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Background: Palmoplantar pustulosis (PPP) and pompholyx are chronic diseases characterized by pustules and vesicles on the palms and soles. These disorders often have similar clinicopathological features, which lead to diagnostic difficulties. We aimed to investigate the expression patterns of keratins and involucrin in PPP and pompholyx using immunohistochemical staining. Methods: Skin biopsies from patients with PPP (n = 40) and pompholyx (n = 22) were immunohistochemically analyzed for Keratin 5, 9, 14, and involucrin expression. Results: K5 expression was higher in PPP than in pompholyx, with diffusely positive expression in the basal, spinous, and granular layers. K14 expression did not differ between groups. K9 expression was observed near the pompholyx vesicle (P = 0.014) and stratum spinosum (P < 0.001) but was almost absent around PPP pustules. Involucrin expression was diffused around the PPP pustules and partially around the pompholyx vesicles, but without statistical significance (P = 0.123). Involucrin expression was elevated in the basal layer of the PPP compared with that in the pompholyx (P = 0.023). Conclusion: PPP and pompholyx exhibited distinctive differentiation in the expression of K5, K9, and involucrin. [ABSTRACT FROM AUTHOR]

Background: Brain metastases frequently occur in patients with non‐small cell lung cancer (NSCLC) resulting in a poor prognosis. Here, we investigated the association between PD‐L1 expression and brain metastasis in patients with NSCLC and its clinical significance. Methods: A total of 270 patients diagnosed with metastatic NSCLC who underwent PD‐L1 testing on their tumor tissue between January 2017 and March 2019 were retrospectively reviewed. The VENTANA PD‐L1 (SP263) assay was used, and positive PD‐L1 expression was defined as staining in ≥1% of tumor cells. Results: Positive PD‐L1 expression was observed in 181 (67.0%) patients, and 74 (27.4%) patients had brain metastasis at diagnosis. Synchronous brain metastases were more frequently observed in PD‐L1‐positive compared with PD‐L1‐negative patients (31.5% vs. 19.1%, p = 0.045). Multiple logistic regression analysis identified positive PD‐L1 expression (odds ratio [OR]: 2.24, p = 0.012) as an independent factor associated with synchronous brain metastasis, along with the histological subtype of nonsquamous cell carcinoma (OR: 2.84, p = 0.003). However, the incidence of central nervous system (CNS) progression was not associated with PD‐L1 positivity, with a two‐year cumulative CNS progression rate of 26.3% and 28.4% in PD‐L1‐positive and PD‐L1‐negative patients, respectively (log rank p = 0.944). Furthermore, positive PD‐L1 expression did not affect CNS progression or overall survival in patients with synchronous brain metastasis (long rank p = 0.513 and 0.592, respectively). Conclusions: Initial brain metastases are common in NSCLC patients with positive PD‐L1 expression. Further studies are necessary to understand the relationship between early brain metastasis and cancer immunity. [ABSTRACT FROM AUTHOR]

Amplification‐independent c‐MYC overexpression is suggested in multiple cancers. Targeting c‐MYC activity has therapeutic potential, but efforts thus far have been mostly unsuccessful. To find a druggable target to modulate c‐MYC activity in cancer, we identified two kinases, MAPKAPK2 (MK2) and the DNA‐dependent protein kinase catalytic subunit (DNA‐PKcs), which phosphorylate the Ser111 and the Ser93 residues of OCT4, respectively, to transcriptionally activate c‐MYC. Using these observations, we present here a novel cell‐based luminescence assay to identify compounds that inhibit the interaction between these kinases and OCT4. After screening approximately 80,000 compounds, we identified 56 compounds ("hits") that inhibited the luminescence reaction between DNA‐PKcs and OCT4, and 65 hits inhibiting the MK2–OCT4 interaction. Using custom antibodies specific for pOCT4S93 and pOCT4S111, the "hits" were validated for their effect on OCT4 phosphorylation and activation. Using a two‐step method for validation, we identified two candidate compounds from the DNA‐PKcs assay and three from the MK2 assay. All five compounds demonstrate a significant ability to kill cancer cells in the nanomolar range. In conclusion, we developed a cell‐based luminescence assay to identify novel inhibitors targeting c‐MYC transcriptional activation, and have found five compounds that may function as lead compounds for further development. [ABSTRACT FROM AUTHOR]

