Cholinergic macrophages promote the resolution of peritoneal inflammation.

The non-neural cholinergic system plays a critical role in regulating immune equilibrium and tissue homeostasis. While the expression of choline acetyltransferase (ChAT), the enzyme catalyzing acetylcholine biosynthesis, has been well documented in lymphocytes, its role in the myeloid compartment is less understood. Here, we identify a significant population of macrophages (Mϕs) expressing ChAT and synthesizing acetylcholine in the resolution phase of acute peritonitis. Using Chat-GFP reporter mice, we observed marked upregulation of ChAT in monocyte-derived small peritoneal Mϕs (SmPMs) in response to Toll-like receptor agonists and bacterial infections. These SmPMs, phenotypically and transcriptionally distinct from tissue-resident large peritoneal macrophages, up-regulated ChAT expression through a MyD88-dependent pathway involving MAPK signaling. Notably, this process was attenuated by the TRIF-dependent TLR signaling pathway, and our tests with a range of neurotransmitters and cytokines failed to induce a similar response. Functionally, Chat deficiency in Mϕs led to significantly decreased peritoneal acetylcholine levels, reduced efferocytosis of apoptotic neutrophils, and a delayed resolution of peritonitis, which were reversible with exogenous ACh supplementation. Intriguingly, despite B lymphocytes being a notable ChAT-expressing population within the peritoneal cavity, Chat deletion in B cells did not significantly alter the resolution process. Collectively, these findings underscore the crucial role of Mϕ-derived acetylcholine in the resolution of inflammation and highlight the importance of the non-neuronal cholinergic system in immune regulation.

Emerging applications of single-cell profiling in precision medicine of atherosclerosis.

Atherosclerosis is a chronic, progressive, inflammatory disease that occurs in the arterial wall. Despite recent advancements in treatment aimed at improving efficacy and prolonging survival, atherosclerosis remains largely incurable. In this review, we discuss emerging single-cell sequencing techniques and their novel insights into atherosclerosis. We provide examples of single-cell profiling studies that reveal phenotypic characteristics of atherosclerosis plaques, blood, liver, and the intestinal tract. Additionally, we highlight the potential clinical applications of single-cell analysis and propose that combining this approach with other techniques can facilitate early diagnosis and treatment, leading to more accurate medical interventions.

Factors associated with continuing education needs in medication administration among school nurses.

AIM: To investigate the continuing education requirements and factors influencing school nurses' needs in relation to medication administration on school campuses. DESIGN: A total of 391 school nurses working in K-12 schools in Taiwan were invited to participate in an online questionnaire survey. METHODS: This cross-sectional study employed a probability proportionate to size technique along with a random sampling method. Data were collected from February to April 2023. RESULTS: School nurses reported a significant demand for continuing education and perceived moderate levels of stress and government support related to medication administration. Among the various dimensions, the highest demand was observed for 'definition of campus medication errors' and 'regulations for campus medical orders.' Moreover, the 'identifying drug interactions' and 'adverse drug effects and referrals' dimensions were identified as the most stressful aspects. Notably, perceived stress emerged as the sole predictive factor for continuing education demand, accounting for 16.1% of the variance. CONCLUSIONS: The study found that there was a significant demand for and moderate stress related to continuing education among school nurses. Therefore, it is crucial for the government and school nursing organizations to develop targeted programs focusing on medication administration. These initiatives should be designed to enhance nurses' capabilities and reduce their stress, thereby ensuring safe medication administration on campuses. IMPACT: Continuing education enables school nurses to acquire up-to-date knowledge and improve the workflow in their practice. This study highlights a strong need for education in medication administration with a focus on 'campus medication error definitions' and 'campus medical order regulations.' The government and relevant school nursing organizations should prioritize the development and implementation of continuing education programs to decrease the school nurses' stress related to medication administration. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution. REPORTING METHOD: This study adhered to the relevant cross-sectional EQUATOR STROBE guidelines.

