The role of multidetector computed tomography in predicting the site of gastroduodenal perforation.

OBJECTIVE: This study aims to evaluate the value of multidetector computed tomography (MDCT) in detecting the location of gastroduodenal perforation. PATIENTS AND METHODS: This cross-sectional descriptive study was conducted with 47 patients who underwent contrast-enhancing MDCT and were diagnosed with gastroduodenal perforation during surgery between July 2021 and June 2022. Radiologic findings included pneumoperitoneum (distribution and quantity) and analyzed the image findings for localizing the site of gastroduodenal perforation. RESULTS: Pneumoperitoneum was the most common finding [95.74% (45 out of 47 patients)]. Regarding air distribution, the sensitivity (Se) and negative predictive value (NPV) of abdominal free air and supramesocolic free air were the highest (100% for both). The accuracy (Acc) of supramesocolic free air was the highest (93.6%), followed by abdominal free air (89.4%). Subphrenic free air also had a high Acc value (89.4%), with Se, specificity (Sp), and positive predictive value (PPV) being 90%, 85,7%, and 97.3%, respectively. The Sp PPV of falciform ligament/ligamentum teres sign, and periportal free air were also high (100% for both). In contrast, retroperitoneal free air was valuable in determining retroperitoneal duodenal perforation with an Sp, Se of 100%, and Acc of 89.4%. The thickness of abdominal free air was ≥5.5 mm, suggesting gastroduodenal perforation with a Se, Sp, PPV, NPV, and Acc of 82.5%, 100%, 100%, 50%, and 85.1%, respectively. CONCLUSIONS: Subphrenic free air, periportal free air, falciform ligament sign, and the air above transverse mesocolon were correlated to gastric and duodenal bulb perforation. Retroperitoneal air indicates the perforation at the retroperitoneal duodenum. The thickness of abdominal free air ≥5.5 mm indicates gastric and duodenal bulb perforation.

Diagnostic performance of quantitative signal intensity measurements on magnetic resonance imaging for distinguishing cerebellopontine angle meningioma from acoustic schwannoma.

OBJECTIVE: Our study investigated magnetic resonance imaging measurements for differentiating cerebellopontine angle (CPA) meningioma from vestibular schwannoma (VS). PATIENTS AND METHODS: This retrospective study compared 36 meningioma and 36 VS patients. The tumor volume (Vtumor) and peritumor edema index (EI) relationship was analyzed. T2-weighted three-dimensional gradient-echo image signal intensity (T23D) and apparent diffusion coefficient (ADC) differentiation cutoff values were defined. Mann-Whitney U test, independent-samples t-test, receiver operating characteristic curve, and Spearman's correlation analyses were applied. RESULTS: Meningioma had higher Vtumor (p=0.009) and EI (p=0.031) values than VS. Meningioma had significantly (p<0.001) lower values than VS for mean ADC (ADCmean: 0.841±0.083×10-3 vs.1.173±0.190×10-3 mm2/s), minimum ADC (ADCmin: 0.716±0.078×10-3 vs.1.045±0.178×10-3 mm2/s), tumor:white matter ADC ratio (rADC: 1.198±0.19 vs. 1.59±0.30), mean T23D (T23Dmean: 142.91±19.9 vs. 218.72±84.73), and tumor:adipose T23D ratio (rT23d: 0.19±0.06 vs. 0.30±0.28) Cutoff, sensitivity (Se), and specificity (Sp) values were ADCmin, 0.856×10-3 mm2/s (Se: 96.6%, Sp: 100%); ADCmean, 0.963×10-3 mm2/s (Se: 96.6%, Sp: 95.5%); rADC, 1.3189 (Se: 93.1%, Sp: 81.8%), T23Dmean (Se: 96.6%, Sp: 100%); rT23D, 0.1951 (Se: 89.7%, Sp: 100%), Vtumor, 14828.65 mm3 (Se: 75.0%, Sp: 66.7%), and EI, 1.1025 (Se: 47.2%, Sp: 100%). CONCLUSIONS: ADCmin, ADCmean, rADC, T23Dmean, rT23D, Vtumor, and EI, effectively discriminated meningioma from VS.

