TGFß promotes mesenchymal phenotype of pancreatic cancer cells, in part, through epigenetic activation of VAV1.

The highly homeostasis-resistant nature of cancer cells leads to their escape from treatment and to liver metastasis, which in turn makes pancreatic ductal adenocarcinoma (PDAC) difficult to treat, especially the squamous/epithelial-to-mesenchymal transition (EMT)-like subtype. As the molecular mechanisms underlying tumour heterogeneity remain elusive, we investigated whether epigenetic regulation might explain inter-individual differences in the progression of specific subtypes. DNA methylation profiling performed on cancer tissues prior to chemo/radiotherapy identified one hypermethylated CpG site (CpG6882469) in the VAV1 gene body that was correlated with demethylation of two promoter CpGs (CpG6772370/CpG6772811) in both PDAC and peripheral blood. Transforming growth factor ß treatment induced gene-body hypermethylation, dissociation of DNMT1 from the promoter, and VAV1 expression via SMAD4 and mutant KrasG12D. Pharmacological inhibition of TGFß-VAV1 signalling decreased the squamous/EMT-like cancer cells, promoted nuclear VAV1 localization, and enhanced the efficacy of gemcitabine in prolonging the survival of KPfl/flC mice. Together, the three VAV1 CpGs serve as biomarkers for prognosis and early detection, and the TGFß-VAV1 axis represents a therapeutic target.

Association between body composition and median neuropathy in patients with physical disabilities.

BACKGROUND: Patients with physical disabilities more often have median neuropathies of the wrist and more than 70% of wheelchair users are overweight or obese. AIM: To explore the effects of body composition on the occurrence of distal median neuropathy and to search for the best probabilistic cutoff value of indicators to predict the likelihood of developing distal median neuropathy in patients with physical disabilities. DESIGN: A prospective study. SETTING: A 1-day annual physical checkup program for employees of a social welfare organization. POPULATION: In total, 72 patients with a physical disability (mean age ± SD, 40.0 ± 8.8 years; 40 women). METHODS: Using electrophysiologic testing to assess distal median nerve function and using a dual-energy X-ray absorptiometry examination to assess body composition. The formula for leg exercise burden index (EBI) was: leg EBI = body fat mass of both legs/lean tissue mass of both legs. RESULTS: The risk of developing a low median sensory nerve conduction velocity in the wrist-to-palm segment (< 43 m/s) was greater for patients with a higher leg EBI, yielding an adjusted odds ratio of 6.88 (P < 0.005). The body mass index (BMI) and being a wheelchair user were predictors of developing long median distal motor latency (> 4 ms). Using receiver operating characteristic analyses, we determined that patients with a physical disability were likely to develop distal median sensory neuropathy if they had a leg EBI of ≥ 0.943 and were likely to develop distal median motor neuropathy if they had a BMI of ≥ 24.5 kg/m2. CONCLUSION: The leg EBI is a predictor of having distal median sensory neuropathy among patients with a physical disability. CLINICAL REHABILITATION IMPACT: The value of the leg EBI can be useful information for identifying risk of distal median sensory neuropathy in patients with a physical disability.

The risk of colorectal cancer is related to frequent hospitalization of IBD in an Asian population: results from a nationwide study.

BACKGROUND: The occurrence of inflammatory bowel disease (IBD) is higher in Western countries and is increasing worldwide. The incidence of IBDs is about nearly 20-fold in Western countries than Asia and has risen in Taiwan over the past few decades. Epidemiological studies have demonstrated an increased risk of colorectal cancer (CRC) in patients with IBD. The prevalence of IBD as well as IBD-associated CRC is changing and the risk of CRC in patients with IBD appears to be greater in Western countries, but CRC risk in IBD patients is less well understood in low endemic areas, such as Asia. METHODS: This population-based cohort study collected data from the Taiwan Health Insurance Research Database (from January 1998 to December 2011). In total, 10 650 patients with confirmed diagnosis of IBD served as the IBD cohort and 42 600 non-IBD subjects were enrolled. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) were used to assess the risk of CRC. RESULTS: The incidence of CRC was slightly lower in the IBD cohort compared with that in the non-IBD cohort (0.94 vs. 1.13 per 1000 person-years), with an adjusted HR of 0.99 (95% CI: 0.71-1.37). More than four hospitalizations were associated with a significantly higher risk of CRC in IBD patients in the Cox model (adjusted HR = 3.48, 95% CI: 1.59-7.63). CONCLUSIONS: The risk for CRC was not increased among IBD patients overall, but appeared to be increased with cumulative frequency of hospitalizations for IBD.

