Temporal characterization of a two-color laser field using tunneling ionization.

The superposition of a fundamental laser pulse and its second harmonic can form an asymmetric laser field that is useful in many applications. The temporal characterization of the two-color laser field becomes necessary. However, the temporal characterization of the two-color laser pulse is a challenging task due to its broad bandwidth and a spectral gap between the two frequency components. Here we demonstrate the temporal characterization of the two-color laser field using multiple ionization yield measurements near the laser focus. This new approach enables the complete temporal characterization of the two-color laser field, including the relative phase between the two frequency components.

Stachydrine alleviates lipid-induced skeletal muscle insulin resistance via AMPK/HO-1-mediated suppression of inflammation and endoplasmic reticulum stress.

OBJECTIVE: Insulin resistance develops due to skeletal muscle inflammation and endoplasmic reticulum (ER) stress. Stachydrine (STA), extracted from Leonurus heterophyllus, has been shown to suppress proliferation and induce apoptosis in breast cancer cells and exert anti-inflammatory properties in the brain, heart, and liver. However, the roles of STA in insulin signaling in skeletal muscle remain unclear. Herein, we examined the impacts of STA on insulin signaling in skeletal muscle under hyperlipidemic conditions and its related molecular mechanisms. METHODS: Various protein expression levels were determined by Western blotting. Levels of mouse serum cytokines were measured by ELISA. RESULTS: We found that STA-ameliorated inflammation and ER stress, leading to attenuation of insulin resistance in palmitate-treated C2C12 myocytes. STA dose-dependently enhanced AMPK phosphorylation and HO-1 expression. Administration of STA attenuated not only insulin resistance but also inflammation and ER stress in the skeletal muscle of high-fat diet (HFD)-fed mice. Additionally, STA-ameliorated glucose tolerance and insulin sensitivity, as well as serum TNFα and MCP-1, in mice fed a HFD. Small interfering (si) RNA-associated suppression of AMPK or HO-1 expression abolished the effects of STA in C2C12 myocytes. CONCLUSIONS: These results suggest that STA activates AMPK/HO-1 signaling, resulting in reduced inflammation and ER stress, thereby improving skeletal muscle insulin resistance. Using STA as a natural ingredient, this research successfully treated insulin resistance and type 2 diabetes.

Role of TGF-ß1 and C-Kit Mutations in the Development of Hepatocellular Carcinoma in Hepatitis C Virus-Infected Patients: in vitro Study.

Transforming growth factor beta (TGF-ß) acts as a tumor-suppressing cytokine in healthy tissues and non-malignant tumors. Yet, in malignancy, TGF-ß can exert the opposite effects that can promote proliferation of cancer cells. C-Kit plays a prominent role in stem cell activation and liver regeneration after injury. However, little is known about the cross-talk between TGF-ß and C-Kit and its role in the progression of hepatocellular carcinoma (HCC). Here, we studied the effect of increasing doses of TGF-ß1 on CD44+CD90+ liver stem cells (LSCs) and C-Kit gene expression in malignant and adjacent non-malignant liver tissues excised from 32 HCC patients. The percentage of LSCs in malignant tumors was two times higher compared to their counterparts from the non-malignant tissues. When treated with increasing doses of TGF-ß1, proliferation of both malignant and non-malignant LSCs was progressively suppressed, but low TGF-ß1 dose failed to suppress the growth of malignant LSCs. Moreover, C-Kit exons 9 and 11 were expressed in malignant LSCs, but not in their non-malignant counterparts. Analysis of C-Kit detected mutations in exon 9 (but not in exon 11) in some malignant liver cells resulting in the changes in the amino acid sequence and dysregulation of protein structure and function. Interestingly, in malignant liver cells, mutations in exon 9 were associated with high-viremia hepatitis C virus (HCV), and expression of this exon was not suppressed by the TGF-ß1 treatment at all doses. To our knowledge, this is the first report that mutations in the C-Kit gene in HCC patients are associated with high- viremia HCV. Our study emphasizes the need for investigation of the TGF-ß1 level and C-Kit mutations in patients with chronic HCV for HCC prevention and better therapy management.

