Validity of Actigraph for Measuring Energy Expenditure in Healthy Adults: A Systematic Review and Meta-Analysis.

PURPOSE: The objective of this systematic review and meta-analysis was to assess the validity of the Actigraph triaxial accelerometer device in measuring physical activity energy expenditure (PAEE) in healthy adults, with indirect calorimetry (IC) serving as the validity criterion. METHODS: A comprehensive search was conducted using the PubMed, Web of Science, and sportdiscuss databases, in addition to manual searches for supplementary sources. Search strategies were employed that involved conducting single keyword searches using the terms "gt3x" and "Actigraph gt3x". The literature search encompassed the timeframe spanning from 1 January 2010 to 1 March 2023. The methodological quality of the studies included in the analysis was evaluated using both the Downs and Black checklist and the Consensus-Based Criteria for Selection of Measurement Instruments (COSMIN) checklist. The meta-analysis was conducted using the Review Manager 5.4 software. The standardized mean difference (SMD) was calculated and expressed as a 95% confidence interval (CI). The significance level was set at α = 0.05. A systematic assessment of the Actigraph's performance was conducted through the descriptive analysis of computed effect sizes. RESULTS: A total of 4738 articles were retrieved from the initial search. After eliminating duplicate articles and excluding those deemed irrelevant, a comprehensive analysis was conducted on a total of 20 studies, encompassing a combined sample size of 1247 participants. The scores on the Downs and Black checklist ranged from 10 to 14, with a mean score of 11.35. The scores on the COSMIN checklist varied from 50% to 100%, with an average score of 65.83%. The meta-analysis findings revealed a small effect size (SMD = 0.01, 95% CI = 0.50-0.52, p = 0.97), indicating no statistically significant difference (p > 0.05). CONCLUSIONS: The meta-analysis revealed a small effect size when comparing the Actigraph and IC, suggesting that the Actigraph can be utilized for assessing total PAEE. Descriptive analyses have indicated that the Actigraph device has limited validity in accurately measuring energy expenditure during specific physical activities, such as high-intensity and low-intensity activities. Therefore, caution should be exercised when utilizing this device for such purposes. Furthermore, there was a significant correlation between the activity counts measured by the Actigraph and the PAEE, indicating that activity counts can be utilized as a predictive variable for PAEE.

Effect of intravenous cell therapy in rats with old myocardial infarction.

Mounting evidence shows that cell therapy provides therapeutic benefits in experimental and clinical settings of chronic heart failure. However, direct cardiac delivery of cells via transendocardial injection is logistically complex, expensive, entails risks, and is not amenable to multiple dosing. Intravenous administration would be a more convenient and clinically applicable route for cell therapy. Thus, we determined whether intravenous infusion of three widely used cell types improves left ventricular (LV) function and structure and compared their efficacy. Rats with a 30-day-old myocardial infarction (MI) received intravenous infusion of vehicle (PBS) or 1 of 3 types of cells: bone marrow mesenchymal stromal cells (MSCs), cardiac mesenchymal cells (CMCs), and c-kit-positive cardiac cells (CPCs), at a dose of 12 × 106 cells. Rats were followed for 35 days after treatment to determine LV functional status by serial echocardiography and hemodynamic studies. Blood samples were collected for Hemavet analysis to determine inflammatory cell profile. LV ejection fraction (EF) dropped ≥ 20 points in all hearts at 30 days after MI and deteriorated further at 35-day follow-up in the vehicle-treated group. In contrast, deterioration of EF was halted in rats that received MSCs and attenuated in those that received CMCs or CPCs. None of the 3 types of cells significantly altered scar size, myocardial content of collagen or CD45-positive cells, or Hemavet profile. This study demonstrates that a single intravenous administration of 3 types of cells in rats with chronic ischemic cardiomyopathy is effective in attenuating the progressive deterioration in LV function. The extent of LV functional improvement was greatest with CPCs, intermediate with CMCs, and least with MSCs.

Exercise-induced late preconditioning in mice is triggered by eNOS-dependent generation of nitric oxide and activation of PKCε and is mediated by increased iNOS activity.