Discrimination between glioblastoma and solitary brain metastasis: a quantitative analysis based on FLAIR signal intensity.

OBJECTIVE: This study determined the diagnostic performance of fluid-attenuated inversion recovery (FLAIR) signal intensity (SI) in discriminating between glioblastoma (GBM) and solitary brain metastasis (SBM). PATIENTS AND METHODS: We recruited 40 patients with a histologically confirmed diagnosis of GBM or SBM who underwent conventional 3 Tesla magnetic resonance imaging before surgery or biopsy between August 2020 and January 2022. Three regions of interest were placed to assess FLAIR SI: the enhancing region (eFLAIR), the peritumoral region (pFLAIR), and the contralateral normal white matter (nFLAIR). The diagnostic performance of significantly different parameters between the two tumor entities was analyzed by receiver operating characteristic (ROC) curve analysis. RESULTS: The pFLAIR SI was significantly lower in GBM than in SBM (p < 0.05). The eFLAIR SI and the SI ratio eFLAIR and nFLAIR (e/nFLAIR) were significantly higher in GBM than in SBM (p < 0.05). On ROC curve analysis, the e/nFLAIR ratio provided the highest area under the curve value of 81%, with a sensitivity of 80.8% and a specificity of 85.7%, for distinguishing between the two tumor types. CONCLUSIONS: The eFLAIR, pFLAIR, and e/nFLAIR parameters are useful for differentiating between GBM and SBM.

Novel urchin-like FeCo oxide nanostructures supported carbon spheres as a highly sensitive sensor for hydrazine sensing application.

Herein, we successfully fabricated a novel nanostructure based on hierarchical urchin-like FeCo oxide supported carbon spheres (FeCo Oxide/CSs) via a two-step hydrothermal method followed by a simple annealing step at 300 °C under air. It was found that such urchin-like FeCo Oxide/CSs structure exhibited superior catalytic activity towards hydrazine oxidation to CSs, Fe Oxide/CSs, Co Oxide/CSs, and FeCo Hydroxide/CSs material. In this regard, the FeCo Oxide/CSs displayed a wide linear detection range of 0.1-516.6 µM, low detection limit of 0.1 µM, and long-term stability. The material also showed good selectivity towards hydrazine detection in the presence of various interferences, such as uric acid, ascorbic acid, urea, dopamine, Na+, SO42-, K+, and Cl-. The excellent sensing performance of the FeCo Oxide/CSs was assumed to the unique hierarchical urchin structure with the high density and uniformity of nano-sized FeCo Oxide nanoneedles, which produced massive electroactive sites and enhanced charge transfer ability. The achieved results implied that the FeCo Oxide/CSs may be a great candidate for sensitive hydrazine detection.

Hybrid capture-based genomic profiling of circulating tumor DNA from patients with estrogen receptor-positive metastatic breast cancer.

BACKGROUND: Genomic changes that occur in breast cancer during the course of disease have been informed by sequencing of primary and metastatic tumor tissue. For patients with relapsed and metastatic disease, evolution of the breast cancer genome highlights the importance of using a recent sample for genomic profiling to guide clinical decision-making. Obtaining a metastatic tissue biopsy can be challenging, and analysis of circulating tumor DNA (ctDNA) from blood may provide a minimally invasive alternative. PATIENTS AND METHODS: Hybrid capture-based genomic profiling was carried out on ctDNA from 254 female patients with estrogen receptor-positive breast cancer. Peripheral blood samples were submitted by clinicians in the course of routine clinical care between May 2016 and March 2017. Sequencing of 62 genes was carried out to a median unique coverage depth of 7503×. Genomic alterations (GAs) in ctDNA were evaluated and compared with matched tissue samples and genomic datasets of tissue from breast cancer. RESULTS: At least 1 GA was reported in 78% of samples. Frequently altered genes were TP53 (38%), ESR1 (31%) and PIK3CA (31%). Temporally matched ctDNA and tissue samples were available for 14 patients; 89% of mutations detected in tissue were also detected in ctDNA. Diverse ESR1 GAs including mutation, rearrangement and amplification, were observed. Multiple concurrent ESR1 GAs were observed in 40% of ESR1-altered cases, suggesting polyclonal origin; ESR1 compound mutations were also observed in two cases. ESR1-altered cases harbored co-occurring GAs in PIK3CA (35%), FGFR1 (16%), ERBB2 (8%), BRCA1/2 (5%), and AKT1 (4%). CONCLUSIONS: GAs relevant to relapsed/metastatic breast cancer management were identified, including diverse ESR1 GAs. Genomic profiling of ctDNA demonstrated sensitive detection of mutations found in tissue. Detection of amplifications was associated with ctDNA fraction. Genomic profiling of ctDNA may provide a complementary and possibly alternative approach to tissue-based genomic testing for patients with estrogen receptor-positive metastatic breast cancer.

