Search

Background: Extracellular adenosine 5'-triphosphate (ATP) is an endogenous signaling molecule involved in multiple biological phenomena, including inflammation. The effects of extracellular ATP in the lung have not been fully clarified. This study examined 1) the biological roles of extracellular ATP in the pathogenesis of lung inflammation and 2) the possibility of involvement of extracellular ATP in mechanical ventilation-induced lung injury.Methods: The effects of intratracheal ATP on lung permeability, edema or lung inflammation were assessed by measurements of the lung wet-to-dry weight ratio and lung permeability index, immunohistochemistry and expression of key cytokines by real-time polymerase chain reaction. The ATP concentration in broncho-alveolar lavage (BAL) fluid from mice mechanically ventilated was measured by luciferin-luciferase assay. The suppressive effects of a P2 receptor antagonist on ventilator-induced lung inflammation were also examined.Results: ATP induced inflammatory reactions in the lung mainly via the ATP-P2Y receptor system. These reactions were alleviated by the co-administration of a specific P2 receptor antagonist. Mechanical ventilation with a large tidal volume caused lung inflammation and increased the ATP concentration in BAL fluid. P2 receptor antagonism partially mitigated the inflammatory effects of large tidal volume ventilation.Conclusion: Our observations suggest that the ATP-P2Y receptor system is partially involved in the pathogenesis of ventilator-induced lung injury. [ABSTRACT FROM AUTHOR]

Lung resection surgery, which is performed as a treatment for lung cancer and metastatic lung tumors, is currently conducted via minimally invasive techniques such as video-assisted thoracoscopic surgery and robot-assisted methods. Postoperative complications related to this surgery, such as pulmonary vein thrombosis and cerebral and other organ infarctions, have been increasingly reported. The primary cause of these complications is thrombus formation in the pulmonary vein stump. Statistical data on the site of lung lobectomy have indicated that surgeries involving the left upper lobe are most frequently associated with embolic complications. Although this issue has not received considerable attention in anesthesiology, the importance of prevention and treatment in postoperative management is growing. The role of anesthesiologists in preventing these complications is critical. These roles involve careful fluid management to avoid hypercoagulable states, consideration of early postoperative anticoagulation therapy, assessment of the suitability of epidural anesthesia for postoperative anticoagulation, and improvement of hospital-wide safety systems and monitoring of high-risk patients. Anesthesiologists need to understand the pathology and risk factors involved and play an active role in preventing and treating these complications through effective collaboration with thoracic surgeons and the in-hospital stroke team., (© 2024. The Author(s) under exclusive licence to Japanese Society of Anesthesiologists.)