The purpose of this study was to assess whether short-term, mild exercise induces protection against myocardial infarction and, if so, what role the eNOS-PKCε-iNOS axis plays. Mice were subjected to 2 bouts/day of treadmill exercise (60 min at 15 m/min) for 2 consecutive days. At 24 h after the last bout of exercise, mice were subjected to a 30-min coronary artery occlusion and 24 h of reperfusion. In the exercise group (group III, wild-type mice), infarct size (25.5 ± 8.8% of risk region) was significantly (P < 0.05) reduced compared with the control groups (sham exercise, group II [63.4 ± 7.8%] and acute myocardial infarction, group I [58.6 ± 7.0%]). This effect was abolished by pretreatment with the NOS inhibitor L-NA (group VI, 56.1 ± 16.2%) and the PKC inhibitor chelerythrine (group VIII, 57.9 ± 12.5%). Moreover, the late PC effect of exercise was completely abrogated in eNOS-/- mice (group XIII, 61.0 ± 11.2%). The myocardial phosphorylated eNOS at Ser-1177 was significantly increased at 30 min after treadmill training (exercise group) compared with sham-exercised hearts. PKCε translocation was significantly increased at 30 min after exercise in WT mice but not in eNOS-/- mice. At 24 h after exercise, iNOS protein was upregulated compared with sham-exercised hearts. The protection of late PC was abrogated in iNOS-/- mice (group XVI, 56.4 ± 12.9%) and in wildtype mice given the selective iNOS inhibitor 1400 W prior to ischemia (group X 62.0 ± 8.8% of risk region). We conclude that 1) even short, mild exercise induces a delayed PC effect that affords powerful protection against infarction; 2) this cardioprotective effect is dependent on activation of eNOS, eNOS-derived NO generation, and subsequent PKCε activation during PC; 3) the translocation of PKCε is dependent on eNOS; 4) the protection 24 h later is dependent on iNOS activity. Thus, eNOS is the trigger and iNOS the mediator of PC induced by mild exercise.

Rapid Lipid Modification of Endothelial Cell Membranes in Cardiac Ischemia/Reperfusion Injury: a Novel Therapeutic Strategy to Reduce Infarct Size.

PURPOSE: Plasma membranes constitute a gathering point for lipids and signaling proteins. Lipids are known to regulate the location and activity of signaling proteins under physiological and pathophysiological conditions. Membrane lipid therapies (MLTs) that gradually modify lipid content of plasma membranes have been developed to treat chronic disease; however, no MLTs have been developed to treat acute conditions such as reperfusion injury following myocardial infarction (MI) and percutaneous coronary intervention (PCI). A fusogenic nanoliposome (FNL) that rapidly incorporates exogenous unsaturated lipids into endothelial cell (EC) membranes was developed to attenuate reperfusion-induced protein signaling. We hypothesized that administration of intracoronary (IC) FNL-MLT interferes with EC membrane protein signaling, leading to reduced microvascular dysfunction and infarct size (IS). METHODS: Using a myocardial ischemia/reperfusion swine model, the efficacy of FNL-MLT in reducing IS following a 60-min coronary artery occlusion was tested. Animals were randomized to receive IC Ringer's lactate solution with or without 10 mg/mL/min of FNLs for 10 min prior to reperfusion (n = 6 per group). RESULTS: The IC FNL-MLT reduced IS (25.45 ± 16.4% vs. 49.7 ± 14.1%, P < 0.02) and enhanced regional myocardial blood flow (RMBF) in the ischemic zone at 15 min of reperfusion (2.13 ± 1.48 mL/min/g vs. 0.70 ± 0.43 mL/min/g, P < 0.001). The total cumulative plasma levels of the cardiac injury biomarker cardiac troponin I (cTnI) were trending downward but were not significant (999.3 ± 38.7 ng/mL vs. 1456.5 ± 64.8 ng/mL, P = 0.1867). However, plasma levels of heart-specific fatty acid binding protein (hFABP), another injury biomarker, were reduced at 2 h of reperfusion (70.3 ± 38.0 ng/mL vs. 137.3 ± 58.2 ng/mL, P = 0.0115).  CONCLUSION: The IC FNL-MLT reduced IS compared to vehicle in this swine model. The FNL-MLT maybe a promising adjuvant to PCI in the treatment of acute MI.

The Effect of Cardiogenic Factors on Cardiac Mesenchymal Cell Anti-Fibrogenic Paracrine Signaling and Therapeutic Performance.

Intrinsic cardiogenic factor expression, a proxy for cardiomyogenic lineage commitment, may be an important determinant of donor cell cardiac reparative capacity in cell therapy applications; however, whether and how this contributes to their salutary effects remain largely ambiguous. Methods: The current study examined the consequences of enhanced cardiogenic factor expression, via lentiviral delivery of GMT (GATA4, MEF2C, and TBX5), on cardiac mesenchymal cell (CMC) anti-fibrogenic paracrine signaling dynamics, in vitro, and cardiac reparative capacity, in vivo. Proteome cytokine array analyses and in vitro cardiac fibroblast activation assays were performed using conditioned medium derived from either GMT- or GFP control-transduced CMCs, to respectively assess cardiotrophic factor secretion and anti-fibrogenic paracrine signaling aptitude. Results: Relative to GFP controls, GMT CMCs exhibited enhanced secretion of cytokines implicated to function in pathways associated with matrix remodeling and collagen catabolism, and more ably impeded activated cardiac fibroblast Col1A1 synthesis in vitro. Following their delivery in a rat model of chronic ischemic cardiomyopathy, conventional echocardiography was unable to detect a therapeutic advantage with either CMC population; however, hemodynamic analyses identified a modest, yet calculable supplemental benefit in surrogate measures of global left ventricular contractility with GMT CMCs relative to GFP controls. This phenomenon was neither associated with a decrease in infarct size nor an increase in viable myocardium, but with only a marginal decrease in regional myocardial collagen deposition. Conclusion: Overall, these results suggest that CMC cardiomyogenic lineage commitment biases cardiac repair and, further, that enhanced anti-fibrogenic paracrine signaling potency may underlie, in part, their improved therapeutic utility.

