Sparse interleaved sampling for high resolution focal construct geometry X-ray tomography.

We demonstrate interleaved sampling by multiplexing conical subshells within the tomosynthesis and raster scanning a phantom through a 150 kV shell X-ray beam. Each view comprises pixels sampled on a regular 1 mm grid, which is then upscaled by padding with null pixels before tomosynthesis. We show that upscaled views comprising 1% sample pixels and 99% null pixels increase the contrast transfer function (CTF) computed from constructed optical sections from approximately 0.6 line pairs/mm to 3 line pairs/mm. The driver of our method is to complement work concerning the application of conical shell beams to the measurement of diffracted photons for materials identification. Our approach is relevant to time-critical, and dose-sensitive analytical scanning applications in security screening, process control and medical imaging.

Comparison of dermoscopic features between congenital and acquired acral melanocytic nevi in Korean patients.

BACKGROUND: The dermoscopic patterns of acral melanocytic nevi (AMNs) are crucial in differentiating them from acral melanoma. Several studies have reported the dermoscopic patterns of acquired acral melanocytic nevi (AAMNs). However, few have investigated the dermoscopic patterns of congenital acral melanocytic nevi (CAMNs). OBJECTIVE: To compare the clinical and dermoscopic features of CAMNs and AAMNs. METHODS: The present study included 43 patients with CAMNs and 40 with AAMNs. We reviewed their medical records as well as their clinical and dermoscopic findings. RESULTS: Congenital acral melanocytic nevis were more asymmetrical than AAMNs (P = 0.002) and presented more frequently as comma-shaped (P = 0.005). Regarding dermoscopic findings, globular pattern (55.8%) was the most common feature of CAMNs, while parallel furrow pattern (37.5%) was the most common feature of AAMNs. The presence of fibrillar, globular, and parallel ridge patterns, and diffuse multi-component pigmentation differed significantly between the groups (P < 0.05). Furthermore, CAMNs showed melanoma-specific dermoscopic patterns, such as parallel ridge (18.6%) and diffuse multi-component pigmentation (25.6%). CONCLUSION: The dermoscopic patterns of CAMNs and AAMNs differed markedly. In terms of dermoscopic patterns, CAMNs resembled acral melanoma more often than AAMNs did.

Tonicity inversely modulates lipocalin-2 (Lcn2/24p3/NGAL) receptor (SLC22A17) and Lcn2 expression via Wnt/ß-catenin signaling in renal inner medullary collecting duct cells: implications for cell fate and bacterial infection.

BACKGROUND: We have previously evidenced apical expression of the 24p3/NGAL/lipocalin-2 receptor (Lcn2-R; SLC22A17) in inner medullary collecting duct (IMCD) cells, which are present in vivo in a hyperosmotic/-tonic environment that activates canonical Wnt/ß-catenin signaling. The localization of Lcn2-R in the inner medulla is intriguing considering local bacterial infections trigger toll-like receptor-4 (TLR-4)-mediated secretion of the bacteriostatic Fe3+-free (apo-)Lcn2. AIM: To determine the effects of osmolarity/tonicity changes, Wnt/ß-catenin and TLR-4 activation on Lcn2-R and Lcn2 expression and cell viability in rat primary IMCD and mouse (m)IMCD3 cells. METHODS: Normosmolarity/-tonicity was 300 mosmol/l whereas hyperosmolarity/-tonicity was induced by adding 100 mmol/l NaCl + 100 mmol/l urea (600 mosmol/l, 1-7 days). Lcn2-R and Lcn2 expression were determined by qPCR, immunoblotting, flow cytometry and immunofluorescence microscopy. ß-catenin was silenced by RNAi. Cell viability/death was determined with MTT and LDH release assays. TLR-4 was activated by bacterial lipopolysaccharides (LPS). RESULTS: Hyperosmotic/-tonic media upregulated Lcn2-R by ~4-fold and decreased Lcn2 expression/secretion, along with Wnt/ß-catenin activation, in IMCD cells. These effects of hyperosmotic/-tonic media on Lcn2-R/Lcn2 expression were reverted by normosmolarity/-tonicity, ß-catenin silencing and/or LPS. Exposure of cells with endogenous or stably overexpressing Lcn2-R to apo-Lcn2 or LPS decreased cell viability. CONCLUSIONS: Lcn2-R upregulation and Lcn2 downregulation via Wnt/ß-catenin may promote adaptive osmotolerant survival of IMCD cells in response to hyperosmolarity/-tonicity whereas Lcn2 upregulation and Lcn2-R downregulation via TLR-4 and/or normosmolarity/-tonicity may protect IMCD cells against bacterial infections and prevent autocrine death induction by Lcn2.

