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Competing Interests: Declaration of competing interest The authors declare that they have no competing interest and that no financial support was received for the publication of this article.

Competing Interests: Disclosures The authors have no relevant conflicts to declare.

Background: Cardiac implantable electronic device (CIED) procedures can cause significant postoperative pain. Opioid use for postoperative pain is associated with risk of persistent use. The benefits of pectoral nerve (PECs) blocks have been established for other chest wall surgeries, but adoption in electrophysiology has been limited., Objectives: The purpose of this study was to evaluate the efficacy of intraoperative ultrasound-guided PECs blocks performed at the time of CIED procedures by the implanting physician from within the device pocket., Methods: Patients undergoing a pectoral CIED procedure at 7 centers from 2022-2023 were included. Patients underwent intraoperative PECs blocks and subcutaneous local anesthetic vs subcutaneous local anesthetic only at the discretion of the operator. Patients were prospectively evaluated for postoperative pain., Results: Six hundred ten patients (age 67 ± 15 years old; 63% male) were enrolled. and half (n = 305) underwent PECs block. Patients who underwent PECs block were more likely to have a history of chronic pain (32% vs 11%, P <.001). PECs block was associated with lower pain scores in the 4 hours after the procedure (1.5 ± 2.1 vs 4.5 ± 2.5, P <.001). Pain scores were not different after 24 hours (2.8 ± 1.7 vs 3.1 ± 2.2) and 2 weeks (0.9 ± 1.4 vs 0.9 ± 1.2). PECs block patients were less likely to receive inpatient opioids (10% vs 48%, P <.001) and to be discharged with an opioid prescription (15% vs 59%, P <.001). In multivariable linear regression, PECs block (P <.001), age (P = .002), and absence of chronic pain (P = .009) were associated with lower acute postoperative pain., Conclusion: Intraoperative PECs block can reduce postoperative pain and opioid use. This procedure can be readily performed by the implanting physician from within the device pocket., Competing Interests: Disclosures The authors have no conflicts of interest to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Microplastics have emerged as significant and concerning pollutants within soil ecosystems. Among the soil biota, entomopathogenic nematodes (EPNs) are lethal parasites of arthropods, and are considered among the most effective biological agents against pests. Infective juveniles (IJs) of EPNs, as they navigate the soil matrix scavenging for arthropod hosts to infect, they could potentially encounter microplastics. Howver, the impact of microplastics on EPNs has not been fully elucidated yet. We addressed this gap by subjecting Steinernema feltiae EPNs to polystyrene microplastics (PS-MPs) with various sizes, concentrations, and exposure durations. After confirming PS-MP ingestion by S. feltiae using fluorescent dyes, we found that the PS-MPs reduced the survival, reproduction, and pathogenicity of the tested EPNs, with effects intensifying for smaller PS-MPs (0.1-1 μm) at higher concentrations (10 5 μg/L). Furthermore, exposure to PS-MPs triggered oxidative stress in S. feltiae, leading to increased reactive oxygen species levels, compromised mitochondrial membrane potential, and increased antioxidative enzyme activity. Furthermore, transcriptome analyses revealed PS-MP-induced suppression of mitochondrial function and oxidative phosphorylation pathways. In conclusion, we show that ingestion of PS-MPs by EPNs can compromise their fitness, due to multple toxicity effects. Our results bear far-reaching consequences, as the presence of microplastics in soil ecosystems could undermine the ecological role of EPNs in regulating pest populations., 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.)