Background and Aims: Hepatocellular carcinoma (HCC) risk in chronic hepatitis B (CHB) substantially decreased in the era of potent antiviral therapy. We developed an optimized HCC risk prediction model for CHB with well‐controlled viremia by nucelos(t)ide analogs (NUCs). Method: We analysed those who achieved virological response (VR; serum HBV‐DNA < 2000 IU/mL on two consecutive assessments) by NUCs. Liver stiffness by transient elastography, ultrasonography and laboratory tests was performed at the time of confirmed VR. Patients with decompensated cirrhosis or HCC at baseline were excluded. Multivariate Cox‐regression analysis was used to determine key variables to construct a novel risk‐scoring model. Results: Among 1511 patients, 9.5% developed HCC. Cirrhosis on ultrasonography (adjusted HR [aHR] 2.47), age (aHR 1.04), male (aHR 1.90), platelet count <135 000/uL (aHR 1.57), albumin <4.5 g/dL (aHR 1.77) and liver stiffness ≥11 kPa (aHR 6.09) were independently associated with HCC. Using these, CAMPAS model was developed with c‐index of 0.874. The predicted and observed HCC probabilities were calibrated with a reliable agreement. Such results were reproduced from internal validation and external validation among the independent cohort (n = 252). The intermediate‐risk (CAMPAS model score 75 ~ 161) and high‐risk (score >161) groups were more likely to develop HCC compared with the low‐risk group (score ≤75) with statistical significances (HRs; 4.43 and 47.693 respectively; both P <.001). Conclusion: CAMPAS model derived through comprehensive clinical evaluation of liver disease allowed the more delicate HCC prediction for CHB patients with well‐controlled viremia by NUCs. [ABSTRACT FROM AUTHOR]

BACKGROUND: The cost of biomass feedstock represents a large portion of the total cost of bioethanol production. Therefore, it is necessary to find candidate materials as cheap feedstock for bioethanol production. Mangosteen pericarp waste (MPW) has potential as a feedstock for the production of bioethanol and other valuable chemicals. RESULTS: We have developed a new method to efficiently convert MPW into bioethanol and other valuable products such as biosugar, α‐mangostin and γ‐mangostin. The biosugar was obtained from in‐house produced cellulase and pectinase at a 90% conversion rate; the biosugar was converted into bioethanol with 75% yield using separate hydrolysis and fermentation. In addition, the extraction of α‐mangostin increased 1.46‐fold after a combination of popping pretreatment and enzymatic hydrolysis. A copper‐doped magnetic nanomatrix (Cu‐MNM) was utilized to purify α‐mangostin from MPW. We also obtained a good yield of γ‐mangostin via o‐demethylation reaction of α‐mangostin. CONCLUSION: The value of MPW can be increased through reuse to produce bioethanol and other valuable active materials such as biosugar, α‐mangostin and γ‐mangostin. We predict that economically beneficial processes could be developed from the reuse of these waste materials. © 2018 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Ceria (CeO2) is an effective precious‐metal‐free catalyst that combusts PM (particulate matter), due to its ability to switch between Ce4+ and Ce3+. In this work, to improve the activity of a ceria‐based catalyst, cerium‐praseodymium mixed oxide catalysts with various Ce−Pr ratios were synthesized with nanofiber morphologies, characterized, and compared with ceria catalysts. Two factors were considered: morphology and Ce−Pr ratio, which result in synergistic effects. In the ceria catalyst, we confirmed that a fibrous morphology is more advantageous for PM oxidation compared to nanocubes and nanorods with cubes, even though these samples have larger surface areas. In addition, the incorporation of Pr into the ceria nanofiber catalyst enhanced its intrinsic properties by promoting the reducibility and formation of oxygen vacancies. The analysis showed improved oxygen storage and supply capacity, especially for oxygen that is chemically adsorbed on the catalytic surface. PM oxidation tests demonstrated the Ce0.5Pr0.5O2‐NF catalyst showed the best activity in air, which was consistent with the characterization results. Thus, the Ce0.5Pr0.5O2‐NF sample was shown to be an effective and promising catalyst for PM oxidation. [ABSTRACT FROM AUTHOR]

