Clinical features and prognosis of patients with idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease.

Idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) share common risk factors. They could therefore be expressed in a single patient. However, the prevalence, clinical characteristics and prognosis of individuals with comorbid IPF and COPD are not known. From 2003 to 2007, the Korean Interstitial Lung Disease Study Group created a register for idiopathic interstitial pneumonia using 2002 ATS/ERS (American Thoracic Society/European Respiratory Society) criteria. Of the 1546 IPF patients assessed, 143 had decreased lung function consistent with COPD (IPF-COPD). COPD was diagnosed based on age (≥40 years) and pulmonary function (forced expiratory volume in 1 sec [FEV1]/forced vital capacity [FVC] ratio < 0.7). The median age of the IPF-COPD group was 71.0 years (interquartile range 66.0-76.0); most patients were male (88.1%). FVC (%) was significantly higher in the IPF-COPD group; however, FEV1 (%) was significantly lower in the IPF-COPD group (P < 0.001). Diffusing capacity of the lung for carbon monoxide (DLCO) was not significantly different between the two groups. In survival analysis, age and FVC (%), but not COPD, were significantly associated with prognosis (respectively P = 0.003, 0.001 and 0.401). COPD severity was also not related to prognosis (P = 0.935). The prevalence of IPF-COPD was estimated to be ∼9.2% among all IPF patients; prognosis of patients with IPF-COPD was not worse than those with IPF alone. .

CXCR3-deficient mesenchymal stem cells fail to infiltrate into the nephritic kidney and do not ameliorate lupus symptoms in MRL. Faslpr mice.

Mesenchymal stem cell therapy is a promising candidate for the treatment of systemic lupus erythematosus (SLE). To exert their efficacy fully, mesenchymal stem cells must infiltrate efficiently into the lesion sites. Here, we examined the role of CXCR3 in mesenchymal stem cell infiltration into the kidney of MRL. Faslpr mice, which highly expressed CXCL10. The phenotypes, production of immunosuppressive mediators, and capacity to inhibit T and B cells of CXCR3-deficient mesenchymal stem cells were similar to those of wild-type mesenchymal stem cells. However, they showed less infiltration into the nephritic kidney, less conjugation with endothelial cells and weaker MMP-9 expression than did wild-type mesenchymal stem cells. Consequently, CXCR3-deficient mesenchymal stem cells did not ameliorate lupus symptoms in MRL. Faslpr mice in comparison with wild-type mesenchymal stem cells. In summary, our data suggest that upregulation of CXCR3 in mesenchymal stem cells will be a good strategy to increase their infiltration into the kidney, which will improve therapeutic outcomes in SLE.

Postoperative pharmacokinetics of meloxicam in horses after surgery for colic syndrome.

NSAIDs are often used in horses with colic syndrome during the postoperative period, due to their ability to contrast endotoxemia and to promote an analgesic and anti-inflammatory effect. As the pharmacokinetics of a drug are often modified in unhealthy animals compared to healthy subjects, the aim of this study was to evaluate the pharmacokinetic profile of meloxicam after i.v. administration in horses undergoing laparotomy for colic syndrome. Eight horses received 0.6 mg/kg of meloxicam i.v. towards the end of surgery. Blood samples were taken at scheduled time points during the following 24 hr. The serum concentration of the drug was determined by HPLC. Terminal half-life (6.88 ± 2.96 hr), volume of distribution at steady-state (186.53 ± 61.20 ml/Kg) and clearance (27.91 ± 5.72 ml kg-1  hr-1 ) were similar to those reported in literature for healthy horses. This result suggests that no adjustment of the approved dose should be necessary when meloxicam is used to treat horses in the immediate postoperative period after surgery for colic syndrome.

RaRF confers RA resistance by sequestering RAR to the nucleolus and regulating MCL1 in leukemia cells.

Retinoic acid (RA) has broad clinical applications for the treatment of various cancers, particularly acute promyelocytic leukemia. However, RA-based therapy is limited by relapse in patients associated with RA resistance, the mechanism of which is poorly understood. Here, we suggest a new molecular mechanism of RA resistance by a repressor, named RA resistance factor (RaRF). RaRF suppressed transcriptional activity of the RA receptor (RAR) by directly interacting with and sequestering RAR to the nucleolus in response to RA. RaRF was highly expressed in RA-resistant leukemia cells and its expression was strongly correlated with RA sensitivity. MCL1 was upregulated by RA treatment upon RaRF depletion, accompanying leukemic myeloblast differentiation, which is negatively regulated by ectopic RaRF expression. Collectively, we propose that RaRF may be a factor in the resistance mechanism and thus a potential target for leukemia therapy using RA.