Oridonin attenuates atherosclerosis by inhibiting foam macrophage formation and inflammation through FABP4/PPARγ signalling.

Both lipid accumulation and inflammatory response in lesion macrophages fuel the progression of atherosclerosis, leading to high mortality of cardiovascular disease. A therapeutic strategy concurrently targeting these two risk factors is promising, but still scarce. Oridonin, the bioactive medicinal compound, is known to protect against inflammatory response and lipid dysfunction. However, its effect on atherosclerosis and the underlying molecular mechanism remain elusive. Here, we showed that oridonin attenuated atherosclerosis in hyperlipidemic ApoE knockout mice. Meanwhile, we confirmed the protective effect of oridonin on the oxidized low-density lipoprotein (oxLDL)-induced foam macrophage formation, resulting from increased cholesterol efflux, as well as reduced inflammatory response. Mechanistically, the network pharmacology prediction and further experiments revealed that oridonin dramatically facilitated the expression of peroxisome proliferator-activated receptor gamma (PPARγ), thereby regulating liver X receptor-alpha (LXRα)-induced ATP-binding cassette transporter A1 (ABCA1) expression and nuclear factor NF-kappa-B (NF-κB) translocation. Antagonist of PPARγ reversed the cholesterol accumulation and inflammatory response mediated by oridonin. Besides, RNA sequencing analysis revealed that fatty acid binding protein 4 (FABP4) was altered responding to lipid modulation effect of oridonin. Overexpression of FABP4 inhibited PPARγ activation and blunted the benefit effect of oridonin on foam macrophages. Taken together, oridonin might have potential to protect against atherosclerosis by modulating the formation and inflammatory response in foam macrophages through FABP4/PPARγ signalling.

The Role of Circular RNAs in Ischemic Stroke.

Ischemic stroke (IS), a devastating condition characterized by intracranial artery stenosis and middle cerebral artery occlusion leading to insufficient oxygen supply to the brain, is a major cause of death and physical disability worldwide. Recent research has demonstrated the critical role of circular RNAs (circRNAs), a class of covalently enclosed noncoding RNAs that are widespread in eukaryotic cells, in regulating various physiological and pathophysiological cellular processes, including cell apoptosis, autophagy, synaptic plasticity, and neuroinflammation. In the past few years, circRNAs have attracted extensive attention in the field of IS research. This review summarizes the current understanding of the mechanisms underlying the involvement of circRNAs in IS development. A better understanding of circRNA-mediated pathogenic mechanisms in IS may pave the way for translating circRNA research into clinical practice, ultimately improving the clinical outcomes of IS patients.

CRISPR-Cas13a-powered electrochemical biosensor for the detection of the L452R mutation in clinical samples of SARS-CoV-2 variants.

Since the end of 2019, a highly contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has deprived numerous lives worldwide, called COVID-19. Up to date, omicron is the latest variant of concern, and BA.5 is replacing the BA.2 variant to become the main subtype rampaging worldwide. These subtypes harbor an L452R mutation, which increases their transmissibility among vaccinated people. Current methods for identifying SARS-CoV-2 variants are mainly based on polymerase chain reaction (PCR) followed by gene sequencing, making time-consuming processes and expensive instrumentation indispensable. In this study, we developed a rapid and ultrasensitive electrochemical biosensor to achieve the goals of high sensitivity, the ability of distinguishing the variants, and the direct detection of RNAs from viruses simultaneously. We used electrodes made of MXene-AuNP (gold nanoparticle) composites for improved sensitivity and the CRISPR/Cas13a system for high specificity in detecting the single-base L452R mutation in RNAs and clinical samples. Our biosensor will be an excellent supplement to the RT-qPCR method enabling the early diagnosis and quick distinguishment of SARS-CoV-2 Omicron BA.5 and BA.2 variants and more potential variants that might arise in the future.

Burnout and Mental Health and Well-Being of School Nurses After the First Wave of the COVID-19 Pandemic: A National Cross-Sectional Survey.

