Performance of Intra-arrest Echocardiography: A Systematic Review.

Introduction: Intra-arrest transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) have been introduced in adult patients with cardiac arrest (CA). Whether the diagnostic performance of TTE or TEE is superior during resuscitation is unclear. We conducted a systematic review following PRISMA guidelines. Methods: We searched databases from PubMed, Embase, and Google Scholar and evaluated articles with intra-arrest TTE and TEE in adult patients with non-traumatic CA. Two authors independently screened and selected articles for inclusion; they then dual-extracted study characteristics and target conditions (pericardial effusion, aortic dissection, pulmonary embolism, myocardial infarction, hypovolemia, left ventricular dysfunction, and sonographic cardiac activity). We performed quality assessment using the Quality Assessment of Diagnostic Accuracy Studies Version 2 criteria. Results: A total of 27 studies were included: 14 studies with 2,145 patients assessed TTE; and 16 with 556 patients assessed TEE. A high risk of bias or applicability concerns in at least one domain was present in 20 studies (74%). Both TTE and TEE found positive findings in nearly one-half of the patients. The etiology of CA was identified in 13% (271/2,145), and intervention was performed in 38% (102/271) of patients in the TTE group. In patients who received TEE, the etiology was identified in 43% (239/556), and intervention was performed in 28% (68/239). In the TEE group, a higher incidence regarding the etiology of CA was observed, particularly for those with aortic dissection. However, the outcome of those with aortic dissection in the TEE group was poor. Conclusion: While TEE could identify more causes of CA than TTE, sonographic cardiac activity was reported much more in the TTE group. The impact of TTE and TEE on the return of spontaneous circulation and further survival was still inconclusive in the current dataset.

Projected Time for the Elimination of Cervical Cancer Under Various Intervention Scenarios: Age-Period-Cohort Macrosimulation Study.

BACKGROUND: The World Health Organization aims for the global elimination of cervical cancer, necessitating modeling studies to forecast long-term outcomes. OBJECTIVE: This paper introduces a macrosimulation framework using age-period-cohort modeling and population attributable fractions to predict the timeline for eliminating cervical cancer in Taiwan. METHODS: Data for cervical cancer cases from 1997 to 2016 were obtained from the Taiwan Cancer Registry. Future incidence rates under the current approach and various intervention strategies, such as scaled-up screening (cytology based or human papillomavirus [HPV] based) and HPV vaccination, were projected. RESULTS: Our projections indicate that Taiwan could eliminate cervical cancer by 2050 with either 70% compliance in cytology-based or HPV-based screening or 90% HPV vaccination coverage. The years projected for elimination are 2047 and 2035 for cytology-based and HPV-based screening, respectively; 2050 for vaccination alone; and 2038 and 2033 for combined screening and vaccination approaches. CONCLUSIONS: The age-period-cohort macrosimulation framework offers a valuable policy analysis tool for cervical cancer control. Our findings can inform strategies in other high-incidence countries, serving as a benchmark for global efforts to eliminate the disease.

Global Prevalence of Helicobacter pylori Infection and Incidence of Gastric Cancer Between 1980 and 2022.

BACKGROUND & AIMS: We aimed to assess the secular trend of the global prevalence of Helicobacter pylori (H pylori) infection in adults and children/adolescents and to show its relation to that of gastric cancer incidence. METHODS: We performed a systematic review and meta-analysis to calculate overall prevalence, adjusted by multivariate meta-regression analysis. The incidence rates of gastric cancer were derived from the Global Burden of Disease Study and Cancer Incidence in Five Continents. RESULTS: Of the 16,976 articles screened, 1748 articles from 111 countries were eligible for analysis. The crude global prevalence of H pylori has reduced from 52.6% (95% confidence interval [CI], 49.6%-55.6%) before 1990 to 43.9% (95% CI, 42.3%-45.5%) in adults during 2015 through 2022, but was as still as high as 35.1% (95% CI, 30.5%-40.1%) in children and adolescents during 2015 through 2022. Secular trend and multivariate regression analyses showed that the global prevalence of H pylori has declined by 15.9% (95% CI, -20.5% to -11.3%) over the last 3 decades in adults, but not in children and adolescents. Significant reduction of H pylori prevalence was observed in adults in the Western Pacific, Southeast Asian, and African regions. However, H pylori prevalence was not significantly reduced in children and adolescents in any World Health Organization regions. The incidence of gastric cancer has decreased globally and in various countries where the prevalence of H pylori infection has declined. CONCLUSIONS: The global prevalence of H pylori infection has declined during the last 3 decades in adults, but not in children and adolescents. The results raised the hypothesis that the public health drive to reduce the prevalence of H pylori as a strategy to reduce the incidence of gastric cancer in the population should be confirmed in large-scale clinical trials.