Environmental exposures and gene-exposure interactions are the major causes of some diseases. Early-life exposome studies are needed to elucidate the role of environmental exposures and their complex interactions with biological mechanisms involved in childhood health. This study aimed to determine the contribution of early-life exposome to DNA damage and the modifying effect of genetic polymorphisms involved in air pollutants metabolism, antioxidant defense, and DNA repair. We conducted a cohort study in 416 Colombian children under five years. Blood samples at baseline were collected to measure DNA damage by the Comet assay and to determine GSTT1, GSTM1, CYP1A1, H2AX, OGG1, and SOD2 genetic polymorphisms. The exposome was estimated using geographic information systems, remote sensing, LUR models, and questionnaires. The association exposome-DNA damage was estimated using the Elastic Net linear regression with log link. Our results suggest that exposure to PM 2.5 one year before the blood draw (BBD) (0.83, 95 %CI: 0.76; 0.91), soft drinks consumption (0.94, 0.89; 0.98), and GSTM1 null genotype (0.05, 0.01; 0.36) diminished the DNA damage, whereas exposure to PM 2.5 one-week BBD (1.18, 1.06; 1.32), NO 2 lag-5 days BBD (1.27, 1.18; 1.36), in-house cockroaches (1.10, 1.00; 1.21) at the recruitment, crowding at home (1.34, 1.08; 1.67) at the recruitment, cereal consumption (1.11, 1.04; 1.19) and H2AX (AG/GG vs. AA) (1.44, 1.11; 1.88) increased the DNA damage. The interactions between H2AX (AG/GG vs. AA) genotypes with crowding and PM 2.5 one week BBD, GSTM1 (null vs. present) with humidity at the first year of life, and OGG1 (SC/CC vs. SS) with walkability at the first year of life were significant. The early-life exposome contributes to elucidating the effect of environmental exposures on DNA damage in Colombian children under five years old. The exposome-DNA damage effect appears to be modulated by genetic variants in DNA repair and antioxidant defense enzymes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The use of opioids occasionally causes tinnitus. However, there is a paucity of data regarding the use of peripherally acting μ-opioid receptor antagonists for opioid-associated tinnitus in patients with cancer., Actual Case: A 74-year-old male with pancreatic cancer complained of abdominal pain. Two days after initiating oxycodone therapy, the patient experienced tinnitus during body movements. Although peripheral tinnitus disappeared after discontinuing oxycodone, it reappeared with hydromorphone or tapentadol administration., Possible Courses of Action: Drug cessation is a preferred intervention for drug-induced tinnitus; however, the cessation of opioids may not be feasible in patients with cancer who are already taking opioids., Formulation of a Plan: Based on the presumed mechanism of peripheral tinnitus, the use of peripherally acting μ-opioid receptor antagonists was planned, and 200 μg/day of naldemedine was prescribed for tinnitus relief., Outcome: Tinnitus disappeared immediately after initiating naldemedine, and the pain was well-controlled. The effect was preserved after increasing or switching opioids., Lessons: The use of peripherally acting μ-opioid receptor antagonists may be an option to treat opioid-associated tinnitus without compromising the analgesic effects., View: Further clinical data regarding the secondary effect of peripherally acting μ-opioid receptor antagonists on opioid-associated complications other than constipation are required., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Exposome studies are advancing in high-income countries to understand how multiple environmental exposures impact health. However, there is a significant research gap in low- and middle-income and tropical countries. We aimed to describe the spatiotemporal variation of the external exposome, its correlation structure between and within exposure groups, and its dimensionality. A one-year follow-up cohort study of 506 children under 5 in two cities in Colombia was conducted to evaluate asthma, acute respiratory infections, and DNA damage. We examined 48 environmental exposures during pregnancy and 168 during childhood in eight exposure groups, including atmospheric pollutants, natural spaces, meteorology, built environment, traffic, indoor exposure, and socioeconomic capital. The exposome was estimated using geographic information systems, remote sensing, spatiotemporal modeling, and questionnaires. The median age of children at study entry was 3.7 years (interquartile range: 2.9-4.3). Air pollution and natural spaces exposure decreased from pregnancy to childhood, while socioeconomic capital increased. The highest median correlations within exposure groups were observed in meteorology (r = 0.85), traffic (r = 0.83), and atmospheric pollutants (r = 0.64). Important correlations between variables from different exposure groups were found, such as atmospheric pollutants and meteorology (r = 0.76), natural spaces (r = -0.34), and the built environment (r = 0.53). Twenty principal components explained 70%, and 57 explained 95% of the total variance in the childhood exposome. Our findings show that there is an important spatiotemporal variation in the exposome of children under 5. This is the first characterization of the external exposome in urban areas of Latin America and highlights its complexity, but also the need to better characterize and understand the exposome in order to optimize its analysis and applications in local interventions aimed at improving the health conditions and well-being of the child population and contributing to environmental health decision-making., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the usefulness of robotic subxiphoid-optical thymectomy (RST)., Methods: Thirty-seven procedures (thymoma, n = 19; thymic carcinoma, n = 1; myasthenia gravis, n = 3; and others, n = 14) performed between October 2020 and December 2023 were included. The right and left 6th intercostal midclavicular lines and subxiphoid, with an assistant port placed in the right third intercostal anterior axillary line, were adapted. Postoperative pain was assessed using a numerical rating scale (NRS)., Results: A good view of the surgical field is obtained. The median console time was 113 min and the time to roll-in was 30 min. The body mass index (BMI) was 21.6. One patient with thymic carcinoma required combined resection of the left phrenic nerve and left brachiocephalic vein without conversion to thoracotomy, and 1 patient had post-pericardiotomy syndrome with bilateral pleural effusion. There was a correlation between the prolonged time to roll-in and BMI (ρ = 0.439; p = 0.007). Pain was controlled with oral medication on postoperative day 1 and significantly decreased at discharge and at the first outpatient visit without epidural anesthesia (median NRS scores: 4, 1, and 1, respectively)., Conclusion: RST is a safe procedure that provides surgeons with a sufficient view of the anterior mediastinum and causes minimal postoperative pain., (© 2024. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Familial episodic pain syndrome (FEPS) is an early childhood onset disorder of severe episodic limb pain caused mainly by pathogenic variants of SCN11A , SCN10A , and SCN9A , which encode three voltage-gated sodium channels (VGSCs) expressed as key determinants of nociceptor excitability in primary sensory neurons. There may still be many undiagnosed patients with FEPS. A better understanding of the associated pathogenesis, epidemiology, and clinical characteristics is needed to provide appropriate diagnosis and care. For this study, nationwide recruitment of Japanese patients was conducted using provisional clinical diagnostic criteria, followed by genetic testing for SCN11A , SCN10A , and SCN9A . In the cohort of 212 recruited patients, genetic testing revealed that 64 patients (30.2%) harbored pathogenic or likely pathogenic variants of these genes, consisting of 42 (19.8%), 14 (6.60%), and 8 (3.77%) patients with variants of SCN11A , SCN10A , and SCN9A , respectively. Meanwhile, the proportions of patients meeting the tentative clinical criteria were 89.1%, 52.0%, and 54.5% among patients with pathogenic or likely pathogenic variants of each of the three genes, suggesting the validity of these clinical criteria, especially for patients with SCN11A variants. These clinical diagnostic criteria of FEPS will accelerate the recruitment of patients with underlying pathogenic variants who are unexpectedly prevalent in Japan.