The aim of this study was to examine the associations between job stressors, COVID-19-related concerns, burnout, and mental health and well-being among school nurses, and whether any of these associations are mediated by burnout. Based on stratified proportional sampling, data collection was conducted by an online questionnaire distributed to 600 school nurses in Taiwan. A total of 256 participants aged between 27 and 62 years (mean = 47.08; standard deviation = 7.28) returned questionnaires. Results showed that burnout was the main mediating variable that fully mediated the relationship between COVID-19-related concerns and mental health and well-being. The effects of job stressors on mental health and well-being included direct negative effects (ß = -.29) and indirect negative effects (ß = -.67) through mediating factors. School health managers should be more aware of burnout and mental health and well-being among school nurses under the impact of COVID-19.

Competence and Stress of Medication Administration Practices for School Nurses in K-12 Taiwan Schools.

We investigated school nurses' experiences, perceived government support, school nurses' acceptance of responsibility for medication administration, perceived stress, and perceived competence of medication administration and analyzed factors associated with perceived competence. In this cross-sectional study, from February to April 2023, we conducted an online survey of 269 school nurses serving at K-12 schools in Taiwan. The results revealed that although 71% of the participants had prior experience with medication administration, they reported low competence and high stress in areas such as drug interactions, adverse drug effects, and referrals. The school nurses' disagreement with responsibilities for medication administration emerged as the only factor to be significantly associated with perceived medication administration competence, accounting for 22.8% of the variance. We recommend implementing continuing training programs to provide school nurses with up-to-date medication information. Additionally, the development of practice guidelines is suggested as a means of enhancing nurses' competence and reducing their stress levels for the administration of medications.

[Reducing the Incidence of Postoperative Hypothermia in Patients Undergoing Robotic-Assisted Mitral Valve Surgery].

BACKGROUND & PROBLEMS: Post-operation hypothermia tends to induce complications. Sixty percent of robotic-assisted mitral valve surgery patients experienced hypothermia while admitted to our intensive care unit (ICU), resulting in prolonged ICU stays and 57% (eight) of those patients with hypothermia also experiencing cardiac arrhythmia. The causes of hypothermia in our ICU included low temperature in the operating room, delayed initiation of blanket coverage after surgery, and lack of postoperative thermal blankets, insufficient cardiopulmonary bypass rewarming time, cold ICU beds, lack of in-service training for hypothermia, and lack of procedure auditing. PURPOSE: This intervention was designed to reduce the incidence of hypothermia in ICU patients undergoing robotic-assisted mitral valve surgery upon ICU admission from 60% to 36% and the one-hour hypothermia rate from 43.3% to 26%. RESOLUTIONS: We implemented several measures including increasing the room temperature, pre-heating the ICU bed, achieving team consensus regarding prolonging the rewarming time after cardiopulmonary bypass, establishing a blanket warming area for postoperative patient use, and holding in-service training to enhance the awareness of the nurses were implemented. RESULTS: The incidence of hypothermia in ICU patients receiving robotic-assisted mitral valve surgery upon ICU admission decreased from 60% to 19.4%, while the one-hour hypothermia rate decreased from 43.3% to 19.4%. CONCLUSIONS: Using systemic interprofessional collaboration, combined thermal care can be achieved to significantly reduce the incidence of postoperative hypothermia in patients undergoing robotic-assisted mitral valve surgeries resulting in higher patient care quality and shorter ICU stays. We recommend applying this combined method to improve the quality of perioperative care for long-duration and major surgical procedures that involve large postoperative wounds and for patients who may require wider exposure during their operation.

Effects of high flow nasal cannula on exercise endurance in patients with chronic obstructive pulmonary disease.