Sporicidal activities and mechanism of surfactant components against Clostridium sporogenes spores.

The sporicidal activities of seven kinds of antimicrobial agent were investigated in order to screen for novel inactivation agents to apply to Clostridium sporogenes spores. Antimicrobial agents based on surfactant components, as poly-l-lysine, thiamine dilaurylsulfate, and torilin, were more effective than other agents. The degree of spore reduction with 1-2% surfactant components was 1.5-2.5 log CFU/mL. The HLB value (hydrophile-lipophile balance) related to denature protein of spores coat on surfactants with sporicidal activity was ranged from 6 to 16. Average HLB value and spore killing effect was inversely correlated. The proteins on spore structures seemed to be disorganized due to binding between polar groups of coats and hydrophilic and hydrophobic groups of surfactant components, resulting in killing of spores. The components that were effective to inactivate C. sporogenes spores had a chemical structure containing CH3, OH, COOH, sulfate groups, and a double bond. Furthermore, hydrophobic surfactants were more effective than hydrophilic surfactants in inactivating spores. This was likely due to the type of hydrophobic surfactant and to the involvement of hydrophobic interactions on coat of spores.

Systematic review and meta-analysis of prostatic artery embolisation for lower urinary tract symptoms related to benign prostatic hyperplasia.

AIM: To evaluate the efficacy of prostatic artery embolisation (PAE) in lower urinary tract symptoms (LUTS) related to benign prostatic hyperplasia (BPH) at short- and mid-term follow-up. MATERIALS AND METHODS: The current study included 484 BPH patients from seven eligible studies. A meta-analysis was performed to determine the mean differences in parameters associated with LUTS, including the international prostate symptom score (IPSS), peak urinary flow (Qmax), post-void residual volume (PVR), quality of life score (QoL), prostate-specific antigen level (PSA), and prostatic volume (PV), between baseline and follow-up periods. RESULTS: Nearly all parameters at follow-up of 3-24 months were significantly improved compared to the baseline. Mean differences in IPSS at 3, 6, 12, and 24 months were -14.06 (95% confidence interval [CI]: -16.47 to -11.64), -12.32 (95% CI: -15.57 to -9.08), -16.41 (95% CI: -19.81 to -13.02), and -17 (95% CI: -17.91 to -16.09), respectively. In addition, mean differences of Qmax, PVR, PV, and QoL between the follow-up period and baseline were improved significantly; however, there were no significant differences in PSA at 24 months. CONCLUSION: The present data shows that PAE could improve LUTS by BPH after short- and mid-term follow-up; however, more cumulative studies for long-term follow-up and comparison with other therapeutic modalities will be needed.

Clinical impact of coexisting retinopathy and vascular calcification on chronic kidney disease progression and cardiovascular events.

BACKGROUND AND AIMS: Retinopathy and vascular calcification (VC) are representative markers of microvascular and macrovascular dysfunction in patients with chronic kidney disease (CKD). However, their relationship and combined effects on clinical outcomes remain undetermined. METHODS AND RESULTS: We included 523 patients with nondialysis-dependent CKD stage 3-5 who had been examined with fundus photography for diabetic or hypertensive retinopathy. Simple radiographs were analyzed for the presence of VC. The clinical significance of VC of the abdominal aorta and iliofemoral artery (apVC) and retinopathy was evaluated in terms of the rate of renal function decline and composite of any cardiovascular event or death. CKD patients with retinopathy showed higher prevalence of apVC than those without retinopathy (25.6% vs. 12.5%, P < 0.001).The presence of retinopathy was independently associated with apVC (OR 2.13, 95% CI 1.31, 3.49). In multivariate analysis, compared with subjects with neither apVC nor retinopathy, the coexistence of both apVC and retinopathy were independently associated with rapid renal function decline (ß = -1.51; 95% CI -2.40, -0.61), whereas apVC or retinopathy alone were not. Compared with subjects with neither apVC nor retinopathy, the HRs for composite end points were 1.05 (95% CI 0.48, 2.27), 1.79 (95% CI 1.14, 2.80), and 2.07 (95% CI 1.17, 3.67) for patients with apVC only, those with retinopathy only, and those with both apVC and retinopathy, respectively. CONCLUSION: The coexistence of VC and retinopathy was independently associated with CKD progression and cardiovascular events or deaths, and its combined effect was stronger than any separate condition.

