Supercritical fluid injection of nonvolatiles with resonant two photon ionization detection in supersonic beam mass spectrometry

Supercritical fluids of N2O and CO2 are used to solubilize nonvolatile compounds for supersonic jet expansions. R2PI is then used to ionize these compounds in a time of flight mass spectrometer. By tuning the dye laser wavelength a cold wavelength ionization spectrum can be obtained that is characteristic of that species.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87289/2/612_1.pd

Oxaliplatin-induced acquired long QT syndrome with torsades de pointes and myocardial injury in a patient with dilated cardiomyopathy and rectal cancer

AbstractA 67-year-old woman presented with a history of dilated cardiomyopathy with congestive heart failure since 2003, who subsequently developed lower rectal cancer (adenocarcinoma) with liver, bone, and lymph node metastasis. Abdominoperineal resection and hepatectomy were performed. The patient received two rounds of intravenous chemotherapy, including 12 and six courses of FOLFOX4 (5-fluorouracil, leucovorin, and oxaliplatin; 85 mg/m2 per cycle). She underwent a third round of intravenous FOLFOX4 because of tumor progression. During the 21st course of FOLFOX4 regimen, the patient developed ST segment depression in lead II and prolongation of QT interval with polymorphic ventricular tachycardia, torsades de pointes right after the start of oxaliplatin infusion. Immediate defibrillation and cardiopulmonary resuscitation were administered, and the patient regained spontaneous circulation and consciousness. Twelve-lead electrocardiogram showed ST segment elevation in III, aVF, and ST segment depression in V4–6 after resuscitation. To our knowledge, prolongation of QT interval with torsades de pointes and coronary spasm with myocardial injury that were stabilized in one patient following oxaliplatin infusion has not been reported. We present a patient with these rare complications

Supercritical fluid jet expansions of polar aromatic carboxylic acids using simple derivatization with detection by resonant two-photon ionization

In this work simple derivatization is used as a means of enhancing the solubility of polar aromatic carboxylic acids in supercritical CO2 and N2O. The supercritical fluid is then expanded from 200 atm and 40[deg]C through a pulsed injection orifice into vacuum as a supersonic jet for analysis by laser resonant two-photon ionization spectroscopy in a time-of-flight mass spectrometer. The use of derivatization reduces the polarity of these carboxylic acids and thus greatly enhances their solubility in these fluids. The result is that strong ionization signals from the jet are detected in the mass spectrometer at relatively low temperatures where these molecules, many of which are thermally labile, will not decompose. The laser ionization method allows soft ionization of these compounds where the molecular ion is generally the base peak and a characteristic fragment due to simple C[alpha]-C[beta] cleavage is often observed. By monitoring the molecular ion as a function of wavelength a cold laser ionization spectrum with sharp spectral features can be obtained in these supersonic expansions from high pressure supercritical fluids thus demonstrating that optical selectivity is still retained even after derivatization.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27585/1/0000629.pd

Porcine circovirus type 2 (PCV2) infection decreases the efficacy of an attenuated classical swine fever virus (CSFV) vaccine

The Lapinized Philippines Coronel (LPC) vaccine, an attenuated strain of classical swine fever virus (CSFV), is an important tool for the prevention and control of CSFV infection and is widely and routinely used in most CSF endemic areas, including Taiwan. The aim of this study was to investigate whether PCV2 infection affects the efficacy of the LPC vaccine. Eighteen 6-week-old, cesarean-derived and colostrum-deprived (CDCD), crossbred pigs were randomly assigned to four groups. A total of 105.3 TCID50 of PCV2 was experimentally inoculated into pigs through both intranasal and intramuscular routes at 0 days post-inoculation (dpi) followed by LPC vaccination 12 days later. All the animals were challenged with wild-type CSFV (ALD stain) at 27 dpi and euthanized at 45 dpi. Following CSFV challenge, the LPC-vaccinated pigs pre-inoculated with PCV2 showed transient fever, viremia, and viral shedding in the saliva and feces. The number of IgM+, CD4+CD8-CD25+, CD4+CD8+CD25+, and CD4-CD8+CD25+ lymphocyte subsets and the level of neutralizing antibodies against CSFV were significantly higher in the animals with LPC vaccination alone than in the pigs with PCV2 inoculation/LPC vaccination. In addition, PCV2-derived inhibition of the CSFV-specific cell proliferative response of peripheral blood mononuclear cells (PBMCs) was demonstrated in an ex vivo experiment. These findings indicate that PCV2 infection decreases the efficacy of the LPC vaccine. This PCV2-derived interference may not only allow the invasion of wild-type CSFV in pig farms but also increases the difficulty of CSF prevention and control in CSF endemic areas

Evaluation of combined prescription of rocker sole shoes and custom-made foot orthoses for the treatment of plantar fasciitis