Next-generation sequencing with a myeloid gene panel in core-binding factor AML showed KIT activation loop and TET2 mutations predictive of outcome.

Clinical outcome and mutations of 96 core-binding factor acute myeloid leukemia (AML) patients 18-60 years old were examined. Complete remission (CR) after induction was 94.6%. There was no significant difference in CR, leukemia-free-survival (LFS) and overall survival (OS) between t(8;21) (N=67) and inv(16) patients (N=29). Univariate analysis showed hematopoietic stem cell transplantation at CR1 as the only clinical parameter associated with superior LFS. Next-generation sequencing based on a myeloid gene panel was performed in 72 patients. Mutations in genes involved in cell signaling were associated with inferior LFS and OS, whereas those in genes involved in DNA methylation were associated with inferior LFS. KIT activation loop (AL) mutations occurred in 25 patients, and were associated with inferior LFS (P=0.003) and OS (P=0.001). TET2 mutations occurred in 8 patients, and were associated with significantly shorter LFS (P=0.015) but not OS. Patients negative for KIT-AL and TET2 mutations (N=41) had significantly better LFS (P<0.001) and OS (P=0.012) than those positive for both or either mutation. Multivariate analysis showed that KIT-AL and TET2 mutations were associated with inferior LFS, whereas age ⩾40 years and marrow blast ⩾70% were associated with inferior OS. These observations provide new insights that may guide better treatment for this AML subtype.

Accuracy of Xpert(®) MTB/RIF assay compared with AdvanSure™ TB/NTM real-time PCR using bronchoscopy specimens.

BACKGROUND: The performance of Xpert(®) MTB/RIF assay, an automated nucleic acid amplification test (NAAT) that was developed for the detection of tuberculosis (TB), has been evaluated in various clinical settings. However, few studies have compared Xpert with other NAATs, especially its performance using lower respiratory tract specimens (LRTS). OBJECTIVE: To compare the practical diagnostic performance of the Xpert assay with that of the AdvanSure™ TB/NTM RT-PCR kit in the detection of pulmonary TB (PTB), using LRTS obtained through bronchoscopy. RESULTS: Of 249 patients included, 105 had culture-confirmed PTB. Using culture as reference, the overall sensitivity of Xpert and AdvanSure was respectively 92.4% and 83.8%. When acid-fast bacilli smear results were taken into consideration, the sensitivity of Xpert for smear-positive and smear-negative LRTS was respectively 100% and 88.9%, while that of the AdvanSure was 100% and 76.4%. Xpert showed better results than AdvanSure in terms of sensitivity in smear-negative LRTS (P = 0.012), but no difference in smear-positive LRTS. CONCLUSIONS: Xpert may be advantageous in the detection of PTB using LRTS, particularly in low microbiological burden settings.

Effect of a c-MYC Gene Polymorphism (g.3350G>C) on Meat Quality Traits in Berkshire.

c-MYC (v-myelocytomatosis viral oncogene homologue) is a transcription factor that plays important role in many biological process including cell growth and differentiation, such as myogenesis and adipogenesis. In this study, we aimed to detect MYC gene polymorphisms, their genotype frequencies and to determine associations between these polymorphisms and meat quality traits in Berkshire pigs. We identified a single nucleotide polymorphism (SNP) in intron 2 of MYC gene by Sanger sequencing, i.e., g.3350G>C (rs321898326), that is only found in Berkshire pigs, but not in other breeds including Duroc, Landrace, and Yorkshire pigs that were used in this study. Genotypes of total 378 Berkshire pigs (138 sows and 240 boars) were determined using Hha I restriction enzyme digestion after polymerase chain reaction. Observed allele frequencies of GG, GC, and CC genotypes were 0.399, 0.508, and 0.093 respectively. Statistical analysis indicated that the g.3350G>C polymorphism was significantly associated with pH45min and cooking loss (p<0.05), suggesting that g.3350G>C SNP can be used for pre-selection of pH45min and cooking loss traits in Berkshire pigs.

New analysis methods for skin fine-structure via optical image and development of 3D skin Cycloscan(™).