Intravenous zolpidem injection in a zolpidem abuser.

Zolpidem abuse has been frequently observed in recent years. This study presents a case of zolpidem abuse. Although numerous cases of zolpidem dependence have been reported, this is the first case to report zolpidem intravenous injection without any history of opiate use. Clinicians should monitor patients with a history of zolpidem abuse and be aware that there is a risk of zolpidem injection.

Rhabdomyolysis and brain ischemic stroke in a heroin-dependent male under methadone maintenance therapy.

OBJECTIVE: There are several complications associated with heroin abuse, some of which are life-threatening. Methadone may aggravate this problem. METHOD: A clinical case description. RESULTS: A 33-year-old man presented with rhabdomyolysis and cerebral ischemic stroke after intravenous heroin. He had used heroin since age 20, and had used 150 mg methadone daily for 6 months. He was found unconsciousness at home and was sent to our hospital. In the ER, his opiate level was 4497 ng/ml. In the ICU, we found rhabdomyolysis, acute renal failure and acute respiratory failure. After transfer to an internal ward, we noted aphasia and weakness of his left limbs. After MRI, we found cerebral ischemic infarction. CONCLUSION: Those using methadone and heroin simultaneously may increase risk of rhabdomyolysis and ischemic stroke. Patients under methadone maintenance therapy should be warned regarding these serious adverse events. Hypotheses of heroin-related rhabdomyolysis and stroke in heroin abusers are discussed.

Microfluidic assisted synthesis of multi-functional polycaprolactone microcapsules: incorporation of CdTe quantum dots, Fe3O4 superparamagnetic nanoparticles and tamoxifen anticancer drugs.

This paper demonstrates a proof-of-concept approach for encapsulating the anticancer drug tamoxifen, Fe3O4 nanoparticles (NPs) and CdTe quantum dots (QDs) into size-controlled polycaprolactone (PCL) microcapsules utilizing microfluidic emulsification, which combined magnetic targeting, fluorescence imaging and drug controlled release properties into one drug delivery system. Cross-linking the composite PCL microcapsules with poly(vinyl alcohol) (PVA) tailored their size, morphology, optical and magnetic properties and drug release behaviors. The flow conditions of the two immiscible solutions were adjusted in order to successfully generate various sizes of polymer droplets. The result showed superparamagnetic and fluorescent properties, and was used as a controlled drug release vehicle. The composite magnetic and fluorescent PCL microcapsules are potential candidates for a smart drug delivery system.

Automatic seamless mosaicing of microscopic images: enhancing appearance with colour degradation compensation and wavelet-based blending.

In order to observe the fine details of biomedical specimens, various kinds of high-magnification microscopes are used. However, they suffer from a limited field of view when visualizing highly magnified specimens. Image mosaicing techniques are necessary to integrate two or more partially overlapping images into one and make the whole specimen visible. In this study, we propose a new system that automatically creates panoramic images by mosaicing all the microscopic images acquired from a specimen. Not only does it effectively compensate for the congenital narrowness in microscopic views, but it also results in the mosaiced image containing as little distortion with respect to the originals as possible. The system consists of four main steps: (1) feature point extraction using multiscale wavelet analysis, (2) image matching based on feature points or by projection profile alignment, (3) colour difference adjustment and optical degradation compensation with a Gaussian-like model and (4) wavelet-based image blending. In addition to providing a precise alignment, the proposed system also takes into account the colour deviations and degradation in image mosaicing. The visible seam lines are eliminated after image blending. The experimental results show that the system performs well on differently stained image sequences and is effective on acquired images with large colour variations and degradation. It is expected to be a practical tool for microscopic image mosaicing.