Background: It is a routine practice to prescribe a combination of rocker shoes and custom-made foot orthoses for patients with plantar fasciitis. Recently, there has been a debate on this practice, and studies have shown that the individual prescription of rocker shoes or custom-made foot orthoses is effective in treating plantar fasciitis. The aim of this study was to evaluate and compare the immediate therapeutic effects of individually prescribed rocker sole shoes and custom-made foot orthoses, and a combined prescription of them on plantar fasciitis. Methods: This was a cross-over study. Fifteen patients with unilateral plantar fasciitis were recruited; they were from both genders and aged between 40 and 65. Subjects performed walking trials which consisted of one 'unshod' condition and four 'shod' conditions while wearing baseline shoes, rocker shoes, baseline shoes with foot orthotics, and rocker shoes with foot orthotics. The study outcome measures were the immediate heel pain intensity levels as reflected by visual analog scale pain ratings and the corresponding dynamic plantar pressure redistribution patterns as evaluated by a pressure insole system. Results: The results showed that a combination of rocker shoes and foot orthoses produced a significantly lower visual analog scale pain score (9.7 mm) than rocker shoes (30.9 mm) and foot orthoses (29.5 mm). With regard to baseline shoes, it also significantly reduced the greatest amount of medial heel peak pressure (- 33.58%) without overloading other plantar regions when compared to rocker shoes (- 7.99%) and foot orthoses (- 28.82%). Discussion: The findings indicate that a combined prescription of rocker sole shoes and custom-made foot orthoses had greater immediate therapeutic effects compared to when each treatment had been individually prescribed

The Effect of Locally Delivered Statins on Treating Periodontal Intrabony Defects: A Systematic Review and Metaâ Analysis

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142319/1/jper0357.pd

Bone-targeting agents in major solid tumour metastases: a multinational cohort study

OBJECTIVE: To describe the epidemiology, clinical characteristics and utilisation patterns of bone-targeting agents (BTAs) in patients with bone metastases from breast, prostate and lung cancer. METHODS: This is a multinational retrospective cohort study including patients with three major solid tumours (breast, prostate and lung cancer) and newly initiated on BTAs (ie, denosumab, zoledronic acid and pamidronate). Records were retrieved from nationwide health databases from Hong Kong and Taiwan (HK and TW: 2013–2017) and Korea (KR: 2012–2016). Descriptive analyses included the annual incidence rates of bone metastases and the cumulative incidence curves of BTA initiation. We used Sankey diagrams to visualise the dynamic BTA utilisation patterns. RESULTS: The annual incidence rate of bone metastases ranged from 3.5% to 4.5% in TW, from 9.6% to 10.3% in HK and from 2.9% to 3.8% in KR. We identified 14.1% (5127), 9.3% (883) and 9.4% (4800) of patients with bone metastases newly initiated on BTAs in TW, HK and KR, respectively. The most frequently used BTA in TW (67.1%) and HK (51.9%) was denosumab, while in KR (84.8%) it was zoledronic acid. Sankey diagrams indicated the proportion of patients remaining on denosumab was highest in TW and HK, while it was zoledronic acid in KR. Specifically, in TW, patients who were on bisphosphonates or had discontinued treatment frequently switched to or reinitiated denosumab. CONCLUSIONS: We found the rate of BTA utilisation remained low across all sites and tumour types in recent years. The dynamic utilisation patterns of BTAs provide better understanding of the treatment landscape for future evaluation of associated outcomes of patients

The Enhanced metastatic potential of hepatocellular carcinoma (HCC) cells with sorafenib resistance

Acquired resistance towards sorafenib treatment was found in HCC patients, which results in poor prognosis. To investigate the enhanced metastatic potential of sorafenib resistance cells, sorafenib-resistant (SorR) cell lines were established by long-term exposure of the HCC cells to the maximum tolerated dose of sorafenib. Cell proliferation assay and qPCR of ABC transporter genes (ABCC1-3) were first performed to confirm the resistance of cells. Migration and invasion assays, and immunoblotting analysis on the expression of epithelial to mesenchymal transition (EMT) regulatory proteins were performed to study the metastatic potential of SorR cells. The expression of CD44 and CD133 were studied by flow cytometry and the gene expressions of pluripotency factors were studied by qPCR to demonstrate the enrichment of cancer stem cells (CSCs) in SorR cells. Control (CTL) and SorR cells were also injected orthotopically to the livers of NOD-SCID mice to investigate the development of lung metastasis. Increased expressions of ABCC1-3 were found in SorR cells. Enhanced migratory and invasive abilities of SorR cells were observed. The changes in expression of EMT regulatory proteins demonstrated an activation of the EMT process in SorR cells. Enriched proportion of CD44+ and CD44+CD133 + cells were also observed in SorR cells. All (8/8) mice injected with SorR cells demonstrated lung metastasis whereas only 1/8 mouse injected with CTL cells showed lung metastasis. HCC cells with sorafenib resistance demonstrated a higher metastatic potential, which may be due to the activated EMT process. Enriched CSCs were also demonstrated in the sorafenib resistant cells. This study suggests that advanced HCC patients with acquired sorafenib resistance may have enhanced tumor growth or distant metastasis, which raises the concern of long-term sorafenib treatment in advanced HCC patients who have developed resistance of sorafenib. © 2013 Chow et al.published_or_final_versio