BACKGROUND: Ventilation limitation has a significant adverse effects on cardiovascular function and tissue oxygenation during exercise in patients with chronic obstructive pulmonary disease (COPD). High flow nasal cannula (HFNC) improve ventilation by washing out the anatomical dead space and providing oxygen at constant concentration. This study aimed to examine the effects of HFNC on the exercise performance and hemodynamic status in COPD patients. METHODS: Fifteen patients with COPD performed two constant load exercise tests (CLET) at the 70% of maximum workload achieved at a previous incremental exercise test on arm ergometer. The CLET were performed with HFNC and with nasal cannula (NC) in random order. The hemodynamics parameters of subjects during exercises were measured by a bioelectrical impedance device. The tissue oxygenation status (oxygenated hemoglobin, deoxygenated hemoglobin (hHb), total hemoglobin) was measured by a near infrared spectrophotometer. RESULTS: The exercise duration was longer for HFNC test than NC test (962.9 ± 281.7 s, vs 823.9 ± 184.9 s, p < 0.05). At the end of CLET, the PetCO2 was lower for HFNC than NC (29.3 ± 5.1 mmHg vs 32.1 ± 5.5 mmHg, p < 0.05). There was no difference in cardiac output (NC: 7.5 ± 1.8 vs HFNC: 7.4 ± 3.0 L,p > 0.05), stroke volume (NC:73.5 ± 21.0 vs HFNC 67.5 ± 16.3 ml, p > 0.05). The changes of hHb in muscle tissues was significantly lower in HFNC test than that in NC test (p < 0.05). CONCLUSION: HFNC resulted in a significant decrease in CO2 production and increase in exercise duration. The application of HFNC may improve the efficiency of exercise training by allowing patients to sustain exercise for longer time.

A six-week inspiratory muscle training and aerobic exercise improves respiratory muscle strength and exercise capacity in lung cancer patients after video-assisted thoracoscopic surgery: A randomized controlled trial.

OBJECTIVE: To compare the postoperative outcomes of inspiratory muscle training and aerobic exercise, along with standard care, on lung cancer patients undergoing video-assisted thoracoscopic surgery (VATS). DESIGN: A parallel-group, single-blind randomized clinical trial. SETTING: Thoracic surgery ward and outpatient clinic in a teaching hospital. SUBJECTS: Overall 63 patients underwent VATS were randomly assigned to a triaging (TG, n = 32) or control group (CG, n = 31). A total of 54 patients (TG, n = 26; CG, n = 28) completed the study. INTERVENTION: TG: six-week threshold inspiratory muscle training and aerobic exercise. CG: standard care. MAIN MEASURES: Maximum inspiratory pressure (PImax), maximum expiratory pressure (PEmax) lung expansion volume, and 6-min walking test (6MWT) were performed on the day of chest tube removal (baseline), and 2, 6, and 12 weeks postoperatively. RESULTS: The TG showed significant improvement in PImax at week 6 (71.6 ± 34.9 vs. 94.3 ± 32.8 cmH2O, P = 0.018), PEmax at week 2 (70.9 ± 24.3 vs. 90.9 ± 28.2 cmH2O, P = 0.015) and week 12 (76.1 ± 20.2 vs. 98.6 ± 35.3 cmH2O, P = 0.012), the lung expansion volume at week 2 (1080 ± 433 vs 1457 ± 624 mL, P = 0.02) and week 12 (1200 ± 387 vs 1885 ± 678 mL, P < 0.001), in addition to the 6MWT at week 2 (332 ± 78 vs 412 ± 74 m, P = 0.002), week 6 (360 ± 70 vs 419 ± 60 m, P = 0.007) and week 12 (360 ± 58 vs 402 ± 65 m, P = 0.036). CONCLUSION: A six weeks of inspiratory muscle training and aerobic exercise had improved respiratory muscle strength and aerobic exercise postoperatively in lung cancer patients after VATS as early as 2 weeks.

Safety and efficacy of dexmedetomidine hydrochloride combined with midazolam in fiberoptic bronchoscopy in children: a prospective randomized controlled study. / ç›é ¸å³ç¾Žæ‰˜å’ªå®šè”åˆå’ªè¾¾å”‘ä»‘åœ¨å„¿ç«¥çº¤ç»´æ”¯æ°”ç®¡é•œæ£€æŸ¥ä¸­çš„å®‰å ¨æ€§å’Œæœ‰æ•ˆæ€§­­å‰çž»æ€§éšæœºå¯¹ç §ç ”究.