Elution, detection, and quantification of polio I, bacteriophages, Salmonella montevideo, and Escherichia coli O157:H7 from seeded strawberries and tomatoes.

This study compared the effect of different physical and chemical treatments of strawberries and tomatoes to determine their ability to recover seeded viral and bacterial pathogens from produce surfaces. Solutions of salts, amino acids, complex media, and detergents were compared as eluants. Phosphate-buffered saline (PBS) containing 0.1% Tween 80 eluted the highest number of seeded microorganisms. Elution with this defined solution was then compared under different conditions of physical agitation. Rotary shaking for 20 min at 36 degrees C eluted higher numbers of viruses and bacteria than did low- or high-speed stomaching. Commercially available and laboratory prepared bacteriological differential media were compared for their ability to recover and distinguish eluted Salmonella Montevideo and Escherichia coli O157:H7 strains from seeded produce. The recovery of seeded bacterial pathogens was low when differential media containing selective ingredients were used (MacConkey sorbitol agar, XLD agar, MacConkey agar). Highest recoveries were obtained on a medium consisting of tryptic soy agar supplemented with sodium thiosulfate and ferric ammonium citrate compared with selective media that inhibited up to 50% of the growth of the eluted microorganisms.

Enhanced broth media for selective growth of Vibrio vulnificus.

Rapid detection of Vibrio vulnificus can be enhanced by optimizing the components of enrichment broth. PNC (5% peptone, 1% NaCl, and 0.08% cellobiose [pH 8.0]) enhanced the growth of V. vulnificus compared to alkaline peptone broth. PNCC (PNC with 1.0 to 4.1 U of colistin methanesulfonate per ml) increased the growth of low levels of V. vulnificus while suppressing non-target bacteria.

[Psychogenic dizziness].

Psychogenic dizziness is defined as recurring or persistent symptoms of balance dysfunction, inconsistent with organic vestibular disease as determined by history, clinical examination and pertinent investigations, and consistent with emotional origin. Of 1,335 patients seen in our dizziness clinic between January 1988 and August 1991, psychogenic dizziness was diagnosed in 180 (13.5%) patients. There were 67 men and 113 women aged from 12 to 77 years (mean age 40.2 years). The characteristics of psychogenic dizziness are: (1) continuous dizziness for long periods of time; (2) younger patients; (3) predominant female; (4) associated symptoms of panic attack, such as headache, breathlessness, nausea, sleep disturbance, paresthesias, anxiety and palpitation; (5) symptoms of aggravation due to stressful life events; (6) normal neurotological bedside examination; (7) hyperventilation reproduced accurately. The electronystagmographic results of 74 patients show normal bithermal caloric responses in 47 patients (63.5%), caloric hyperactivity in 21 patients (28.4%), canal paresis in four patients (5.4%), canal paresis with directional preponderance in two patients (2.7%), large random voluntary eye swings or severe blinking in 35 patients (47.3%), and spontaneous nystagmus (slow phase velocity < 6.5 degrees/s) in four patients (5.4%). There were 31 patients who consulted psychiatrists with diagnoses of anxiety (51.6%), depression (16.1%), insomnia (12.9%), psychosomatic disorder and adjustment disorder. Treatment of patients with psychogenic dizziness must be directed at the underlying anxiety. Psychiatric consultation is necessary.

Domain inversion in MgO-diffused LiNbO(3).

We obtain the periodic modulation of domain polarization by patterning MgO on the positive C-face of LiNbO(3), followed by Li outdiffusion to induce domain inversion. We obtain domain inversion lines (1.5 microm) by heat treating LiNbO(3) at 1000 degrees C for 2 h with a 1-microm inversion depth. This process may be suitable for fabrication of first-order gratings that are needed for high second-harmonic conversion efficiency by using a quasi-phase-matched technique.