Urban-Rural Disparity in Birth Cohort Effects on Breast Cancer Incidence.

Breast cancer is the most commonly diagnosed cancer among women worldwide. Studies have reported minimal birth cohort effects on the incidence rates of breast cancer in Western countries but have reported notable birth cohort effects in some Asian countries. The risks of breast cancer may also vary within a country. In the present study, we abstracted female invasive breast cancer data from the Taiwan Cancer Registry for the period 1997-2016. We used the age-period-cohort model to compare birth cohort effects on breast cancer incidence rates between urban and rural regions in Taiwan. We identified a notable urban-rural disparity in birth cohort effects on breast cancer incidence rates in women in Taiwan. The incidence rates in the urban regions were higher than those in the rural regions across all cohorts. However, the incidence rates rose faster in the rural regions than in the urban regions across the cohorts. The risks of breast cancer observed for women born in 1992 were approximately 22 and 11 times than those observed for women born in 1917 in rural and urban regions, respectively. The observed gap in breast cancer incidence rates between the urban and rural regions gradually disappeared across the cohorts. Accordingly, we speculate that urbanization and westernization in Taiwan may be the drivers of female breast cancer incidence rates across birth cohorts.

Birth Cohort Effects in Breast Cancer Incidence: Global Patterns and Trends.

Breast cancer is the most common neoplasm in the world among women. The age-specific incidences and onset ages vary widely between Asian and Western countries/regions. Invasive breast cancer cases among women from 1997 to 2011 were abstracted from the International Agency for Research on Cancer and the Taiwan Cancer Registry. Age-period-cohort analysis was performed to examine the trends. The cohort effect was prominent in South Korea, Taiwan, Japan, and Thailand, possibly related to the timing of westernization. The risk of breast cancer initially rose with the birth cohorts in Hong Kong and India (both former British colonies), peaked, and then declined in recent birth cohorts. Unlike other Asian countries/regions, virtually no birth cohort effect was identified in the Philippines (a Spanish colony in 1565 and the first Asian country to adopt Western cultural aspects). Moreover, an at-most negligible birth cohort effect was identified for all ethnic groups (including Asian immigrants) in the United States. This global study identified birth cohort effects in most Asian countries/regions but virtually no impact in Western countries/regions. The timing of westernization was associated with the birth cohort effect.

Forecast of a future leveling of the incidence trends of female breast cancer in Taiwan: an age-period-cohort analysis.

Breast cancer is the most common cancer among women in Taiwan. The age-standardized incidence rate has doubled in just 20 years, causing considerable concern to health professionals and the general public. This study used an ensemble of age-period-cohort models to estimate breast cancer incidence trends in Taiwan from 1997 to 2016 and project trends up to 2035. The (truncated) world standard population (World Health Organization 2000) proportions (age groups: 25-29, 30-34, …, 80-84, and older than 85 years) were used to calculate age-standardized incidence rates. The age-standardized incidence rate from 1997 (60.33/100,000 population) to 2016 (128.20/100,000 population) increased rapidly. The projection is that the increase in the age-standardized incidence will subsequently slow and exhibit a plateau in 2031 (151.32/100,000 population). From 2026 to 2035, the age-specific incidence rates for women older than 55 years old (postmenopausal breast cancer) are projected to increase with larger percentage increments for older women. A future leveling of female breast cancer incidence trends in Taiwan is anticipated. The majority of the patients with breast cancer in the future will be women aged 55 years and older. Education on lifestyle recommendations and mammography screening is required to reduce the burden of breast cancer. The results should have implications for other countries which are also confronted with the same public health problem of rapidly increasing breast cancer incidences.