Low bone density, fragility, and microarchitectural disintegration are the symptoms of osteoporosis. An imbalance between bone growth and resorption can lead to osteoporosis. This study evaluated the effects of amino-calcium (AC) on bone protection in ovariectomized control group (NC) rats. Amino-calcium (AC) was characterized using Fourier-transform infrared spectroscopy (FT-IR), energy-dispersive X-ray spectroscopy (EDS), and nuclear magnetic resonance spectroscopy analyses (NMR). After determining the biocompatibility of amino-calcium (AC) with MC3T3-E1 cells, alkaline phosphatase staining revealed significant changes on day 7. Three of the four groups underwent ovariectomy, whereas one group received a placebo. On micro-computed tomography, in vivo, data showed increased bone volume fraction in the femoral head and shaft areas in the amino-calcium (AC) group. Hematoxylin and eosin staining showed a bone mass and architectural protection in the amino-calcium (AC) group compared with the calcium carbonate and OVX control group. RNA sequencing analysis revealed high expression of osteogenesis-related genes in MC3T3-E1 cells. RNA sequencing revealed a significant fold change in the expression of integrin-binding sialoprotein (IBSP), bone gamma-carboxyglutamate proteins 1 and 2(BGLAP1 and BGLAP2), and periostin (POSTN). The study concluded that supplementing the OVX rats with calcium enhanced bone protection., 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 © 2023 Elsevier Inc. All rights reserved.)

Purpose: Emerging data suggest that higher radiation doses in post-mastectomy radiotherapy may be associated with an increased risk of reconstruction complications. This study aimed to validate previous findings regarding the impact of radiation dose on complications among women with breast cancer using a multi-center dataset., Methods: Fifteen institutions participated, and women with breast cancer who received radiotherapy after either autologous or prosthetic breast reconstruction were included. The primary endpoint was major post-radiation therapy complications requiring re-operation for explantation, flap failure, or bleeding control., Results: In total, 314 patients were included. Radiotherapy was performed using both conventional fractionation and hypofractionation in various schedules. The range of the radiation therapy dose in Equivalent Dose in 2 Gy fractions (EQD2; α/β = 3.5) varied from 43.4 to 71.0 Gy (median dose: 48.6 Gy). Boost radiation therapy was administered to 49 patients. Major post-radiation therapy complications were observed in 24 (7.6%) patients. In multivariate analysis, an increasing EQD2 per Gy (odds ratio [OR]: 1.58, 95% confidence interval [CI]: 1.26-1.98; p < 0.001), current smoking status (OR: 25.48, 95% CI: 1.56-415.65; p = 0.023), and prosthetic breast reconstruction (OR: 9.28, 95% CI: 1.84-46.70; p = 0.007) were independently associated with an increased risk of major complications., Conclusion: A dose-response relationship between radiation dose and the risk of complications was validated in this multi-center dataset. In this context, we hypothesize that the use of hypofractionated radiotherapy (40 Gy in 15 fractions) may improve breast reconstruction outcomes. Our multi-center prospective observational study (NCT03523078) is underway to further validate this hypothesis., Competing Interests: Declaration of competing interest None., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