Aim: To compare pancreatic volume and fat amount, and their associations with glucose homeostasis, in a Korean and a white population. Materials and methods: In 43 healthy Korean and 43 healthy white people, matched for age (±3 years) and body mass index (BMI; ±1 kg/m2), we measured pancreatic volume and fat amount in the pancreas and abdomen using computed tomography. Pancreatic β‐cell function and insulin resistance were estimated according to biochemical characteristics and a 75‐g oral glucose tolerance test. Body composition and resting energy expenditure (REE) were examined using bioimpedance and indirect calorimetry, respectively. Results: The mean ±SD age of the participants was 29.9 ± 5.9 years and 30.0 ± 5.2 years, and BMI was 24.0 ±3.7 and 24.1 ±3.2 kg/m2 in the white participants and the Korean participants, respectively. Pancreatic volume in the white participants was greater than that in Korean participants (77.8 ±11.6 vs 68.2 ±12.1 cm3; P < .001). Pancreatic fat content in Korean participants was 22.8% higher than in white participants (P = .051). Insulinogenic index, disposition index, muscle mass and REE were significantly lower in Korean participants. Pancreatic volume was positively associated with indices linked to β‐cell function; fat content in the pancreas was negatively associated with such indices, and positively with insulin resistance after adjusting for relevant variables including REE. Conclusions: A smaller pancreas and higher fat deposition might be crucial determinants of vulnerability to diabetes in Korean people compared with white people with similar BMI and body fat levels. [ABSTRACT FROM AUTHOR]

High mobility group box 1 (HMGB1) has been proposed as crucial in the pathogenesis of many diseases including sepsis. Acetylation of HMGB1 prevents its entry into the nucleus and leads to its secretion from the cell where it can trigger inflammation. We hypothesized that histone deacetylase 4 (HDAC4) controls the acetylation of HMGB1 in lipopolysaccharide (LPS)‐stimulated RAW264.7 cells via the janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway. The results showed that LPS treatment promoted the degradation of HDAC4 in a proteasome‐dependent manner, which led to HMGB1 acetylation. In LPS‐activated RAW264.7 cells, treatment with TAK‐242 (a toll like receptor 4 inhibitor) and pyridone 6 (a JAK inhibitor) significantly inhibited HDAC4 degradation and acetylation of HMGB1, and thus prevented secretion of HMGB1. Decreased phosphorylation of STAT1 was also observed. Interestingly, HDAC4 overexpression significantly prevented the acetylation and secretion of HMGB1 in both RAW264.7 cells and isolated murine peritoneal macrophages. We conclude that HDAC4 might be a useful target for the treatment of sepsis. [ABSTRACT FROM AUTHOR]

The Amundsen Sea polynya (ASP) is reportedly the most productive among the coastal polynyas around Antarctica. However, observational constraints limit our understanding of the biological pump and carbon cycle in the ASP. We measured various carbon-related parameters such as primary production, bacterial production, sinking flux of particulate organic carbon (POC), and accumulation of organic carbon in the sediment as well as hydrographic parameters during field observations and by instrument moorings. Over 95% of the photosynthetically produced POC was converted to suspended POC and/or dissolved carbon forms in the upper ~400 m layer. We postulate that most of the carbon transported to the water column by the biological pump in the ASP was flushed out of the shelf without being sequestered for long-term storage in sediments. Lack of bottom water formation due to intrusion of Circumpolar Deep Water in the lower layer reduces carbon sequestration efficiency. [ABSTRACT FROM AUTHOR]