Diet-induced obesity reduces the production of influenza vaccine-induced antibodies via impaired macrophage function.

Obesity is a metabolic disease characterized by low-level chronic inflammation. Obese individuals are susceptible to infection by viruses, and vaccination against these pathogens is less effective than in nonobese individuals. Here, we sought to explore the immunological environment in a mouse model of obesity induced by a high-fat diet (HFD). HFD treatment increased the body weight and epididymal fat mass. The proportion of activated B cells, T cells, and macrophages was similar between mice in the HFD group and the regular-fat diet (RFD) group. The Th1 cell subpopulation in the HFD group was increased, whereas the proportion of Treg cells was reduced compared with the RFD group. Moreover, T-cell proliferation and cytokine production did not differ between the groups when cells were stimulated with anti-CD3 and anti-CD28 antibodies in vitro. In macrophages, phagocytic activity was higher in mice fed an HFD than in those fed an RFD, but expression levels of CD86 and MHC class II antigens were similar. When macrophages were cultured in vitro, the proportion of CD86-expressing macrophages was lower in those isolated from mice in the HFD group than in those isolated from the RFD group. Furthermore, lipopolysaccharide-induced interleukin 6 (IL-6) and tumor necrosis factor alpha secretions were significantly reduced in macrophages isolated from the HFD group. In addition, influenza vaccine-induced antibodies in the HFD group diminished more rapidly than in the RFD group. These results suggest that poor functionality of macrophages during obesity might contribute to a reduction in vaccine efficacy.

Lysophosphatidylcholine as a prognostic marker in community-acquired pneumonia requiring hospitalization: a pilot study.

Clinical prediction indicators such as the pneumonia severity index (PSI) and CURB-65 score are useful, but they are complex and often not followed. Therefore, biomarkers that improve hospital outcome predictions are emerging. This study evaluated the prognostic value of a new sepsis biomarker, serum lysophosphatidylcholine (LPC) concentrations, in community-acquired pneumonia (CAP) patients. We prospectively collected blood samples from emergency department CAP patients on days 1 and 7 (post-admission) and analyzed their plasma LPC concentrations. We retrospectively reviewed patient medical records and analyzed correlations between plasma LPC concentrations and clinical parameters and hospital outcomes. A total of 56 CAP patients were included in this study; 24 (42.9 %) required intubation and 15 (26.8 %) died. The mean LPC concentrations on days 1 (p = 0.015) and 7 (p = 0.002) of hospitalization were significantly lower in the non-survivors. Day 1 LPC concentrations were inversely correlated with the PSI (ρ = -269) and CURB-65 scores (ρ = -386). For predicting hospital mortality, the day 1 LPC concentration was comparable with the CURB-65 or PSI scores. Day 1 LPC cut-off levels <29.6 µmol/L were associated with hospital CAP outcomes, including the need for mechanical ventilation, vasopressors, intensive care unit admission, and hospital mortality. Additionally, day 7 LPC concentrations were correlated with in-hospital mortality. Initial serum LPC concentrations predicted hospital outcomes in CAP patients requiring hospitalization. These values were correlated with prognostic markers, such as the PSI and CURB-65 scores. Additionally, follow-up LPC measurements predicted the clinical course of CAP patients.

Cloning and characterization of microbial activated Aedes aegypti†MEK4 (AaMEK4): influences of noncatalytic domains on enzymatic activity.

