Search Results (243)

Background/Objectives: Rhomboid intercostal block (RIB) is a new interfascial plane block. RIB is a simple and clinically effective technique. Paravertebral block (PVB) is offered as a first-line regional anesthesia technique for thoracoscopic surgeries. In this study, we aim to compare the analgesic efficacy of RIB to PVB in video-assisted thoracoscopic surgeries (VATSs). Methods: This is a prospective randomized study with 84 patients aged 18–75 and ASA I–III, undergoing VATS for primary lung cancer. The study was approved by an ethical committee and registered under clinicaltrials.org. With informed consent, patients were randomized to receive ultrasound-guided RIB or PVB at T5-level with 20 mL of %0.25 bupivacaine preoperatively. Surgeries were performed under general anesthesia. Postoperatively, patient-controlled IV fentanyl analgesia was prescribed, delivering 10 μg boluses upon request with 10 min of a lock-out period. Patients received paracetamol 1 g IV three times a day and tramadol 50 mg IV for breakthrough pain. The postoperative Numeric Rating Scale (NRS) for pain, total opioid consumption, and rescue analgesic requirements were recorded postoperatively at 1, 3, 6, 12, and 24 h. Results: There were no significant differences in 24 h total opioid consumption between the RIB and PVB groups [PVB: 48.5 (39.5–55) mcg; RIB: 48.6 (40.2–65) mcg; p = 0.258], nor in rescue analgesic requirements [PVB: seven patients (20%); RIB: seven patients (17.1%); p = 0.570]. NRS pain scores were also similar between the groups, with no significant difference in overall pain control efficacy (p = 0.833). Conclusions: RIB is comparable to PVB in analgesic efficacy for VATS and can be considered as an alternative analgesic modality. Full article

This work provides insight into carbamazepine polymorphs (Forms I, II, III, IV, and V), with reports on the cytoprotective, exploratory, motor, CNS-depressant, and anticonvulsant properties of carbamazepine (CBZ), carbamazepine formulation (CBZ-F), topiramate (TOP), oxcarbazepine (OXC), and diazepam (DZP) in mice. Structural analysis highlighted the significant difference in molecular conformations, which directly influence the physicochemical properties; and density functional theory description provided indications about CBZ reactivity and stability. In addition to neuron viability assessment in vitro, animals were treated orally with vehicle 10 mL/kg, as well as CBZ, CBZ-F, TOP, OXC, and DZP at the dose of 5 mg/kg and exposed to open-field, rotarod, barbiturate sleep induction and pentylenetetrazol (PTZ 70 mg/kg)-induced seizure. The involvement of GABAergic mechanisms in the activity of these drugs was evaluated with the intraperitoneal pretreatment of flumazenil (2 mg/kg). The CBZ, CBZ-F, and TOP mildly preserved neuronal viability. The CBZ-F and the reference AEDs potentiated barbiturate sleep, altered motor activities, and attenuated PTZ-induced convulsion. However, flumazenil pretreatment blocked these effects. Additional preclinical assessments could further establish the promising utility of CBZ-F in clinical settings while expanding the scope of AED formulations and designs. Full article

The programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) immune checkpoint constitutes an inhibitory pathway best known for its regulation of cluster of differentiation 8 (CD8)⁺ T cell-mediated immune responses. Engagement of PD-L1 with PD-1 expressed on CD8⁺ T cells activates downstream signaling pathways that culminate in T cell exhaustion and/or apoptosis. Physiologically, these immunosuppressive effects exist to prevent autoimmunity, but cancer cells exploit this pathway by overexpressing PD-L1 to facilitate immune escape. Intravenously (IV) administered immune checkpoint inhibitors (ICIs) that block the interaction between PD-1/PD-L1 have achieved great success in reversing T cell exhaustion and promoting tumor regression in various malignancies. However, these ICIs can cause immune-related adverse events (irAEs) due to off-tumor toxicities which limits their therapeutic potential. Therefore, considerable effort has been channeled into exploring alternative delivery strategies that enhance tumor-directed delivery of PD-1/PD-L1 ICIs and reduce irAEs. Here, we briefly describe PD-1/PD-L1-targeted cancer immunotherapy and associated irAEs. We then provide a detailed review of alternative delivery approaches, including locoregional (LDD)-, oncolytic virus (OV)-, nanoparticle (NP)-, and ultrasound and microbubble (USMB)-mediated delivery that are currently under investigation for enhancing tumor-specific delivery to minimize toxic off-tumor effects. We conclude with a commentary on key challenges associated with these delivery methods and potential strategies to mitigate them. Full article