Background: Low-dose tranexamic acid (TXA) has been recently recommended for cardiopulmonary bypass (CPB) to reduce associated complications. Although point-of-care laboratory tests for TXA concentrations are unavailable, a novel TPA-test on the ClotPro® system can measure TXA-induced inhibition of fibrinolysis. We evaluated the performance of the TPA-test in vitro and in patients undergoing surgery requiring CPB., Methods: Blood samples were obtained from six volunteers for in vitro evaluation of tissue plasminogen activator (tPA)-triggered fibrinolysis and the effects of TXA. This was followed by an observational study in 20 cardiac surgery patients to assess clinical effects of TXA on the TPA-test., Results: Hyperfibrinolysis induced by tPA was inhibited by TXA ≥2 mg L -1 in a concentration-dependent manner, and was completely inhibited at TXA ≥10 mg L -1 . In patients undergoing CPB, antifibrinolytic effect was detectable on TPA-test parameters after a 0.1 g bolus of TXA at the end of CPB, and complete inhibition of fibrinolysis was obtained with TXA ≥0.5 g. The antifibrinolytic effects of 1 g TXA on TPA-test parameters were gradually attenuated over 18 h after surgery. However, the fibrinolytic inhibition continued in four patients with estimated glomerular filtration rate (eGFR) ≤30 ml min -1 1.73 m -2 . The eGFR had strong correlations with TPA-test parameters at 18 h after surgery (r=0.86-0.92; P<0.0001)., Conclusions: The TPA-test is sensitive to low concentrations of TXA and serves as a practical monitoring tool for postoperative fibrinolytic activity in cardiac surgery patients. This test might be particularly useful in patients with severe renal impairment., (Copyright © 2024 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

To explore the current status of anesthesia research activity in Japan, we analyzed the number of abstracts presented at the Japanese Society of Anesthesiologists (JSA) annual meetings by several factors including gender, society branches, and subspecialty categories. The number of abstracts at JSA annual meetings has declined sharply since 2016 with no gender gap. A decrease in the neurological field predated the overall decline, but other subspecialty categories showed a similar decline. Although the Tokyo, Tokai-Hokuriku, and Kyushu branches were responsible for more than half of the reduction, the trend was similar among all branches. In a survey regarding academic activities of university hospital residents and faculty, Ph.D. aspirants' rate was only 20-30%. Residents had never presented an abstract at scientific conferences and never published any papers at nearly 40% and 30% of the university hospitals, respectively. Our survey suggests that junior anesthetists are losing interest in research. Senior faculty and mentors must redouble efforts to embed and encourage research in departments and by anesthetists in training. If a revival of anesthesia research in Japan does not occur then a service only specialty awaits., (© 2023. The Author(s) under exclusive licence to Japanese Society of Anesthesiologists.)

Post-intensive care syndrome comprises physical, cognitive, and mental impairments in patients treated in an intensive care unit (ICU). It occurs either during the ICU stay or following ICU discharge and is related to the patients' long-term prognosis. The same concept also applies to pediatric patients, and it can greatly affect the mental status of family members. In the 10 years since post-intensive care syndrome was first proposed, research has greatly expanded. Here, we summarize the recent evidence on post-intensive care syndrome regarding its pathophysiology, epidemiology, assessment, risk factors, prevention, and treatments. We highlight new topics, future directions, and strategies to overcome post-intensive care syndrome among people treated in an ICU. Clinical and basic research are still needed to elucidate the mechanistic insights and to discover therapeutic targets and new interventions for post-intensive care syndrome., Competing Interests: Dr. Yutaka Kondo is an Editorial Board member of AMS Journal and a co‐author of this article. To minimize bias, they were excluded from all editorial decision‐making related to the acceptance of this article for publication. The other authors declare no conflicts of interest in relation to this review article., (© 2024 The Authors. Acute Medicine & Surgery published by John Wiley & Sons Australia, Ltd on behalf of Japanese Association for Acute Medicine.)

Acute zoster-associated pain develops in most patients with herpes zoster. Nonopioid analgesics are usually used to treat acute zoster-associated pain but are frequently ineffective. We administered intravenous fosphenytoin, the prodrug of phenytoin, to patients with acute zoster-associated pain to examine its analgesic efficacy and safety. At 13 medical institutions in Japan, we conducted a phase II, double-blind, placebo-controlled, randomized trial of intravenous fosphenytoin in Japanese inpatients with acute zoster-associated pain for whom nonopioid analgesics had shown an insufficient analgesic effect. The patients were randomly assigned (1:1:1) to receive a single intravenous dose of fosphenytoin at 18 mg/kg (high dose), a single intravenous dose of fosphenytoin at 12 mg/kg (low dose), or placebo. The primary endpoint was the mean change per hour (slope) in the numerical rating scale score from the baseline score until 120 min after dosing. Seventeen patients were randomly assigned to the low-dose fosphenytoin group (n = 6, median age 62.5 years, range 39-75 years), high-dose fosphenytoin group (n = 5, median age 69.0 years, range 22-75 years), and placebo group (n = 5, median age 52.0 years, range 38-72 years). One patient was excluded because of investigational drug dilution failure. This study was discontinued because of the influences of coronavirus disease 2019. The slope was significantly lower in the high- and low-dose fosphenytoin groups than in the placebo group (P < 0.001 and P = 0.016, respectively). Responsiveness to intravenous fosphenytoin (≥2-point reduction in the numerical rating scale score from baseline to 120 min after dosing) was inferred at plasma total phenytoin concentrations of 10-15 μg/mL. Treatment-emergent adverse events caused no safety concerns in the clinical setting and intravenous fosphenytoin was well tolerated. Intravenous fosphenytoin appears to be an effective and promising alternative treatment for acute zoster-associated pain. Trial Registration: ClinicalTrials.gov NCT04139330., (© 2023 The Authors. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.)