Remote ischaemic conditioning for prevention of acute kidney injury after valvular heart surgery: a randomised controlled trial.

BACKGROUND: Repeated remote ischaemic conditioning (RIC) during weaning from cardiopulmonary bypass and in the early postoperative period may confer protection against acute kidney injury (AKI). We evaluated the effect of repeated RIC on the incidence of AKI in patients undergoing valvular heart surgery. METHODS: Patients were randomised into either the RIC (n=120) or control (n=124) group. A pneumatic tourniquet was placed on each patient's thigh. Upon removal of the aortic cross-clamp, three cycles of inflation for 5 min at 250 mm Hg (with 5 min intervals) were applied in the RIC group. Additionally, three cycles of RIC were repeated at postoperative 12 and 24 h. AKI was diagnosed based on the Kidney Disease: Improving Global Outcomes guideline. The incidences of renal replacement therapy, permanent stroke, sternal wound infection, newly developed atrial fibrillation, mechanical ventilation >24 h, and reoperation for bleeding during hospitalisation were recorded. RESULTS: The incidences of AKI were not significantly different between the control (19.4%) and RIC (15.8%) groups (a difference of 3.5 percentage points; 95% confidence interval: -6.8%-13.9%; P=0.470). Perioperative serum creatinine concentrations were similar in the control and RIC groups (P=0.494). Fluid balance, urine output, blood loss, transfusion, and vasopressor/inotropic requirements were not significantly different between the groups (all P>0.05). The occurrences of a composite of morbidity and mortality endpoints were not significantly different between the control (46.0%) and RIC (39.2%) groups (a difference of 6.8 percentage points; 95% confidence interval: -6.4%-20.0%; P=0.283). CONCLUSIONS: The results of our study do not support repeated RIC to decrease the incidence of AKI after valvular heart surgery. CLINICAL TRIAL REGISTRATION: NCT02720549.

Test of Special Relativity Using a Fiber Network of Optical Clocks.

Phase compensated optical fiber links enable high accuracy atomic clocks separated by thousands of kilometers to be compared with unprecedented statistical resolution. By searching for a daily variation of the frequency difference between four strontium optical lattice clocks in different locations throughout Europe connected by such links, we improve upon previous tests of time dilation predicted by special relativity. We obtain a constraint on the Robertson-Mansouri-Sexl parameter |α|≲1.1×10^{-8}, quantifying a violation of time dilation, thus improving by a factor of around 2 the best known constraint obtained with Ives-Stilwell type experiments, and by 2 orders of magnitude the best constraint obtained by comparing atomic clocks. This work is the first of a new generation of tests of fundamental physics using optical clocks and fiber links. As clocks improve, and as fiber links are routinely operated, we expect that the tests initiated in this Letter will improve by orders of magnitude in the near future.

Micro- and nano-patterned elastin-like polypeptide hydrogels for stem cell culture.

We show that submicron-sized patterns can be imprinted into soft, recombinant-engineered protein hydrogels (here elastin-like proteins, ELP) by transferring wavy patterns from polydimethylsiloxane (PDMS) molds. The high-precision topographical tunability of the relatively stiff PDMS is translated to a bio-responsive, soft material, enabling topographical cell response studies at elastic moduli matching those of tissues. Aligned and unaligned wavy patterns with mold periodicities of 0.24-4.54 µm were imprinted and characterized by coherent anti-Stokes Raman scattering and atomic force microscopy. The pattern was successfully transferred down to 0.37 µm periodicity (width in ELP: 250 ± 50 nm, height: 70 ± 40 nm). The limit was set by inherent protein assemblies (diameter: 124-180 nm) that formed due to lower critical solution temperature behavior of the ELP during molding. The width/height of the ELP ridges depended on the degree of hydration; from complete dehydration to full hydration, ELP ridge width ranged from 79 ± 9% to 150 ± 40% of the mold width. The surface of the ridged ELP featured densely packed protein aggregates that were larger in size than those observed in bulk/flat ELP. Adipose-derived stem cells (ADSCs) oriented along hydrated aligned patterns with periodicities ≥0.60 µm (height ≥170 ± 100 nm), while random orientation was observed for smaller distances/amplitudes, as well as flat and unaligned wavy ELP surfaces. Hence, micro-molding of ELP is a promising approach to create tissue-mimicking, hierarchical architectures composed of tunable micron-sized structures with nano-sized protein aggregates, which opens the way for orthogonal screening of cell responses to topography and cell-adhesion ligands at relevant elastic moduli.

