C-kit-derived CD11b+ cells are critical for cardiac allograft prolongation by autologous C-kit+ progenitor cells.

Autologous C-kit+ cells robustly prolong cardiac allografts. As C-kit+ cells can transdifferentiate to hematopoietic cells as well as non-hematopoietic cells, we aimed to clarify the class(es) of C-kit-derived cell(s) required for cardiac allograft prolongation. Autologous C-kit+ cells were administered post-cardiac transplantation and allografts were evaluated for C-kit+ inoculum-derived cells. Results suggested that alloimmunity was a major signal for trafficking of C-kit-derived cells to the allograft and demonstrated that C-kit+ inoculum-derived cells expressed CD11b early after transfer. Allograft survival studies with CD11b-DTR C-kit+ cells demonstrated a requirement for C-kit+-derived CD11b+ cells. Co-therapy studies demonstrated near complete abrogation of acute rejection with concomitant CTLA4-Ig therapy and no loss of prolongation in combination with Cyclosporine A. These results strongly implicate a C-kit-derived myeloid population as critical for allograft preservation and demonstrate the potential therapeutic application of autologous C-kit+ progenitor cells as calcineurin inhibitor-sparing agents and possibly as co-therapeutics for durable graft survival.

Lack of the P2X7 receptor protects against AMD-like defects and microparticle accumulation in a chronic oxidative stress-induced mouse model of AMD.

The P2X7 receptor (P2X7R) is an ATP-gated ion channel that is a key player in oxidative stress under pathological conditions. The P2X7R is expressed in the retinal pigmented epithelium (RPE) and neural retina. Chronic oxidative stress contributes to the pathogenesis of age-related macular degeneration (AMD). Mice lacking Cu, Zn superoxide dismutase (Sod1) developed chronic oxidative stress as well as AMD-like features, but whether the P2X7R plays a causative role in oxidative stress-induced AMD is unknown. Thus, the main purpose of this study was to test if concurrent knockout (KO) of P2X7R could block AMD-like defects seen in Sod1 KO mice. Using multiple approaches, we demonstrate that Sod1 KO causes AMD-like defects, including positive staining for oxidative stress markers, 3-nitrotyrosine and carboxymethyl lysine, thinning of the RPE and retina, thickening of Bruch's membrane, presence of basal laminar and linear deposits, RPE barrier disruption and accumulation of microglia/macrophages. Moreover, we find that Sod1 KO mice accumulate more microparticles (MPs) within RPE/choroid tissues. Concurrent KO of the P2X7R protects against AMD-like defects and MP accumulation in Sod1 KO mice. Together, we show for the first time, that deficiency of P2X7R prevents in vivo oxidative stress-induced accumulation of MPs and AMD-like defects. This work could potentially lead to novel therapies for AMD and other oxidative stress-driven diseases.

Interferon Gamma and Contact-dependent Cytotoxicity Are Each Rate Limiting for Natural Killer Cell-Mediated Antibody-dependent Chronic Rejection.

Natural killer (NK) cells are key components of the innate immune system. In murine cardiac transplant models, donor-specific antibodies (DSA), in concert with NK cells, are sufficient to inflict chronic allograft vasculopathy independently of T and B cells. In this study, we aimed to determine the effector mechanism(s) required by NK cells to trigger chronic allograft vasculopathy during antibody-mediated rejection. Specifically, we tested the relative contribution of the proinflammatory cytokine interferon gamma (IFN-γ) versus the contact-dependent cytotoxic mediators of perforin and the CD95/CD95L (Fas/Fas ligand [FasL]) pathway for triggering these lesions. C3H/HeJ cardiac allografts were transplanted into immune-deficient C57BL/6 rag-/- γc-/- recipients, who also received monoclonal anti-major histocompatibility complex (MHC) class I DSA. The combination of DSA and wild-type NK cell transfer triggered aggressive chronic allograft vasculopathy. However, transfer of IFN-γ-deficient NK cells or host IFN-γ neutralization led to amelioration of these lesions. Use of either perforin-deficient NK cells or CD95 (Fas)-deficient donors alone did not alter development of vasculopathy, but simultaneous disruption of NK cell-derived perforin and allograft Fas expression resulted in prevention of these abnormalities. Therefore, both NK cell IFN-γ production and contact-dependent cytotoxic activity are rate-limiting effector pathways that contribute to this form of antibody-induced chronic allograft vasculopathy.