A hallmark of the initiation step of HIV-1 reverse transcription, in which viral RNA genome is converted into double-stranded DNA, is that it is slow and non-processive. Biochemical studies have identified specific sites along the viral RNA genomic template in which reverse transcriptase (RT) stalls. These stalling points, which occur after the addition of three and five template dNTPs, may serve as checkpoints to regulate the precise timing of HIV-1 reverse transcription following viral entry. Structural studies of reverse transcriptase initiation complexes (RTICs) have revealed unique conformations that may explain the slow rate of incorporation; however, questions remain about the temporal evolution of the complex and features that contribute to strong pausing during initiation. Here we present cryo-electron microscopy and single-molecule characterization of an RTIC after three rounds of dNTP incorporation (+3), the first major pausing point during reverse transcription initiation. Cryo-electron microscopy structures of a +3 extended RTIC reveal conformational heterogeneity within the RTIC core. Three distinct conformations were identified, two of which adopt unique, likely off-pathway, intermediates in the canonical polymerization cycle. Single-molecule Förster resonance energy transfer experiments confirm that the +3 RTIC is more structurally dynamic than earlier-stage RTICs. These alternative conformations were selectively disrupted through structure-guided point mutations to shift single-molecule Förster resonance energy transfer populations back toward the on-pathway conformation. Our results support the hypothesis that conformational heterogeneity within the HIV-1 RTIC during pausing serves as an additional means of regulating HIV-1 replication., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The Y-box binding protein-1 (YB-1) is a transcription/translation regulatory protein, and the expression thereof is associated with cancer aggressiveness. In the present study, we explored the regulatory effects of YB-1 during the transforming growth factor-β1 (TGF-β1)-induced epithelial-to-mesenchymal transition (EMT) in lung adenocarcinoma cells. Downregulation of YB-1 increased E-cadherin promoter activity, and upregulation of YB-1 decreased promoter activity, suggesting that the YB-1 level may be correlated with the EMT. TGF-β1 induced YB-1 expression, and TGF-β1 translocated cytosolic YB-1 into the nucleus. YB-1 overexpression promoted TGF-β1-induced downregulation of epithelial markers, upregulation of mesenchymal markers, and cell migration. Moreover, YB-1 overexpression enhanced the expression of E-cadherin transcriptional repressors via TGF-β1-induced Akt activation. Our findings afford new insights into the role played by YB-1 in the TGF-β1 signaling pathway., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The aims of this study were to determine (1) the pathogenesis of experimental infection with a Korean type 1 porcine reproductive and respiratory syndrome virus (PRRSV) by defining the viral distribution and the sites of viral replication and (2) the relationship between viral replication and apoptosis in stillborn fetuses and live born piglets from infected pregnant gilts. At 3 weeks ante partum, four pregnant gilts were inoculated intranasally with Korean type 1 PRRSV. Stillborn fetuses from the infected gilts were of crown-to-rump length 25.8-27.1 cm consistent with fetal death between 106 and 110 days of gestation. Type 1 PRRSV was isolated from the fetal tissues and these isolates were shown to be identical to the challenge virus by sequence analysis. Type 1 PRRSV RNA was detected in the lung, lymph node, heart, tonsil, thymus, liver, adrenal gland and spleen of live born piglets and stillborn fetuses from the infected gilts. The mean number of apoptotic cells per unit area of lung (P = 0.003), heart (P = 0.011), thymus (P = 0.003), liver (P = 0.011) and spleen (P = 0.002) was significantly higher in stillborn fetuses than in live born piglets. Dual labelling showed that the majority of cells either contained type 1 PRRSV or were apoptotic, but not both. Apoptotic cells were more numerous than PRRSV(+) cells. The results of the study demonstrated that type 1 PRRSV induces reproductive failure in pregnant gilts. Apoptosis induced by type 1 PRRSV may be associated with the incidence of stillborn fetuses in PRRSV-infected pregnant gilts., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Hydrogen peroxide (H(2)O(2)) regulates the structure and function of 2-Cys peroxiredoxins (Prxs). Upon oxidation by excess H(2)O(2), Prxs become overoxidized to a sulfinic acid of its peroxidatic cysteine residue, resulting in a structural change from a small oligomer with peroxidase function to a large oligomer with chaperone function. Then, sulfiredoxin (Srx) reduces the overoxidized Prxs by an ATP-dependent mechanism. Although Srx is known to repair the overoxidized forms of Prx, the role of Srx in the reversal of Prx oligomerization remains to be elucidated. Here we investigated whether Srx1 directly facilitates the dissociation of yeast Prx1 (YPrx1) from a high-molecular-weight (HMW) complex to a low-molecular-weight (LMW) complex in vitro. Srx1 reactivates the YPrx1 peroxidase activity that is inactivated by H(2)O(2), whereas it decreases the chaperone activity enhanced by H(2)O(2). We show that Srx1 dissociates the H(2)O(2)-induced HMW YPrx1 complex, and that the Srx1 Cys84 residue is critical for its dissociation. In contrast to wild-type Srx1, an inactive Srx1 mutant (Srx1-C84S) did not induce the reactivation of inactivated YPrx1 or dissociation of the HMW YPrx1 complex. We revealed that Srx1 interacts directly with YPrx1 in yeast cells using bimolecular fluorescence complementation. Taken together, these findings suggest that Srx1 regulates YPrx1 function and structure in yeast cells through a direct interaction., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Human peroxiredoxin 1 (hPrx1), a member of the peroxiredoxin family, detoxifies peroxide substrates and has been implicated in numerous biological processes, including cell growth, proliferation, differentiation, apoptosis, and redox signaling. To date, Prx1 has not been implicated in RNA metabolism. Here, we investigated the ability of hPrx1 to bind RNA and act as an RNA chaperone. In vitro, hPrx1 bound to RNA and DNA, and unwound nucleic acid duplexes. hPrx1 also acted as a transcription anti-terminator in an assay using an Escherichia coli strain containing a stem-loop structure upstream of the chloramphenicol resistance gene. The overall cellular level of hPrx1 expression was not increased at low temperatures, but the nuclear level of hPrx1 was increased. In addition, hPrx1 overexpression enhanced the survival of cells exposed to cold stress, whereas hPrx1 knockdown significantly reduced cell survival under the same conditions. These findings suggest that hPrx1 may perform biological functions as a RNA-binding protein, which are distinctive from known functions of hPrx1 as a reactive oxygen species scavenger., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The epithelial-to-mesenchymal transition (EMT), which is induced by transforming growth factor-β1 (TGF-β1), is an important event that allows cancer cells to obtain invasive and metastatic characteristics. Although human peroxiredoxin 1 (hPrx1) has been implicated in tumor progression (e.g., invasion and metastasis), little is known about the role of hPrx1 in the EMT process during tumorigenesis. Here, we investigated the regulatory effect of hPrx1 during TGF-β1-induced EMT in A549 lung adenocarcinoma cells. We observed that high hPrx1 levels downregulated E-cadherin expression, and low hPrx1 levels upregulated E-cadherin expression, suggesting that the hPrx1 level may be correlated with EMT. Knockdown of hPrx1 significantly inhibited TGF-β1-induced EMT and cell migration, whereas hPrx1 overexpression enhanced TGF-β1-induced EMT and cell migration. In contrast to wild-type hPrx1, a peroxidase-inactive hPrx1 mutant (hPrx1-C51S) resulted in markedly increased E-cadherin expression. Moreover, hPrx1 regulated the expression of two E-cadherin transcriptional repressors, Snail and Slug. These findings provide new insight into the role of hPrx1 in regulating TGF-β1-induced EMT., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Favorable outcomes after liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) are well described for patients who fall within defined tumor criteria. The effectiveness of tumor therapies to maintain tumor characteristics within these criteria or to downstage more advanced tumors to fall within these criteria is not well understood. The aim of this study was to examine the response to transcatheter arterial chemoinfusion (TACI) in HCC patients awaiting LT and its efficacy for downstaging or bridging to transplantation. We performed a retrospective study of 248 consecutive TACI cases in 122 HCC patients at a single U.S. medical center. Patients were divided into two groups: those who met the Milan criteria on initial HCC diagnosis (n = 95) and those with more advanced disease (n = 27). With TACI treatment, 87% of the Milan criteria group remained within the Milan criteria and 63% of patients with more advanced disease were successfully downstaged to fall within the Milan criteria. In conclusion, TACI appears to be an effective treatment as a bridge to LT for nearly 90% patients presenting within the Milan criteria and an effective downstaging modality for over half of those whose tumor burden was initially beyond the Milan criteria.