6-Azido-6-deoxy- N-acetylglucosamine ( 6AzGlcNAc) was recently introduced as a new selective metabolic chemical reporter ( MCR) for labeling O- GlcNAc-modified proteins in cells. To investigate whether O- 6AzGlcNAc is readily cleaved by O- GlcNAcase ( OGA), the enzyme responsible for removing the O- GlcNAc modification, we synthesized PNP-6AzGlcNAc. This analog mimics O- GlcNAc and can be used in vitro to define the kinetic parameters for OGA thereby defining whether O- 6AzGlcNAc can be employed as an appropriate tool to monitor O- GlcNAc dynamics in cells. Both PNP-6AzGlcNAc and PNP-GlcNAc were efficiently hydrolyzed by OGA with similar kinetics suggesting that an azido-modification at the GlcNAc C6 position does not significantly interfere with the β-hexosaminidase activity of OGA. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 54-year-old male patient who was admitted to the hospital with the complaints of inelastic skin of the neck, face and shoulder and pendulous. The patient was diagnosed with enophthalmos and entropion and has to underwent ophthalmologic surgery. Further examination of the patient revealed generalized acquired cutis laxa. The patient was suggested with cosmetic surgery as the option of the treatment.

Charcot-Marie-Tooth disease ( CMT) is the most common inherited peripheral neuropathy. Mutations in the pyruvate dehydrogenase kinase isoenzyme 3 ( PDK3) gene have been found to cause X-linked dominant CMT type 6 ( CMTX6). This study identified the p. R158H PDK3 mutation after screening 67 probable X-linked CMT families. The mutation fully segregated with the phenotype, and genotyping the family indicated the mutation arose on a different haplotype compared with the original Australian CMTX6 family. Results of bisulphite sequencing suggest that methylated deamination of a CpG dinucleotide may cause the recurrent p. R158H mutation. The frequency of the p. R158H PDK3 mutation in Koreans is very rare. Magnetic resonance imaging revealed fatty infiltration involving distal muscles in the lower extremities. In addition, fatty infiltrations were predominantly observed in the soleus muscles, with a lesser extent in tibialis anterior muscles. This differs from demyelinating CMT1A patients and is similar to axonal CMT2A patients. The clinical, neuroimaging, and electrophysiological findings from a second CMTX6 family with the p. R158H PDK3 mutation were similar to the axonal neuropathy reported in the Australian family. [ABSTRACT FROM AUTHOR]

The purpose of this study was to develop and test a novel mode of negative pressure wound therapy (NPWT) that minimises pain while preserving the efficacy in wound healing. A porcine model was used in this study. Wounds were generated in animals and treated with either simple dressing or various treatment modes of NPWT. The wound volume, perfusion level and vasculature status were analysed and compared among different groups. Clinical application was performed to evaluate the level of pain occurring when negative pressure is applied. Among the NPWT groups, the Cyclic-50 group showed most decrement in wound volume, even though statistical relevance was not found ( P = 0·302). The perfusion level was significantly increased in the Cyclic-50 group compared with the Intermittent group ( P < 0·001) and the Cyclic-100 group ( P = 0·004). Evaluation of blood vessel formation revealed that the Cyclic-50 group showed the highest number of vasculature with statistical significance ( P < 0·001). In clinical application, the cyclic group showed significant decrease in pain compared with the intermittent group ( P = 0·001). The cyclic NPWT mode decreased patient discomfort while maintaining superior wound healing effects as the intermittent mode. [ABSTRACT FROM AUTHOR]