BACKGROUND/PURPOSE: This study was conducted to develop methods for measuring skin fine-structure via optical image and apparatus for photographing to analyze efficacy of anti-aging. METHODS: We developed an apparatus named 3D Skin CycloScan(™) to evaluate the efficacy of cosmetics by imagification of skin fine-structure such as wrinkles, pores, and skin texture. The semi-sphere shaped device has 12 different sequential flashing light sources captures optical image simultaneously in one second to exclude the influence of the subject's movement. The normal map that is extracted through shape from shading method is composed of face contour and skin fine-structure parts. When the low-frequency component which is the result of the Gaussian Filter application is eliminated, we can get only skin fine-structure. In this normal map, it is possible to extract two-dimensional vector map called direction map and we can regulate the intensity of the image of wrinkles, pores, and skin texture after filtering the direction map. We performed a clinical study to apply this new apparatus and methods to evaluate an anti-aging efficacy of cosmetics visually and validate with other conventional methods. RESULTS: After using anti-aging cream including 2% adenosine for 8 weeks, the total amount of fine wrinkle around eye area detected via 3D Skin CycloScan(™) was reduced by 12.1%. Also, wrinkles on crow's feet measured by PRIMOS COMPACT(®) (GFMesstechnik GmbH, Germany) reduced 11.7%. CONCLUSION: According to an aspect of the present study, by changing the direction of the lights toward to subject's skin, we can obtain the information about the fine structures present on the skin such as wrinkles, pores, or skin texture and represent it as an image.

USP11-dependent selective cIAP2 deubiquitylation and stabilization determine sensitivity to Smac mimetics.

Given their crucial role in apoptosis suppression, inhibitor of apoptosis proteins (IAPs) have recently become attractive targets for cancer therapy. Here, we report that cellular IAP2 (cIAP2) is specifically stabilized in several cancer cell lines, leading to resistance to Smac mimetics, such as BV6 and birinapant. In particular, our results showed that cIAP2 depletion, but not cIAP1 depletion, sensitized cancer cells to Smac mimetic-induced apoptosis. Ubiquitin-specific protease 11 (USP11) is a deubiquitylase that directly stabilizes cIAP2. USP11 overexpression is frequently found in colorectal cancer and melanoma and is correlated with poor survival. In our study, cancer cell lines expressing high levels of USP11 exhibited strong resistance to Smac mimetic-induced cIAP2 degradation. Furthermore, USP11 downregulation sensitized these cells to apoptosis induced by TRAIL and BV6 and suppressed tumor growth in a xenograft model. Finally, the TNFα/JNK pathway induced USP11 expression and maintained cIAP2 stability, suggesting an alternative TNFα-dependent cell survival pathway. Collectively, our data suggest that USP11-stabilized cIAP2 may serve as a barrier against IAP-targeted clinical approaches.

A case-controlled, retrospective, comparative study on the use of biodegradable synthetic polyurethane foam versus polyvinyl acetate sponge after nasal fracture reduction.

One of the most frequently used packing materials in closed reduction of a nasal bone fracture is the hydroxylated polyvinyl acetate sponge (PVAS; Merocel(®)); however this may cause synechia, epistaxis, and pain. Synthetic polyurethane foam (SPF; Nasopore(®) Forte) has recently been used in septoplasty to prevent synechia or restenosis and haematoma formation. The purpose of this study was to compare the effects of PVAS and SPF on postoperative appearance and discomfort following the reduction of nasal bone fractures. We retrospectively reviewed all patient questionnaires and medical histories, and clinical photographs and computed tomography scans obtained before and after surgery. Outcomes were assessed using the Global Aesthetic Improvement Scale (GAIS) score and visual analogue scale (VAS) scores, which were used to assess discomfort during the 6-month follow-up period. Postoperatively, there was no statistically significant difference in the GAIS for the two packing materials (P > 0.05). Postoperative epistaxis was observed at a significantly lower rate in the SPF group than in the PVAS group, whereas anterior rhinorrhea and posterior nasal drip occurred at significantly higher rates following removal of packing in the SPF group (P < 0.05). The results of this study suggest that synthetic dissolvable polyurethane may be a reliable alternative material for nasal packing and postoperative management following the reduction of nasal bone fractures.

Brain and spinal tumour.