Protein kinases are known to be involved in a number of signal transduction cascades. Both the stress-activated Jun N-terminal kinase (JNK) and mitogen-activated protein kinase (MAPK) p38 pathways have been shown to correlate with the insect immune response to microbial infection. MAP kinase kinase 4 (MEK4) is an upstream kinase of JNK and p38 kinase. The cDNA of AaMEK4 was cloned and characterized. AaMEK4 was activated by microbial lysates of Gram-positive, Gram-negative bacteria and yeast. The conserved lysine (K112 ) and the putative phosphorylation sites (S238 and T242 ) were shown to be important for kinase activity by site-directed mutagenesis. A common MAPK docking site (MAPK_dsA) was found and in addition, a new nearby docking site, MAPK_dsB, was identified in the N-terminal noncatalytic domain of AaMEK4. MAPK_dsB was shown to be a unique element in the MEK4 family. In this study, both MAPK_dsA and _dsB were demonstrated to be important to AaMEK4 enzymatic activity for the downstream protein kinase, Aap38.

Endovascular coil embolization in internal carotid artery bifurcation aneurysms.

AIM: To present the clinical and radiological results of coil embolization in internal carotid artery (ICA) bifurcation aneurysms (BA). MATERIALS AND METHODS: The records of 65 patients with 66 ICA BA were retrieved from data prospectively accrued between September 1999 and July 2013. Clinical and morphological outcomes of the aneurysms were assessed, including technical aspects of treatment. RESULTS: The aneurysms under study were directed either superiorly (41/66, 62.1%), anteriorly (24/66, 36.4%), or posteriorly (1/66, 1.5%), and all were devoid of perforators. Aneurysmal necks were situated symmetrically at the terminal ICA (37/66, 56.1%) or slightly deviated to the proximal A1 segment (29/66, 43.9%). The steam-shaped S microcatheter (73.8%) was most commonly used to select the aneurysms, and the single microcatheter technique was most commonly applied (56.1%) to perform coil embolization, followed by balloon remodelling (21.2%), multiple microcatheter (15.1%), and stent-protection (7.6%). Successful aneurysmal occlusion was achieved in 100% of cases, with no procedure-related morbidity or mortality. Imaging performed in the course of follow-up (mean duration 27.3 months) confirmed stable occlusion of most lesions (47/53, 88.7%). CONCLUSION: Through tailored technical strategies, ICA BA are amenable to safe and effective endovascular coil embolization, with a tendency for stable occlusion long-term.

Angle change of the parent arteries after stent-assisted coil embolization of wide-necked intracranial bifurcation aneurysms.

AIM: To investigate the angle changes of the parent arteries after stent-assisted coil embolization of wide-necked intracranial bifurcation aneurysms. MATERIALS AND METHODS: The adjacent parent arterial angles before and after stent-assisted coil embolization were measured in 38 patients with aneurysms of the anterior communicating artery (ACoAA) and 41 patients with bifurcation aneurysms of the middle cerebral artery (MCABA). Variables were analysed in relation to the angle changes. RESULTS: Vascular angles of the parent arteries significantly increased by 27.8° (±18.5°) immediately after stent-assisted coil embolization in 79 cases (p < 0.001), with 25.7° (±14.8°) in ACoAA and 29.7° (±21.4°) in MCABA, respectively. In 51 (64.6%) cases with follow-up angiography (mean interval 13.5 ± 4.1 months), vascular angles increased by 27.2° (±17.1°) immediately after treatment and further increased by 20.7° (±14.3°) at the last follow-up (all p < 0.001). More acute pre-stent angles of the parent arteries correlated with greater post-stent angle changes (p = 0.006). Younger age tended to be inversely related to post-stent angle changes (p = 0.091). CONCLUSION: Stent placement during coil embolization induced significant changes in the aneurysm-parent artery relationship. Further study is needed to elicit the association between angle change of the parent arteries and aneurysmal stability after coil embolization.

Data Build-up for the Construction of Korean Specific Greenhouse Gas Emission Inventory in Livestock Categories.