Inhibition of WNT signaling attenuates self-renewal of SHH-subgroup medulloblastoma.

The SMOOTHENED inhibitor vismodegib is FDA approved for advanced basal cell carcinoma (BCC), and shows promise in clinical trials for SONIC HEDGEHOG (SHH)-subgroup medulloblastoma (MB) patients. Clinical experience with BCC patients shows that continuous exposure to vismodegib is necessary to prevent tumor recurrence, suggesting the existence of a vismodegib-resistant reservoir of tumor-propagating cells. We isolated such tumor-propagating cells from a mouse model of SHH-subgroup MB and grew them as sphere cultures. These cultures were enriched for the MB progenitor marker SOX2 and formed tumors in vivo. Moreover, while their ability to self-renew was resistant to SHH inhibitors, as has been previously suggested, this self-renewal was instead WNT-dependent. We show here that loss of Trp53 activates canonical WNT signaling in these SOX2-enriched cultures. Importantly, a small molecule WNT inhibitor was able to reduce the propagation and growth of SHH-subgroup MB in vivo, in an on-target manner, leading to increased survival. Our results imply that the tumor-propagating cells driving the growth of bulk SHH-dependent MB are themselves WNT dependent. Further, our data suggest combination therapy with WNT and SHH inhibitors as a therapeutic strategy in patients with SHH-subgroup MB, in order to decrease the tumor recurrence commonly observed in patients treated with vismodegib.

Coherently Tunable Triangular Trefoil Phaseonium Metamaterial.

Phaseonium is a three-level Λ quantum system, in which a coherent microwave and an optical control (pump) beams can be used to actively modulate the dielectric response. Here we propose a new metamaterial structure comprising of a periodic array of triangular phaseonium metamolecules arranged as a trefoil. We present a computational study of the spatial distribution of magnetic and electric fields of the probe light and the corresponding transmission and reflection, for various parameters of the optical and microwave beams. For specific values of the probing frequencies and control fields, the phaseonium can display either metallic or dielectric optical response. We find that, in the metallic regime, the phaseonium metamaterial structure supports extremely large transmission, with optical amplification at large enough intensity of the microwave thanks to strong surface plasmon coupling; while, in the dielectric regime without microwave excitation, the transmission bandwidth can be tuned by varying the control beam intensity. Implementation of such phaseonium metamaterial structure in solid-state systems, such as patterned crystals doped with rare-earth elements or dielectric matrices embedded with quantum dots, could enable a new class of actively tunable quantum metamaterials.

Effect of organoclay on morphology and properties of linear low density polyethylene and Vietnamese cassava starch biobased blend.

Linear low density polyethylene (LLDPE)/thermal plastic starch (TPS) blend was studied to prepare the biobased nanocomposite material using organoclay nanofil15 (N15) modified by alkilammonium as the reinforced phase. The LLDPE/TPS blend and its nanocomposites were elaborated by melt mixing method at 160 °C for 7 min. And the compounded sample was filmed by blowing method at three different zones of temperature profile which are 160-170-165 °C. The good dispersion of clay in the polymer blend matrix is showed by X-ray diffraction (XRD) and transmission electronic microscopy (TEM), and a semi-exfoliated structure was obtained. The thermal and mechanical properties of materials are enhanced when N15 is added to the mixture. The effect of N15 on morphology and particles size of TPS phase is also investigated. The biodegradation test shows that more than 60% in weight of LLDPE/TPS film is degraded into CO2, H2O, methane and biomass after 5 months in compost soil.