This study investigates the reservoir physical properties, present-day stress, hydraulic fracturing, and production capacity of No. 3 coal in the Shizhuang south block, Qinshui Basin. It analyzes the control of in situ stress on permeability and hydraulic fracturing, as well as the influence of geo-engineering parameters on coalbed methane (CBM) production capacity. Presently, the direction of maximum horizontal stress is northeast–southwest, with local variations. The stress magnitude increases with burial depth, while the stress gradient decreases. The stress field of strike-slip faults is dominant and vertically continuous. The stress field of normal faults is mostly found at depths greater than 800 m, whereas the stress field of reverse faults is typically found at depths shallower than 700 m. Permeability, ranging from 0.003 to 1.08 mD, is controlled by in situ stress and coal texture, both of which vary significantly with tectonics. Hydraulic fracturing design should consider variations in stress conditions, pre-existing fractures, depth, structural trends, and coal texture, rather than employing generic schemes. At greater depths, higher pumping rates and treatment pressures are required to reduce fracture complexity and enhance proppant filling efficiency. The Shizhuang south block is divided into five zones based on in situ stress characteristics. Zones III and IV exhibit favorable geological conditions, including high porosity, permeability, and gas content. These zones also benefit from shorter gas breakthrough times, relatively higher gas breakthrough pressures, lower daily water production, and a higher ratio of critical desorption pressure to initial reservoir pressure. Tailored fracturing fluid and proppant programs are proposed for different zones to optimize subsequent CBM development. Full article

Under the background of the worsening global food and water crisis, efficient agricultural practices have become increasingly important. This study investigated the impact of different irrigation and cultivation modes on rice growth parameters, gas exchange, rice yield components, and water footprints in Jiangsu, China. Four treatments were employed in a randomized complete block design with three replications: (i) transplanted rice with frequent shallow irrigation (T-FSI), (ii) transplanted rice with rain-catching and controlled irrigation (T-RCCI), (iii) direct-seeded rice with frequent shallow irrigation (D-FSI), (iv) and direct-seeded rice with rain-catching and controlled irrigation (D-RCCI). The results revealed that the D-RCCI treatment significantly improved growth and physiological parameters. The D-FSI treatment drastically increased rice yield whereas T-RCCI increased the stem bending resistance and reduced lodging risk. The water footprint analysis showed significant water savings by optimized management practices. Compared to T-FSI, the T-RCCI, D-FSI, and D-RCCI treatments reduced the blue-green water footprint by 33%, 25%, and 25%, respectively. Additionally, water production efficiency increased by 13%, 106%, and 154% for T-RCCI, D-FSI, and D-RCCI respectively. The water footprint per unit yield of T-RCCI, D-FSI, and D-RCCI treatments was significantly reduced by 12%, 5,3%, and 63% compared to T-FSI. Overall, D-RCCI is the optimal strategy for rice cultivation in Jiangsu province and similar climatic areas due to its positive impact on yield, water savings, and environmental benefits. Full article