Many studies on methane (CH4) and nitrous oxide (N2O) emissions from livestock industries have revealed that livestock production directly contributes to greenhouse gas (GHG) emissions through enteric fermentation and manure management, which causes negative impacts on animal environment sustainability. In the present study, three essential values for GHG emission were measured; i.e., i) maximum CH4 producing capacity at mesophilic temperature (37°C) from anaerobically stored manure in livestock category (B0,KM, Korean livestock manure for B0), ii) EF3(s) value representing an emission factor for direct N2O emissions from manure management system S in the country, kg N2O-N kg N(-1), at mesophilic (37°C) and thermophilic (55°C) temperatures, and iii) Nex(T) emissions showing annual N excretion for livestock category T, kg N animal(-1) yr(-1), from different livestock manure. Static incubation with and without aeration was performed to obtain the N2O and CH4 emissions from each sample, respectively. Chemical compositions of pre- and post-incubated manure were analyzed. Contents of total solids (% TS) and volatile solid (% VS), and the ratio of carbon to nitrogen (C/N) decrease significantly in all the samples by C-containing biogas generation, whereas moisture content (%) and pH increased after incubation. A big difference of total nitrogen content was not observed in pre- and post-incubation during CH4 and N2O emissions. CH4 emissions (g CH4 kg VS(-1)) from all the three manures (sows, layers and Korean cattle) were different and high C/N ratio resulted in high CH4 emission. Similarly, N2O emission was found to be affected by % VS, pH, and temperature. The B0,KM values for sows, layers, and Korean cattle obtained at 37°C are 0.0579, 0.0006, and 0.0828 m(3) CH4 kg VS(-1), respectively, which are much less than the default values in IPCC guideline (GL) except the value from Korean cattle. For sows and Korean cattle, Nex(T) values of 7.67 and 28.19 kg N yr(-1), respectively, are 2.5 fold less than those values in IPCC GL as well. However, Nex(T) value of layers 0.63 kg N yr(-1) is very similar to the default value of 0.6 kg N yr(-1) in IPCC GLs for National greenhouse gas inventories for countries such as South Korea/Asia. The EF3(s) value obtained at 37°C and 55°C were found to be far less than the default value.

Sex differences in the global burden of multidrug- resistant tuberculosis without extensive drug resistance in the general population and people living with HIV/AIDS, 1990-2019.

OBJECTIVE: Currently, human immunodeficiency virus (HIV) and multi-drug resistant tuberculosis (MDR-TB) without extensive drug resistance (XDR) are significant challenges in terms of the global burden of disease. This study aimed to evaluate the trends of the global burden of MDR-TB without XDR and HIV/AIDS-MDR-TB without XDR, focusing on differences in socioeconomic status and sex for 204 countries and territories across periods from 1990 to 2019. MATERIALS AND METHODS: Data from the Global Burden of Disease (GBD) 2019 study were obtained to construct a separate index measuring the burden of MDR-TB without XDR and HIV/AIDS-MDR-TB without XDR. Incidence, prevalence, mortality, and disability-adjusted life years (DALYs) were calculated for each case and group. A population-attributable fraction approach was used to assess mortality and incidence of HIV/AIDS and MDR-TB coinfection. 95% uncertainty intervals (UIs) were presented for all measures. RESULTS: Our global estimates suggest that there were approximately 450,000 (95% UI 247,000-785,000) incident cases of MDR-TB without XDR and 109,000 (43,000-210,000) deaths caused by MDR-TB without XDR among individuals who were HIV-negative in 2019. For HIV-positive individuals, the corresponding figures were approximately 47,000 (33,000-67,000) incident cases of MDR-TB and 19,000 (8,000-36,000) deaths due to MDR-TB in the same year. In 2019, higher numbers of incident cases and deaths were observed in males compared to females among individuals who were HIV-negative. Conversely, for HIV-positive individuals, females had higher numbers of incident cases and deaths compared to males. Specifically, the estimated numbers for incident cases were 23,000 (15,000-33,000) for females and 24,000 (17,000-35,000) for males, while the estimated numbers for deaths were 9,600 (4,000-17,900) for females and 9,800 (4,100-18,500) for males. Male-to-female ratios have remained above 1.0 from 1990 to 2019 in both incident cases and number of deaths for HIV-negative individuals. However, for HIV and MDR-TB coinfection, both ratios were below 1.0 in most of the time series. CONCLUSIONS: Males had more cases and deaths due to MDR-TB without XDR than females in HIV-negative patients, while females faced a higher incidence and mortality in HIV/AIDS-MDR-TB without XDR. Interventions are needed to deal with such factors, which increase the burden of coinfection among females across the world.