This study reviewed the epidemiology of brain and spinal tumours in Sarawak from January 2009 till December 2012. The crude incidence of brain tumour in Sarawak was 4.6 per 100,000 population/year with cumulative rate 0.5%. Meningioma was the most common brain tumour (32.3%) and followed by astrocytoma (19.4%). Only brain metastases showed a rising trend and cases were doubled in 4 years. This accounted for 15.4% and lung carcinoma was the commonest primary. Others tumour load were consistent. Primitive neuroectodermal tumour (PNET) and astrocytoma were common in paediatrics (60%). We encountered more primary spinal tumour rather than spinal metastases. Intradural schwannoma was the commonest and frequently located at thoracic level. The current healthcare system in Sarawak enables a more consolidate data collection to reflect accurate brain tumours incidence. This advantage allows subsequent future survival outcome research and benchmarking for healthcare resource planning.

Ultrafast response sensor to formaldehyde gas based on metal oxide.

Thick film semiconductor gas sensors based on indium oxide were fabricated on Si substrate. The sensing materials on Si substrate were characterized using optical microscopy, X-ray diffraction (XRD) and scanning electron microscopy (SEM), and so on. They were very fine and uniform and we found out that particle sizes were about 20~30 nm through XRD analysis. Gas responses of fabricated sensors were measured in a chamber where gas flow was controlled by mass flow controller (MFC). Their resistance changes were monitored in real time by using data acquisition board and personal computer. Gas response characteristics were examined for formaldehyde (HCHO) gas which was known as the cause of sick building syndrome. Particularly, the sensors showed responses to formaldehyde gas at sub ppm (cf, standard of natural environment in building is about 80 ppb by ministry of environment in Korea), as a function of operating temperatures and gas concentrations. Also, we investigated sensitivity, repetition, selectivity, response speed and reproducibility of the sensors. The lowest detection limit is HCHO 25 ppb and sensitivity at 800 ppb is over 25% at 350 °C operating temperature. The response time (8 s) and recovery time (15 s) to HCHO gas at 200 ppb were very fast compared to other commercial products in flow type measurement condition. Repetition measurement was very good with ±3% in full measurement range. The fabricated metal oxide gas sensor showed good performance to HCHO gas and proved that it could be adaptable to indoor environment in building.

Clinical course and outcome of rheumatoid arthritis-related usual interstitial pneumonia.

BACKGROUND: Although the prognosis of interstitial pneumonia in connective tissue disorders is better than that of idiopathic pulmonary fibrosis (IPF), the prognosis of rheumatoid arthritis (RA) related usual interstitial pneumonia (UIP) is controversial. OBJECTIVES: To determine prognosis, clinical course and prognostic factors of the patients with RA-UIP and compare them to IPF. DESIGN: Retrospective review of 84 patients with RA-UIP (biopsy-proven: 30) from two tertiary referral centers. RESULTS: The median follow-up period was 33 months. One half of the patients were stable, one third progressed, 17% had acute exacerbation and 6% improved. TLC % predicted was the only significant predictor for the stable group. Among non-AEx patients, 41% was treated due to poor initial lung function or progression of the disease and one half of them improved or had stable lung function. Despite of worse initial lung function, the survival of treated group was similar to untreated group. Age, FVC and change in DLco during 6 months were significant predictors for mortality. The prognosis of RA-UIP was significantly better than that of IPF matched with age, sex, smoking and baseline lung function (median survival, 53 vs. 41 months respectively, p = 0.015). CONCLUSIONS: In spite of variable clinical course of RA-UIP, overall prognosis of RA-UIP was significantly better compared to IPF. Our data supported the treatment of the patients with significant functional impairments or progression.

Resveratrol prevents development of eosinophilic rhinosinusitis with nasal polyps in a mouse model.