Initial autophagic protection switches to disruption of autophagic flux by lysosomal instability during cadmium stress accrual in renal NRK-52E cells.

The renal proximal tubule (PT) is the major target of cadmium (Cd2+) toxicity where Cd2+ causes stress and apoptosis. Autophagy is induced by cell stress, e.g., endoplasmic reticulum (ER) stress, and may contribute to cell survival or death. The role of autophagy in Cd2+-induced nephrotoxicity remains unsettled due to contradictory results and lack of evidence for autophagic machinery damage by Cd2+. Cd2+-induced autophagy in rat kidney PT cell line NRK-52E and its role in cell death was investigated. Increased LC3-II and decreased p62 as autophagy markers indicate rapid induction of autophagic flux by Cd2+ (5-10 µM) after 1 h, accompanied by ER stress (increased p-PERK, p-eIF2α, CHOP). Cd2+ exposure exceeding 3 h results in p62/LC3-II accumulation, but diminished effect of lysosomal inhibitors (bafilomycin A1, pepstatin A +E-64d) on p62/LC3-II levels, indicating decreased autophagic flux and cargo degradation. At 24 h exposure, Cd2+ (5-25 µM) activates intrinsic apoptotic pathways (Bax/Bcl-2, PARP-1), which is not evident earlier (≤6 h) although cell viability by MTT assay is decreased. Autophagy inducer rapamycin (100 nM) does not overcome autophagy inhibition or Cd2+-induced cell viability loss. The autophagosome-lysosome fusion inhibitor liensinine (5 µM) increases CHOP and Bax/Bcl-2-dependent apoptosis by low Cd2+ stress, but not by high Cd2+. Lysosomal instability by Cd2+ (5 µM; 6 h) is indicated by increases in cellular sphingomyelin and membrane fluidity and decreases in cathepsins and LAMP1. The data suggest dual and temporal impact of Cd2+ on autophagy: Low Cd2+ stress rapidly activates autophagy counteracting damage but Cd2+ stress accrual disrupts autophagic flux and lysosomal stability, possibly resulting in lysosomal cell death.

Association of bone mineral density and diabetic retinopathy in diabetic subjects: the 2008-2011 Korea National Health and Nutrition Examination Survey.

UNLABELLED: Because diabetic retinopathy increases fracture risk, we studied the association between bone mineral density (BMD) and diabetic retinopathy in a nationally representative sample. A significant association between the presence of diabetic retinopathy and low BMD was observed. Therefore, diabetic retinopathy might be considered as a marker of low BMD. INTRODUCTION: Several diabetic complications, including nephropathy, retinopathy, and peripheral neuropathy, are associated with a higher fracture risk in diabetic subjects. However, in contrast to diabetic nephropathy and peripheral neuropathy, which are associated with low bone mineral density (BMD), little is known about the association between BMD and diabetic retinopathy. The aim of the present study was to determine whether the prevalence of diabetic retinopathy is associated with BMD. METHODS: This cross-sectional study included a nationally representative sample consisting of 4357 men aged 50 years and older and 4392 postmenopausal women who participated in the Korea National Health and Nutritional Examination Survey (KNHANES) from 2008 to 2011 and underwent BMD measurement by dual-energy X-ray absorptiometry (DXA) and diabetic retinopathy assessments using seven standard gradable photographs. RESULTS: The diabetic women with retinopathy had lower mean BMD at all measured sites than those without retinopathy, although the BMD difference between the two groups was small (3-5 %). In addition, the diabetic women with retinopathy were 2.27 times more likely to have osteoporosis following adjustments for all clinically relevant covariates. However, the prevalence of diabetes mellitus (DM) or diabetic retinopathy was not associated with the prevalence of osteoporosis in men. CONCLUSIONS: This study has shown that the presence of diabetic retinopathy is significantly associated with a reduced BMD and increased prevalence of osteoporosis in diabetic women.