Clarifying the mechanism of effect of the Bionator for treatment of maxillary protrusion: A percentile growth study.

AIM: The reported effects of Bionator treatment in patients with mandibular retrognathism are conflicting. This study evaluated the changes in craniofacial morphology resulting from treatment with a Bionator, based on measurement percentiles previously reported, to clarify the mechanism of the effect of this commonly used functional device. MATERIALS AND METHODS: Study Design: Retrospective. SETTING: A private orthodontic clinic. PARTICIPANTS: Forty-two children (mean age, 10.13 years) requiring treatment with a Bionator for Class II malocclusion (mandibular retrognathism). Children were randomly assigned to a Bionator group with or without an expansion screw. Measurements on lateral cephalometric radiographs were taken before and upon completion of Bionator treatment. All parameters measured were characterised according to the measurement percentiles previously reported. Each parameter was compared before and after treatment for all patients and for each treatment group using Wilcoxon's test. RESULTS: No significant differences in cranial length or mandibular body length were seen in any of the 3 groups, but anterior cranial base length and maxillary length were significantly decreased while mandibular ramus height and mandibular length were significantly increased after treatment in the Bionator with expansion screw group and in the all-patient group. CONCLUSIONS: The findings suggest that treatment with a Bionator with expansion screw during the growth and development stage results in increased mandible length and ramus height and inhibits the growth of the maxilla and anterior cranial base bone.

[Features of peripheral nerve injuries in workers exposed to vibration: an analysis of 197 cases].

Objective: To investigate the features of peripheral nerve injuries in workers exposed to vibration. Methods: A total of 197 male workers [median age: 34 years (21-50 years) ; median working years of vibration exposure: 7.3 years (1-20 years) ] engaged in grinding in an enterprise were enrolled. Their clinical data and electromyography results were analyzed to investigate the features of peripheral nerve impairment. Results: Of all workers, 96 (48.73%) had abnormal electromyography results. Of all workers, 88 (44.7%) had simple mild median nerve injury in the wrist, who accounted for 91.7% (88/96) of all workers with abnormal electromy-ography results. Six workers had ulnar nerve injury, superficial radial nerve injury, or/and superficial peroneal nerve injury and accounted for 6.3% of all workers with abnormal electromyography results. Of all workers, 88 had a reduced amplitude of median nerve sensory transduction, and 28 had slowed median nerve sensory transduction. A total of 46 workers were diagnosed with occupational hand-arm vibration disease and hospitalized for treatment. They were followed up for more than 4 months after leaving their jobs, and most of them showed improvements in neural electromyography results and returned to a normal state. Conclusion: Workers exposed to vibration have a high incidence rate of nerve injury in the hand, mainly sensory function impairment at the distal end of the median nerve, and all injuries are mild peripheral nerve injuries. After leaving the vibration job and being treated, most workers can achieve improvements and return to a normal state.

Home sleep study for patients with myasthenia gravis.

OBJECTIVES: The objective of the study was to examine predictors for sleep-disordered breathing (SDB) in patients with myasthenia gravis (MG) using Watch-PAT. MATERIALS AND METHODS: We prospectively studied 58 consecutive patients with MG without respiratory symptoms for a full-night Watch-PAT with concomitant recording of the MG score and acetylcholine receptor antibody concentration and analyzed potential risk factors of SDB. RESULTS: Twenty-four patients (41%) had definitive SDB, which was mild in 12 patients, moderate in six, and severe in six. Assessing risk factors with multivariate models, we found four significant predictors (BMI, age, male gender, and use of azathioprine); BMI was the most powerful predictor. The severity and prevalence of sleep-disordered breathing had no significant association with MG score, myasthenia stage, or seropositivity of acetylcholine receptor antibody. CONCLUSIONS: The prevalence of SDB in myasthenic patients with mild and moderate weakness was high when using the Watch-PAT. Both myasthenia-specific factors (use of azathioprine) and general predictors in terms of BMI, age, and male gender predisposed the development of SDB in patients with myasthenia gravis. Careful screening of patients with myasthenia gravis at risk of SDB using Watch-PAT might improve the quality of sleep and cardiovascular health through proper treatment of underlying SDB.