Reliability of Gradient-Echo Magnetic Resonance Elastography of Lumbar Muscles: Phantom and Clinical Studies.

Magnetic resonance elastography (MRE) has been used to successfully characterize the mechanical behavior of healthy and diseased muscles, but no study has been performed to investigate the reliability of MRE on lumbar muscles. The objective of this work was to determine the reliability of MRE techniques on lumbar muscles in both ex vivo phantom and in vivo human studies. In this study, fresh porcine leg muscles were used in the phantom study, and 80 healthy adults (38.6 ± 11.2 years, 40 women) were recruited in the human study. Five repeated stiffness maps were obtained from both the phantom and human muscles by using a gradient-echo MRE sequence with a pneumatic vibration on a 1.5 T MR scanner. The technical failure rate, coefficient of variation (CV), and quality score were assessed to evaluate the reliability of MRE, respectively. Analysis of variance was performed to compare the stiffness between different lumbar muscles, and the difference was significant if p < 0.05 after Bonferroni correction. The results showed that the MRE achieved a zero technical failure rate and a low CV of stiffness (6.24 ± 1.41%) in the phantom muscles. However, in the human study, the MRE exhibited high CVs of stiffness (21.57%−25.24%) in the lumbar muscles, and the technical failure rate was higher in psoas muscles (60.0−66.3% in) than in paraspinal muscles (0.0−2.5%). Further, higher quality scores were noticed in paraspinal muscles (7.31−7.71) than those in psoas muscles (1.83−2.06). In conclusion, the MRE was a reliable technique to investigate the mechanical property of lumbar muscles, but it was less reliable to assess stiffness in psoas muscles than paraspinal muscles.

Fabrication and characterization of lignin-xylan hybrid nanospheres as pesticide carriers with enzyme-mediated release property.

Lignin nanospheres (LNPs) are an emerging high-value material platform to realize lignin valorization. The modification or introduction of new functions to LNPs is of great significance to expand its downstream applications. This work evaluated the technical feasibility of preparing lignin-xylan hybrid nanospheres (LXNPs) through a simple solution-based self-assembly process, with the goal of achieving the application as pesticide carriers for enzyme-mediated controlled release. Hybrid LXNPs with various weigh ratios (lignin to xylan, 3 : 1, 1 : 1, 1 : 3) were obtained using deep eutectic solvent-extracted condensed lignin and water-insoluble xylan fragments, which exhibited a nanosphere size of about 166-210 nm with considerable stability in the pH range of 4-10. LXNPs with lignin to xylan ratios of 3 : 1 and 1 : 1 showed well-defined core-shell structures with enriched hydroxyl groups on the surface. It was proposed that lignin could anchor xylan fragments through van der Waals force and hydrophobic interactions between lignin phenylpropanes and xylan molecular backbones, thus facilitating the self-assembly process for the formation of this specific spherical structure. The resulting hydrophobic LXNPs core enabled the facile encapsulation of the biological pesticide avermectin (AVM) with 57.9-67.0% efficiency using one-pot synthesis. When these AVM-encapsulated LXNPs were subjected to enzymatic hydrolysis using xylanase, considerable AVM release of 44.8-55.1% was achieved after 16 h, in comparison to the 4.1% release only for those without xylanase. This work showed the high promise of fabricating hybrid LXNPs through the self-assembly process and also provided a universal nanosphere carrier for drug encapsulation and subsequent enzyme-mediated controlled release.

Distinctive incidence patterns of follicular lymphoma in Taiwan: Implications of ethnic differences.