Epigenetically modified cardiac mesenchymal stromal cells limit myocardial fibrosis and promote functional recovery in a model of chronic ischemic cardiomyopathy.

Preclinical investigations support the concept that donor cells more oriented towards a cardiovascular phenotype favor repair. In light of this philosophy, we previously identified HDAC1 as a mediator of cardiac mesenchymal cell (CMC) cardiomyogenic lineage commitment and paracrine signaling potency in vitro-suggesting HDAC1 as a potential therapeutically exploitable target to enhance CMC cardiac reparative capacity. In the current study, we examined the effects of pharmacologic HDAC1 inhibition, using the benzamide class 1 isoform-selective HDAC inhibitor entinostat (MS-275), on CMC cardiomyogenic lineage commitment and CMC-mediated myocardial repair in vivo. Human CMCs pre-treated with entinostat or DMSO diluent control were delivered intramyocardially in an athymic nude rat model of chronic ischemic cardiomyopathy 30 days after a reperfused myocardial infarction. Indices of cardiac function were assessed by echocardiography and left ventricular (LV) Millar conductance catheterization 35 days after treatment. Compared with naïve CMCs, entinostat-treated CMCs exhibited heightened capacity for myocyte-like differentiation in vitro and superior ability to attenuate LV remodeling and systolic dysfunction in vivo. The improvement in CMC therapeutic efficacy observed with entinostat pre-treatment was not associated with enhanced donor cell engraftment, cardiomyogenesis, or vasculogenesis, but instead with more efficient inhibition of myocardial fibrosis and greater increase in myocyte size. These results suggest that HDAC inhibition enhances the reparative capacity of CMCs, likely via a paracrine mechanism that improves ventricular compliance and contraction and augments myocyte growth and function.

Repeated Administrations of Cardiac Progenitor Cells Are Superior to a Single Administration of an Equivalent Cumulative Dose.

BACKGROUND: We have recently found that 3 repeated doses (12×106 each) of c-kitPOS cardiac progenitor cells (CPCs) were markedly more effective than a single dose of 12×106 cells in alleviating postinfarction left ventricular dysfunction and remodeling. However, since the single-dose group received only one third of the total number of CPCs given to the multiple-dose group, it is unknown whether the superior therapeutic efficacy was caused by repeated treatments per se or by administration of a higher total number of CPCs. This issue has major clinical implications because multiple cell injections in patients pose significant challenges, which would be obviated by using 1 large injection. Accordingly, we determined whether the beneficial effects of 3 repeated CPC doses can be recapitulated by 1 large dose containing the same total number of cells. METHODS AND RESULTS: Rats with a 30-day-old myocardial infarction received 3 echo-guided intraventricular infusions, 35 days apart, of vehicle-vehicle-vehicle, 36×106 CPCs-vehicle-vehicle, or 3 equal doses of 12×106 CPCs. Infusion of a single, large dose of CPCs (36×106 cells) produced an initial improvement in left ventricular function, but no further improvement was observed after the second and third infusions (both vehicle). In contrast, each of the 3 doses of CPCs (12×106) caused a progressive improvement in left ventricular function, the cumulative magnitude of which was greater than with a single dose. Unlike the single dose, repeated doses reduced collagen content and immune cell infiltration. CONCLUSIONS: Three repeated doses of CPCs are superior to 1 dose even though the total number of cells infused is the same, possibly because of greater antifibrotic and anti-inflammatory actions.

Comparison between Minimally Invasive Transforaminal Lumbar Interbody Fusion and Conventional Open Transforaminal Lumbar Interbody Fusion: An Updated Meta-analysis.

BACKGROUND: The previous studies agree that minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) has better function outcomes, less blood loss, and shorter hospital stay, when compared to open-TLIF. However, there are no significance differences on operative time, complication, and reoperation rate between the two procedures. This could be from less relative literatures and lower grade evidence. The further meta-analysis is needed with more and higher grade evidences to compare the above two TLIF procedures. METHODS: Prospective and retrospective studies that compared open-TLIF and MIS-TLIF were identified by searching the Medline, Embase, Web of Science, China National Knowledge Infrastructure, Wanfang, and VIP database (the literature search comprised Medical Subject Heading terms and key words or Emtree term). The retrieval time ranged from the date when the database was founded to January 2015. Pooled risk ratios (RR s) and weighted mean differences (WMDs) with 95% confidence intervals were calculated for the clinical outcomes and perioperative data. RESULTS: Twenty-four studies (n = 1967 patients) were included in this review (n = 951, open-TLIF, n = 1016, MIS-TLIF). MIS-TLIF was associated with a significant decrease in the visual analog score (VAS)-back pain score (WMD = -0.44; P = 0.001), Oswestry Disabilities Index (WMD = -1.57; P = 0.005), early ambulation (WMD = -1.77; P = 0.0001), less blood loss (WMD = -265.59; P < 0.00001), and a shorter hospital stay (WMD = -1.89; P < 0.0001). However, there were no significant differences in the fusion rate (RR = 0.99; P = 0.34), VAS-leg pain (WMD = -0.10; P = 0.26), complication rate (RR = 0.84; P = 0.35), operation time (WMD = -5.23; P = 0.82), or reoperation rate (RR = 0.73; P = 0.32). CONCLUSIONS: MIS-TLIF resulted in a similar fusion rate with better functional outcome, less blood loss, shorter ambulation, and hospital stay; furthermore, it did not increase the complication or reoperation rate based on the existing evidence.