OBJECTIVES: To study the safety and efficacy of dexmedetomidine hydrochloride combined with midazolam in fiberoptic bronchoscopy in children. METHODS: A total of 118 children who planned to undergo fiberoptic bronchoscopy from September 2018 to February 2021 were enrolled. They were divided into a control group (n=60) and an observation group (n=58) using a random number table. The observation group received intravenous pumping of dexmedetomidine hydrochloride (2 µg/mL) at 1 µg/kg and then intravenous injection of midazolam at 0.05 mg/kg, followed by dexmedetomidine hydrochloride pumped intravenously at 0.5-0.7 µg/(kg·h) 10 minutes later to maintain anesthesia. The control group was given intravenous pumping of propofol at 2 mg/kg and then intravenous injection of midazolam at 0.05 mg/kg, followed by propofol pumped intravenously at 4-6 mg/(kg·h) 10 minutes later to maintain anesthesia. Fiberoptic bronchoscopy was performed after the children were unconscious. Heart rate (HR), respiratory rate, blood oxygen saturation, and mean arterial pressure (MAP) were recorded before inserting the bronchoscope (T0), at the time of inserting the bronchoscope (T1), when the bronchoscope reached the glottis (T2), when the bronchoscope reached the carina (T3), and when the bronchoscope entered the bronchus (T4). The intraoperative peak airway pressure (Ppeak), examination time, degree of sedation, extent of amnesia, incidence of adverse reactions, postoperative awakening time, and postoperative agitation score were also recorded. RESULTS: Compared with the control group, the observation group had significantly decreased MAP at T1 to T4 and HR at T1 to T3 (P<0.05). Compared with that at T0, MAP was significantly increased at T1 to T4 in the control group and at T3 in the observation group (P<0.05). HR was significantly higher at T1 to T3 than at T0 (P<0.05). Compared with the control group, the observation group showed significantly lower intraoperative Ppeak value, incidence of intraoperative adverse reactions, and postoperative agitation score, significantly shorter examination time, and better effects of amnesia and anesthesia (P<0.05). There was no significant difference in the degree of intraoperative sedation and postoperative awakening time between the two groups (P>0.05). CONCLUSIONS: Dexmedetomidine hydrochloride combined with midazolam is a safe and effective way to administer general anesthesia for fiberoptic bronchoscopy in children, which can ensure stable vital signs during examination, reduce intraoperative adverse reactions and postoperative agitation, shorten examination time, and increase amnesic effect.

A chemiluminescence immunoassay for the detection of NT-proBNP.

BACKGROUND: The aim of the study was to assess the analytical performance of the HISCL NT-proBNP assay, a newly developed chemiluminescence immunoassay, for the detection of NT-proBNP. METHODS: The within-run and total imprecision of the NT-proBNP assay were determined with HISCL cardiac marker controls. The linear ranges of the NT-proBNP assays were evaluated based on the CLSI EP6-A document using selected serum samples. Two hundred serum samples were evaluated to compare the HISCL NT-proBNP and Elecsys NT-proBNP assays. Five additional high NT-proBNP concentrations serum samples were evaluated to assess if there was high-dose hook effect in the HISCL NT-proBNP assay. RESULTS: The total and within-run imprecision values of the HISCL NT-proBNP assay were 5.85%, 0.81%, 2.56% and 0.54% and 6.07%, 0.73%, 2.61% and 0.59% at 6.1, 129.83, 3732.84and39737.33 pg/ml, respectively. The assay was verified to be linear for NT-proBNP levels ranging between 6.1 and 39737.33 pg/ml. The assay comparison showed that HISCL NT-proBNP = 0.9803 × Elecsys NT-proBNP -4.383. The sensitivity of HISCL NT-proBNP was 87.23%, and the specificity was 85.61%. The AUC of HISCL NT-proBNP (0.90 (95% CI, 0.86-0.93)) did not differ from that of Elecsys NT-proBNP(0.89 (95% CI, 0.85-0.93)) (P = 0.638). The results of five high NT-proBNP concentrations samples (44448, 54206, 55634, 55728 and 109406 pg/ml, measured with the Elecsys NT-proBNP assay) tested with HISCL NT-proBNP assay were all displayed with ">40000 pg/ml". CONCLUSIONS: The HISCL NT-proBNP chemiluminescence immunoassay showed good analytical and diagnostic performance for the detection of NT-proBNP and could be used in routine clinical practice.