SIRPalpha and SIRPbeta1, the two major isoforms of the signal regulatory protein (SIRP) family, are co-expressed in human leukocytes but mediate distinct extracellular binding interactions and divergent cell signaling responses. Previous studies have demonstrated that binding of SIRPalpha with CD47, another important cell surface molecule, through the extracellular IgV domain regulates important leukocyte functions including macrophage recognition, leukocyte adhesion and transmigration. Although SIRPbeta1 shares highly homologous extracellular IgV structure with SIRPalpha, it does not bind to CD47. Here, we defined key amino acid residues exclusively expressing in the IgV domain of SIRPalpha, but not SIRPbeta1, which determine the extracellular binding interaction of SIRPalpha to CD47. These key residues include Gln67, a small hydrophobic amino acid (Ala or Val) at the 57th position and Met102. We found that Gln67 and Ala/Val57 are critical. Mutation of either of these residues abates SIRPalpha directly binding to CD47. Functional cell adhesion and leukocyte transmigration assays further demonstrated central roles of Gln67 and Ala/Val57 in SIRPalpha extracellular binding mediated cell interactions and cell migration. Another SIRPalpha-specific residue, Met102, appears to assist SIRPalpha IgV binding through Gln67 and Ala/Val57. An essential role of these amino acid residues in SIRPalpha binding to CD47 was further confirmed by introducing these residues into the SIRPbeta1 IgV domain, which dramatically converts SIRPbeta1 into a CD47-binding molecule. Our results thus revealed the molecular basis by which SIRPalpha binds to CD47 and shed new light into the structural mechanisms of SIRP isoform mediated distinctive extracellular interactions and cellular responses.