Repeated Administrations of Cardiac Progenitor Cells Are Markedly More Effective Than a Single Administration: A New Paradigm in Cell Therapy.

RATIONALE: The effects of c-kit(POS) cardiac progenitor cells (CPCs, and adult cell therapy in general) on left ventricular (LV) function have been regarded as modest or inconsistent. OBJECTIVE: To determine whether 3 CPC infusions have greater efficacy than 1 infusion. METHODS AND RESULTS: Rats with a 30-day-old myocardial infarction received 1 or 3 CPC infusions into the LV cavity, 35 days apart. Compared with vehicle-treated rats, the single-dose group exhibited improved LV function after the first infusion (consisting of CPCs) but not after the second and third (vehicle). In contrast, in the multiple-dose group, regional and global LV function improved by a similar degree after each CPC infusion, resulting in greater cumulative effects. For example, the total increase in LV ejection fraction was approximately triple in the multiple-dose group versus the single-dose group (P<0.01). The multiple-dose group also exhibited more viable tissue and less scar, less collagen in the risk and noninfarcted regions, and greater myocyte density in the risk region. CONCLUSIONS: This is the first demonstration that repeated CPC administrations are markedly more effective than a single administration. The concept that the full effects of CPCs require repeated doses has significant implications for both preclinical and clinical studies; it suggests that the benefits of cell therapy may be underestimated or even overlooked if they are measured after a single dose, and that repeated administrations are necessary to evaluate the effectiveness of a cell product properly. In addition, we describe a new method that enables studies of repeated cell administrations in rodents.

Preconditioning Human Cardiac Stem Cells with an HO-1 Inducer Exerts Beneficial Effects After Cell Transplantation in the Infarcted Murine Heart.

The regenerative potential of c-kit(+) cardiac stem cells (CSCs) is severely limited by the poor survival of cells after transplantation in the infarcted heart. We have previously demonstrated that preconditioning human CSCs (hCSCs) with the heme oxygenase-1 inducer, cobalt protoporphyrin (CoPP), has significant cytoprotective effects in vitro. Here, we examined whether preconditioning hCSCs with CoPP enhances CSC survival and improves cardiac function after transplantation in a model of myocardial infarction induced by a 45-minute coronary occlusion and 35-day reperfusion in immunodeficient mice. At 30 minutes of reperfusion, CoPP-preconditioned hCSCs(GFP+), hCSCs(GFP+), or medium were injected into the border zone. Quantitative analysis with real-time qPCR for the expression of the human-specific gene HLA revealed that the number of survived hCSCs was significantly greater in the preconditioned-hCSC group at 24 hours and 7 and 35 days compared with the hCSC group. Coimmunostaining of tissue sections for both green fluorescent protein (GFP) and human nuclear antigen further confirmed greater hCSC numbers at 35 days in the preconditioned-hCSC group. At 35 days, compared with the hCSC group, the preconditioned-hCSC group exhibited increased positive and negative left ventricular (LV) dP/dt, end-systolic elastance, and anterior wall/apical strain rate (although ejection fraction was similar), reduced LV remodeling, and increased proliferation of transplanted cells and of cells apparently committed to cardiac lineage. In conclusion, CoPP-preconditioning of hCSCs enhances their survival and/or proliferation, promotes greater proliferation of cells expressing cardiac markers, and results in greater improvement in LV remodeling and in indices of cardiac function after infarction.

Observation of magnetic field effects on transient fluorescence spectra of cryptochrome 1 from homing pigeons.

Cryptochromes are suggested to be involved in the bird magnetoreception based on the radical pair mechanism (RPM), a well established theory of weak magnetic field effects on chemical reactions. Two members of cryptochrome/photolyase family were found to respond to magnetic field, however, no direct responses of bird cryptochrome to magnetic field as weak as the Earth's magnetic field have been obtained so far. In this study, we used transient fluorescence spectroscopy to characterize the weak magnetic field effects of bird cryptochromes. To do this, we cloned the cryptochrome 1 gene (clCRY1) from the retina of homing pigeons (Columba livia), expressed it in insect Sf9 cells and analyzed the transient fluorescence of purified clCRY1 by application of 45-300 µT magnetic fields. The flavin adenine dinucleotide (FADox ) and glucose oxidase (GOD) in PBS buffer were set as controls which could be excited by light to generate radicals, but would not be sensitive to magnetic field. We observed that the transient fluorescence spectra of clCRY1 were sensitive to the applied magnetic field at room temperature. Our result provides a new proof of the cryptochrome-based model of avian magnetoreception in vitro.