Purpose: The reduced effects of allogeneic transfusion with acute normovolemic hemodilution (ANH) have been reported. Harvesting a large volume of blood may maximize the effect in patients with low body weight, and the prevention of hypotension is important. Remimazolam is an anesthetic with few circulatory responses. Our aim was to evaluate whether high-volume ANH reduces the need for transfusion in cardiac patients under remimazolam anesthesia., Methods: In this retrospective single-center study, we enrolled cardiopulmonary bypass (CPB) patients who received remimazolam anesthesia. Changes in hemodynamic parameters were assessed. The numbers of blood transfusions and chest tube outputs were also evaluated., Results: In a total of 51 patients, ANH was performed in 27 patients with a mean body mass index of 23.2 (ANH volume: 740 ± 222 mL). No significant differences were observed in mean blood pressure during blood collection. The intraoperative amount of red blood cell (RBC) transfusion was significantly lower in the ANH group than in the control group (431 ± 678 and 1260 ± 572 mL, p < 0.001). The avoidance rates of RBC were 66.7 and 4.2%, respectively. The multivariate analysis result revealed that ANH correlated with RBC, with an odds ratio of 0.067 (95% confidence interval 0.005-0.84, p < 0.05). The postoperative bleeding at 24 h was significantly lower in the ANH group (455 ± 228 and 797 ± 535 mL, p < 0.01)., Conclusion: In patients undergoing CPB, ANH reduced intraoperative transfusion amount and postoperative bleeding. Hemodynamic changes during blood collection were minimal under remimazolam anesthesia and high-volume ANH was feasible., (© 2023. The Author(s) under exclusive licence to Japanese Society of Anesthesiologists.)

Background: IL-1β plays a critical role in the pathophysiology of neuroinflammation. The presence of cleaved IL-1β (cIL-1β) in the neurons of the dorsal root ganglion (DRG) implicates its function in biological signaling arising from the sensory neuron. This study was conducted to analyze the role of IL-1β in nociceptive transduction after tissue injury. Methods: A plantar incision was made in C57BL/6 mice, following which immunohistochemistry and RNA scope in situ hybridization were performed at various time points to analyze cIL-1β, caspase-1, and IL-1 receptor 1 (IL-1R1) expression in the DRG. The effect of intrathecal administration of a caspase-1 inhibitor or regional anesthesia using local anesthetics on cIL-1β expression and pain hypersensitivity was analyzed by immunohistochemistry and behavioral analysis. ERK phosphorylation was also analyzed to investigate the effect of IL-1β on the activity of spinal dorsal horn neurons. Results: cIL-1β expression was significantly increased in caspase-1-positive DRG neurons 5 min after the plantar incision. Intrathecal caspase-1 inhibitor treatment inhibited IL-1β cleavage and pain hypersensitivity after the plantar incision. IL-1R1 was also detected in the DRG neurons, although the majority of IL-1R1-expressing neurons lacked cIL-1β expression. Regional anesthesia using local anesthetics prevented cIL-1β processing. Plantar incision-induced phosphorylation of ERK was inhibited by the caspase-1 inhibitor. Conclusion: IL-1β in the DRG neuron undergoes rapid cleavage in response to tissue injury in an activity-dependent manner. Cleaved IL-1β causes injury-induced functional activation of sensory neurons and pain hypersensitivity. IL-1β in the primary afferent neurons is involved in physiological nociceptive signal transduction., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: Preoperative opioid treatment increases postoperative adverse events. This study was aimed to analyze preoperative opioid prevalence in countries with low opioid consumption. Additionally, the effect of low opioid usage on postoperative outcomes was also investigated., Methods: We conducted this single center retrospective cohort analysis in a Japanese university-affiliated hospital to investigate opioid usage and its impact on the duration of postoperative hospitalization and in-hospital mortality. Adult patients who underwent general anesthesia between 2015 and 2020 were included. We extracted the patients' characteristics, surgical information and postoperative outcomes. Subgroup analysis to address opioid dose effect was performed in high and low dose opioid subgroups., Results: Among 20,306 inpatients, 535 (2.63%) patients used opioids preoperatively. Tramadol was the most frequently used opioid. The median morphine equivalent (MME) dose was 15 mg/day. Median duration of hospitalization was 18 and 9 days in the opioid and non-opioid groups, and in-hospital mortality was 2.06% and 0.42%. Multivariable regression analysis demonstrated that preoperative opioid use was associated with a longer duration of hospitalization and in-hospital mortality. Subgroup analysis demonstrated longer durations of hospitalization in both high (> 30 mg/day MME) and low (≤ 30 mg/day MME) dose opioid groups, while higher in-hospital mortality was seen only in the high dose opioid group., Conclusions: Preoperative opioid usage was one-tenth of the United States average. Despite its low prevalence and small dosage, preoperative opioid usage was associated with poor postoperative outcomes. Dedicated perioperative interventions to prevent opioid-associated adverse events should be developed even in countries with low opioid consumption., (© 2023. The Author(s) under exclusive licence to Japanese Society of Anesthesiologists.)