In this study, we evaluated the ability of the synthetic amphipathic helical peptide (SAHP), L-37pA, which mediates pathogen recognition and innate immune responses, to treat acute respiratory distress syndrome (ARDS) accompanied by diffuse alveolar damage (DAD) and chronic pulmonary fibrosis (PF). For the modeling of ARDS/DAD, male ICR mice were used. Intrabronchial instillation (IB) of 200 µL of inflammatory agents was performed by an intravenous catheter 20 G into the left lung lobe only, leaving the right lobe unaffected. Intravenous injections (IVs) of L-37pA, dexamethasone (DEX) and physiological saline (saline) were used as therapies for ARDS/DAD. L37pA inhibited the circulating levels of inflammatory cytokines, such as IL-8, TNFα, IL1α, IL4, IL5, IL6, IL9 and IL10, by 75–95%. In all cases, the computed tomography (CT) data indicate that L-37pA reduced lung density faster to −335 ± 23 Hounsfield units (HU) on day 7 than with DEX and saline, to −105 ± 29 HU and −23 ± 11 HU, respectively. The results of functional tests showed that L-37pA treatment 6 h after ARDS/DAD initiation resulted in a more rapid improvement in the physiological respiratory lung by 30–45% functions compared with the comparison drugs. Our data suggest that synthetic amphipathic helical peptide L-37pA blocked a cytokine storm, inhibited acute and chronic pulmonary inflammation, prevented fibrosis development and improved physiological respiratory lung function in the ARDS/DAD mouse model. We concluded that a therapeutic strategy using SAHPs targeting SR-B receptors is a potential novel effective treatment for inflammation-induced ARDS, DAD and lung fibrosis of various etiologies. Full article

The human epidermal growth factor receptor 2 (HER2) is a transmembrane tyrosine kinase receptor and tumor-associated antigen abnormally expressed in various types of cancer, including breast, ovarian, and gastric cancer. HER2 overexpression is highly correlated with increased tumor aggressiveness, poorer prognosis, and shorter overall survival. Consequently, multiple HER2-targeted therapies have been developed and approved; however, only a subset of patients benefit from these treatments, and relapses are common. More potent and durable HER2-targeted therapies are desperately needed for patients with HER2-positive cancers. In this study, we developed a lipid nanoparticle (LNP)-based therapy formulated with mRNA encoding a novel HER2-CD3-Fc bispecific antibody (bsAb) for HER2-positive cancers. The LNPs efficiently transfected various types of cells, such as HEK293S, SKOV-3, and A1847, leading to robust and sustained secretion of the HER2-CD3-Fc bsAb with high binding affinity to both HER2 and CD3. The bsAb induced potent T-cell-directed cytotoxicity, along with secretion of IFN-λ, TNF-α, and granzyme B, against various types of HER2-positive tumor cells in vitro, including A549, NCI-H460, SKOV-3, A1847, SKBR3, and MDA-MB-231. The bsAb-mediated antitumor effect is highly specific and strictly dependent on its binding to HER2, as evidenced by the gained resistance of A549 and A1847 her2 knockout cells and the acquired sensitivity of mouse 4T1 cells overexpressing the human HER2 extracellular domain (ECD) or epitope-containing subdomain IV to the bsAb-induced T cell cytotoxicity. The bsAb also relies on its binding to CD3 for T-cell recruitment, as ablation of CD3 binding abolished the bsAb’s ability to elicit antitumor activity. Importantly, intratumoral injection of the HER2-CD3-Fc mRNA-LNPs triggers a strong antitumor response and completely blocks HER2-positive tumor growth in a mouse xenograft model of human ovarian cancer. These results indicate that the novel HER2-CD3-Fc mRNA-LNP-based therapy has the potential to effectively treat HER2-positive cancer. Full article