Association between prolonged breastfeeding and bone mineral density and osteoporosis in postmenopausal women: KNHANES 2010-2011.

UNLABELLED: This study showed that a negative correlation between duration of breastfeeding and bone mineral density (BMD) in the lumbar spine and prolonged breastfeeding is an independent risk for osteoporosis in postmenopausal women. The present study suggests that postmenopausal women with a history of prolonged breastfeeding require more careful screening for osteoporosis. INTRODUCTION: Several studies suggest that breastfeeding and childbirth lead to maternal calcium loss and a decline in BMD. While the association between breastfeeding and BMD immediately after weaning is well-established, the effects of breastfeeding on postmenopausal women have been controversial. The aim of this study was to examine the effects of breastfeeding on bone mineral density (BMD) and the prevalence of osteoporosis in postmenopausal women. METHODS: The present study was a cross-sectional survey based on the Korea National Health and Nutrition Examination Survey (KNHANES) 2010 and 2011 data. The association between breastfeeding and BMD and osteoporosis was examined in 1222 postmenopausal women. RESULTS: The duration of breastfeeding and BMD in the lumbar spine showed a negative correlation. The association between duration of breastfeeding and BMD remained significant after adjustment for reproductive factors and other confounding factors (P = 0.008). However, the number of deliveries and age at the time of delivery did not correlate with BMD at any site after adjustment. Moreover, the prevalence of osteoporosis in postmenopausal women with a history of prolonged breastfeeding was significantly higher than that in women with a short history of breastfeeding (≥37 months, OR = 3.292; 95 % CI 1.485-7.299). The prevalence of lumbar spine fracture showed a significant increasing trend with the increase in the duration of breastfeeding. CONCLUSION: Prolonged breastfeeding was significantly associated with low BMD in the lumbar spine and higher prevalence of osteoporosis. However, the number of deliveries or age at the time of childbirth did not influence BMD.

Nephrolithiasis among male patients with newly diagnosed gout.

INTRODUCTION: An elevated serum urate level is recognised as a cause of gouty arthritis and uric acid stone. The level of serum uric acid that accelerates kidney stone formation, however, has not yet been clarified. This study aimed to find out if a high serum urate level is associated with nephrolithiasis. METHODS: Patients were recruited from the rheumatology clinic of Taipei City Hospital (Renai and Zhongxing branches) in Taiwan from March 2015 to February 2016. A total of 120 Chinese male patients with newly diagnosed gout and serum urate concentration of >7 mg/dL and no history of kidney stones were divided into two groups according to their serum urate level: <10 mg/dL (group 1, n=80) and ≥10 mg/dL (group 2, n=40). The mean body mass index, blood urea nitrogen level, creatinine level, urinary pH, and kidney ultrasonography were compared between the two groups. RESULTS: There were no significant differences in blood urea nitrogen or creatinine level between the two groups. The urine pH in both groups was similar and not statistically significant. Kidney stone formation was detected via ultrasonography in 6.3% (5/80) and 82.5% (33/40) of patients in groups 1 and 2, respectively (P<0.05). CONCLUSION: A serum urate level of ≥10 mg/dL may precipitate nephrolithiasis. Further studies are warranted to substantiate the relationship between serum urate level and kidney stone formation.

A genetic variation in microRNA target site of KRT81 gene is associated with survival in early-stage non-small-cell lung cancer.