BACKGROUND: Since the recent establishment of a murine model of eosinophilic chronic rhinosinusitis with nasal polyps (CRSwNP), both the development of new drugs for treatment or prevention of eosinophilic CRSwNP and elucidation of their pathogenesis have been feasible. We investigated the therapeutic effects of resveratrol on CRSwNP and its mechanism of action using a murine model. METHODS: After induction of eosinophilic CRSwNP, the therapeutic effects of resveratrol were tested and compared with those of triamcinolone acetonide. Histopathologic changes were evaluated using hematoxylin and eosin for overall inflammation, Sirius red for eosinophils, and Masson's trichrome stain for collagen. The expression levels of the interleukin (IL)-4, IL-5, prostaglandin D synthase, and leukotriene C4 synthase genes were assessed by quantitative real-time PCR. Cyclooxygense-2 and 5-lipoxygense levels were evaluated by immunohistochemical staining and Western blot analysis. RESULTS: The degree of eosinophilic infiltration and subepithelial fibrosis was significantly decreased by administration of high-dose resveratrol, the potency of which was similar to that of triamcinolone acetonide. The expression levels of the IL-4, IL-5, prostaglandin D synthase, and leukotriene C4 synthase genes were significantly decreased by administration of low- or high-dose resveratrol. The production of 5-lipoxygenase was strongly inhibited by high-dose resveratrol. CONCLUSIONS: Resveratrol may be useful for the prevention of eosinophilic CRSwNP. A key mechanism of its action is believed to be its anti-inflammatory effect, particularly on eosinophils, by inhibiting the lipoxygenase pathway.

Decreased postoperative pain after reduction of fractured nasal bones using a nerve block of the anterior ethmoidal nerve.

There is consensus that all patients should experience minimal pain following reduction of a fractured nasal bone. The issue requiring further study is what technique will provide patients with the greatest pain relief following the reduction of nasal fractures. This study investigated the use of an anterior ethmoidal nerve block as preemptive analgesia for the management of postoperative pain associated with reduction of nasal bone fractures. The medical documents of 85 patients were reviewed for a retrospective case-controlled comparative study. Patients in the nerve block group (n=45) were injected with 2% lidocaine containing epinephrine into the anterior ethmoidal nerve and dorsal periosteum, and those in the control group (n=40) were not. The rate of patients requiring postoperative injectable analgesics was compared between the two groups. The rate of patients who received a postoperative analgesic injection was significantly lower in the nerve block group than in the control group (P=0.034). The use of an anterior ethmoidal nerve block and dorsal periosteal injection of anaesthetic solution during reduction of fractured nasal bones under general anaesthesia resulted in the effective reduction of postoperative pain. Thus, this is regarded as a good method for enhancing patient quality of care and compliance in the reduction of fractured nasal bones.

Low-power-Consumption metal oxide NO2 gas sensor based on micro-heater and screen printing technology.

An NO2 micro gas sensor was fabricated based on a micro-heater using tin oxide nano-powders for effective gas detection and monitoring system with low power consumption and high sensitivity. The processes of the fabrication were acceptable to the conventional CMOS processes for mass-production. Semiconducting SnO2 nano-powders were synthesized via the co-precipitation method; and to increase the sensitivity of the NO2 gas rare metal dopants were added. In the structure of the micro-heater, the resistances of two semi-circular Pt heaters were connected to the spreader for thermal uniformity. The resistance of each heater becomes an electrically equal Wheatstone-bridge, which was divided in half by the heat spreading structure. Based on the aforementioned design, a low-power-consumption micro-heater was fabricated using the CMOS-compatible MEMS processes. A bridge-type micro-heater based on the Si substrate was fabricated via surface micro-machining. The NO2 sensing properties of a screen-printed tin oxide thick film device were measured The micro gas sensors showed substantial sensitivity down to 0.5 ppm NO2 at a low power consumption (34.2 mW).

Xanthogranuloma of the sellar region. A case report.

Xanthogranuloma of the sellar region is a rare tumor. We describe a 41-year-old man complaining of several years of headache and passing out. Physical examination revealed absence of pubic and axillary hair while laboratory analysis showed panhypopituitarism. Magnetic resonance imaging showed a partially calcified slightly enhancing intrasellar mass with suprasellar extension which was slightly hyperintense on T1 images and hypointense on T2 images. Complete resection of the tumor mass using trans-sphenoidal approach was performed. On histopathologic analysis, there was a combination of fibrous scar tissue with chronic inflammation, highlighted by CD45 immunostaining, and extensively calcified necrotic debris, including cholesterol crystals consistent with a diagnosis of xanthogranuloma.

Differential diagnosis of cerebral hemispheric pathology: multimodal approach.

This article gives a comprehensive review and illustrations of the imaging features of various pathological conditions and clinical syndromes associated with cerebral hemispheric involvement. The various conditions are described and defined to provide a basis for the differential diagnostics. The hypotheses relating to the pathology of the various syndromes are discussed with special emphasis on excitotoxic mechanisms for explaining the subsequent cerebral hemiatrophy.