MutT Homolog 1 (MTH1) maintains multiple KRAS-driven pro-malignant pathways.

Oncogenic RAS promotes production of reactive oxygen species (ROS), which mediate pro-malignant signaling but can also trigger DNA damage-induced tumor suppression. Thus RAS-driven tumor cells require redox-protective mechanisms to mitigate the damaging aspects of ROS. Here, we show that MutT Homolog 1 (MTH1), the mammalian 8-oxodGTPase that sanitizes oxidative damage in the nucleotide pool, is important for maintaining several KRAS-driven pro-malignant traits in a nonsmall cell lung carcinoma (NSCLC) model. MTH1 suppression in KRAS-mutant NSCLC cells impairs proliferation and xenograft tumor formation. Furthermore, MTH1 levels modulate KRAS-induced transformation of immortalized lung epithelial cells. MTH1 expression is upregulated by oncogenic KRAS and correlates positively with high KRAS levels in NSCLC human tumors. At a molecular level, in p53-competent KRAS-mutant cells, MTH1 loss provokes DNA damage and induction of oncogene-induced senescence. In p53-nonfunctional KRAS-mutant cells, MTH1 suppression does not produce DNA damage but reduces proliferation and leads to an adaptive decrease in KRAS expression levels. Thus, MTH1 not only enables evasion of oxidative DNA damage and its consequences, but can also function as a molecular rheostat for maintaining oncogene expression at optimal levels. Accordingly, our results indicate MTH1 is a novel and critical component of oncogenic KRAS-associated malignancy and its inhibition is likely to yield significant tumor-suppressive outcomes in KRAS-driven tumors.

The hedgehog processing pathway is required for NSCLC growth and survival.

Considerable interest has been generated from the results of recent clinical trials using smoothened (SMO) antagonists to inhibit the growth of hedgehog (HH) signaling-dependent tumors. This interest is tempered by the discovery of SMO mutations mediating resistance, underscoring the rationale for developing therapeutic strategies that interrupt HH signaling at levels distinct from those inhibiting SMO function. Here, we demonstrate that HH-dependent non-small cell lung carcinoma (NSCLC) growth is sensitive to blockade of the HH pathway upstream of SMO, at the level of HH ligand processing. Individually, the use of different lentivirally delivered shRNA constructs targeting two functionally distinct HH-processing proteins, skinny hedgehog (SKN) or dispatched-1 (DISP-1), in NSCLC cell lines produced similar decreases in cell proliferation and increased cell death. Further, providing either an exogenous source of processed HH or a SMO agonist reverses these effects. The attenuation of HH processing, by knocking down either of these gene products, also abrogated tumor growth in mouse xenografts. Finally, we extended these findings to primary clinical specimens, showing that SKN is frequently overexpressed in NSCLC and that higher DISP-1 expression is associated with an unfavorable clinical outcome. Our results show a critical role for HH processing in HH-dependent tumors, identifies two potential druggable targets in the HH pathway, and suggest that similar therapeutic strategies could be explored to treat patients harboring HH ligand-dependent cancers.

Demonstration of polarization pulling using a fiber-optic parametric amplifier.

We report the observation of all-optical polarization pulling of an initially polarization-scrambled signal using parametric amplification in a highly nonlinear optical fiber. Broadband polarization pulling has been achieved both for the signal and idler waves with up to 25 dB gain using the strong polarization sensitivity of parametric amplifiers. We further derive the probability distribution function for the final polarization state, assuming a randomly polarized initial state, and we show that it agrees well with the experiments.

Hospitalization of paediatric patients for methicillin-resistant Staphylococcus aureus skin and soft-tissue infection, 1998-2006.