This article presents an asset-level security risk management framework to assist stakeholders of critical assets with allocating limited budgets for enhancing their safety and security against terrorist attack. The proposed framework models the security system of an asset, considers various threat scenarios, and models the sequential decision framework of attackers during the attack. Its novel contributions are the introduction of the notion of partial neutralization of attackers by defenders, estimation of total loss from successful, partially successful, and unsuccessful actions of attackers at various stages of an attack, and inclusion of the effects of these losses on the choices made by terrorists at various stages of the attack. The application of the proposed method is demonstrated in an example dealing with security risk management of a U.S. commercial airport, in which a set of plausible threat scenarios and risk mitigation options are considered. It is found that a combination of providing blast-resistant cargo containers and a video surveillance system on the airport perimeter fence is the best option based on minimum expected life-cycle cost considering a 10-year service period. [ABSTRACT FROM AUTHOR]

Multiple lines of evidence suggest that natural compounds can prevent skin ageing induced by ultraviolet light. Luteolin, a bioactive compound found in chilli, onion, broccoli, celery and carrot, has been reported to exhibit anti-photoageing effects in vitro. However, the molecular targets and mechanisms of luteolin are still poorly understood. In this study, we sought to investigate the effects of luteolin on UVB-induced photoageing and the molecular mechanisms involved, using HaCaT human keratinocytes and SKH-1 hairless mice. Luteolin was found to inhibit UVB-induced MMP-1 expression in HaCaT cells, as well as UVB-induced activation of AP-1, a well-known transcription factor targeting the MMP-1 promoter region, as well as c-Fos and c-Jun, which comprise the AP-1 complex. In contrast, Western blot data showed that UVB-induced phosphorylation of JNK, ERK and p90RSK was not inhibited by luteolin. In vitro kinase assay data revealed that luteolin significantly suppressed JNK1 and p90RSK activity, but not that of JNK2 and ERK2. Pull-down assays showed that luteolin binds JNK1 in an ATP-competitive manner and p90RSK2 in an ATP-independent manner. Luteolin also inhibited UVB-induced wrinkle formation and MMP-13 expression, a rodent interstitial collagenase in mouse skin, in vivo. Taken together, our observations suggest that luteolin exhibits anti-photoageing effects in vitro and in vivo and may have potential as a treatment for the prevention of skin ageing. [ABSTRACT FROM AUTHOR]

Melatonin (N-acetyl-5-methoxytryptamine) has differentiated the effects on apoptosis in normal and cancer cells. The mechanisms that account for the opposite effects on these cells are not adequately understood. In this study, we investigated the combined effect of melatonin and thapsigargin (TG) on apoptosis of renal cancer cells. Cotreatment with melatonin (1 m m) and TG (50 n m) induced approximately 10-fold expression levels of CCAAT-enhancer-binding proteins homologous protein (CHOP) compared with that of TG (50 n m) alone. Downregulation of CHOP expression using small interfering RNAs markedly attenuated melatonin plus TG-mediated apoptosis. In addition, cotreatment with TG- and melatonin-induced CHOP upregulation likely relates to melatonin's antioxidant capacity because we proved that this CHOP upregulation is melatonin receptor independent. Our results collectively demonstrate that the upregulation of CHOP contributes to the enhancing effect of melatonin plus TG on apoptosis in cancer cells. [ABSTRACT FROM AUTHOR]

Qureshi ZA, Kwak EJ, Nguyen MH, Silveira FP. Ochroconis gallopava: a dematiaceous mold causing infections in transplant recipients. Clin Transplant 2012: 26: E17-E23. © 2011 John Wiley & Sons A/S. Abstract: The dematiaceous mold Ochroconis gallopava is increasingly recognized as a human pathogen. Infection is almost always associated with immunosuppression. We describe a case with a unique presentation in a kidney transplant recipient and retrospectively review all 10 cases of O. gallopava at our institution over 18 yr, all in organ transplant recipients. Sixty percent of infections at our institution occurred in the last five yr studied. Infection generally occurred late after transplantation, and pulmonary infection was the most common manifestation. Use of almetuzumab for induction was associated with infection in the first six months post-transplant (p = 0.03). Attributable mortality at six months was 20%. Ochroconis gallopava is a rare but important pathogen in immunosuppressed individuals and organ transplantation is the most common underlying condition. Pulmonary involvement is the most common manifestation among patients with organ transplant. Optimal therapy remains undefined. Prognosis in organ transplant recipients is good if infection is diagnosed prior to dissemination. [ABSTRACT FROM AUTHOR]