Background: Family with sequence similarity 134, member B (FAM134B), also known as Reticulophagy regulator 1 (RETREG1), is an ER-phagy receptor involved in ER homeostasis. Congenital mutations in the FAM134B gene have been reported to be associated with hereditary sensory and autonomic neuropathy type 2B (HSAN2B); however, the molecular differences between wild-type and HSAN2B-linked FAM134B are not fully understood., Methods and Results: We prepared several human FAM134B constructs, such as the HSAN2B-linked mutant, and compared their features with those of wild-type FAM134B by transfecting these constructs into FAM134B-deficient Neuro2a cells. Although intrinsic FAM134B protein expression in wild-type Neuro2a cells was affected by the supply of amino acids in the culture medium, the expression of each HSAN2B-linked mutant FAM134B protein was hardly affected by serum and amino acid deprivation. On the other hand, the intracellular localization of GFP-tagged HSAN2B-linked mutants, except for P7Gfs133X, overlapped well with ER-localized SP-RFP KDEL and did not differ from that of GFP-tagged wild-type FAM134B. However, analysis of protein‒protein interactions using the NanoBiT reporter assay revealed the difference between wild-type and C-terminal truncated mutant FAM134B. Furthermore, this NanoBiT assay demonstrated that both wild-type and G216R FAM134B interacted with LC3/GABARAPL1 to the same extent, but the FAM134B construct with mutations near the LC3-interacting region (LIR) did not. Similar to the NanoBiT assay, the C-terminal-truncated FAM134B showed lower ER-phagy activities, as assessed by the cotransfection of GFP-tagged reporters., Conclusions: We showed that wild-type and HSAN2B-linked FAM134B have different molecular characteristics by transfecting cells with various types of constructs. Thus, this study provides new insights into the molecular mechanisms underlying HSAN2B as well as the regulation of ER-phagy., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Chelsea, Massachusetts, had one of the highest COVID-19 transmission rates in New England in the summer of 2020. The Chelsea Project was a collaborative effort in which government entities, local nonprofit organizations, and startups partnered to deploy wastewater analysis, targeted polymerase chain reaction testing and vaccine outreach, and a community-led communications strategy. The strategy helped increase both testing rates and vaccination rates in Chelsea. Today Chelsea has one of the highest vaccination rates among US cities with comparable demographics. ( Am J Public Health. 2023;113(6):627-630. https://doi.org/10.2105/AJPH.2023.307253).

A 61-year-old woman with chronic renal dysfunction was scheduled to undergo aortic valve replacement. After a bolus of 1 g tranexamic acid (TXA), the TPA (tissue-plasminogen activator)-test result with the ClotPro system demonstrated extensive inhibition of fibrinolysis. Plasma TXA level decreased from 71 to 25 μg/dL at 6 hours postoperatively; however, no further decrease was observed. Although TXA levels dropped to 6.9 μg/dL after hemodialysis on postoperative day (PoD) 1, fibrinolytic shutdown on the TPA-test remained unchanged until PoD 2. In dialysis patients, low-dose TXA <1 g may be considered for reducing seizure and thromboembolic complications after cardiac surgery., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 International Anesthesia Research Society.)