BACKGROUND: MicroRNAs (miRNAs) have a key role in carcinogenesis through negative regulation of their target genes. Therefore, genetic variations in miRNAs or their target sites may affect miRNA-mRNA interactions, thereby result in altered expression of target genes. This study was conducted to investigate the associations between single-nucleotide polymorphisms (SNP) located in the miRNA target sites (poly-miRTSs) and survival of patients with early-stage non-small-cell lung cancer (NSCLC). METHODS: Using public SNP database and miRNA target sites prediction program, 354 poly-miRTSs were selected for genotyping. Among these, 154 SNPs applicable to Sequenom's MassARRAY platform were investigated in 357 patients. A replication study was carried out on an independent patient population (n = 479). Renilla luciferase assay and reverse transcription-polymerase chain reaction were conducted to examine functional relevance of potentially functional poly-miRTSs. RESULTS: Of the 154 SNPs analyzed in a discovery set, 14 SNPs were significantly associated with survival outcomes. Among these, KRT81 rs3660G>C was found to be associated with survival outcomes in the validation cohort. In the combined analysis, patients with the rs3660 GC + CC genotype had a significantly better overall survival compared with those with GG genotype [adjusted hazard ratio (aHR) for OS, 0.65; 95% confidence interval (CI) 0.50-0.85; P = 0.001]. An increased expression of the reporter gene for the C allele of rs3660 compared with the G allele was observed by luciferase assay. Consistently, the C allele was associated with higher relative expression level of KRT81 in tumor tissues. CONCLUSION: The rs3660G>C affects KRT81 expression and thus influences survival in early-stage NSCLC. The analysis of the rs3660G>C polymorphism may be useful to identify patients at high risk of a poor disease outcome.

Type of anaesthesia and patient quality of recovery: a randomized trial comparing propofol-remifentanil total i.v. anaesthesia with desflurane anaesthesia.

BACKGROUND: Two common general anaesthetic methods are total i.v. anaesthesia (TIVA) and inhalation anaesthesia, but it is unclear whether this affects the patient's perception of their quality of recovery. The Quality of Recovery-40 questionnaire (QoR-40) is a valid and reliable method to evaluate the extent of functional recovery after surgery with general anaesthesia. This study therefore compared patient recovery using the QoR-40 in surgical patients who received TIVA with those who received desflurane anaesthesia. METHODS: Eighty females (20-65 years old) undergoing thyroid surgery were prospectively recruited and randomized to either the TIVA (effect-site target controlled infusion using propofol and remifentanil) or DES (desflurane inhalation with manual infusion of remifentanil) groups. The QoR-40 was administered by an investigator blind to group allocation before surgery, and postoperative days 1 and 2 (POD1 and POD2). Additional data including the incidence of nausea or vomiting, the consumption of antiemetic and analgesic agents in the post-anaesthesia care unit, and the duration of the hospital stay, were collected in all cases. RESULTS: The QoR-40 score on POD1 was significantly higher in the TIVA group compared with the DES group (174 vs 161, respectively; P=0.004), indicating a better quality of recovery in the TIVA group. Among the five dimensions of the QoR-40, physical comfort and physical independence were significantly better on POD1 and POD2 in the TIVA group. CONCLUSION: This study demonstrates that the quality of recovery for female thyroid surgery patients is significantly better with TIVA compared with desflurane anaesthesia. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.org; ref.: NCT01760018.

Renal cells exposed to cadmium in vitro and in vivo: normalizing gene expression data.

Cadmium (Cd) is a toxic metal with a long half-life in biological systems. This half-life is partly as a result of metallothioneins (MTs), metal-binding proteins with a high affinity for Cd. The high retention properties of the kidneys reside in proximal tubular cells that possess transport mechanisms for Cd-MT uptake, ultimately leading to more Cd accumulation. Researchers have studied MT-metal interactions using various techniques including quantitative real-time PCR (qPCR), an efficient tool for quantifying gene expression. Often a poor choice of reference genes, which is represented by their instability and condition dependency, leads to inefficient normalization of gene expression data and misinterpretations. This study demonstrates the importance of an efficient normalization strategy in toxicological research. A selection of stable reference genes was proposed in order to acquire reliable and reproducible gene quantification under metal stress using MT expression as an example. Moreover, in vitro and in vivo setups were compared to identify the influence of toxicological compounds in function of the experimental design. This study shows that glyceraldehyde-3-phosphate dehydrogenase (Gapdh), tyrosine monooxygenase/tryptophan5-monooxygenase activation-protein, zeta polypeptide (Ywhaz) and beta-actin (Actb) are the most stable reference genes in a kidney proximal tubular cell line exposed to moderate and high Cd concentrations, applied as CdCl2 . A slightly different sequence in reference gene stability was found in renal cells isolated from rats in vivo exposed to Cd. It was further shown that three reference genes are required for efficient normalization in this experimental setup. This study demonstrates the importance of an efficient normalization strategy in toxicological research.