Segment-specific targeting via RNA interference mediates down-regulation of OPN expression in hepatocellular carcinoma cells.

Osteopontin (OPN) plays an important role in the metastasis and recurrence of tumors after resection of hepatocellular carcinoma (HCC). In this study, the down-regulation effect on OPN expression in HCC cells of RNA interference (RNAi) molecules designed to target different segments of OPN was investigated to identify a more effective site for OPN knockdown. Specific small interfering RNAs (siRNAs A, B, and C) of OPN were synthesized and transfected into an HCC cell line (HEP-G2; representing the OPNi-A, OPNi-B, and OPNi-C groups). Fluorescent quantitative polymerase chain reaction and immunohistochemical methods were used to detect the mRNA and protein expression of OPN before and after RNAi. Results showed that after transfection, the fluorescence intensity of the OPNi-A group was greater than those of the OPNi-B and OPNi-C groups. After 48 h of transfection, the ΔCT values of OPN mRNA expression in the OPNi-A-C groups increased from 8.31 ± 1.58, 8.78 ± 1.49, and 8.25 ± 1.51 to 12.14 ± 1.43, 10.22 ± 1.97, and 10.48 ± 1.88, respectively (P < 0.05), and the OPN protein levels (immunohistochemistry scores) decreased from 6.44 ± 1.67, 5.43 ± 2.05, and 5.45 ± 2.52 to 2.84 ± 1.52, 4.43 ± 1.65, and 3.95 ± 1.43 points, respectively. These results indicated that RNAi based on different segments of the OPN gene had different down-regulatory effects on OPN expression. Synthesis of targeted siRNA aimed at specific OPN segments might have important significance for dealing with the invasiveness and metastasis of HCC cells.

Inpatient expenditures on alcohol-attributed diseases and alcohol tax policy: a nationwide analysis in Taiwan from 1996 to 2010.

OBJECTIVES: To assess the two opposing effects of alcohol tax policy interventions (tax rate increase in 2002 and decrease in 2009) on hospitalization in monetary terms of alcohol-attributed diseases (AADs) in Taiwan. STUDY DESIGN: An interrupted time-series analysis. METHODS: Admissions data from 1996 to 2010 were retrieved from the National Health Insurance Research Database claims file and analysed in this study. Data for 430,388 males and 34,874 females aged 15 or above who were admitted due to an AAD were collected. An interrupted time-series analysis examining the effects of the implementation of alcohol tax policy on quarterly adjusted hospital inpatient charges (HICs) for AADs was employed. RESULTS: The study showed significant (p < 0.001) changes in the adjusted HICs for AADs in 2002. Quarterly HICs showed an abrupt 14.8% decline (i.e., a 1.3 million US dollar reduction) after the first tax policy was implemented. No change in quarterly HICs for AADs was found after the alcohol tax increase. The total cost of treating these AAD inpatients over the course of the 15-year period was 640.9 million US dollars. Each inpatient with an AAD costs an average of $900-$2000 depending on the patient's sex and age with the cost increasing gradually after the two tax interventions. More than 80% of the HICs were attributed to alcoholic liver diseases. Psychoses accounted for 6%-18% of the total HICs. Alcohol abuse and alcohol poisoning accounted for less than 2% of the total HICs. CONCLUSIONS: This study provides evidence that alcohol taxation has resulted in an immediate reduction of medical expenditures related to AADs. The policy of increasing alcohol tax rates may have favourable influences on health care resources related to treating AADs.

Sex-age differences in association with particulate matter and emergency admissions for cardiovascular diseases: a hospital-based study in Taiwan.

OBJECTIVE: To explore the association between short-term exposure to particulate matter (PM) and cardiovascular diseases (CVDs) emergency room visits. STUDY DESIGN: Case-control study. METHODS: 2785 Emergency visits with presented cardiovascular diseases and 24,572 controls from ten hospitals in 2005 were obtained from a Taiwan's National Health Database. Daily PM10 data and meteorological information collected from an air monitoring station near the ten hospitals were used to calculate the exposure levels. Using multiple logistic regression analysis, adjusted odds ratios (AOR) were estimated for the associations of PM and temperature with ischaemic heart disease (IHD) and hypertension heart disease (HHD). RESULTS: A positive association (AOR = 1.05-1.75) between IHD emergency admission among women older than 65 and exposure to daily levels of PM10 pollution standard index (PSI) ≥50 compared with respondents exposed to PM10 PSI <50. CONCLUSIONS: To prevent exacerbation of IHD, people, especially elderly women, should be urged to reduce exposure to unhealthy PSI levels.