Hospital discharge reports have provided data for studies of methicillin-resistant Staphylococcus aureus (MRSA) skin and soft-tissue infection (SSTI) studies. This analysis determined the sensitivity and positive predictive value of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code combinations to calculate hospitalization incidence rates, representativeness of a set of three ICD-9-CM codes to define MRSA SSTI, and hospitalization incidence rate trends for paediatric MRSA SSTIs in Los Angeles County (LAC). Using 133 cases from 31 hospitals, we found that the set of three ICD-9-CM codes used to define laboratory-confirmed cases had one of the highest positive predictive values (49%). There was no difference in age and race between those categorized using three codes vs. other code combinations. A dramatic increase in paediatric MRSA SSTI cases occurred in LAC during 1998-2006. We conclude that this combination of codes may be used to determine the rise of MRSA SSTIs in paediatric populations.

Cisplatin enhances the antitumor effect of tumor necrosis factor-related apoptosis-inducing ligand gene therapy via recruitment of the mitochondria-dependent death signaling pathway.

Despite adequately expressing tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptors DR4/DR5, malignant cells are frequently refractory to the cytotoxic effect of this apoptosis-inducing ligand. The susceptibility of cancer cells to TRAIL can be potentiated by cisplatin (CDDP). This study was designed to evaluate the ability of cisplatin to enhance the cytotoxic effect of TRAIL gene therapy using the recombinant adenovirus-mediated tumor-selective expression of membrane-bound green fluorescence protein (GFP)-TRAIL fusion protein (AdVgTRAIL) on thoracic cancer cells and to elucidate the putative mechanisms responsible for this synergistic combination effect. While causing little death of cultured thoracic cancer cells by itself, AdVgTRAIL in combination with CDDP, on the other hand, mediated profound supra-additive cytotoxicity and apoptosis via a strong bystander effect. CDDP/AdVgTRAIL-induced cytotoxicity was completely abrogated either by the pancaspase inhibitor zVAD-fmk or by the selective caspase 9 inhibitor or by transient knockdown of caspase 9 by siRNA, indicating that this process was caspase-mediated and mitochondria-dependent. This was confirmed by the observation that Bcl2 overexpression protected the cells from combination-induced cytotoxicity. Robust activation of caspase 8 activity in combination-treated cells was blocked by overexpression of Bcl2, indicating that caspase 8 activation was secondary to the mitochondria-mediated amplification feedback loop. Combining CDDP with AdVgTRAIL greatly enhances its tumoricidal efficacy in cultured thoracic cancer cells in vitro. The two agents interact to mediate profound activation of caspase cascade via recruitment of the mitochondria and positive feedback loop. The CDDP/AdVgTRAIL combination also exhibits a strong antitumor effect in in vivo animal model of human cancer xenografts.

Dynamic transcriptional regulatory complexes including BORIS, CTCF and Sp1 modulate NY-ESO-1 expression in lung cancer cells.

Previously, we reported that the paralogous zinc-finger proteins--CTCF and brother of the regulator of imprinted sites (BORIS), directly contribute to transcriptional regulation of NY-ESO-1 in lung cancer cells. To further examine mechanisms that mediate expression of this cancer-testis gene, we performed software-guided analysis of the NY-ESO-1 promoter region, which revealed several potential Sp1-binding motifs. Sequential 5-aza-2'deoxycytidine/depsipeptide FK228 treatment markedly induced BORIS expression and enhanced nuclear translocation of Sp1 in lung cancer cells. Transient transfection assays using promoter-reporter constructs, as well as gel-shift and chromatin immunoprecipitation experiments revealed that NY-ESO-1 promoter activity coincided with occupancy of the proximal Sp1-binding site in lung cancer cells. Mutations within the Sp1 recognition sequence specifically eliminated binding of Sp1 to this motif in vitro, and markedly diminished NY-ESO-1 promoter activity in vivo. siRNA-mediated inhibition of Sp1 expression decreased NY-ESO-1 promoter activity, whereas knock down of CTCF expression augmented NY-ESO-1 transcription in lung cancer cells. Co-immunoprecipitation experiments indicated that Sp1 physically interacts with BORIS but not with CTCF in vivo. Collectively, these findings suggest that BORIS recruits Sp1 to mediate de-repression of NY-ESO-1 during pulmonary carcinogenesis.