Background: Air pollution contains a mixture of different pollutants from multiple sources. However, the interaction of these pollutants with other environmental exposures, as well as their harmful effects on children under five in tropical countries, is not well known., Objective: This study aims to characterize the external exposome (ambient and indoor exposures) and its contribution to clinical respiratory and early biological effects in children., Materials and Methods: A cohort study will be conducted on children under five (n = 500) with a one-year follow-up. Enrolled children will be followed monthly (phone call) and at months 6 and 12 (in person) post-enrolment with upper and lower Acute Respiratory Infections (ARI) examinations, asthma development, asthma control, and genotoxic damage. The asthma diagnosis will be pediatric pulmonologist-based and a standardized protocol will be used. Exposure, effect, and susceptibility biomarkers will be measured on buccal cells samples. For environmental exposures PM2.5 will be sampled, and questionnaires, geographic information, dispersion models and Land Use Regression models for PM2.5 and NO2 will be used. Different statistical methods that include Bayesian and machine learning techniques will be used for the ambient and indoor exposures-and outcomes. This study was approved by the ethics committee at Universidad Pontificia Bolivariana., Expected Study Outcomes/findings: To estimate i) The toxic effect of particulate matter transcending the approach based on pollutant concentration levels; ii) The risk of developing an upper and lower ARI, based on different exposure windows; iii) A baseline of early biological damage in children under five, and describe its progression after a one-year follow-up; and iv) How physical and chemical PM2.5 characteristics influence toxicity and children's health., Competing Interests: JCT is the owner and CEO of ATB SERVICE SAS. He does not have access to any children’s information and the Environmental information is transmitted in real time and the data will be public. JMA and SM are employed by the Healthcare Company, SURA. JJB is employed by GENES laboratory. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The other authors do not have conflicts of interest to declare, (Copyright: © 2023 Marín et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Activation of neurons and glial cells in the dorsal root ganglion is one of the key mechanisms for the development of hyperalgesia. The aim of the present study was to examine the role of neuroglial activity in the development of opioid-induced hyperalgesia. Male rats were treated with morphine daily for 3 days. The resultant phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 in the dorsal root ganglion was analyzed by immunohistochemistry and Western blotting. Pain hypersensitivity was analyzed using behavioral studies. The amount of cytokine expression in the dorsal root ganglion was also analyzed. Repeated morphine treatment induced hyperalgesia and marked induction of phosphorylated ERK1/2 in the neurons and satellite glial cells on day 3. An opioid receptor antagonist, toll like receptor-4 inhibitor, MAP/ERK kinase (MEK) inhibitor and gap junction inhibitor inhibited morphine-induced hyperalgesia and ERK1/2 phosphorylation. Morphine treatment induced alteration of cytokine expression, which was inhibited by the opioid receptor antagonist, toll like receptor-4 inhibitor, MEK inhibitor and gap junction inhibitor. Dexamethasone inhibited morphine-induced hyperalgesia and ERK1/2 phosphorylation after morphine treatment. The peripherally restricted opioid receptor antagonist, methylnaltrexone, inhibited hyperalgesia and ERK1/2 phosphorylation. Morphine activates ERK1/2 in neurons and satellite glial cells in the dorsal root ganglion via the opioid receptor and toll like receptor-4. ERK1/2 phosphorylation is gap junction-dependent and is associated with the alteration of cytokine expression. Inhibition of neuroinflammation by activation of neurons and glia might be a promising target to prevent opioid-induced hyperalgesia., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Viscoelastic coagulation tests have been increasingly used for hemostasis management in cardiac surgery. The ClotPro system is a novel viscoelastic device based on principles of rotational thromboelastometry. We aimed to compare ClotPro with ROTEM and plasma coagulation assays in cardiopulmonary bypass (CPB) patients. Blood samples were collected from 25 CPB patients at (1) baseline, (2) start of CPB, (3) end of CPB, and (4) end of surgery. The EX-test, IN-test, HI-test, FIB-test parameters on ClotPro were compared with corresponding ROTEM assay (EXTEM, INTEM, HEPTEM, and FIBTEM). Standard plasma coagulation assays and endogenous thrombin generation (TG) were simultaneously evaluated. Pearson correlation analyses showed moderate correlations between clotting times (CTs) (r = 0.63-0.67; p < 0.001, respectively), and strong correlations with maximal clot firmness (MCF) (r = 0.93-0.98; p < 0.001, respectively) between ClotPro and ROTEM. EX-test and IN-test MCF parameters were interchangeable with acceptable percentage errors (EX-test MCF: 7.3%, IN-test MCF: 8.3%), but FIB-test MCF (27.0%) and CT results were not (EX-test CT: 44.7%, IN-test CT: 31.4%). The correlations of PT/INR or peak TG with EX-test CTs were higher than with EXTEM CTs (PT/INR: r = 0.80 and 0.41, peak TG: 0.43 and 0.18, respectively). FIB-test MCF has strong correlation with plasma fibrinogen and factor XIII level (r = 0.84 and 0.66, respectively). ROC analyses showed that ClotPro was capable of emulating well-established ROTEM thresholds (area under curves: 0.83-1.00). ClotPro demonstrated strong correlations in MCF parameters of ROTEM in CPB patients. It may be reasonable to modify ROTEM-based transfusion algorithm pertaining to MCF parameters to establish cut-off values for ClotPro device., (© 2022. The Author(s).)