BACKGROUND: Follicular lymphoma (FL) is less prevalent in Asians, but detailed epidemiological analyses were not available. This study aimed to characterize the epidemiologic features of FL in Taiwan to explore the factors relevant to disease development and prognosis. METHODS: We obtained epidemiological data for Taiwanese citizens during 1990-2012 from Taiwan's National Cancer Registry Database, and the corresponding data for US Caucasians from the Surveillance, Epidemiology, and End Results Program. Changes in incidence rates were evaluated with age-period-cohort (APC) analyses. Patient outcomes were compared with 5-year relative survival rates (RS) estimates. RESULTS: Incidence rates of FL in Taiwan increased continuously during the study period (0.34 to 0.91 per 100 000 person-year from 1993-1997 to 2008-2012 in men, and from 0.29 [1993-1997] to 0.81 [2008-2012] in women), while rates in the US remained stable in both sexes, ranging between 3.73 and 3.96 in men and between 3.24 and 3.55 in women. Estimates of average annual percentage changes in incidence were significantly positive in Taiwan, but not in US Caucasians. Notably, the APC analysis identified a strong birth-cohort effect in Taiwan, corresponding to environmental alterations present during the study period. The estimated 5-year RS rates in both populations showed steady improvement, but the RS in Taiwanese patients was consistently 10% lower than in US Caucasians. CONCLUSION: A distinct increasing trend of incidence with a strong birth-cohort effect was identified in Taiwan, providing evidence of the association between environmental factors and disease development.

Sexual and bladder dysfunction in male ketamine abusers: A large-scale questionnaire study.

PURPOSE: To evaluate the prevalence of lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) in the illicit male ketamine abusers (KA). MATERIALS AND METHODS: The male street KAs caught by policemen and patients visiting urologic clinics were invited to answer a structured questionnaire including demographic data, illicit drug use related details (duration, frequency, dosage and abstinence status), international prostate symptoms score (IPSS), interstitial cystitis symptoms and problem index (ICSI and ICPI) and International index of erectile function (IIEF-5). Erectile dysfunction was defined as IIEF-5 ≦21. RESULTS: Finally, we included 1056 participants (993 street, 63 hospital KAs) with a mean age of 27.4 ±6.2 years. ED presented in 30.8% of all KAs. and Hospital KAs were more subject to having ED than street KAs (69.6% vs. 28.0%, p<0.01). Multi-variate analysis revealed that risk factor for male ED were age ≧30 years (OR = 1.765). Subgroup analysis on male street KAs disclosed that abstinence ≧3 months is a protective factor for ED. Lower urinary tract symptoms (ICSI+ICPI ≧12) was prevalent in KAs and multivariate analysis disclosed that significant risk factors for LUTS (ICSI+ICPI ≧12) were age ≧30 years, duration ≧24 months and co-use of other illicit drugs. CONCLUSIONS: Male ED and LUTS were frequently observed in the ketamine abusers. We suggested that street ketamine abuse should be considered in young men presented with ED and LUTS in the clinics.

Essential role of amino acid position 71 in substrate preference by meso-diaminopimelate dehydrogenase from Symbiobacterium thermophilum IAM14863.

meso--Diaminopimelate dehydrogenase (meso-DAPDH) catalyzes the reversible oxidative deamination of the d-configuration of meso-2,6-diaminopimelate (meso-DAP) and is thought to have substrate specificity toward meso-DAP. The discovery of the meso-DAPDH from Symbiobacterium thermophilum IAM14863 (StDAPDH) revealed meso-DAPDH members with broad substrate specificity. In order to elucidate the substrate-preference mechanism of StDAPDH, it is necessary to identify the key residues related to this mechanism. Our previous work suggested that the non-active-site R71 of StDAPDH was related to substrate preference. Here, we report the key roles of the non-active site on the catalysis of StDAPDH. In order to explore the mechanism through which non-active-site R71 only affected the amination activity of StDAPDH, we performed molecular dynamic simulations and investigated the functional role of R71 in the type II meso-DAPDH StDAPDH. Site-directed mutagenesis with the allelic site A69 of CgDAPDH as a target proved that when replaced by Arg at position 71 of StDAPDH, the CgA69R mutant showed higher catalytic efficiencies toward a series of 2-keto acids, ranging from 1.2- to 1.5-fold. These findings provide some guidelines for improving our understanding of the broad substrate specificity of StDAPDH.

A population-based case-control study of hospitalisation due to head injuries among bicyclists and motorcyclists in Taiwan.