Background: Robot-assisted laparoscopic partial nephrectomy (RAPN) for renal tumor treatment provides ergonomic advantages to surgeons and improves surgical outcomes. However, moderate-to-severe pain is unavoidable even after minimally invasive surgery. Despite the growing interest in multimodal analgesia, few studies have directly compared its efficacy with intrathecal morphine, a traditional opioid-based analgesic. Methods: We retrospectively investigated the efficacy of multimodal analgesia compared with that of intrathecal analgesia and intravenous patient-controlled analgesia (IV-PCA) in patients who underwent transperitoneal RAPN at our institute between 2020 and 2022. Among the 334 patients who met the inclusion criteria, intrathecal analgesia using morphine 200 µg was performed in 131 patients, and multimodal analgesia, including transversus abdominis plane block and intraoperative infusion of paracetamol 1 g and nefopam 20 mg, was administered to 105 patients. The remaining 98 patients received postoperative IV-PCA alone. Results: As the primary outcome, the area under the curve of pain scores over 24 h was significantly lower in the intrathecal analgesia and multimodal analgesia groups than in the IV-PCA group (89 [62–108] vs. 86 [65–115] vs. 108 [87–126] h, p < 0.001). Cumulative opioid requirements were also significantly lower in the intrathecal analgesia and multimodal analgesia groups at 24 h after surgery (p < 0.001). However, postoperative nausea and vomiting were significantly increased in the intrathecal analgesia group (27.5% vs. 13.3% vs. 13.3%, p = 0.005). Conclusions: Multimodal analgesia with a transversus abdominis plane block is an efficient analgesic method with fewer adverse effects compared to other analgesic methods. Our findings suggest the efficacy and safety of a multimodal approach for opioid-sparing analgesia after RAPN in the current opioid epidemic. Full article

The crystal structures of two newly synthesized nitrilotriacetate oxidovanadium(IV) salts, namely [QH][VO(nta)(H₂O)](H₂O)₂ (I) and [(acr)H][VO(nta)(H₂O)](H₂O)₂ (II), were determined. Additionally, the cytotoxic effects of four N-heterocyclic nitrilotriacetate oxidovanadium(IV) salts—1,10-phenanthrolinium, [(phen)H][VO(nta)(H₂O)](H₂O)_0.5 (III), 2,2′-bipyridinium [(bpy)H][VO(nta)(H₂O)](H₂O) (IV), and two newly synthesized compounds (I) and (II)—were evaluated against prostate cancer (PC3) and breast cancer (MCF-7) cells. All the compounds exhibited strong cytotoxic effects on cancer cells and normal cells (HaCaT human keratinocytes). The structure–activity relationship analysis revealed that the number and arrangement of conjugated aromatic rings in the counterion had an impact on the antitumor effect. The compound (III), the 1,10-phenanthrolinium analogue, exhibited the greatest activity, whereas the acridinium salt (II), with a different arrangement of three conjugated aromatic rings, showed the lowest toxicity. The increased concentrations of the compounds resulted in alterations to the cell cycle distribution with different effects in MCF-7 and PC3 cells. In MCF-7 cells, compounds I and II were observed to block the G₂/M phase, while compounds III and IV were found to arrest the cell cycle in the G₀/G₁ phase. In PC3 cells, all compounds increased the rates of cells in the G₀/G₁ phase. Full article

This study assessed the analgesic and motor effects of the GIN-TONIC block, a combination of the greater ischiatic notch plane block and the caudal lateral quadratus lumborum block, in 24 dogs undergoing pelvic limb surgery. Dogs were randomly divided into two equal groups: G_A received acepromazine [(20 µg kg⁻¹ intravenously (IV)] as premedication, and G_D received dexmedetomidine (2 µg kg⁻¹ IV). General anesthesia was maintained with isoflurane, and both groups received a GIN-TONIC block using 2% lidocaine. Nociception during surgery and postoperative pain [assessed using the Glasgow Composite Measure Pain Score (GCMPS-SF)] were assessed. Fentanyl (2 µg kg⁻¹ IV) was administered if nociception was noted and morphine (0.5 mg kg⁻¹ IV) was administered during recovery if the pain scores exceeded the predefined threshold. Motor function was assessed during the recovery period using descriptors previously reported. All dogs received analgesics at the 4 h mark before being discharged. Three and two dogs in G_D and G_A required fentanyl once. Postoperative pain scores remained ≤4/20 for all dogs except one. Dogs achieved non-ataxic ambulation within 38.9 ± 10.3 and 35.1 ± 11.1 min after extubation in G_D and G_A, respectively. This study highlighted the potential of the GIN-TONIC block as a feasible regional anesthesia method for delivering perioperative analgesia in dogs undergoing pelvic limb orthopedic surgery. Full article

