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Current evidence suggests that activation of glial and immune cells leads to increased production of proinflammatory mediators, creating a neuroinflammatory state. Neuroinflammation has been proven to be a fundamental mechanism in the genesis of acute pain and its transition to neuropathic and chronic pain. A noxious event that stimulates peripheral afferent nerve fibers may also activate pronociceptive receptors situated at the dorsal root ganglion and dorsal horn of the spinal cord, as well as peripheral glial cells, setting off the so-called peripheral sensitization and spreading neuroinflammation to the brain. Once activated, microglia produce cytokines, chemokines, and neuropeptides that can increase the sensitivity and firing properties of second-order neurons, upregulating the signaling of nociceptive information to the cerebral cortex. This process, known as central sensitization, is crucial for chronification of acute pain. Immune-neuronal interactions are also implicated in the lesser-known complex regulatory relationship between pain and opioids. Current evidence suggests that activated immune and glial cells can alter neuronal function, induce, and maintain pathological pain, and disrupt the analgesic effects of opioid drugs by contributing to the development of tolerance and dependence, even causing paradoxical hyperalgesia. Such alterations may occur when the neuronal environment is impacted by trauma, inflammation, and immune-derived molecules, or when opioids induce proinflammatory glial activation. Hence, understanding these intricate interactions may help in managing pain signaling and opioid efficacy beyond the classical pharmacological approach.

Tomato brown rugose fruit virus (ToBRFV), being a mechanically transmitted disease, is usually difficult to control; therefore, an effective alternative to reduce transmission and replication in the crop is by spraying with chlorine dioxide (ClO2) during routine crop management. In this research, the efficacy of chlorine dioxide (ClO2) for ToBRFV management in a greenhouse and open field was determined. The phytotoxicity of ClO2 and its effective concentration against ToBRFV in Nicotiana longiflora plants were evaluated. Subsequently, the effect of ClO2 on ToBRFV was evaluated in tomato plants grown in an open field. Finally, the effectiveness of ClO2 on plants inoculated with ToBRFV under greenhouse conditions was evaluated and the number of necrotic local lesions (NLLs) was quantified. The results revealed that ClO2 at 760 mg L−1 did not show phytotoxicity and reduced the number of NLLs in N. longiflora plants. It also decreased ToBRFV transmission and replication in field- and greenhouse-grown tomato plants, improving agronomic parameters. ClO2 reduced replication in plants inoculated with different amounts of ToBRFV inoculum in a greenhouse. N. longiflora leaves expressed lower numbers of NLLs when inoculated with ClO2-treated tomato plant extracts. Finally, the results demonstrate that ClO2 represents an effective management alternative when used by direct application to plants. To our knowledge, this is the first study where the use of an antiviral compound is carried out under field and greenhouse conditions.

Local lidocaine infiltration before Tuohy needle insertion is essential for epidural analgesia. Lidocaine can be administered intradermally or subcutaneously, but the technique that causes less pain for laboring patients is unclear. Pain is typically assessed using the subjective Numeric Rating Scale (NRS), while the Critical-Care Pain Observation Tool (CPOT) offers an objective alternative, evaluating facial expressions, body movements, muscle tension, and vocalizations. This pilot study compared subcutaneous (SC) and intradermal (ID) lidocaine administration to evaluate lidocaine injection pain and its analgesic efficacy. In this double-blind randomized trial, laboring parturients received 3 mL of 1% lidocaine via SC (90-degree angle) or ID (60-degree angle) injection using a one-inch 25G needle. Primary outcomes included procedural pain during lidocaine administration, assessed using CPOT (clinician-centric) scores. Secondary outcomes encompassed lidocaine's analgesic efficacy during Tuohy needle insertion with both CPOT and NRS, hemodynamic stability, patient satisfaction, and NRS for two lidocaine injection techniques as references. Fifty-one patients were randomized into the SC Group (n = 26) and the ID Group (n = 25). No significant differences were observed in overall CPOT or NRS scores between groups, but SC administration yielded significantly lower muscle tension scores (Krushkal-Wallis test p = 0.018). The analgesic efficacy on Tuohy needle insertion, patient satisfaction, and hemodynamic values was not significantly different between the two techniques. A weak correlation between CPOT and NRS scores (Spearman's r = 0.32, p = 0.024) highlighted the complementary roles of objective and subjective, patient-centric, pain assessments. There was no statistical significance of interobserver variation for CPOT assessment. This pilot trial establishes proof of concept for validating the CPOT in obstetric settings and highlights both the need for and feasibility of future studies aimed at optimizing lidocaine administration protocols during labor epidural placement. While this study found no global differences in pain scores between subcutaneous and intradermal lidocaine, subcutaneous injections demonstrated less muscle tension with similar analgesic efficacy. The discordance between CPOT and NRS underscores the value of integrating both tools for comprehensive procedural pain evaluation.