Complications and clinical outcomes of minimally invasive transforaminal lumbar interbody fusion for the treatment of one- or two-level degenerative disc diseases of the lumbar spine in patients older than 65 years.

BACKGROUND: Minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) has been successfully used to treat degenerative diseases of the lumbar spine. There are few reports comparing the complications and clinical outcomes in older patients who have undergone one- or two-level MIS-TLIF with those of younger patients. The aim of this study was to investigate the clinical outcomes of MIS-TLIF in the treatment of degenerative disc disease of lumbar spine of the patients older than 65 years, with an emphasis on perioperative complications compared to the younger patients. METHODS: One hundred and fifty-one consecutive cases of one- or two-level degenerative disc disease of lumbar spine treated with MIS-TLIF were reviewed for the radiological and clinical outcomes. They were divided into elderly group (age ≥ 65 years old) and younger group (age < 65 years old), and were followed for at least 6 months. Radiographs were obtained before and after surgery, 3 months postoperatively, and at the final follow-up to determine the presence of fusion, hardware-related problems. The clinical outcomes were evaluated using the Oswestry Disability Index (ODI) before and after surgery, and at the final follow-up. The visual analogue scale (VAS) score of back and leg pain were evaluated as well. The intra-operative data and peri-operative complications were recorded. RESULTS: The mean age of these patients at operation was (57.7 ± 14.2) years (range 26 - 82 years). Of 151 patients, 62 were 65 years or older. The elderly patients had more comorbidities and more porportion of lumbar canal stenosis. The overall fusion rate was 88.4% at the final follow-up, with no significant difference between younger and elderly patients. The ODI, the VAS of back pain and radicular pain of both young and elderly group were significantly improved after surgery and at the final follow-up, without significant difference between two groups. There were 16 complications with an incidence of 10.6%, including 7 major complications and 9 minor complications. There was no significant difference of the incidence of complications between two groups. The incidence of dura tear was significantly related to bilateral deompression. CONCLUSIONS: The clinical and radiological outcomes of MIS-TLIF in the treatment of one- or two-level degenerative disc diseases of lumbar spine in the elderly patients were satisfactory. Though there are more pre-operative comorbidities, with proper patient selection, the elderly patients are not at increased risk of perioperative complications compared to younger patients. Screw malposition and dura tear, which are the most frequent complications, were more related to the surgical technique and should be avoided.

Genetic background, gender, age, body temperature, and arterial blood pH have a major impact on myocardial infarct size in the mouse and need to be carefully measured and/or taken into account: results of a comprehensive analysis of determinants of infarct size in 1,074 mice.

In order to determine whether the myocardial response to ischemia/reperfusion (I/R) injury varies depending on genetic background, gender, age, body temperature, and arterial blood pH, we studied 1,074 mice from 19 strains (including 129S6/SvEvTac (129S6), B6/129P2-Ptgs2(tm1Unc), B6/129SvF(2)/J, B6/129/D2, B6/CBAF1, B6/DBA/1JNcr, BALB/c, BPH2/J, C57BL/6/J (B6/J), C3H/DBA, C3H/FB/FF, C3H/HeJ-Pde6b(rd1), FVB/N/J [FVB/N], FVB/B6, FVB/ICR and Crl:ICR/H [ICR]) and distributed them into 69 groups depending on strain and: (1) two phases of ischemic preconditioning (PC); (2) coronary artery occlusion (O) time; (3) gender; (4) age; (5) blood transfusion; (6) core body temperature; and (7) arterial blood pH. Mice underwent O either without (non-preconditioned [naive]) or with prior cyclic O/reperfusion (R) (PC stimulus) consisting of six 4-min O/4-min R cycles 10 min (early PC, EPC) or 24 h (late PC, LPC) prior to 30 or 45-min O and 24 h R. In B6/J and B6/129/D2 mice, almost the entire risk region was infarcted after a 60-min O. Of the naive mouse hearts, B6/ecSOD(WT) and FVB/N mice had infarct sizes significantly smaller than those of the other mice. All strains except FVB/N benefited from the cardioprotection afforded by the early phase of PC; in contrast, development of LPC was inconsistent amongst groups and was strain-dependent. Female gender (1) was associated with reduced infarct size in ICR mice, (2) determined whether LPC developed in ICR mice, and (3) limited the protection afforded by EPC in 129S6 mice. Importantly, mild hypothermia (1 °C decrease in core temperature) and mild acidosis (0.18 decrease in blood pH) resulted in a striking cardioprotective effect in ICR mice: 67.5 and 43.0 % decrease in infarct size, respectively. Replacing blood losses with crystalloid fluids (instead of blood) during surgery also reduced infarct size. To our knowledge, this is the largest analysis of the determinants of infarct size in mice ever published. The results demonstrate that genetic background, gender, age (but not in ICR), body temperature and arterial blood pH have a major impact on infarct size, and thus need to be carefully measured and/or taken into account when designing a study of myocardial infarction in mice; failure to do so makes results uninterpretable. For example, core temperature and blood pH need to be measured, respiratory acidosis (or alkalosis) and hypothermia (or hyperthermia) must be avoided, and comparisons cannot be made between mouse strains or genders that exhibit different susceptibility to I/R injury (e.g., FVB/N male mice and ICR female mice are inherently protected against I/R injury).

