaccinated fish 14 days after vaccination. The analysis revealed 893 differentially expressed genes (DEGs), with notable up-regulation of immune-related genes such as annexin A1a, coxsackievirus and adenovirus receptor homolog, V-set domain-containing T-cell activation inhibitor 1-like, and heat shock protein 90 alpha class A member 1 tandem duplicate 2, indicating a vigorous innate immune response. Furthermore, KEGG enrichment analysis highlighted significant enrichment of DEGs in processes related to antigen processing and presentation, necroptosis, and viral carcinogenesis. GO enrichment analysis further revealed enrichment of DEGs related to the regulation of type I interferon (IFN) production, type I IFN production, and negative regulation of viral processes. Moreover, protein-protein interaction network analysis identified central hub genes, including IRF3 and HSP90AA1.2, suggesting their crucial roles in coordinating the immune response elicited by the vaccine. These findings not only confirm the effectiveness of our vaccine formulation but also offer valuable insights into the underlying immunological mechanisms, which can be valuable for future vaccine development and disease management in the aquaculture industry.
BACKGROUND: Rotator cuff calcific tendinitis (RCCT) is a common shoulder disease whose main symptoms include shoulder pain, limited mobility, and calcification deposits in the shoulder. Traditional treatment methods have certain limitations, so finding new treatment methods has become the focus of research. Extracorporeal shock wave (ESW) and platelet-rich plasma (PRP) treatments have attracted much attention due to their non-invasive and tissue repair-promoting properties; however, the efficacy of their combined treatment in RCCT remains unclear.
METHODS: This study is designed as a single-center, assessment-blind, randomized controlled clinical trial with three parallel groups. Sixty subjects will be recruited and randomly divided into the ESW group, PRP group, and ESW combined with PRP group, in a 1:1:1 ratio. The entire intervention period is 4 weeks, and the follow-up period is 4 weeks. Outcomes will be measured at baseline (T0), after 1 week of intervention (T1), after 2 weeks of intervention (T2), after 4 weeks of intervention (T3), and after an additional 4 weeks of follow-up period (T4). The primary endpoint is the VAS score. Secondary endpoints are ASES, CMS, UCLA, and the location and size of calcified areas.
DISCUSSION: This study aims to evaluate the efficacy of ESW therapy combined with PRP in treating RCCT. We compare the effects of single and combined treatments to explore their impact on disease symptoms, functional improvement, and calcification regression. This provides a scientific basis for identifying more effective treatment options.
TRIAL REGISTRATION: ClinicalTrials.gov NCT06372600. Registered on April 17, 2024; version 1.
Enterotoxigenic Escherichia coli (ETEC) K88 is the most common cause of diarrhea in neonatal and postweaning pigs. After adhering to small intestinal epithelial cells via glycoprotein receptor recognition, the pathogen can produce enterotoxins, impair intestinal integrity, trigger watery diarrhea, and induce inflammation via nuclear factor κB (NF-κB) and mitogen-activated protein kinase phosphatase (MAPK) pathways. Inhibiting ETEC K88 adhesion to cell surfaces by interfering with the receptor-fimbriae recognition provides a promising strategy to prevent the initiation and progression of infection. Ovomucin is a highly glycosylated protein in chicken egg white with diverse bioactivities. Ovomucin hydrolysates prepared by the enzymes Protex 26L (OP) and pepsin/pancreatin (OPP) were previously revealed to prevent adhesion of ETEC K88 to IPEC-J2 cells. Herein, we investigated the protective effects of ovomucin hydrolysates on ETEC K88-induced barrier integrity damage and inflammation in IPEC-J2 and Caco-2 cells. Both hydrolysates inhibited ETEC K88 adhesion to cells and protected epithelial cell integrity by restoring transepithelial electronic resistance (TEER) values. Removing sialic acids in the hydrolysates reduced their antiadhesive capacities. Ovomucin hydrolysates suppressed ETEC-induced activation of NF-κB and MAPK signaling pathways in both cell lines. The ability of ETEC K88 in activating calcium/calmodulin-dependent protein kinase 2 (CaMK II), elevating intracellular Ca2+ concentration, and inducing oxidative stress was attenuated by both hydrolysates. In conclusion, this study demonstrated the potential of ovomucin hydrolysates to prevent ETEC K88 adhesion and alleviate inflammation and oxidative stress in intestinal epithelial cells.
Inflammation is a protective mechanism against endogenous and exogenous pathogens. It is a typical feature of numerous chronic diseases and their complications. Keap1 is an essential target in oxidative stress and inflammatory diseases. Among them, the Keap1-Nrf2-ARE pathway (including Keap1-Nrf2-HO-1) is the most significant pathway of Keap1 targets, which participates in the control of inflammation in multiple organs (including renal inflammation, lung inflammation, liver inflammation, neuroinflammation, etc.). Identifying new Keap1 inhibitors is crucial for new drug discovery. However, most drugs have specificity issues as they covalently bind to cysteine residues of Keap1, causing off-target effects. Therefore, direct inhibition of Keap1-Nrf2 PPIs is a new research idea. Through non-electrophilic and non-covalent binding, its inhibitors have better specificity and ability to activate Nrf2, and targeting therapy against Keap1-Nrf2 PPIs has become a new method for drug development in chronic diseases. This review summarizes the members and downstream genes of the Keap1-related pathway and their roles in inflammatory disease models. In addition, we summarize all the research progress of anti-inflammatory drugs targeting Keap1 from 2010 to 2024, mainly describing their biological functions, molecular mechanisms of action, and therapeutic roles in inflammatory diseases.