Summary Purpose: The aim of this study was to evaluate phospholipid metabolism in patients with malformations of cortical development (MCDs). Methods: Thirty-seven patients with MCDs and 31 control subjects were studied using three-dimensional phosphorus magnetic resonance spectroscopy (31P-MRS) at 3.0 T. The voxels in the lesions and in the frontoparietal cortex of the control subjects were compared (the effective volumes were 12.5 cm3). Robust quantification methods were applied to fit the time-domain data to the following resonances: phosphoethanolamine (PE); phosphocholine (PC); inorganic phosphate (Pi); glycerophosphoethanolamine (GPE); glycerophosphocholine (GPC); phosphocreatine (PCr); and α-, β-, and γ-adenosine triphosphate (ATP). We also estimated the total ATP (ATPt = α-+β-+γ-ATP), phosphodiesters (PDE = GPC+GPE), phosphomonoesters (PME = PE+PC), and the PME/PDE, PCr/ATPt and PCr/Pi ratios. The magnesium (Mg2+) levels and pH values were calculated based on PCr, Pi, and β-ATP chemical shifts. Key Findings: Compared to controls and assuming that a p-value < 0.05 indicates statistical significance, the patients with MCDs exhibited significantly lower pH values and higher Mg2+ levels. In addition, the patients with MCDs had lower GPC and PDE and an increased PME/PDE ratio. Significance: Mg2+ and pH are important in the regulation of bioenergetics and are involved in many electrical activity pathways in the brain. Our data support the idea that neurometabolic impairments occur during seizure onset and propagation. The GPC, PDE, and PME/PDE abnormalities also demonstrate that there are membrane turnover disturbances in patients with MCDs. [ABSTRACT FROM AUTHOR]

Microbial biohydrogenation of dietary poly-unsaturated fatty acids (PUFA) to saturated fatty acids (SFA) in the rumen results in the high ratio of SFA/PUFA in ruminant products, such as meat and milk. In vitro, Butyrivibrio proteoclasticus-related bacteria extensively biohydrogenate PUFA to SFA, yet their contribution in the rumen has not been confirmed. The aim of this study was to evaluate the role of Butyrivibrio proteoclasticus group bacteria in ruminal biohydrogenation and to assess the possible role of other bacteria. Fish oil at 0%, 1.5% and 3% dry matter intake was fed to eight Holstein × Friesian steers, in order to elicit changes in the extent of PUFA biohydrogenation. Fatty acid and B. proteoclasticus group 16S rRNA concentrations in rumen digesta were determined. Correlation between digesta 18:0 concentration and B. proteoclasticus group 16S rRNA concentration was low. Terminal restriction fragment length polymorphism and denaturing gradient gel electrophoresis (DGGE) coupled with multivariate statistics revealed that many terminal restriction fragments (T-RFs) and DGGE bands were linked to cis-9, trans-11 conjugated linoleic acid (CLA), 18:1 trans-11 and 18:0 ruminal concentrations. MiCA T-RF predictive identification software showed that these linked T-RFs were likely to originate from as yet uncultured bacteria classified as Prevotella, Lachnospiraceae incertae sedis, and unclassified Bacteroidales, Clostridiales and Ruminococcaceae. Sequencing of linked DGGE bands also revealed that as yet uncultured bacteria classified as Prevotella, Anaerovoax (member of the Lachnospiraceae incertae sedis family), and unclassified Clostridiales and Ruminococcaceae may play a role in biohydrogenation. [ABSTRACT FROM AUTHOR]