The COX-2/PGI2 receptor axis plays an obligatory role in mediating the cardioprotection conferred by the late phase of ischemic preconditioning.

BACKGROUND: Pharmacologic studies with cyclooxygenase-2 (COX-2) inhibitors suggest that the late phase of ischemic preconditioning (PC) is mediated by COX-2. However, nonspecific effects of COX-2 inhibitors cannot be ruled out, and the selectivity of these inhibitors for COX-2 vs. COX-1 is only relative. Furthermore, the specific prostaglandin (PG) receptors responsible for the salubrious actions of COX-2-derived prostanoids remain unclear. OBJECTIVE: To determine the role of COX-2 and prostacyclin receptor (IP) in late PC by gene deletion. METHODS: COX-2 knockout (KO) mice (COX-2(-/-)), prostacyclin receptor KO (IP(-/-)) mice, and respective wildtype (WT, COX-2(+/+) and IP(+/+)) mice underwent sham surgery or PC with six 4-min coronary occlusion (O)/4-min R cycles 24 h before a 30-min O/24 h R. RESULTS: There were no significant differences in infarct size (IS) between non-preconditioned (non-PC) COX-2(+/+), COX-2(-/-), IP(+/+), and IP(-/-) mice, indicating that neither COX-2 nor IP modulates IS in the absence of PC. When COX-2(-/-) or IP(-/-) mice were preconditioned, IS was not reduced, indicating that the protection of late PC was completely abrogated by deletion of either the COX-2 or the IP gene. Administration of the IP selective antagonist, RO3244794 to C57BL6/J (B6) mice 30 min prior to the 30-min O had no effect on IS. When B6 mice were preconditioned 24 h prior to the 30-min O, IS was markedly reduced; however, the protection of late PC was completely abrogated by pretreatment of RO3244794. CONCLUSIONS: This is the first study to demonstrate that targeted disruption of the COX-2 gene completely abrogates the infarct-sparing effect of late PC, and that the IP, downstream of the COX-2/prostanoid pathway, is a key mediator of the late PC. These results provide unequivocal molecular genetic evidence for an essential role of the COX-2/PGI2 receptor axis in the cardioprotection afforded by the late PC.

Cage subsidence does not, but cervical lordosis improvement does affect the long-term results of anterior cervical fusion with stand-alone cage for degenerative cervical disc disease: a retrospective study.

OBJECTIVE: Clinical outcomes of the stand-alone cage have been encouraging when used in anterior cervical discectomy and fusion (ACDF), but concerns remain regarding its complications, especially cage subsidence. This retrospective study was undertaken to investigate the long-term radiological and clinical outcomes of the stand-alone titanium cage and to evaluate the incidence of cage subsidence in relation to the clinical outcome in the surgical treatment of degenerative cervical disc disease. METHODS: A total of 57 consecutive patients (68 levels) who underwent ACDF using a titanium box cage for the treatment of cervical radiculopathy and/or myelopathy were reviewed for the radiological and clinical outcomes. They were followed for at least 5 years. Radiographs were obtained before and after surgery, 3 months postoperatively, and at the final follow-up to determine the presence of fusion and cage subsidence. The Cobb angle of C2-C7 and the vertebral bodies adjacent to the treated disc were measured to evaluate the cervical sagittal alignment and local lordosis. The disc height was measured as well. The clinical outcomes were evaluated using the Japanese Orthopaedic Association (JOA) score for cervical myelopathy, before and after surgery, and at the final follow-up. The recovery rate of JOA score was also calculated. The Visual Analogue Scale (VAS) score of neck and radicular pain were evaluated as well. The fusion rate was 95.6% (65/68) 3 months after surgery. RESULTS: Successful bone fusion was achieved in all patients at the final follow-up. Cage subsidence occurred in 13 cages (19.1%) at 3-month follow-up; however, there was no relation between fusion and cage subsidence. Cervical and local lordosis improved after surgery, with the improvement preserved at the final follow-up. The preoperative disc height of both subsidence and non-subsidence patients was similar; however, postoperative posterior disc height (PDH) of subsidence group was significantly greater than of non-subsidence group. Significant improvement of the JOA score was noted immediately after surgery and at the final follow-up. There was no significant difference of the recovery rate of JOA score between subsidence and non-subsidence groups. The recovery rate of JOA score was significantly related to the improvement of the C2-C7 Cobb angle. The VAS score regarding neck and radicular pain was significantly improved after surgery and at the final follow-up. There was no significant difference of the neck and radicular pain between both subsidence and non-subsidence groups. CONCLUSIONS: The results suggest that the clinical and radiological outcomes of the stand-alone titanium box cage for the surgical treatment of one- or two-level degenerative cervical disc disease are satisfactory. Cage subsidence does not exert significant impact upon the long-term clinical outcome although it is common for the stand-alone cages. The cervical lordosis may be more important for the long-term clinical outcome than cage subsidence.