Potentiation of the anticancer effect of valproic acid, an antiepileptic agent with histone deacetylase inhibitory activity, by the kinase inhibitor Staurosporine or its clinically relevant analogue UCN-01.

Histone deacetylase inhibitors (HDACIs) are novel anticancer agents with potent cytotoxicity against a wide range of malignancies. We have previously demonstrated that either Calphostin C (CC) (a protein kinase C (PKC) inhibitor) or Parthenolide (an NF-kappaB inhibitor) abrogates HDACI-induced transcriptional activation of NF-kappaB and p21, which is associated with profound potentiation of HDACI-mediated induction of apoptosis. Valproic acid (VA), a commonly used antiepileptic agent, has recently been shown to be an HDACI. This study was aimed to evaluate the anticancer property of VA in thoracic cancer cells and the development of clinically relevant strategies to enhance VA-mediated induction of apoptosis using kinase inhibitors Staurosporine (STP) or its analogue UCN-01. Treating cultured thoracic cancer cells with VA (0.62-10.0 mM) resulted in significant cell line- and dose-dependent growth inhibition (IC(50) values: 4.1-6.0 mM) and cell cycle arrest at G1/S checkpoint with profound accumulation of cells at G0/G1 phase but little induction of apoptosis. Valproic acid, being an HDACI, caused significant dose-dependent accumulation of hyperacetylated histones, following 24 h of treatment. Valproic acid-mediated 5-20-fold upregulation of transcriptional activity of NF-kappaB was substantially (50-90%) suppressed by cotreatment with CC, STP or UCN-01. Whereas minimal death (<20%) was observed in cells treated with either VA (1.0 or 5.0 mM) alone or kinase inhibitors alone, 60-90% of cells underwent apoptosis following exposure to combinations of VA+kinase inhibitors. Kinase inhibitor-mediated suppression of NF-kappaB transcriptional activity played an important role in sensitising cancer cells to VA as direct inhibition of NF-kappaB by Parthenolide drastically synergised with VA to induce apoptosis (VA+Parthenolide: 60-90% compared to <20% following single-drug treatments). In conclusion, VA, a well-known antiepileptic drug, has mild growth-inhibitory activity on cultured cancer cells. The weak VA-mediated induction of apoptosis of thoracic cancer cells can be profoundly enhanced either by Parthenolide, a pharmacologic inhibitor of NF-kappaB, or by UCN-01 a kinase inhibitor that has already undergone phase I clinical development. Combinations of VA with either a PKC inhibitor or an NF-kappaB inhibitor are promising novel molecularly targeted therapeutics for thoracic cancers.

Enhancement of paclitaxel-mediated cytotoxicity in lung cancer cells by 17-allylamino geldanamycin: in vitro and in vivo analysis.

BACKGROUND: It has previously been demonstrated that 17-allylamino geldanamycin (17-AAG) enhances paclitaxel-mediated cytotoxicity and downregulates vascular endothelial factor expression in non-small cell lung cancer. This project was designed to evaluate the tumoricidal and antiangiogeneic effects of 17-AAG and paclitaxel in H358 non-small cell lung cancer cells grown as xenografts in nude mice. METHODS: In vitro cytotoxic drug combination effects were evaluated by (4, 5-dimethylthiazo-2-yl)-2, 5-diphenyl tetrazolium bromide-based proliferation assays. The combinations of 17-AAG and paclitaxel were administered intraperitoneally in nude mice bearing H358 tumor xenografts. Tumor volumes were measured weekly. Tumor expression of erbB2, vascular endothelial cell growth factor, von Willebrand factor (tumor microvasculature), and activated caspase 3 (apoptosis) were determined by immunohistochemistry. RESULTS: Five- to 22-fold enhancement of paclitaxel cytotoxicity was achieved by paclitaxel + 17-AAG combination that was paralleled with marked induction of apoptosis. This combination treatment profoundly suppressed tumor growth and significantly prolonged survival of mice bearing H358 xenografts. Immunohistochemical staining of tumor tissues indicated profound reduction of vascular endothelial cell growth factor expression associated with reduction of microvasculature in tumors treated with 17-AAG. Apoptotic cells were more abundant in tumors treated with 17-AAG + paclitaxel than in those treated with 17-AAG or paclitaxel alone. CONCLUSIONS: Concurrent exposure of H358 cells to 17-AAG and paclitaxel resulted in supraadditive growth inhibition effects in vitro and in vivo. Analysis of molecular markers of tumor tissues indicated that therapeutic drug levels could be achieved with this chemotherapy regimen leading to significant biological responses. Moreover, 17-AAG-mediated suppression of vascular endothelial cell growth factor production by tumor cells may contribute to the antitumor effects of this drug combination in vivo.