Background: After breast surgery with or without immediate reconstruction, chronic pain can be a major problem for patients. However, few studies have examined the details of the sites of long-lasting postoperative pain. In this study, we specified the postoperative pain location after breast surgery, including reconstruction, to find ways to improve surgical procedures or provide effective pain relief., Methods: The subjects were 205 Japanese women undergoing mastectomy or breast reconstruction with a tissue expander (TE)/implant or a deep inferior epigastric perforator (DIEP) flap. Patients were asked whether they had pain in different parts of the body at 1 year after surgery. Differences were assessed by cross-tabulation and χ2 statistics., Results: Surveys were completed by 157 subjects. Deep inferior epigastric perforator flap cases had significantly more pain and TE/Imp cases had significantly less pain in the medial breast, upper breast, breast upper medial quadrant, and abdomen (P = 0.006, P = 0.006, P < 0.001, P < 0.001, respectively). In the neck area, pain in TE/Imp cases was significantly worse than that in all other patients (P = 0.025). There was no significant difference in chronic pain in any other body regions among the mastectomy only, TE/Imp, and DIEP flap groups., Conclusions: The results of the present study revealed that the localization of prolonged postoperative pain after breast surgery differs depending on the surgical procedure. In DIEP flap reconstruction, there was a marked tendency for pain in the inner and upper chest and in the abdomen, whereas TE/IMP surgery resulted in pain around the neck of the affected side. These findings may help improve surgical methods and establish effective pain relief that focuses on the identified pain areas., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Dynamic regulation of G-protein-coupled receptor (GPCR) kinase 2 (GRK2) expression restores cellular function by protecting from overstimulation via GPCR and non-GPCR signaling. In the primary afferent neurons, GRK2 negatively regulates nociceptive tone. The present study tested the hypothesis that induction of GRK2 in the primary afferent neurons contributes to the resolution of acute pain after tissue injury. GRK2 expression in the dorsal root ganglion (DRG) was analyzed at 1 and 7 days after the incision. Intraperitoneal administration of a GRK2 inhibitor was performed 7 days post-incision in male Sprague-Dawley rats who underwent plantar incisions to analyze the pain-related behavioral effect of the GRK2 inhibitor. Separately, GRK2 expression was analyzed after injecting insulin-like growth factor 1 (IGF1) into the rat hind paw. In addition, an IGF1 receptor (IGF1R) inhibitor was administered in the plantar incision rats to determine its effect on the incision-induced hyperalgesia and GRK2 expression. Plantar incision induced an increase in GRK2 in the DRG at 7 days, but not at 1 day post-incision. Acute hyperalgesia after the plantar incision disappeared by 7 days post-incision. Intraperitoneal injection of the GRK2 inhibitor at this time reinstated mechanical hyperalgesia, although the GRK2 inhibitor did not produce hyperalgesia in naive rats. After the incision, IGF1 expression increased in the paw, but not in the DRG. Intraplantar injection of IGF1 increased GRK2 expression in the ipsilateral DRG. IGF1R inhibitor administration prevented both the induction of GRK2 and resolution of hyperalgesia after the plantar incision. These findings demonstrate that induction of GRK2 expression driven by tissue IGF1 has potent analgesic effects and produces resolution of hyperalgesia after tissue injury. Dysregulation of IGF1-GRK2 signaling could potentially lead to failure of the spontaneous resolution of acute pain and, hence, development of chronic pain after surgery., (Copyright © 2021. Published by Elsevier Inc.)

The type III secretion systems (T3SS) encoded in pathogenicity islands SPI-1 and SPI-2 are key virulence factors of Salmonella . These systems translocate proteins known as effectors into eukaryotic cells during infection. To characterize the functionality of T3SS effectors, gene fusions to the CyaA' reporter of Bordetella pertussis are often used. CyaA' is a calmodulin-dependent adenylate cyclase that is only active within eukaryotic cells. Thus, the translocation of an effector fused to CyaA' can be evaluated by measuring cAMP levels in infected cells. Here, we report the construction of plasmids pCyaA'-Kan and pCyaA'-Cam, which contain the ORF encoding CyaA' adjacent to a cassette that confers resistance to kanamycin or chloramphenicol, respectively, flanked by Flp recombinase target (FRT) sites. A PCR product from pCyaA'-Kan or pCyaA'-Cam containing these genetic elements can be introduced into the bacterial chromosome to generate gene fusions by homologous recombination using the Red recombination system from bacteriophage λ. Subsequently, the resistance cassette can be removed by recombination between the FRT sites using the Flp recombinase. As a proof of concept, the plasmids pCyaA'-Kan and pCyaA'-Cam were used to generate unmarked chromosomal fusions of 10 T3SS effectors to CyaA' in S . Typhimurium. Each fusion protein was detected by Western blot using an anti-CyaA' monoclonal antibody when the corresponding mutant strain was grown under conditions that induce the expression of the native gene. In addition, T3SS-1-dependent secretion of fusion protein SipA-CyaA' during in vitro growth was verified by Western blot analysis of culture supernatants. Finally, efficient translocation of SipA-CyaA' into HeLa cells was evidenced by increased intracellular cAMP levels at different times of infection. Therefore, the plasmids pCyaA'-Kan and pCyaA'-Cam can be used to generate unmarked chromosomal cyaA ' translational fusion to study regulated expression, secretion and translocation of Salmonella T3SS effectors into eukaryotic cells.

Transurethral resection of the prostate (TURP) is the most common standard surgical procedure used for benign prostatic hyperplasia. Transurethral resection in saline (TURis) is a bipolar electrosurgery system used to prevent TURP (or TUR) syndrome. The bicarbonate Ringer's solution is not generally used as perfusate for TURP. Hence, we compared the efficacy of the bicarbonate Ringer's solution with that of physiological saline as perfusate during TURP. This prospective, multicenter, cooperative study was conducted on 40 adult patients admitted to a medical college hospital. After obtaining informed consent from all the patients, they were divided into two groups (20 patients per group). For patients of one group, bicarbonate Ringer's solution, and for other group, physiological saline was used as perfusate. Compared to the physiological saline, the electrolyte composition of the bicarbonate Ringer's solution was closer to that of plasma. Hence, the group using bicarbonate Ringer's solution as perfusate was exhibited less variation in plasma electrolytes and blood gas data. The primary endpoints were adverse events of grade 1 or higher according to the JCOG postoperative complication criteria ver. 2.0, unintended diseases, or related signs in patients who underwent the protocol therapy. The secondary endpoints were changes in blood pH, bicarbonate ion level, anion gap (AG), base excess (BE), and chloride (C1), which occurred during and after the surgeries. Therefore, bicarbonate Ringer's solution has superior with that of physiological saline as perfusate during TURP which is directly administered into the blood vessels as an infusion solution.Bicarbonate Ringer's solution is directly administered into the blood vessels as an infusion solution., Competing Interests: The authors declare that they have no competing interests., (© 2021 Published by Elsevier Inc.)