INTRODUCTION: According to official statistics in Taiwan, the main body region of injury causing bicyclist deaths is the head, and bicyclists are 2.6 times more likely to be fatally injured than motorcyclists. There is currently a national helmet law for motorcyclists but not for bicyclists. OBJECTIVES: The primary aim of this study was to determine whether bicyclist casualties have higher odds of head-related hospitalisation than motorcyclists. This study also aims to investigate the determinants of head injury-related hospitalisation among bicyclists and motorcyclists. METHODS: Using linked data from the National Traffic Accident Dataset and the National Health Insurance Research Database for the period 2003-2012, this study investigates the crash characteristics of bicyclist and motorcyclist casualties presenting to hospitals due to motor vehicle crashes. Head injury-related hospitalisation was used as the study outcome for both road users to evaluate whether various factors (eg, human attributes, road and weather conditions, vehicle characteristics) are related to hospital admission of those who sustained serious injuries. RESULTS: Among 1 239 474 bicyclist and motorcyclist casualties, the proportion of bicyclists hospitalised for head injuries was higher than that of motorcyclists (10.0% vs 6.5%). However, the multiple logistic regression model shows that, after adjustment of this result for other factors such as helmet use, bicyclists were 18% significantly less likely to be hospitalised for head injuries than motorcyclists (AOR 0.82, 95% CI 0.79 to 0.85). Other important determinants of head injury-related hospitalisation for bicyclists and motorcyclists include female riders, elderly riders, crashes occurring in rural areas, moped riders, riding unhelmeted, intoxicated bicyclists and motorcyclists, unlicensed motorcyclists, dusk and dawn conditions and single-vehicle crashes. CONCLUSIONS: Our finding underscores the importance of helmet use in reducing hospitalisation due to head injuries among bicyclists while current helmet use is relatively low.

[Effect of Dangua Recipe on Hepatic Adiponectin Receptor 2 Expression in Diabetic Apolipoprotein E Knockout Mice].

Objective To observe the effect of Dangua Recipe (DR) on adiponectin receptor 2 (AdipoR2) expression in liver of apolipoprotein E knockout (ApoE⁻¹â») diabetic mice. Methods Eight- week-old ApoE⁻¹â» mice were randomly divided into the model control group, the DR group, the pioglitazone group, and the combined treatment group. Besides, a C57 group was set up consisting of same age C57BL/ 6J mice. Streptozotocin (STZ) was injected to ApoE⁻¹â» mice in the four groups to induce diabetic model, and they were intervened by corresponding drugs. After 12 weeks the effect of DF on glucose-lipid metabolism was observed. mRNA and protein expressions of AdipoR2 in liver were detected. Histomorphological changes of the liver were observed by hematoxylineosin ( HE) staining, red Ο fat dyeing, and Masson staining, respectively. Results Contents of fasting blood glucose (FBG) , total cholesterol (TC) , and low-density lipoprotein cholesterol (LDL-C) were reduced more significantly in the DR group than in the model group. DR could promote liver expression of AdipoR2 mRNA and protein expressions in ApoE⁻¹â» mice, which was significantly higher than that of the model group (P <0. 01) , and better than that of pioglitazone (P <0. 05, P <0. 01). DR could improve ectopic fat deposition and fibrosis of liver cells in diabet- ic ApoE⁻¹â» mice significantly, which was better than that of the pioglitazone group and the combined treatment group. Conclusion DR could significantly improve liver lipid metabolism , and reduce liver fat deposition and fibrosis, which might possibly be associated with promoting AdipoR2 expression in liver.

[Effect of dangua recipe on glycolipid metabolism and VCAM-1 and its mRNA expression level in Apo E(-/-) mice with diabetes mellitus].