Shortening analgesic onset has been researched and it has been documented that prewarming epidural medications to body temperature (37°C) prior to administration increases medication efficacy. Our double-blind randomized controlled trial was designed to investigate if a lower degree of prewarming in providers’ pockets could achieve similar results without the need of a bedside incubator. A total of 136 parturients were randomized into either the pocket-warmed group or the room temperature group to receive 10 mL of 0.125% bupivacaine with 2 μg/mL fentanyl epidural bolus at either the 27.8 ±1.7°C or 22.1 ±1.0°C temperatures, respectively. Primary outcome, time to analgesic onset (verbal rating scale pain score ≤ 3) was recorded in 0-, 5-, 10-, 15-, 20-, 30-, and 60-minutes intervals. It was observed that the pocket-warming group (n = 64) and room temperature group (n = 72) had no significant difference of analgesic onset time (median 8 vs. 6.2 minutes; p = 0.322). The incidence of adverse events such as hypotension, fever (≥ 38°C), nausea, vomiting, and number of top-off epidural boluses, as well as patient satisfaction rates and mode of delivery, were not significantly different between the groups as well. Further research is warranted to confirm these findings and explore the impact of different temperatures on analgesic onset time as well as the logistical issues associated with their clinical implementations.

Postoperative nausea and vomiting (PONV) have been widely studied as a multifactorial entity, being of female gender the strongest risk factor. Reported PONV incidence in female surgical populations is extremely variable among randomized clinical trials. In this narrative review, we intend to summarize the incidence, independent predictors, pharmacological and non-pharmacological interventions for PONV reported in recently published clinical trials carried out in female patients undergoing breast and gynecologic surgery, as well as the implications of the anesthetic agents on the incidence of PONV. A literature search of manuscripts describing PONV management in female surgical populations (breast surgery and gynecologic surgery) was carried out in PubMed, MEDLINE, and Embase databases. Postoperative nausea and vomiting incidence were highly variable in patients receiving placebo or no prophylaxis among RCTs whereas consistent results were observed in patients receiving 1 or 2 prophylactic interventions for PONV. Despite efforts made, a considerable number of female patients still experienced significant PONV. It is critical for the anesthesia provider to be aware that the coexistence of independent risk factors such as the level of sex hormones (pre- and postmenopausal), preoperative anxiety or depression, pharmacogenomic pleomorphisms, and ethnicity further enhances the probability of experiencing PONV in female patients. Future RCTs should closely assess the overall risk of PONV in female patients considering patient- and surgery-related factors, and the level of compliance with current guidelines for prevention and management of PONV.