Scooter injuries: a new pediatric morbidity.

OBJECTIVE: To describe types of injuries, mechanisms of injury, and treatment of injuries caused by scooter use in children, and to discuss issues of injury prevention in children who use scooters. STUDY DESIGN: Data were collected from 14 children seen by a general pediatrician and an orthopedic surgeon over a 3-month period in the summer of 2000. Detailed histories were obtained from patients and their families, and medical records were reviewed. RESULTS: Eleven of the 14 patients suffered fractures. The injuries in the other 3 patients were a large abrasion, a laceration, and a septic knee. Half (7) of the children were injured within the first day of riding their scooter, and 13 of the 14 injuries occurred within the first month of scooter use. Only 5 patients used protective gear at the time of their injuries, and those patients were injured in unprotected parts of their bodies. CONCLUSIONS: The popularity of scooters presents a new cause of pediatric injuries and a significant health hazard to children. In our study, most injuries occurred shortly after children began scooter use, and younger children suffered the most severe injuries. Additional studies are needed to determine how scooter-related injuries can be prevented or minimized. scooters, injuries.

Targets for molecular intervention in multistep pulmonary carcinogenesis.

Lung cancers are a leading cause of mortality worldwide, and most of these neoplasms are directly attributable to tobacco abuse. Recent studies have begun to elucidate molecular mechanisms of multistep aero-digestive tract carcinogenesis, revealing novel targets for intervention in lung cancers and their precursor lesions. This review summarizes the molecular biology of lung cancers in relation to the prognosis and treatment of patients with these neoplasms.

Sequential 5-Aza-2 deoxycytidine-depsipeptide FR901228 treatment induces apoptosis preferentially in cancer cells and facilitates their recognition by cytolytic T lymphocytes specific for NY-ESO-1.

Global alterations in chromatin structure profoundly influence gene expression in thoracic neoplasms, silencing tumor suppressors while facilitating the expression of various cancer testis antigens such as NY-ESO-1. Although recent studies have shown that histone deacetylase inhibitors can potentiate tumor suppressor gene induction mediated by demethylating agents in cancer cells, the ability of these agents to augment cancer testis antigen expression have not been fully defined. The authors designed the current study to determine whether the histone deacetylase inhibitor, depsipeptide FR901228 (DP), could enhance NY-ESO-1 induction mediated by the DNA demethylating agent 5-Aza-2'-deoxycytidine (DAC) in cell lines established primarily from thoracic cancers. Quantitative reverse-transcriptase polymerase chain reaction analysis revealed that, under exposure conditions potentially achievable in clinical settings, DAC dramatically induced NY-ESO-1 expression in cultured cancer lines. DP alone mediated negligible target gene induction but significantly augmented DAC-mediated induction of NY-ESO-1. After DAC or sequential DAC-DP treatment, HLA-A*0201 cancer cells were recognized by an HLA-A*0201 CTL specific for NY-ESO-1. Although sequential DAC/DP exposure did not uniformly enhance immune recognition of target cells compared with DAC alone, this treatment mediated profound induction of apoptosis in cancer cells but not normal human bronchial epithelia. The apoptotic effects of DAC, DP, or sequential DAC-DP did not correlate in an obvious manner with histology, or the magnitude of NY-ESO-1 induction in cancer cells. Although the mechanisms have not been fully defined, sequential DAC-DP treatment may be a novel strategy to augment antitumor immunity in cancer patients.