[The evaluation of posterior ligament complex injury as well as the analysis of its effects in thoracic-lumbar fractures].

OBJECTIVES: To evaluate and analyze the role of posterior ligament complex (PLC) in determining therapeutic principle for traumatic thoracic-lumbar fracture. METHODS: From August 2005 to May 2008, 60 patients (38 male, 22 female) who suffered from the traumatic thoracic-lumbar fracture were carried out posterior operations. According to the Magerl traumatic thoracic-lumbar fracture classification system, these cases were classified to subtype A, B and C. The average age was 34 years (21 - 65 years). Magnetic resonance imaging (MRI) scan, which including both T1/T2 weight and fat-stir sequence, as well as the MRI negative film reading technique were used to evaluate the state of PLC. Furthermore, related physical or neurological examinations (such as severe skin bruising and sinking, broadening spinous process gap and tenderness, spinal cord or nerve root injury) and another X-ray or CT reconstruction films were taken to evaluate the the state of PLC synthetically. Above-mentioned results were compared with the final exploration results during operation and some parameters were analyzed. RESULTS: The sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), misdiagnosis rate and rate of missed diagnosis of these sixty patients were 85.3%, 80.8%, 83.3%, 85.3%, 80.8%, 19.2%, 14.7% respectively. After 13 cases of thoracic-lumbar fracture-dislocation were eliminated, the sensitivity, specificity, accuracy, PPV, NPV, misdiagnosis rate and rate of missed diagnosis of remaining 47 cases were 81.0%, 80.8%, 80.9%, 77.3%, 84.0%, 19.2%, 19.0% respectively. There were 5 cases with MRI negative results before operation but positive results during operation. Contrarily, 5 cases with MRI positive results before operation but negative results during operation occurred. CONCLUSIONS: MRI is a main means for evaluating the state of PLC. Although the MRI fat-stir sequence as well as the MRI negative film reading technique are adopted, the state of PLC can not be estimated exactly before operation (especially for those unfracture dislocation cases). In order to estimate the state of PLC exactly, the related local physical examination and image technology as well as the location of the abnormal image signal in MRI film and time of injury must be analyzed synthetically.

[Design of plant leaf bionic camouflage materials based on spectral analysis].

The influence of structure parameters and contents of plant leaves on their reflectance spectra was analyzed using the PROSPECT model. The result showed that the bionic camouflage materials should be provided with coarse surface and spongy inner structure, the refractive index of main content must be close to that of plant leaves, the contents of materials should contain chlorophyll and water, and the content of C-H bond must be strictly controlled. Based on the analysis above, a novel camouflage material, which was constituted by coarse transparent waterproof surface, chlorophyll, water and spongy material, was designed. The result of verifiable experiment showed that the reflectance spectra of camouflage material exhibited the same characteristics as those of plant leaves. The similarity coefficient of reflectance spectrum of the camouflage material and camphor leaves was 0.988 1, and the characteristics of camouflage material did not change after sunlight treatment for three months. The bionic camouflage material, who exhibited a high spectral similarity with plant leaves and a good weather resistance, will be an available method for reconnaissance of hyperspectral imaging hopefully.

Gene transfer as a strategy to achieve permanent cardioprotection I: rAAV-mediated gene therapy with inducible nitric oxide synthase limits infarct size 1 year later without adverse functional consequences.