Introduction: Acute perioperative blood loss is a common and potentially major complication of multilevel spinal surgery, usually worsened by the number of levels fused and of osteotomies performed. Pharmacological approaches to blood conservation during spinal surgery include the use of intravenous tranexamic acid (TXA), an anti-fibrinolytic that has been widely used to reduce blood loss in cardiac and orthopedic surgery. The primary objective of this study was to assess the efficacy of intraoperative TXA in reducing estimated blood loss (EBL) and red blood cell (RBC) transfusion requirements in patients undergoing multilevel spinal fusion. Materials and Methods: This a single-center, retrospective study of subjects who underwent multilevel (≥7) spinal fusion surgery who received (TXA group) or did not receive (control group) IV TXA at The Ohio State University Wexner Medical Center between January 1st, 2016 and November 30th, 2018. Patient demographics, EBL, TXA doses, blood product requirements and postoperative complications were recorded. Results: A total of 76 adult subjects were included, of whom 34 received TXA during surgery (TXA group). The mean fusion length was 12 levels. The mean total loading, maintenance surgery and total dose of IV TXA was 1.5, 2.1 mg per kilo (mg/kg) per hour and 33.8 mg/kg, respectively. The mean EBL in the control was higher than the TXA group, 3,594.1 [2,689.7, 4,298.5] vs. 2,184.2 [1,290.2, 3,078.3] ml. Among all subjects, the mean number of intraoperative RBC and FFP units transfused was significantly higher in the control than in the TXA group. The total mean number of RBC and FFP units transfused in the control group was 8.1 [6.6, 9.7] and 7.7 [6.1, 9.4] compared with 5.1 [3.4, 6.8] and 4.6 [2.8, 6.4], respectively. There were no statistically significant differences in postoperative blood product transfusion rates between both groups. Additionally, there were no significant differences in the incidence of 30-days postoperative complications between both groups. Conclusion: Our results suggest that the prophylactic use of TXA may reduce intraoperative EBL and RBC unit transfusion requirements in patients undergoing multilevel spinal fusion procedures ≥7 levels.

Tomato brown rugose fruit virus (ToBRFV) is considered an emerging disease and a viral pandemic for tomato consumers. The objectives of this research were to analyze the biological and physicochemical characteristics of ToBRFV in tomato and tobacco plants, as well as to evaluate its natural host range. Inoculant seeds were recovered from ToBRFV-infected tomato samples in Coahuila, Mexico, and confirmed by RT-PCR. In the first greenhouse experiment, tomato plants of the F1 hybrid variety 172–300 (Yüksel), infected with ToBRFV, were used to evaluate viral inclusions (VI), dilution endpoint (DEP), the incubation period (IP), and latency period (LP). In a greenhouse experiment, Nicotiana longiflora plants were inoculated with ToBRFV to determine the in vitro longevity (IVL) and thermal inactivation (TI) of the virus in sap. Finally, the inoculation of tomato plants grown in open fields was carried out to evaluate transmission to natural hosts. The plants tested for possible ToBRFV reservoirs near the inoculum source were inspected and confirmed by a double-antibody sandwich enzyme-linked immunosorbent assay (DAS-ELISA). The results indicate that the VIs on tomato leaves manifested as X-bodies and rounded, stacked plaques within epidermal cells. The DEP required to induce the infection in plants was from a ToBRFV concentration of 1 × 10−5.5, the IP of ToBRFV occurred 9 to 12 days post-inoculation, and LP could be detected one day after inoculation. The TI of ToBRFV in N. longiflora plants occurred at 85 °C for 30 min. Ipomoea purpurea, Mirabilis jalapa, Clematis drummondii, and Solanum tuberosum were newly identified hosts of ToBRFV. The results found contribute to a better understanding of the impact of ToBRFV, managing and preventing the spread of ToBRFV in diverse environments.

Background Simulation-based education (SBE) with high-fidelity simulation (HFS) offers medical students early exposure to the clinical environment, allowing development of clinical scenarios and management. We hypothesized that supplementation of standard pulmonary physiology curriculum with HFS would improve the performance of first-year medical students on written tests of pulmonary physiology. Methods This observational pilot study included SBE with three HFS scenarios of patient care that highlighted basic pulmonary physiology. First-year medical students’ test scores of their cardio-pulmonary curriculum were compared between students who participated in SBE versus only lecture-based education (LBE). A survey was administered to the SBE group to assess their perception of the HFS. Results From a class of 188 first-year medical students, 89 (47%) participated in the SBE and the remaining 99 were considered as the LBE group. On their cardio-pulmonary curriculum test, the SBE group had a median score of 106 [IQR: 97,110] and LBE group of 99 [IQR: 89,105] ( p  < 0.001). For the pulmonary physiology subsection, scores were also significantly different between groups ( p  < 0.001). Conclusions Implementation of supplemental SBE could be an adequate technique to improve learning enhancement and overall satisfaction in preclinical medical students.