A multistep validation process of biomarkers for preclinical drug development.

Biomarkers that can be measured in preclinical models in a high-throughput, reproducible manner offer the potential to increase the speed and efficacy of drug development. Development of therapeutic agents for many conditions is hampered by the limited number of validated preclinical biomarkers available to gauge pharmacoefficacy and disease progression, but the validation process for preclinical biomarkers has received limited attention. This report defines a five-step preclinical biomarker validation process and applies the process to a case study of diabetic retinopathy. By showing that a gene expression panel is highly reproducible, coincides with disease manifestation, accurately classifies individual animals and identifies animals treated with a known therapeutic agent, a biomarker panel can be considered validated. This particular biomarker panel consisting of 14 genes (C1inh, C1s, Carhsp1, Chi3l1, Gat3, Gbp2, Hspb1, Icam1, Jak3, Kcne2, Lama5, Lgals3, Nppa, Timp1) can be used in diabetic retinopathy pharmacotherapeutic research, and the biomarker development process outlined here is applicable to drug development efforts for other diseases.

Prolonged time to pregnancy in residents exposed to ionising radiation in cobalt-60-contaminated buildings.

OBJECTIVES: Radiation-induced cytogenetic damage in somatic cells has raised concern that low-dose ionising radiation can also damage germ cells and influence gamete production and/or function, resulting in decreased fertility. Time to pregnancy (TTP) was used to investigate whether exposure to gamma-radiation affected fertility among the residents of cobalt-60-contaminated buildings in Taiwan. METHODS: This was a retrospective pregnancy-based study of 357 pregnancies born to 124 exposed couples. Both the cumulative dose and the dose rate for each pregnancy was estimated based on a physical dose reconstruction programme. The comparison population consisted of 612 pregnancies born to 225 couples randomly sampled from the Taiwan general population. Information on TTP was collected by personal interviews. Fecundability ratios (FRs) were calculated with a discrete proportional hazards model. RESULTS: For exposed mothers, fertility decreased significantly when unprotected intercourse began during the period of living in the radiation-contaminated buildings (FR 0.75, 95% CI 0.61 to 0.92). The effect was borderline significant for fathers (FR 0.83, 95% CI 0.68 to 1.02). There was evidence that prolonged TTP was associated with the rate of exposure for both mothers and fathers (tests for trend: female, p=0.0006; male, p=0.03), especially evident for dose rates > or =10 mSv/year (female, FR 0.60, 95% CI 0.43 to 0.84; male, FR 0.68, 95% CI 0.49 to 0.96). CONCLUSIONS: Our findings suggest that exposure to low-dose ionising radiation of cobalt-60-contaminated buildings may decrease fertility, especially in females. Fertility declined with increasing concurrent dose but not with cumulative dose.

Pressure-dependent electronic structures in multiferroic DyMnO(3): A combined lifetime-broadening-suppressed x-ray absorption spectroscopy and ab initio electronic structure study.

Variations in the electronic structure and structural distortion in multiferroic DyMnO(3) were probed by synchrotron x-ray diffraction, lifetime-broadening-suppressed x-ray absorption spectroscopy (XAS), and ab initio electronic structure calculations. The refined x-ray diffraction data enabled an observation of a diminished local Jahn-Teller distortion of Mn sites within MnO(6) octahedra in DyMnO(3) on applying the hydrostatic pressure. The intensity of the white line in Mn K-edge x-ray absorption spectra of DyMnO(3) progressively increased with the increasing pressure. With the increasing hydrostatic pressure, the absorption threshold of an Mn K-edge spectra of DyMnO(3) shifted toward a greater energy, whereas the pre-edge line slightly shifted to a smaller energy. We provide the spectral evidence for the pressure-induced bandwidth broadening for manganites. The intensity enhancement of the white line in Mn K-edge spectra is attributed to a diminished Jahn-Teller distortion of MnO(6) octahedra in compressed DyMnO(3). A comparison of the pressure-dependent XAS spectra with the ab initio electronic structure calculations and full calculations of multiple scattering using the code FDMNES shows the satisfactory agreement between experimental and calculated Mn K-edge spectra.