Factors associated with spiritual care competencies in Taiwan's clinical nurses: A descriptive correlational study.

AIMS AND OBJECTIVES: To determine factors associated with nurses' spiritual care competencies. BACKGROUND: Holistic nursing care includes biopsychosocial and spiritual care. However, nurses are limited by a lack of knowledge, time constraints and apprehension of assessing spiritual issues, which leaves them unable to assess and meet patients' spiritual needs. Thus, when patients experience spiritual distress, clinical nurses lose the opportunity to support spiritual growth and self-actualisation. In Taiwan, spiritual care, religion and culture are unique compared to those in other countries. Overall, factors associated with Taiwanese nurses' spiritual care competencies lack comprehensive exploration. METHODS: This study adopted a descriptive correlational design using cross-sectional survey (see Appendix S1). Cluster sampling was used to select clinical nurses from fourteen units of a medical centre and a regional hospital. Data were collected from January-June 2018 with a 97.03% response rate. Clinical nurses completed a background questionnaire, spiritual care practice questionnaire, spirituality and spiritual care-related scales. Data were analysed using descriptive and linear regression. This report followed the STROBE checklist. RESULTS: Spiritual care competence ranged from 44-123 (mean 84.67 ± 12.88; range 27-135). The majority of clinical nurses rated their spiritual care competence as moderate (64-98). The significant factors associated with nurses' spiritual care competence were education, religion, interest in spiritual care, having role models, past life events, barriers to providing spiritual care of the spiritual care practice score, and spiritual attitude and involvement score. The overall model was significant (p < .001) and accounted for 55.0% of variance (adjusted R2  = .488). CONCLUSIONS: Most clinical nurses have moderate spiritual care competence. Objective factors identified affect clinical nurses' spiritual care competencies. RELEVANCE TO CLINICAL PRACTICE: To improve nurses' spiritual care competencies, objective factors that affect clinical nurses' spiritual care competencies must be emphasised. Multiple strategies for enhancing nurses' own spiritual well-being can be provided via employee health promotion projects and activities, and promoting nurses' spirituality and spiritual care competencies can be explored in clinical settings through bedside teaching, situational simulation, objective structured clinical examinations and self-reflection.

Multimedia-assisted instruction on pain assessment learning of new nurses: a quasi-experimental study.

BACKGROUND: Pain assessment and treatment are key factors affecting the quality and safety of care for patients and capabilities related to them are crucial for new nursing staff. Consequently, we developed a multimedia-assisted teaching program for nursing newcomers' pain assessment learning to facilitate their practical pain assessment ability. The goal of this study was to evaluate a multimedia instructional program to boost new nurses' ability to conduct pain assessment and treatment, through simulated scenario instruction. METHODS: A quasi-experimental, pretest-posttest design with purposive sampling was used in this study. Eighty-six nurses were enrolled (control group, n = 39; experimental group, n = 47). Both groups underwent traditional pain assessment training in the classroom. The control group received lectures using PowerPoint files; while the experimental group undertook pain assessment training with the same content but delivered via multimedia-assisted instruction based on the ADDIE model. Pre- and post-instruction questionnaires relating to pain knowledge were completed. Participants' competence in performing pain assessment was subsequently evaluated one-month post instruction. RESULTS: The experimental group had significantly higher satisfaction scores (27.67 ± 3.76 vs. 31.36 ± 3.42, p < .01, respectively), and demonstrated greater knowledge of pain assessment (7.73 ± 0.67 vs. 7.08 ± 0.90, p < .05, respectively) than did the control group. Additionally, when evaluated at the one month follow-up, newcomers in the experimental group had better communication ability to perform pain assessment (26.58 ± 3.01 vs. 25.08 ± 3.32, p < .05, respectively). CONCLUSIONS: The program can improve nurses' pain assessment knowledge and competence. Newcomers were able to better respond to patients in pain, which is essential for pain assessment. This pilot study thus suggests a new, multimedia program for training nursing newcomers in pain assessment.