The Life Impact Burn Recovery Evaluation (LIBRE) Profile is a patient-reported outcome measure developed to assess social participation in adult burn survivors. This study identified numeric score cut-points that define different levels of social participation ability and described each level. An expert panel identified numeric score cut-points that distinguish different levels of social participation for the six LIBRE Profile domains. Methods employed an iterative, modified-Delphi approach, and bookmarking to review calibrated item banks. Analyses (using calibration sample data and repeated in a validation sample) examined means, SDs, and sample distributions for each level. Analyses of variance examined score differences between levels. The panel developed descriptions for each established level. Initial cut-points resulted in four levels for five domains (Social Activities, Social Interactions, Romantic Relationships, Sexual Relationships, and Work & Employment) and five levels for the sixth domain (Relationships with Family & Friends). Comparisons demonstrated significant differences between level mean scores for all domains (P < .05) except Relationships with Family & Friends. Based on follow-up surveys, Relationships with Family & Friends score cut-points were adjusted to identify four levels with significant score differences between all levels. Panelists reached consensus for level descriptions. Score cut-points and descriptions identify different levels of social participation, providing a relevant context for interpreting LIBRE Profile numeric scores. LIBRE Profile Social Participation levels will help clinicians and persons with burn injury interpret LIBRE Profile numeric scores and promote use of this important new assessment., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Decreased range of motion is a common secondary complication of motor neuron disease (MND) that can contribute to functional decline and decreased participation in daily activities., Aim: The purpose of this study was to develop and assess the effectiveness of educational brochures and videos aimed at improving knowledge regarding the importance of a regular stretching program., Design: This was a quality improvement (QI) project., Setting: Participants were seen in an outpatient multidisciplinary neuromuscular clinic., Population: Individuals with motor neuron disease were invited to participate in this QI study., Methods: Individuals were asked to complete surveys asking questions regarding current stretching program, pain levels, and knowledge of benefits of stretching before and after receiving the stretching brochures or videos., Results: A total of 53 participants completed the pre-intervention survey, 28 in the brochure group and 25 in the video group. Of those, 86% and 88% completed the post-intervention survey in the brochure and video groups, respectively. The video group increased stretching frequency significantly more than the brochure group (2.04 and 0.62 days/week respectively, P=0.004). Significantly more participants in the video group reported usage of stretches from the educational materials on a regular basis (54% for brochure group and 86% for video group, P=0.024)., Conclusions: Educational brochures and videos are two different strategies to improve knowledge of benefits of stretching for individuals with MND. Both groups increased frequency of stretching. Videos may be better able to improve frequency of stretching when compared to brochures., Clinical Rehabilitation Impact: The brochures and videos developed for this study can be used by clinicians treating individuals with MND. By improving knowledge regarding the benefits of stretching, individuals with MND may choose to prioritize stretching as a part of their routine. This in turn may help to prevent or address potential joint or muscle length issues or assist patients to incorporate preventative measures into their treatment plans.

The present study was performed to determine neuronal loci and individual molecular mechanisms responsible for remifentanil-induced hyperalgesia. The effect of methylnaltrexone (MNX) on remifentanil-induced behavioral hyperalgesia was assessed to distinguish contributions of the peripheral and/or central nervous system to remifentanil-induced hyperalgesia. Phosphorylation of p38 mitogen-activated protein kinase (p38MAPK) in the dorsal root ganglion (DRG) neurons after remifentanil infusion, and the effect of a p38MAPK inhibitor on remifentanil-induced hyperalgesia were analyzed to investigate involvement of p38MAPK in the peripheral mechanisms of remifentanil-induced hyperalgesia. Spinal levels of prodynorphin mRNA after remifentanil infusion, and the effect of the BK2 bradykinin receptor antagonist on remifentanil-induced hyperalgesia were investigated to assess potential spinal mechanisms. The effects of MNX and BK2 antagonists on remifentanil-induced exacerbation of post-incisional hyperalgesia were also investigated using behavioral analysis. Remifentanil infusion induced hyperalgesia in the early (4 h to 2 days) and late (8-14 days) post-infusion periods. MNX inhibited hyperalgesia only during the early post-infusion period. p38MAPK phosphorylation was observed in the DRG neuron, and the p38MAPK inhibitor inhibited hyperalgesia during the early post-infusion period. Prodynorphin expression increased in the spinal cord, and a BK2 antagonist inhibited hyperalgesia during the late post-infusion period. Remifentanil-induced exacerbation of incisional hyperalgesia was inhibited by MNX and the BK2 antagonist. The present study demonstrated that remifentanil activates peripheral and spinal neurons to promote chronologically distinctive hyperalgesia. p38MAPK phosphorylation in the DRG neuron leads to peripherally-driven hyperalgesia during the early post-infusion period, while spinal dynorphin-bradykinin signaling promotes hyperalgesia during the late post-infusion period., (Copyright © 2020 IBRO. Published by Elsevier Ltd. All rights reserved.)