OBJECTIVE: To study the effect of Dangua Recipe (DGR) on glycolipid metabolism, vascular cell adhesion molecule-1 (VCAM-1) and its mRNA expression level of transgenic Apo E(-/-) mouse with spontaneous atherosclerosis, thus revealing its partial mechanism for curing diabetes mellitus (DM) with angiopathy. METHODS: Diabetic model was prepared by peritoneally injecting streptozotocin (STZ) to Apo E(-/-) mouse. Totally 32 modeled mice were stratified by body weight, and then divided into 4 groups referring to blood glucose levels from low to high by random digit table, i.e., the model group (MOD, fed with sterile water, at the daily dose of 15 mL/kg), the DGR group (fed with DGR at the daily dose of 15 mL/kg), the combination group (COM, fed with DGR at the daily dose of 15 mL/kg and pioglitazone at the daily dose of 4.3 mg/kg), and the pioglitazone group (PIO, at the daily dose of 4.3 mg/kg), 8 in each group. Another 8 normal glucose C57 mouse of the same age and strain were recruited as the control group. All interventions lasted for 12 weeks by gastrogavage. The fasting blood glucose (FBG), body weight, food intake, water intake, skin temperature, the length of tail, and the degree of fatty liver were monitored. The hemoglobin A1c (HbA1c), total cholesterol (TC), and LDL-C were determined. Endothelin-1 (ET-1) was determined by radioimmunoassay. Nitrogen monoxidum (NO) was determined by nitrate reductase. The kidney tissue VCAM-1 level was analyzed with ELISA. The expression of VCAM-1 mRNA in the kidney tissue was detected with real time quantitative PCR. RESULTS: Compared with the control group, the body weight and food intake decreased, water intake increased in all the other model groups (P < 0.05). Besides, the curve of blood glucose was higher in all the other model groups than in the control group (P < 0.01). Compared with the model group, the body weight increased; levels of HbAlc, TC, LDL-C, ET-1, and VCAM-1 were significantly lower; and skin temperature was higher in the DGR group (P < 0.05, P < 0.01). Compared with the PIO group, body weight, the increment of body weight, FBG, TC, and LDL-C were lower (P < 0.05, P < 0.01); food intake and water intake increased more and the tail length was longer in the DRG group (P < 0.01). There was no statistical difference in the level of NO among groups. The degree of fatty liver in the model group was significantly severer than that in the control group (P < 0.05). It was obviously alleviated in the DGR group (P < 0.05) when compared with the model group and the PIO group (P < 0.05, P < 0.01). But it was severer in the PIO group than in the model group (P < 0.01). The degree of fatty liver in the combination group ranged between that of the DGR group and the PIO group (P < 0.05). The level of VCAM-1 mRNA expression was significantly lower in the DGR group than in the model group, the PIO group, and the combination group (P < 0.05). CONCLUSIONS: DGR had effect in lowering blood glucose and blood lipids, and fighting against fatty liver of transgenic Apo E(-/-) mouse with spontaneous atherosclerosis. DGR played an effective role in preventing and treating DM with angiopathy by comprehensively regulating glycolipid metabolism and promoting the vascular function.

Zoledronic acid infusion for lumbar interbody fusion in osteoporosis.

BACKGROUND: Clinical outcomes of intravenous (IV) infusion of zoledronic acid (ZOL) for lumbar interbody fusion surgery (LIFS) remain unknown. We investigated the efficacy of IV ZOL on clinical outcome and bone fusion after LIFS. MATERIALS AND METHODS: We retrospectively analyzed 64 patients with both degenerative lumbar spondylolisthesis and osteoporosis who underwent LIFS from January 2007 to April 2010. All patients were followed up for 2 y. Thirty-two were treated with an IV infusion of ZOL 3 d after surgery and a second injection 1 y later, and the other 32 patients did not receive ZOL. Preoperatively and every 3 mo postoperatively, oswestry disability index questionnaire and visual analog scale (VAS) scores for back and leg were compared. Preoperative and final postoperative follow-up to evaluate for subsequent compression fractures were also performed. Pedicle screw loosening, cage subsidence, and fusion rate were documented 2 y after surgery. RESULTS: At 2-y follow-up, a solid fusion was achieved in 75% of the ZOL group and only 56% of the control group. At final follow up, the incidence of final subsequent vertebral compression fractures (19% of the ZOL group and 51% of the control group, P = 0.006), pedicle screw loosening (18% of the ZOL group and 45% of the control group, P = 0.03), and cage subsidence >2 mm (28% of the ZOL group and only 54% of the control group, P = 0.04) were significantly lower in the ZOL group than in the control group. The ZOL group demonstrated improvement in VAS (for leg pain VAS, 2/10 for the ZOL group and 5/10 for the control group; for back pain VAS, 2/10 for the ZOL group and 6/10 for the control group) and oswestry disability index scores (7/25 for the ZOL group and 16/25 for the control group). CONCLUSIONS: ZOL treatment has beneficial effects on instrumented LIFS both radiographic and clinically. Thus, ZOL treatment can be recommended for osteoporosis patients undergoing LIFS.