This study estimated the burden of premature death due to smoking in Korea between 1990 and 1999 using the years of life lost (YLL) due to premature death method. To implement this study, age-group-specific YLL due to premature death were calculated by employing the standard expected years of life lost method. YLL due to smoking were calculated based on assumptions and methods developed by the Global Burden of Disease Study Group. The burden of premature death due to smoking was estimated by multiplying the population attributable risk by the YLL of smoking-related diseases. In 1999, the burden of premature death due to smoking was 57.7% in males and 11.4% in females in Korea. The burden of premature death due to smoking increased from 1643 person years per 100,000 in 1990 to 1888 person years in 1999 for males, and increased from 151 person years in 1990 to 225 person years in 1999 for females in Korea. Our results suggest that the method employed in this study, generated in quantified terms, enabled the burden of premature death due to smoking to be obtained comparably with methods used by other international studies in this field, and thus can provide a rational basis for national health policy planning regarding premature death from smoking and the related risk factors in Korea.

Free flaps are frequently used to reconstruct the defect following radical resection of pharyngoesophageal malignancy but postoperative monitoring of buried flaps is difficult. We have designed a monitoring-muscle flap using the short head of the biceps femoris muscle when using a free lateral thigh flap. The third and fourth perforators of the profunda femoris artery, the main vascular pedicle of the lateral thigh flap, pass through the short head of the biceps femoris. Partial excision of the short head of the biceps femoris muscle does not result in any functional disturbance of the leg, and the viability of the buried lateral thigh flap can be monitored by observing the exposed muscle through a small window in the neck. Between April and October 1998 five patients underwent pharyngoesophageal reconstruction by this method. The short head of the biceps femoris was used to monitor the main flap in three patients and to obliterate the dead space after neck dissection in two patients. There were no recipient-site complications such as fistula or infection and no disturbance of thigh function., (Copyright 2001 The British Association of Plastic Surgeons.)

Heat shock exposure to NIH3T3 cells for 15 min at 45 degrees C activated Akt, which is mediated by PI3-kinase, as evidenced by the significant inhibition of heat-shock-induced phosphorylation by specific inhibitors of PI3-kinase. The phosphorylated Akt was gradually decreased to the basal level within 9 h after heat shock. This resulted in growth arrest, but cell growth could be recovered within 24 h accompanied with a high rate of proliferation. However, heat shock for 60 min failed to activate Akt, resulting in apoptosis. The recovery of cell growth after heat-shock-inducing activation of Akt was completely blocked by wortmannin. Moreover, overexpression of a dominant-negative Akt mutant significantly inhibited the apoptosis-suppressive effect of heat shock, indicating the direct involvement of heat-shock-induced Akt activation in the apoptosis suppression. The results indicate that a signal transduction pathway, namely, PI3-kinase/Akt, may contribute to an apoptosis-suppressive function after heat shock in NIH3T3 cells., (Copyright 2000 Academic Press.)