Waldenström macroglobulinaemia presenting as a perirenal mass: a case report.

Perirenal masses are a rare manifestation of Waldenström macroglobulinaemia (WM). We report a 70-year-old male diagnosed with Waldenström macroglobulinaemia arising as a huge perirenal mass, which was discovered by abdominal ultrasound and computed tomography. The patient underwent ultrasound-guided aspiration biopsy and the histopathological examination showed a monoclonal lymphoplasmocitoid proliferation of B-cells arranged in a diffuse pattern. This case report shows not only the importance of image and biopsy studies, but also the good response to chemotherapy with the CHOP regimen.

A simple allometric diffusion-based biokinetic model to predict Cu(II) uptake across gills of freshwater clam Corbicula fluminea.

The purpose of this study was to link Fick's type mass transfer and biokinetics together with Michaelis-Menten kinetics to arrive at a simple predictive framework for quantifying biouptake mechanisms in gills of freshwater clam Corbicula fluminea exposed to Cu(II). A diffusion-based Cu(II) influx and permeability can be calculated using physiological and allometric-related parameters. Simulations indicate that Cu(II) bioconcentration factor of gills was 42. Estimated steady-state Cu(II) gill uptake influx and permeability were 0.097 nmol cm(-2) s(-1) and 0.48 cm s(-1), respectively. The proposed simple allometric diffusion-based biokinetic model meets the need for describing nonequilibrium aspects of biouptake mechanisms in bivalve gills.

[Analysis of CT features of 15 Children with 2019 novel coronavirus infection].

Objective: To explore imaging characteristics of children with 2019 novel coronavirus (2019-nCoV) infection. Methods: A retrospective analysis was performed on clinical data and chest CT images of 15 children diagnosed with 2019-nCoV. They were admitted to the third people's Hospital of Shenzhen from January 16 to February 6, 2020. The distribution and morphology of pulmonary lesions on chest CT images were analyzed. Results: Among the 15 children, there were 5 males and 10 females, aged from 4 to 14 years old. Five of the 15 children were febrile and 10 were asymptomatic on first visit. The first nasal or pharyngeal swab samples in all the 15 cases were positive for 2019-nCoV nucleic acid. For their first chest CT images, 6 patients had no lesions, while 9 patients had pulmonary inflammation lesions. Seven cases of small nodular ground glass opacities and 2 cases of speckled ground glass opacities were found. After 3 to 5 days of treatment, 2019-nCoV nucleic acid in a second respiratory sample turned negative in 6 cases. Among them, chest CT images showed less lesions in 2 cases, no lesion in 3 cases, and no improvement in 1 case. Other 9 cases were still positive in a second nucleic acid test. Six patients showed similar chest CT inflammation, while 3 patients had new lesions, which were all small nodular ground glass opacities. Conclusions: The early chest CT images of children with 2019-nCoV infection are mostly small nodular ground glass opacities. The clinical symptoms of children with 2019-nCoV infection are nonspecific. Dynamic reexamination of chest CT and nucleic acid are important.

[Analysis of CT features of 15 children with 2019 novel coronavirus infection].

Objective: To explore imaging characteristics of children with 2019 novel coronavirus (2019-nCoV) infection. Methods: A retrospective analysis was performed on clinical data and chest CT images of 15 children diagnosed with 2019-nCoV infection. They were admitted to the Third People's Hospital of Shenzhen from January 16 to February 6, 2020. The distribution and morphology of pulmonary lesions on chest CT images were analyzed. Results: Among the 15 children, 5 were males and 10 females, aged from 4 to 14 years. Five of the 15 children were febrile and 10 were asymptomatic on the first visit. The first nasal or pharyngeal swab samples in all the 15 cases were positive for 2019-nCoV nucleic acid. For their first chest CT images, 6 patients had no lesions, while 9 patients had pulmonary inflammatory lesions. Seven cases had small nodular ground glass opacities and 2 cases had speckled ground glass opacities. After 3 to 5 days of treatment, 2019-nCoV nucleic acid in a second respiratory sample turned negative in 6 cases. Among them, chest CT images showed less lesions in 2 cases, no lesion in 3 cases, and no improvement in 1 case. The remaining 9 cases were still positive in a second nucleic acid test. Six patients showed similar chest CT inflammation, while 3 patients had new lesions, which were all small nodular ground glass opacities. Conclusions: The early chest CT images of children with 2019-nCoV infection are mostly small nodular ground glass opacities. The clinical symptoms of children with 2019-nCoV infection are nonspecific. Dynamic reexamination of chest CT and nucleic acid are important.