Predictive factors for tuberculosis in patients with a TB-PCR-negative bronchial aspirate.

PURPOSE: Pulmonary tuberculosis (PTB), with a tuberculosis (TB)-polymerase chain reaction (PCR)-negative bronchial aspirate (BA), but a positive culture result is often encountered in clinical practice. However, limited data are available concerning clinical judgment in patients with suspected PTB and a TB-PCR-negative BA pending culture results. The present study aimed to identify predictors for PTB in patients with a TB-PCR-negative BA. METHODS: A retrospective study was conducted on patients who had undergone a bronchoscopy because of suspected PTB. Clinical, laboratory, and computed tomography (CT) findings were investigated in PTB patients with TB-PCR-negative but positive culture BA results, and non-PTB patients with a radiographic lesion comparable to the former. RESULTS: Of 250 patients screened, 31 (12 %) were diagnosed with PTB by positive culture results only. Of these 31 patients, 30 (97 %) had a lesion within one-third of the hemithorax as determined by chest radiography. In the final analysis of 30 PTB and 65 non-PTB patients with comparable radiographic lesions, a positive QuantiFERON-TB Gold In-Tube (QFT) result was independently associated with an increased risk of a positive TB culture. CT findings of consolidation were a negative predictor for PTB. Patients with a negative QFT result and consolidation had a negative predictive value of 95 % for PTB, while patients with a positive QFT result and nodular CT abnormalities without consolidation had a positive predictive value of 86 % for PTB. CONCLUSION: The simple combination of CT findings of consolidation and QFT test results may help clinicians to refine decision-making in patients with a TB-PCR-negative BA.

Congenital pseudarthrosis of the clavicle: a rare and challenging diagnosis.

Congenital pseudarthrosis of the clavicle is a rare clinical entity, first described in 1910. We report on a newborn baby girl who presented with a painless lump over mid-portion of right clavicle at her routine newborn examination, which was subsequently diagnosed as a congenital pseudarthrosis. Here we explore its pathogenesis, elaborate on its differential diagnoses in paediatric patients, and comment on its distinct radiological features.

Aggravated capillary non-perfusion after intravitreal bevacizumab for macular edema secondary to systemic lupus erythematosus and anti-phospholipid syndrome.

A 22-year-old female with history of systemic lupus erythematosus (SLE) was referred for evaluation of decreased visual acuity in her right eye. Her best-corrected visual acuity (BCVA) at the time of presentation was 20/160. Widespread cotton wool spots and macular edema were seen on biomicroscopy. Fluorescein angiography (FA) revealed retinal arterial and venous obstruction with capillary nonperfusion at the superotemporal retina. Antiphospholipid syndrome (APS) was diagnosed based on positive lupus anti-coagulant and ocular manifestations. Scattered laser photocoagulation was applied at the nonperfusion area but the visual acuity continued to deteriorate due to macular edema. Intravitreal bevacizumab (IVB) was administered for macular edema. One day after IVB, the BCVA decreased to count fingers. FA revealed extended non-perfusion from the superotemporal area to the posterior pole. Use of intravitreal bevacizumab for macular edema secondary to SLE or APS should be considered carefully and patients monitored closely for vascular complications.

CT appearances of abdominal tuberculosis.

The purpose of this article is to review and illustrate the spectrum of computed tomography (CT) appearances of abdominal tuberculosis. Tuberculosis can affect any organ or tissue in the abdomen, and can be mistaken for other inflammatory or neoplastic conditions. The most common sites of tuberculosis in the abdomen include lymph nodes, genitourinary tract, peritoneal cavity and gastrointestinal tract. The liver, spleen, biliary tract, pancreas and adrenals are rarely affected, but are more likely in HIV-seropositive patients and in miliary tuberculosis. This article should alert the radiologist to consider abdominal tuberculosis in the correct clinical setting to ensure timely diagnosis and enable appropriate treatment.

Isoflurane-induced post-conditioning in senescent hearts is attenuated by failure to activate reperfusion injury salvage kinase pathway.