Gene transfer of the S24F regulated on activation normal T-cell expressed and secreted-chemokine ligand 5 variant attenuates cardiac allograft rejection.

BACKGROUND: Regulated on activation normal T-cell expressed and secreted (RANTES)-chemokine ligand 5 plays a key role in mediating heart transplant rejection. Suppression of RANTES-mediated signals can reduce leukocyte recruitment and mitigate transplant rejection severity. The present study describes the construction of an adenovirus overexpression vector encoding a natural S24F RANTES variant as a means of reducing leukocyte recruitment, resulting in the prevention of allograft rejection. METHODS: The in vitro transendothelial chemotaxis assay was used to compare RANTES-induced transmigration of peripheral blood mononuclear cells across human umbilical vein endothelial cells cultured on the upper Transwell chamber. Intracoronary delivery of Ad-S24F, Ad-Null, or phosphate-buffered saline was performed in BALB/c donor hearts that were transplanted into the abdominal cavity of C57BL/6 recipients as a measure of allograft survival. Intragraft inflammatory cell infiltrates and associated proinflammatory cytokine expression profiles were detected by immunohistochemistry and quantitative real-time polymerase chain reaction on day 6 after transplantation, respectively. RESULTS: Regulated on activation normal T-cell expressed and secreted-induced peripheral blood mononuclear cell transendothelial chemotaxis is inhibited by S24F (Ad-S24F, 9.2%±0.02%; Ad-Null, 17.7%±0.02%; medium control, 15.1%±0.01%; P<0.05). Cardiac allograft survival was prolonged after delivery of 1×10 plaque-forming units of Ad-S24F (13.00±0.33 days compared with 9.38±0.60 and 9.00±0.38 days after Ad-Null or phosphate-buffered saline treatment, respectively, P<0.05). S24F gene transfer reduced the number of intragraft CD8 T lymphocytes, monocyte-macrophages, and T-cell receptor αß cell infiltrates (P<0.05) and decreased transcripts for RANTES and interferon-γ (P<0.05). CONCLUSION: S24F is an important component of the chemokine network involved in regulating the biologic activity of RANTES, and its expression can be used in the prevention and treatment of cardiac allograft rejection.

Organic/Metallic nanohybrids based on amphiphilic dumbbell-shaped dendrimers.

In this study, we synthesized a series of amphiphilic dumbbell-shaped dendrimers through the addition reactions of a hydrophilic poly(oxyalkylene) with hydrophobic dendrons based on 4-isocyanate-4'-(3,3-dimethyl-2,4-dioxo-azetidine)diphenylmethane with different numbers of branching generations. The addition reaction of azetidine-2,4-diones of dendrons to amines of poly(oxyalkylene) was proceeded by stirring the reactants in dry tetrahydrofuran (THF) under nitrogen at 60 °C. In aqueous media, the dumbbell-shaped dendrimers self-assembled into micelles with their hydrophobic dendrons in the core and their hydrophilic poly(oxyalkylene) segments forming loops in the corona shell. Employing the unique self-assembled micelle structures as templates for subsequent chemical reduction of the Ag(+) ions, we generated new types of organic/metallic [silver nanoparticle (AgNP)] nanohybrid clusters. The long poly(oxyalkylene) loops that extended into the aqueous phase complexed with the Ag(+) ions, providing the suspension with steric stabilization to prevent the AgNPs from collision and flocculation. After reduction, the AgNPs were present in a homogeneous distribution in the round dendrimer micelle-stabilized nanoclusters. The diameter of each AgNP was less than 10 nm; the diameter of each round nanocluster was in the range of 50-200 nm. The encapsulation efficiency of the AgNPs in micelles was about 54-69% for the dumbbell-shaped dendrimer based organic/AgNP nanohybrid.