Grating coupler acceptance design utilizing a tapered waveguide structure.

A tapered waveguide film was deposited on a substrate with a grating structure resulting in a hybridthin-film waveguide coupler that could be designed for a broader or narrower acceptance for wavelength or incidence angle. The optimized couplers were designed and fabricated. The couplers were found to be as efficient as traditional grating couplers but with much broader acceptance. The maximum broadening was calculated to be a coupling FWHM of 2° (or 12 nm) and was confirmed experimentally. This is 4.3 times the acceptance of an identical untapered structure.

Stress fracture of the diaphysis of the ulna.

Stress fracture of the diaphysis of the ulna is rare and only 6 cases were found in a literature review. We present a further case occurring in a weightlifter.

Arnold-Chiari type 1 malformation and syringomyelia.

A 12-year-old boy had a long history of headache since the age of 4 years. Numbness and weakness of the upper extremities and chest tightness, especially in the morning, were noted since 2 years ago. The headache became more severe and frequent and attacked even in sleep since one year ago. Arnold-Chiari type 1 malformation, cervical syringomyelia and mild hydrocephalus were demonstrated by MRI scan of the central nervous system. Headache and other symptoms disappeared immediately after surgical intervention. The formation of syringomyelia may be multifactorial, but Arnold-Chiari type 1 malformation and uneventful birth history play an important role in the underlying cause of this case. We presented this youngest case who had Arnold-Chiari type 1 malformation and onset of headache from the age of 4 years, discussed the pathogenesis of syringomyelia and reviewed the literature.

[Gilles de la Tourette syndrome associated with epileptiform discharges: report of three cases].

This report presents the clinical observation of 3 cases of Gilles de la Tourette Syndrome (GTS) with epileptiform discharge of electroencephalogram (EEG). During the past 2 years (1986-1987), 8 cases of GTS were diagnosed in the pediatric department of National Taiwan University Hospital. Three of them presented epileptiform discharges. Diffuse bilateral parieto-occipital spikes in waking and light sleep periods were noted in case 1, who was a 10-year-old girl. Case 2 was a 9-year-old boy, his EEG showed sporadic spikes over right fronto-central area during light sleep. In case 3, a 6-year-old boy, frequent sharps and spikes appeared in left centro-temporal area in waking and sleep EEG. Case 3 had received antiepileptic therapy. The EEG recovered to normal, the symptoms of the involuntary movement became more prominent. All of the 3 cases improved significantly after haloperidol monotherapy. Based on the clinical observations and literature review, we noted that the incidence of epileptiform discharge in GTS was higher than that in nonepileptic normal population. Although some authors suggested that a seizure state possibly play a subtle role in the genesis of Tourette's symptoms, this inference was not supported by our experience. We observed that haloperidol was effective to this syndrome with or without epileptiform discharge. Therefore, antiepileptic agents, which might alter the metabolism of dopamine, was not recommended for treating GTS patients.

[Harlequin fetus--a case report].

A one-day-old male premature baby was born to a G4P4 mother with the gestation age of 30 weeks. His birth weight was 2000 gm. He was noted to be covered with a thick, armor-like skin which is split by deep fissures and makes the feature of Ectropion and eclabium. His nose was flattened, only the nostrils were visible, and the external ears were underdeveloped. The hands and feet appeared to be swollen and crumpled. The genital organ was covered with thick fissured skin and it was impossible to distinguish sex by external appearance. Three days after delivery, the patient died of respiratory distress. He was found normal through general laboratory and chromosome study. However, dermatohistology showed hyperkeratosis, focal parakeratosis and hypogranulosis. Pathology showed PDA (patent ductus arteriosus), enlarged thymus and congestion of internal organs. Its etiology and pathogenesis somehow remain unknown. We hereby reported this harlequin fetus, the most severe type of lamellar ichthyosis, and discussed its incidence, pathogenesis, pathohistology, prognosis and the recent development in treatment.