BACKGROUND: We investigated the cardioprotective effects of isoflurane administered at the onset of reperfusion in senescent rat in vivo, and the activation of the reperfusion injury salvage kinase (RISK) pathway to address a possible mechanism underlying age-related differences. METHODS: Male Wistar rats were assigned to age groups (young, 3-5 months; old, 20-24 months), and randomly selected to receive isoflurane (1 minimum alveolar concentration) or not for 3 min before and 2 min after reperfusion (ISO postC). Rats were subjected to coronary occlusion for 30 min followed by 2 h of reperfusion. Western blot analysis was used to assess the phosphorylation of extracellular signal-regulated kinase (ERK1/2), Akt, and GSK3ß 15 min after reperfusion. RESULTS: Brief administration of isoflurane 3 min before and 2 min after the initiation of early reperfusion reduced infarct size (56 ± 8% of left ventricular area at risk, mean ± standard deviation) compared with controls (68 ± 4%) in young rats, but had no effect in old rats (56 ± 8% in ISO postC and 56 ± 10% in control, respectively). Phosphorylation of ERK1/2, Akt, and GSK3ß were increased in the young ISO postC group but not in the old ISO postC group compared with control groups of the respective ages. CONCLUSIONS: We demonstrated that isoflurane post-conditions the heart in young but not in senescent rats. Failure to activate RISK pathway may contribute to attenuation of isoflurane-induced post-conditioning effect in senescent rats.

Frequency of CYP2C9 variant alleles, including CYP2C9*13 in a Korean population and effect on glimepiride pharmacokinetics.

WHAT IS KNOWN AND OBJECTIVE: Cytochrome P450 (CYP) 2C9 is a clinically important enzyme involved in the metabolism of many drugs commonly used in humans. Of several allelic variants known to affect the catalytic activity of the CYP2C9 enzyme, the frequencies of the CYP2C9*3 and CYP2C9*13 alleles in the Korean population have been reported as 1·1% and 0·6%, respectively. Our objective was to re-evaluate the frequencies of CYP2C9 allelic variants in the Korean population, including the CYP2C9*13 allele by pyrosequencing, and to investigate the pharmacokinetics of glimepiride in relation to CYP2C9 genotypes, including CYP2C9*3/*3. METHODS: 295 subjects were genotyped for CYP2C9*2 and CYP2C9*3 using the TaqMan procedure, and for CYP2C9*13 using pyrosequencing. These data were combined with our previously reported data to assess the CYP2C9 allele and genotype frequencies in 869 Korean subjects. Data from 24 of the 295 genotyped subjects (22 CYP2C9*1/*1 homozygotes, one CYP2C9*1/*3 heterozygote and one CYP2C9*3/*3 homozygote) who had participated in a bioequivalence study were analysed retrospectively to examine the effects of CYP2C9 genotype on glimepiride pharmacokinetics. RESULTS: The frequencies of the CYP2C9*1/*3, *3/*3, and *1/*13 genotypes in the study population (n = 295) were 0·081 (n = 24), 0·010 (n = 3) and 0·003 (n = 1), respectively. In the 869 subjects from the combined studies, allele frequencies for CYP2C9*3 and CYP2C9*13 were 0·025 (95% CI: 0·018, 0·033) and 0·002 (95% CI: 0·000, 0·010), respectively. Relative to CYP2C9*1 homozygotes, the one CYP2C9*3 homozygous subject was found to have a higher AUC(0-∞) value (490% of the reference value) and a lower oral clearance rate (18% of the reference). WHAT IS NEW AND CONCLUSION: This study is the first examination of CYP2C9*3 homozygotes in the Korean population. Our data on the one subject with this genotype suggest that CYP2C9*3/*3 momozygotes have lower clearance of glimepiride and are exposed to higher levels of the drug than wild-type homozygotes. Although we identified a subject with the CYP2C9*13 allele using a new pyrosequencing assay, we were unfortunately unable to investigate its effects on glimepiride pharmacokinetics.

Colloid coalescence with focused x rays.

We show direct evidence that focused x rays enable us to merge polymer colloidal particles at room temperature. This phenomenon is ascribed to the photochemical scission of colloids with x rays, reducing the molecular weight, glass transition temperature, surface tension, and viscosity of colloids. The observation of the neck bridge growth with time shows that the x-ray-induced colloid coalescence is analogous to viscoelastic coalescence. This finding suggests a feasible protocol of photonic nanofabrication by sintering or welding of polymers, without thermal damage, using x-ray photonics.