Using 31phosphorus magnetic resonance spectroscopy (31P-MRS) and surface coils, we noninvasively assessed the intracellular changes in delayed skin flaps of the high-energy phosphometabolites, ATP and phosphocreatine, which are basic energy sources of living cells. In 5 rats, a 3.5 x 7.5 cm bipedicled skin flap was elevated from the dorsum and its caudal base divided after a delay period of 2 weeks. MRS spectra were collected at four times: immediately, 1 week and 2 weeks after elevation of the bipedicled flap, and 18 hours after division of its caudal base. From the spectra, we calculated the intracellular pH and the following ratios: Pi/PCr, PCr/(PCr + Pi), ATP/(PCr + Pi) (PCr, phosphocreatine; Pi, inorganic phosphate; ATP, adenosine triphosphate). As an undelayed control group, cranially based skin flaps of the same size were elevated in another 5 rats, and MRS spectra were obtained 18 hours later. The length of the surviving area was longer in the delayed flaps than in the undelayed flaps. Intracellular pH and ATP/(PCr + Pi) showed no significant alteration in the delayed skin flaps, not only during the delay period but also after conversion of the flaps into cranially based flaps by division of their caudal base. In contrast, PCr/(PCr + Pi) decreased with each surgical procedure (bipedicled flap elevation and base division). Compared with the necrotic distal portion of the undelayed flaps, the surviving distal portion of the delayed flaps had higher levels of intracellular pH and ATP/(PCr + Pi) and lower levels of PCr/(PCr + Pi). Intracellular pH and ATP/(PCr + Pi) showed a strong correlation with the viability of the delayed and undelayed skin flaps, and they can be prognostic indices for predicting the fate of skin flaps. The reason the surviving distal portions of the delayed flaps maintained their level of ATP despite the low intracellular level of PCr may be that the accumulation of mitochondrial creatine kinase enhances the so-called 'energy transport' function of the creatine kinase/phosphocreatine system.

We have developed a model of endotoxemic acute renal failure in the anesthetized male rat in which acute endotoxin infusion induces renal vasoconstriction and decreased glomerular filtration rate (GFR) in the absence of systemic hypotension. Because increased levels of platelet activating factor (PAF) have been observed in experimental models of endotoxemia, we pretreated rats with PAF receptor antagonist BN 52021 or SRI 63-675 before administering endotoxin. Compared with treatment with vehicle, treatment with BN 52021 led to significant preservation of RBF, GFR, and urine flow rate. Pretreatment with SRI 63-675 resulted in significant improvement in RBF while completely preventing the fall in GFR and urine flow rate. Intrarenal artery infusion of exogenous PAF (30 ng/kg/min) resulted in renal vasoconstriction, decreased GFR, and oliguria. These effects were also prevented by pretreatment with SRI 63-675. Thus, the adverse renal hemodynamic effects of endotoxemia were blunted or prevented by pretreatment with PAF receptor antagonists. We conclude that endogenously produced PAF is an important mediator of endotoxemic acute renal failure.

Pulmonary vascular impedance is a measure of the pulsatile characteristic of pressure and flow that occurs in the proximal pulmonary arteries. Pulmonary vascular resistance (PVR) is most influenced by the distal circulation of the lung. This study was performed to evaluate the changes that occurred in pulmonary vascular impedance, as well as in other hemodynamic variables, following pneumonectomy by a closed-chest method in 10 anesthetized dogs. The following observations were made (numbers compare mean values for the 10 dogs before and after pneumonectomy): (1) PVR increased from 447 to 761 dyne sec cm-5 (p = .02); (2) the oscillatory work of the right ventricle increased from 1.23 to 1.76 J/min (p = .006); (3) the mean pulmonary artery pressure increased from 14 to 18.8 mm Hg (p = .0001); and (4) cardiac output and heart rate remained unchanged. Surprisingly, the estimated characteristic impedance (the impedance to oscillatory flow in the proximal bed) did not change significantly (279 to 296 dyne sec cm-5). This observation cannot be explained by the usual lumped compartmental models classically used to characterize the pulmonary vascular bed.