Danish Prostatic Symptom Score is not associated with lower urinary tract symptom severity.

OBJECTIVES: Lower urinary tract symptoms (LUTS) are associated with sexual dysfunction; however, these can vary by population. Thus, the prevalence, severity, and predisposing factors for sexual dysfunction in Taiwanese men (> 40 y) who visited a urologic clinic for LUTS was determined. METHODS: During 2005 and 2006, a prospective survey was carried out which included 412 men with LUTS. Demographic data were collected during face-to-face interviews. Sexual dysfunction and LUTS were evaluated using the Danish Prostatic Symptom Score (DAN-PSS) and the International Prostate Symptom Score (IPSS) questionnaire, respectively. RESULTS: Mild, moderate, and severe LUTS were observed in 25.61%, 47.80%, and 26.59% of the patients, respectively. Reduced or absence of erection, reduced or no ejaculation, and pain upon ejaculation were found in 78.29%, 76.59%, and 6.11% of the patients, respectively. However, only 26.9%, 22.1%, and 4.4% of patients with erectile dysfunction (ED), ejaculatory dysfunction, and pain upon ejaculation were bothered by the sexual dysfunction, respectively. Age was significantly associated with ED, ejaculatory dysfunction (EjD), and pain with ejaculation (p < 0.001). The prevalence of sexual dysfunction increased with the severity of LUTS but was not significantly different. Patients with diabetes were 5.96 times more likely to have sexual dysfunction (95% CI = 1.39 to 25.60; p = 0.017). CONCLUSIONS: Over 70% of LUTS patients in this study suffered from sexual dysfunction. Although age and diabetes were associated with sexual dysfunction, LUTS severity was not.

Holmium: yttrium-aluminum-garnet laser endoureterotomy for benign ureteral strictures: a single-centre experience.

PURPOSE: This study aimed to report the results of endoureterotomy for benign ureteral strictures using the holmium: yttrium-aluminum-garnet laser. MATERIAL AND METHODS: Nineteen patients (8 men and 11 women, mean age 51.47 years) underwent holmium: yttrium-aluminum-garnet laser endoureterotomy for benign ureteral strictures (8 proximal, 3 middle, and 8 distal) using semi-rigid ureteroscopy and 360-microm fibre at 1.2 J/pulse and 10 Hz. After completion of the incision, a 7-Fr double-J ureteral stent was left for 6 weeks. Thereafter, the patients were followed-up by ultrasound and/or intravenous urography at 3-6 monthly intervals. RESULTS: Success was defined as the absence of symptoms plus radiographic resolution of obstructions as assessed by diuretic renography and/or intravenous urography. With a mean follow-up of 40.2 months, success was achieved in 10 (52.6%) of the 19 patients. Nine patients developed recurrent strictures and were considered treatment failures. The stricture length and severity of hydronephrosis correlated with successful outcome, but gender, aetiology, side and location of strictures did not predict outcome. CONCLUSIONS: Although endoureterotomy using a holmium : yttrium-aluminum-garnet laser has an equivocal outcome, the procedure is recommended as a safe, less invasive therapeutic option for the initial management of benign ureteral strictures.

Redshift of edge emission from AlGaInP light-emitting diodes and correlation with electron-hole recombination lifetime.

The edge emission from AlGaInP light-emitting diodes showed a red-shifted peak in addition to the peak of surface emission. This shift resulted from the quantum-well absorption of the guided wave. Although the shift degrades the color quality and the extraction efficiency of the device, it helps elucidate many important optical properties of the material and the dynamics of carrier recombination, including the electron-hole recombination lifetime, the optical joint density of state, the spontaneous emission spectrum and the absorption spectrum. A simple concept of the bimolecular recombination is established. The corresponding coefficient can be expressed by a simple formula and was therefore determined.