Ethnic and sex differences in the distributions of body mass index and waist circumference among adults: a binationally representative study in South Korea and the United States.

OBJECTIVE: The ethnic and sex differences in the distributions of body mass index (BMI) and waist circumference (WC) among adults are largely unknown. Therefore, we aimed to investigate the percentiles of BMI and WC in groups divided according to age, sex, and ethnicity. PATIENTS AND METHODS: We conducted a population-based binational study of adults aged ≥20 years based on data from two sources: US National Health and Nutrition Examination Survey (2015 to 2020) and Korea National Health and Nutrition Examination Survey (2016 to 2019). RESULTS: Weight, height, and WC were measured in 13,144 American adults and 30,191 Korean adults. Overall, BMI increased at younger ages and decreased at older ages, which indicates a reversed U-shaped relationship, and differed in terms of age, sex, and ethnicity. Women in the other Hispanic, non-Hispanic white, non-Hispanic black, and "other ethnic groups" showed a common BMI peak at ages 50-54 years. The patterns of WC distribution were similar to those of BMI distribution. CONCLUSIONS: In this binational representative study, we found varied distributions of ethnic and sex differences in BMI and WC. Considering the differences in these distributions may help improve individual and personalized treatment strategies.

National prevalence and socioeconomic factors associated with the acceptance of COVID-19 vaccines in South Korea: a large-scale representative study in 2021.

OBJECTIVE: Among the global efforts toward preventing the COVID-19 pandemic, vaccines are a pivotal factor in ending the pandemic. Thus, through a large-scale population-based study, we investigated the individual-, social-, and family-associated factors affecting the acceptance of COVID-19 vaccines in South Korea. PATIENTS AND METHODS: Data were obtained from a nationwide representative study (Korea Community Health) conducted in 2021. To determine the individual-, social-, and family-associated variables for COVID-19 vaccination acceptance, we investigated data from 225,319 individuals. RESULTS: In the total sample (n=225,319), 184,529 COVID-19-vaccinated people and 40,790 non-vaccinated people were evaluated. The factors related to the acceptance of COVID-19 vaccination were significantly associated with the demographic factors, namely, older age group, female sex, and a history of influenza vaccination, as well as medical conditions such as diabetes, hypertension, and depression. Socioeconomic conditions influencing the acceptance of COVID-19 vaccination were significantly associated with low-income families and blue-collar workers. Health-related risk factors were high in the obese group. However, a noteworthy negative association was found between the acceptance of vaccination and smoking habits and alcohol consumption. Conversely, a positive association was observed between academic level and vaccination acceptance. CONCLUSIONS: Our findings suggest that old age, female sex, a history of influenza vaccination, medical conditions, such as diabetes, hypertension, and depression, low-income families, blue-collar workers, and health-related risk factors, such as obesity, were associated with the acceptance of COVID-19 vaccination. Additionally, a high academic level, absence of smoking habits, and non-current alcohol use were positively associated with vaccine acceptance.

National prevalence and determinants of COVID-19 vaccine hesitancy during the initial phase pandemic.

OBJECTIVE: Although previous studies have explored the causes of COVID-19 vaccine hesitancy during the pandemic, there is a lack of generality and reproducibility in these studies. Therefore, we aimed to comprehensively identify the determinants of COVID-19 vaccine hesitancy through a representative nationwide cross-sectional study conducted in South Korea. SUBJECTS AND METHODS: We used a nationwide, representative, and large-scale dataset from the 2021 Community Health Survey. By analyzing 193,495 participants, we investigated the nationwide incidence of COVID-19 vaccine hesitancy and the various causes thereof. RESULTS: The national prevalence of COVID-19 vaccine hesitancy was 5.7% (95% CI, 5.5-5.8). COVID-19 vaccine hesitancy was associated with an increased incidence of the following factors: (1) demographic factors including early-middle adulthood [vs. late; odds ratio (OR), 1.51; 95% CI, 1.38-1.65] and male sex (vs. female sex; OR, 1.08; 95% CI, 1.01-1.14); (2) physically healthy subjects; (3) lower socio-economic status (vs. high household income; OR, 1.28; 95% CI, 1.19-1.38); (4) having mental illness (vs. normal mental status; OR, 1.25; 95% CI, 1.13-1.38); and (5) unhealthy habits such as current smoking (vs. non-smoking; OR, 1.22; 95% CI, 1.13-1.31); and insufficient physical activity (vs. sufficient; OR, 1.08; 95% CI, 1.01-1.17). Common reasons for vaccine hesitancy were concerns about side effects (41.34%), health problems (24.60%), and inability to select the type of vaccine (14.13%). CONCLUSIONS: This representative large-scale nationwide study conducted in South Korea investigated the nationwide prevalence and determinants of vaccine hesitancy. Our results provide useful public health information, especially on novel aspects of vaccination strategies, for policymakers to improve the acceptance of COVID-19 vaccines.