An interprofessional training program for intrahospital transport of critically ill patients: model build-up and assessment.

Intrahospital transport of critically ill patients for diagnostic or therapeutic procedures can be compromised by patient instability, equipment problems or inexperienced teamworking. This quasi-experimental study aimed to assess the effectiveness of an in-situ interprofessional simulation-based training (IIST) model for junior member transport teams. Newly registered postgraduate physicians, nurses and respiratory therapists underwent the IIST. The technical skills (TS) of each participant and non-technical skills (NTS) of each interprofessional team were assessed using well-validated checklists. Thirty-six participants enrolled and were randomly assigned to six experimental and six control teams. Most participants achieved a significantly higher level of both TS and NTS. Both the control and experimental teams overvalued their NTS in the pretest, while the posttest self-assessment scores among the experimental groups more closely matched the expert assessments. Despite challenges in scheduling and the setting, the IIST was successfully conducted in a crowded hospital, which enabled trainees to optimize their learning in a real-life environment. In conclusion, the IIST model can facilitate the development of both TS and NTS for transport team members. Transport teams made up of newly registered staff from different disciplines may lack insight into their NTS in critical patient transfer management, but simulation training may cause improvements.

Treponema pallidum promotes macrophage polarization and activates the NLRP3 inflammasome pathway to induce interleukin-1ß production.

BACKGROUND: The involvement of inflammasome activation and macrophage polarization during the process of syphilis infection remains unknown. In this study, A series of experiments were performed using human macrophages to research the role of NLRP3 inflammasome regulation in interleukin (IL)-1ß production and its influence on macrophage polarization triggered by T. pallidum. RESULTS: The results showed that in M0 macrophages treated with T. pallidum, the M1-associated markers inducible nitric oxide synthase (iNOS), IL-1ß and TNF-α were upregulated, and the M2-associated markers CD206 and IL-10 were downregulated. In addition, we observed NLRP3 inflammasome activation and IL-1ß secretion in T. pallidum-treated macrophages, and the observed production of IL-1ß occurred in a dose- and time-dependent manner. Moreover, the secretion of IL-1ß by macrophages after T. pallidum treatment was notably reduced by anti-NLRP3 siRNA and caspase-1 inhibitor treatment. NAC, KCl, and CA074-ME treatment also suppressed IL-1ß release from T. pallidum-treated macrophages. CONCLUSIONS: These findings showed that T. pallidum induces M0 macrophages to undergo M1 macrophage polarization and elevate IL-1ß secretion through NLRP3. Moreover, the process of NLRP3 inflammasome activation and IL-1ß production in macrophages in response to T. pallidum infection involves K+ efflux, mitochondrial ROS production and cathepsin release. This study provides a new insight into the innate immune response to T. pallidum infection.

Aerosol delivery during spontaneous breathing with different types of nebulizers- in vitro/ex vivo models evaluation.