The ovariectomy (OVE) procedure can trigger somatosensory and visceral peritoneal nociception. Sacrococcygeal epidural (ScE) anesthesia may complement or replace systemic analgesia used for feline OVE, reducing opioid consumption and their related undesirable adverse effects and consequently reducing or completely blocking the sympathetic nervous system activation during this procedure. The present study aimed to evaluate the activation of the sympathetic nervous system resulting from adding an ScE injection of bupivacaine 0.25% (0.3 mL kg⁻¹) in feline OVE and identify whether this translates to hemodynamic variables stability. A Parasympathetic Tone Activity (PTA) monitor was applied given that it performs analysis of heart rate variability (HRV) detecting changes in sympathetic and parasympathetic tone, making it a good tool for detecting activation of the sympathetic nervous system during the study. Two groups of animals were evaluated in five perioperative times, namely, the control group (CG) (n = 18) with systemic analgesia alone and the sacrococcygeal epidural group (ScEG) (n = 20) with 0.25% bupivacaine combined with systemic analgesia. Thirty-eight female cats were selected. All animals assigned to CG and ScEG were premedicated with dexmedetomidine (20 μg kg⁻¹ IM) and methadone (0.2 mg kg⁻¹ IM). General anesthesia was induced with propofol IV ad effectum and maintained with isoflurane in 100% oxygen. Heart rate, non-invasive systolic and median blood pressure, respiratory rate, and instantaneous parasympathetic tone activity were recorded. Compared to systemic analgesia alone (CG), sacrococcygeal epidural (ScEG) reduced the rise of common hemodynamic variables but did not prevent sympathetic nervous system activation. Full article

According to the WHO 2016 classification, glioblastoma is the most prevalent primary tumor in the adult central nervous system (CNS) and is categorized as grade IV. With an average lifespan of about 15 months from diagnosis, glioblastoma has a poor prognosis and presents a significant treatment challenge. Aberrant angiogenesis, which promotes tumor neovascularization and is a prospective target for molecular target treatment, is one of its unique and aggressive characteristics. Recently, the existence of glioma stem cells (GSCs) within the tumor, which are tolerant to chemotherapy and radiation, has been linked to the highly aggressive form of glioblastoma. Anti-angiogenic medications have not significantly improved overall survival (OS), despite various preclinical investigations and clinical trials demonstrating encouraging results. This suggests the need to discover new treatment options. Glioblastoma is one of the numerous cancers for which metformin, an anti-hyperglycemic medication belonging to the Biguanides family, is used as first-line therapy for type 2 diabetes mellitus (T2DM), and it has shown both in vitro and in vivo anti-tumoral activity. Based on these findings, the medication has been repurposed, which has shown the inhibition of many oncopromoter mechanisms and, as a result, identified the molecular pathways involved. Metformin inhibits cancer cell growth by blocking the LKB1/AMPK/mTOR/S6K1 pathway, leading to selective cell death in GSCs and inhibiting the proliferation of CD133+ cells. It has minimal impact on differentiated glioblastoma cells and normal human stem cells. The systematic retrieval of information was performed on PubMed. A total of 106 articles were found in a search on metformin for glioblastoma. Out of these six articles were Meta-analyses, Randomized Controlled Trials, clinical trials, and Systematic Reviews. The rest were Literature review articles. These articles were from the years 2011 to 2024. Appropriate studies were isolated, and important information from each of them was understood and entered into a database from which the information was used in this article. The clinical trials on metformin use in the treatment of glioblastoma were searched on clinicaltrials.gov. In this article, we examine and evaluate metformin’s possible anti-tumoral effects on glioblastoma, determining whether or not it may appropriately function as an anti-angiogenic substance and be safely added to the treatment and management of glioblastoma patients. Full article