NiO and Co3O4 nanoparticles induce lung DTH-like responses and alveolar lipoproteinosis.

Lung exposure to metal oxide nanoparticles (NPs) comprising soluble metal haptens may produce T-helper cell type 1 (Th1)- and Th17-associated delayed-type hypersensitivity (DTH) responses and pulmonary alveolar proteinosis (PAP). In order to study this, haptenic metal oxide NPs (NiO, Co(3)O(4), Cr(2)O(3) and CuO) were instilled into the lungs of female Wistar rats, and the immunoinflammatory responses were assessed at 24 h and 4 weeks post-instillation. Primary culture of alveolar macrophages from Wistar rats was used to evaluate the effect of the NPs on the ability to clear surfactant. NiO NPs induced chronic interstitial inflammation and pro-inflammatory Th1 and Th17 immune responses characterised by increases in the cytokines monocyte chemotactic protein (MCP)-1/CCL2, interleukin (IL)-12 p40, interferon-γ and IL-17A, whilst similar pathological responses induced by Co(3)O(4) NPs were associated with increases in MCP-1/CCL2 and IL-12 p40. However, neither Cr(2)O(3) nor CuO NPs elicited immunoinflammatory reactions. PAP was induced by both NiO and Co(3)O(4) NPs during the chronic phase. PAP was associated with over-production of surfactant by proliferation of type II cells and impaired clearance of surfactant by macrophages. These findings have implications for the risk management of occupational NP exposure and provide evidence that haptenic metal oxide NPs can induce chronic progressive lung immune responses via a DTH-like mechanism.

Stereotactic radiosurgery for primary and metastatic sarcomas involving the spine.

The treatment for spinal sarcomas is difficult due to inadequate surgical margin and an inability to deliver high dose radiation. Advanced technology of stereotactic radiosurgery (SRS) enabled higher biological effective doses of radiation to be delivered to spinal sarcomas by hypofractionation method. The authors evaluated local control rate following SRS for primary and metastatic spinal sarcomas. Thirty-two spinal sarcomas (10 primary tumors, 22 metastatic tumors) in 27 patients were treated by SRS from November 2002 to September 2009. Patients were assessed for pain status, neurological status and radiological response by regular follow-up. Overall survival and local progression-free survival were calculated and prognostic factors were sought. Median tumor volume was 18.6 ml. Radiation doses to the tumor margins ranged from 16 to 45 Gy in one to three fractions, and the median single session equivalent dose was 21.8 Gy. Follow-up ranged from 4 to 68 months (median, 22 months). Overall median survival was 29 months and no related prognostic factors were identified. During follow-up, pain was controlled in 89.3% (25/28) lesions at 6 months, in 68.2% (15/22) at 1 year, and in 61.5% (8/13) at 2 years. Tumor volume was found to be significantly related to post-SRS pain control rate. Radiological evaluation showed that local control was maintained in 96.7% (29/30) lesions at 6 months, in 78.3% (18/23) at 1 year, and in 76.9% (10/13) at 2 years. Radiation dose and tumor volume were found to be related to radiological control at 24 months following SRS. Nine cases developed recurrence between 2 and 33 months, median local progression-free survival was 23 months. Age was found to be predictive of local progression-free survival (P = 0.009). SRS proved to be an effective modality for the local control of primary and metastatic spinal sarcomas, and age was significantly related to local recurrence.