The ultimate goal of prophylactic gene therapy is to confer permanent protection against ischemia. Although gene therapy with inducible nitric oxide synthase (iNOS) is known to protect against myocardial infarction at 3 days and up to 2 months, the long-term effects on myocardial ischemic injury and function are unknown. To address this issue, we created a recombinant adeno-associated viral vector carrying the iNOS gene (rAAV/iNOS), which enables long-lasting transgene expression. The ability of rAAV/iNOS to direct the expression of functional iNOS protein was confirmed in COS-7 cells before in vivo gene transfer. Mice received injections in the anterior LV wall of rAAV/LacZ or rAAV/iNOS; 1 year later, they underwent a 30-min coronary occlusion (O) and 4 h of reperfusion (R). iNOS gene transfer resulted in elevated iNOS protein expression (+3-fold vs. the LacZ group, n = 6; P < 0.05) and iNOS activity (+4.4-fold vs. the LacZ group, n = 6; P < 0.05) 1 year later. Infarct size (% of risk region) was dramatically reduced at 1 year after iNOS gene transfer (13.5 ± 2.2%, n = 12, vs. 41.7 ± 2.9%, n = 10, in the LacZ group; P < 0.05). The infarct-sparing effect of iNOS gene therapy at 1 year was as powerful as that observed 24 h after ischemic preconditioning (six 4-min O/4-min R cycles) (19.3 ± 2.3%, n = 11; P < 0.05). Importantly, compared with the LacZ group (n = 11), iNOS gene transfer (n = 10) had no effect on LV dimensions or function for up to 1 year (at 1 year: FS 34.5 ± 2.0 vs. 34.6 ± 2.6%, EF 57.0 ± 2.0 vs. 59.7 ± 2.9%, LVEDD 4.3 ± 0.1 vs. 4.2 ± 0.2 mm, LVESD 2.8 ± 0.1 vs. 2.9 ± 0.2 mm) (echocardiography). These data demonstrate, for the first time, that rAAV-mediated iNOS gene transfer affords long-term, probably permanent (1 year), cardioprotection without adverse functional consequences, providing a strong rationale for further preclinical testing of prophylactic gene therapy.

Gene transfer as a strategy to achieve permanent cardioprotection II: rAAV-mediated gene therapy with heme oxygenase-1 limits infarct size 1 year later without adverse functional consequences.

Extensive evidence indicates that heme oxygenase-1 (HO-1) exerts potent cytoprotective effects in response to stress. Previous studies have shown that gene therapy with HO-1 protects against myocardial ischemia/reperfusion injury for up to 8 weeks after gene transfer. However, the long-term effects of HO-1 gene therapy on myocardial ischemic injury and function are unknown. To address this issue, we created a recombinant adeno-associated viral vector carrying the HO-1 gene (rAAV/HO-1) that enables long-lasting transgene expression. Mice received injections in the anterior LV wall of rAAV/LacZ (LacZ group) or rAAV/HO-1 (HO-1 group); 1 year later, they were subjected to a 30-min coronary occlusion (O) and 4 h of reperfusion (R). Cardiac HO-1 gene expression was confirmed at 1 month and 1 year after gene transfer by immunoblotting and immunohistochemistry analyses. In the HO-1 group, infarct size (% of risk region) was dramatically reduced at 1 year after gene transfer (11.2 ± 2.1%, n = 12, vs. 44.7 ± 3.6%, n = 8, in the LacZ group; P < 0.05). The infarct-sparing effects of HO-1 gene therapy at 1 year were as powerful as those observed 24 h after ischemic PC (six 4-min O/4-min R cycles) (15.0 ± 1.7%, n = 10). There were no appreciable changes in LV fractional shortening, LV ejection fraction, or LV end-diastolic or end-systolic diameter at 1 year after HO-1 gene transfer as compared to the age-matched controls or with the LacZ group. Histology showed no inflammation in the myocardium 1 year after rAAV/HO-1-mediated gene transfer. These results demonstrate, for the first time, that rAAV-mediated HO-1 gene transfer confers long-term (1 year), possibly permanent, cardioprotection without adverse functional consequences, providing proof of principle for the concept of achieving prophylactic cardioprotection (i.e., "immunization against infarction").

Intracoronary administration of cardiac stem cells in mice: a new, improved technique for cell therapy in murine models.

A model of intracoronary stem cell delivery that enables transgenesis/gene targeting would be a powerful tool but is still lacking. To address this gap, we compared intracoronary and intramyocardial delivery of lin(-)/c-kit(+)/GFP(+) cardiac stem cells (CSCs) in a murine model of reperfused myocardial infarction (MI). Lin(-)/c-kit(+)/GFP(+) CSCs were successfully expanded from GFP transgenic hearts and cultured with no detectable phenotypic change for up to ten passages. Intracoronary delivery of CSCs 2 days post-MI resulted in significant alleviation of adverse LV remodeling and dysfunction, which was at least equivalent, if not superior, to that achieved with intramyocardial delivery. Compared with intramyocardial injection, intracoronary infusion was associated with a more homogeneous distribution of CSCs in the infarcted region and a greater increase in viable tissue in this region, suggesting greater formation of new cardiomyocytes. Intracoronary CSC delivery resulted in improved function in the infarcted region, as well as in improved global LV systolic and diastolic function, and in decreased LV dilation and LV expansion index; the magnitude of these effects was similar to that observed after intramyocardial injection. We conclude that, in the murine model of reperfused MI, intracoronary CSC infusion is at least as effective as intramyocardial injection in limiting LV remodeling and improving both regional and global LV function. The intracoronary route appears to be superior in terms of uniformity of cell distribution, myocyte regeneration, and amount of viable tissue in the risk region. To our knowledge, this is the first study to report that intracoronary infusion of stem cells in mice is feasible and effective.