With half-cut photovoltaic (PV) modules being the dominant technology on the market, there is an increasing necessity for accurate modeling of this module type. Circuit simulators such as Simulink are widely used to study different topics regarding photovoltaics, often employing a solar cell block available from the Simcape library. The purpose of this work is to validate this model against measurements for a partially shaded half-cut PV module. Diverse shading scenarios are created by varying the number of shaded substrings, the number of shaded solar cells in the substring, and the shading level. For every shading scenario, the PV module’s I-V curve is measured, along with in-plane irradiance, air temperature, and module temperature. A comprehensive evaluation of simulation accuracy is presented. The results confirm a high accuracy of the model with mean nRMSE values of 2.2% for I-V curves and 2.8% when P-V curves are considered. It is found that the simulation errors tend to increase when increasing the number of shaded substrings. At the same time, no obvious dependency of simulation accuracy on the shading level or the number of shaded solar cells in the substring is found. Full article

The purpose of this study was to evaluate the quality of recovery from general anesthesia with the administration of two low doses of dexmedetomidine in canine patients. For this blind randomized clinical trial study, 30 dogs undergoing general anesthesia for diagnostic procedures or elective surgery (ovariectomy/castration) were included. The patients were randomly divided into three groups, and at the end of anesthesia, they received a bolus of dexmedetomidine at 1 mcg/kg IV (D1), or a bolus of dexmedetomidine at 0.5 mcg/kg (D0.5), or a bolus of NaCl, in a total of 0.5 mL of solution for all three groups. After administration of the bolus, the anesthetist monitored the patients every 5 min by measuring heart rate, systolic and mean blood pressure, respiratory rate, and oxygen saturation. The quality of recovery was also assessed using 4 different scales. The extubation time, time of headlift, and standing position were also recorded. Both groups receiving dexmedetomidine had better awakening and a lower incidence of delirium when compared to saline administration. The heart rate was lower, while the systolic pressure was higher in the two groups D1 and D0.5 compared to the NaCl with a low presence of atrioventricular blocks. The extubation time resulted significantly higher in the D1 (17 ± 6 min) compared to the D0.5 (10 ± 4 min) and NaCl (8 ± 3 min) (p < 0.0001); the headlift time D1 (25 ± 10 min) resulted significantly longer than the NaCl group (11 ± 5 min) (p = 0.0023) but not than the D0.5 (18 ± 9 min). No significant differences were found among the three groups for standing positioning (D1 50 ± 18 min, D0.5 39 ± 22 min, NaCl 28 ± 17 min). The preventive administration of a bolus of dexmedetomidine at a dosage of 0.5 mcg/kg or 1 mcg/kg IV during the recovery phase improves the quality of recovery in patients undergoing general anesthesia. Full article

The ubiquitin–proteasome system (UPS) is an essential mechanism responsible for the selective degradation of substrate proteins via their conjugation with ubiquitin. Since cardiomyocytes have very limited self-renewal capacity, as they are prone to protein damage due to constant mechanical and metabolic stress, the UPS has a key role in cardiac physiology and pathophysiology. While altered proteasomal activity contributes to a variety of cardiac pathologies, such as heart failure and ischemia/reperfusion injury (IRI), the environmental cues affecting its activity are still unknown, and they are the focus of this work. Following a recent study by Ciechanover’s group showing that amino acid (AA) starvation in cultured cancer cell lines modulates proteasome intracellular localization and activity, we tested two hypotheses in human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs, CMs): (i) AA starvation causes proteasome translocation in CMs, similarly to the observation in cultured cancer cell lines; (ii) manipulation of subcellular proteasomal compartmentalization is associated with electrophysiological abnormalities in the form of arrhythmias, mediated via altered intracellular Ca²⁺ handling. The major findings are: (i) starving CMs to AAs results in proteasome translocation from the nucleus to the cytoplasm, while supplementation with the aromatic amino acids tyrosine (Y), tryptophan (W) and phenylalanine (F) (YWF) inhibits the proteasome recruitment; (ii) AA-deficient treatments cause arrhythmias; (iii) the arrhythmias observed upon nuclear proteasome sequestration(-AA+YWF) are blocked by KB-R7943, an inhibitor of the reverse mode of the sodium–calcium exchanger NCX; (iv) the retrograde perfusion of isolated rat hearts with AA starvation media is associated with arrhythmias. Collectively, our novel findings describe a newly identified mechanism linking the UPS to arrhythmia generation in CMs and whole hearts. Full article