BACKGROUND: Nebulizers for spontaneous breathing have been evaluated through different study designs. There are limitations in simulated bench models related to patient and nebulizer factors. The aim of this study was to determine the correlation of inhaled drug mass between in vitro and ex vivo studies by testing aerosol deposition of various types of nebulizers. METHODS: Ten healthy subjects were recruited to receive aerosol therapy with five nebulizers in random order: 1) a jet nebulizer (JN); 2) a breath-enhanced nebulizer (BEN); 3) a manually triggered nebulizer (MTN), 4) a breath-actuated nebulizer (BAN), and 5) a vibrating mesh nebulizer (VMN) with valved-adapter. A unit dose of salbutamol containing 5 mg in 2.5 mL was placed into the nebulizer and administered for 10 min. For the ex vivo study, minute ventilation of healthy subjects was recorded for 1 min. For the in vitro study a breathing simulator was utilized with adult breathing patterns. Aerosolized drug from the nebulizers and the accessory tubes was captured using inspiratory and expiratory collecting filters. Captured drug was eluted, measured and expressed as inhaled and exhaled mass using spectrophotometry at a wavelength of 276 nm. RESULTS: 10 healthy subjects were recruited, aged 20.8 ±â€¯0.7 years old, with a mean height of 166.2 ±â€¯9.2 cm and weight of 64.7 ±â€¯12.4 kg. There was no significant difference in the inhaled drug dose between the JN and BEN (15.0 ±â€¯1.94% and 17.74 ±â€¯2.65%, respectively, p = .763), yet the inhaled doses were lower than the other three nebulizers (p < .001). The VMN delivered greater inhaled dose than the other four nebulizers (p < .01). The respiratory rate of the cohorts was significantly correlated with the inhaled drug dose. For the in vitro model, the JN delivered a lower inhaled dose (11.6 ±â€¯1.6, p < .001) than the other nebulizers, whereas the MTN and BAN deposited significantly lower exhaled doses (1.7 ±â€¯0.4 and 2.7 ±â€¯0.2, respectively, p < .001). The VMN demonstrated a greater drug dose with the in vitro study than the ex vivo model (44.0 ±â€¯0.9% and 35.5 ±â€¯6.3% respectively, p = .003), whereas the JN in the ex vivo model resulted in a greater inhaled drug dose (15.0 ±â€¯1.9% for ex vivo vs 11.6 ±â€¯1.6% for in vitro, p = .008). CONCLUSIONS: These in vitro/ex vivo model comparisons of nebulizers performance indicated that breath-related nebulizers can be estimated using an in vitro model; however, the JN and VMN delivered inhaled drug mass differed between models. There was a significant correlation between respiratory rate and inhaled mass, and the inhaled drug dose generated by VMN correlated with minute ventilation. This study demonstrated that the VMN produced greater inhaled drug dose and lowest residual dose, whereas the BEN, BAN, and MTN produced lower exhaled drug dose in both in vitro and ex vivo models.

Size distribution of salbutamol/ipratropium aerosols produced by different nebulizers in the absence and presence of heat and humidification.

BACKGROUND: Few studies have evaluated the size distribution of inhaled and exhaled aerosolized drugs, or the effect of heated humidification on particle size and lung deposition. The present study evaluated these aspects of bronchodilator (salbutamol/ipratropium) delivery using a lung model in the absence and presence of heat and humidification. METHODS: We positioned filters to collect and measure the initial drug, inhaled drug, and exhaled drug. Particle size distribution was evaluated using an 8-stage Marple personal cascade impactor with 0.2-µm polycarbonate filters. RESULTS: A greater inhaled drug mass was delivered using a vibrating mesh nebulizer (VMN) than by using a small volume nebulizer (SVN), when heated humidifiers were not employed. When heated and humidified medical gas was used, there was no significant difference between the inhaled drug mass delivered by the VMN and that delivered by the SVN. A significantly greater mass of inhaled 1.55-µm drug particles was produced by the VMN than with the SVN, under heated and humidified conditions. However, the mass median aerodynamic diameters (MMADs) of the aerosolized drug produced by the SVN and VMN did not differ significantly under the same conditions. CONCLUSIONS: The VMN produced more fine particles of salbutamol/ipratropium, and the drug particle size clearly increased in the presence of heat and humidification.