(1) Background: Chitosan-coated gold nanoparticles (CH-AuNPs) have important theranostic applications in biomedical sciences, including cancer research. However, although cell cytotoxicity has been studied in cancerous cells, little is known about their effect in proliferating primary leukocytes. Here, we assessed the effect of CH-AuNPs and the implication of ROS on non-cancerous endothelial and fibroblast cell lines and in proliferative lymphoid cells. (2) Methods: The Turkevich method was used to synthetize gold nanoparticles. We tested cell viability, cell death, ROS production, and cell cycle in primary lymphoid cells, compared with non-cancer and cancer cell lines. Concanavalin A (ConA) or lipopolysaccharide (LPS) were used to induce proliferation on lymphoid cells. (3) Results: CH-AuNPs presented high cytotoxicity and ROS production against cancer cells compared to non-cancer cells; they also induced a different pattern of ROS production in peripheral blood mononuclear cells (PBMCs). No significant cell-death difference was found in PBMCs, splenic mononuclear cells, and bone marrow cells (BMC) with or without a proliferative stimuli. (4) Conclusions: Taken together, our results highlight the selectivity of CH-AuNPs to cancer cells, discarding a consistent cytotoxicity upon proliferative cells including endothelial, fibroblast, and lymphoid cells, and suggest their application in cancer treatment without affecting immune cells.

BackgroundPectoralis nerve blocks (PECS) have been shown in numerous studies to be a safe and effective method to treat postoperative pain and reduce postoperative opioid consumption after breast surgery. However, there are few publications evaluating the PECS block effectiveness in conjunction with multimodal analgesia (MMA) in outpatient breast surgery. This retrospective study aims to evaluate the efficacy of PECS's blocks on perioperative pain management and opioid consumption.MethodsWe conducted a retrospective study to assess the efficacy of preoperative PECS block in addition to preoperative MMA (oral acetaminophen and/or gabapentin) in reducing opioid consumption in adult female subjects undergoing outpatient elective breast surgery between 2015 and 2020. A total of 228 subjects were included in the study and divided in two groups: PECS block group (received PECS block + MMA) and control Group (received only MMA). The primary outcome was to compare postoperative opioid consumption between both groups. The secondary outcome was intergroup comparisons of the following: postoperative nausea and vomiting (PONV), incidence of rescue antiemetic medication, PACU non-opioid analgesic medication required, length of PACU stay and the incidence of 30-day postoperative complications between both groups.ResultsTwo hundred and twenty-eight subjects ( n = 228) were included in the study. A total of 174 subjects were allocated in the control group and 54 subjects were allocated in the PECS block group. Breast reduction and mastectomy/lumpectomy surgeries were the most commonly performed procedures (48% and 28%, respectively). The total amount of perioperative (intraoperative and PACU) MME was 27 [19, 38] in the control group and 28.5 [22, 38] in the PECS groups ( p = 0.21). PACU opioid consumption was 14.3 [7, 24.5] MME for the control group and 17 [8, 23] MME (p = 0.732) for the PECS group. Lastly, the mean overall incidence of postsurgical complications at 30 days was 3% ( N = 5), being wound infection, the only complication observed in the PECS groups ( N = 2), and hematoma ( N = 2) and wound dehiscence ( N = 1) in the control group.ConclusionPECS block combined with MMA may not reduce intraoperative and/or PACU opioid consumption in patients undergoing outpatient elective breast surgery.