The proper identification of illicit plants such as Papaver somniferum L (opium poppy) is important for law enforcement agencies. The identification of opium poppy was presently tested using 10 genetic markers that are universal for all plants or specific to a few poppy plants. The genetic distances of universal markers such as nuclear internal transcribed spacer (ITS), 18S rRNA, plastid rbcL, and trnL- trnF intergenic spacer (IGS) of 14 species included in the Papaveraceae and Fumariaceae family were acquired by sequence comparisons. Both the ITS region and trnL- trnF IGS showed high levels of interspecific divergence. Six Papaver genera-specific markers were developed from coding regions involved in morphine biosynthesis. Three markers (TYDC, NCS, and BBE) produced amplicons only in opium poppy, providing a presence/absence test for opium poppy, while three additional markers (CYP80B1, SAT, and COR) were genus specific. These 10 markers might be useful for the forensic DNA analysis of opium poppy. [ABSTRACT FROM AUTHOR]

Background Osteoporosis or low bone mass has been associated with cardiovascular disease and calcification in several clinical studies. However, few studies have assessed the relationship between bone mass and valvular calcification. The aim of this study was to evaluate the relationship between low bone mass and aortic valve sclerosis in Korean men and women. Methods A total of 211 men and 117 women were included in this study. Each subject’s bone mineral density (BMD) was measured with dual-energy X-ray absorptiometry, and aortic valve sclerosis was assessed using transthoracic echocardiography. Association between low bone mass and aortic valve sclerosis was assessed with multivariate logistic regression analysis in this cross-sectional study. Results Of 328 total subjects enrolled in this study, 50 men (23·7%) and 18 women (15·4%) were found to have aortic valve sclerosis. The mean (±SD) BMD T-scores were −0·5 (±0·8) in men and −0·9 (±1·0) in women. After adjusting for covariates, only women with aortic valve sclerosis had significantly lower BMD T-scores than those without it. Multivariate logistic regression analysis showed that age, smoking and hypertension were independently associated with increased risk of aortic valve sclerosis in men. In women, however, logistic regression analysis showed that BMD T-score, as well as age, was an independent variable for aortic valve sclerosis. We also found that a T-score of less than −1·5 was significantly associated with increased risk of aortic valve sclerosis in women compared to normal T-scores. Conclusion Low bone mass might be independently associated with increased risk of aortic valve sclerosis in women, but not in men. Women with low bone mass should be further evaluated for the presence of aortic valve sclerosis and related cardiovascular diseases. [ABSTRACT FROM AUTHOR]

CpG island hypermethylation and genomic DNA hypomethylation are found not only in gastric cancers but also in associated premalignant lesions. Helicobacter pylori infection induces aberrant CpG island hypermethylation in gastric mucosae. However, little is known about the relationship between H. pylori infection and aberrant methylation in premalignant lesions. The present study characterized methylation changes in a subset of genes and repetitive DNA elements ( ALU, LINE-1, SAT2) and examined their relationship with H. pylori infection in premalignant lesions of gastric cancers. We performed MethyLight analysis of 25 genes and SAT2 and COBRA analysis of ALU and LINE-1 in 212 gastric tissue samples. H. pylori infection was closely associated with enhanced hypermethylation of CpG island loci in chronic gastritis samples, but this association was not found among intestinal metaplasias, gastric adenomas and gastric cancers. The number of methylated genes was greater in intestinal metaplasia and gastric adenoma samples than in chronic gastritis samples, regardless of H. pylori infection. Methylation of repetitive DNA elements in gastric lesions generally decreased with progression of the gastric lesion along the multistep carcinogenesis. No difference was noted in the number of methylated genes in chronic gastritis or intestinal metaplasia between gastric cancer patients and non-cancer subjects. In conclusion, we found that there was no enhanced CpG island hypermethylation in gastric cancer and premalignant lesions in association with H. pylori infection and our findings suggest that CpG island hypermethylation and repetitive DNA hypomethylation are enhanced with progression of the gastric lesion through the multistep carcinogenesis, regardless of the status of H. pylori infection. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Abstract: The present study is the first demonstration of prolonged nociceptive behavior in the trigeminal region following compression of the trigeminal ganglion in rats. Experiments were carried out on male Sprague–Dawley rats mounted onto a stereotaxic frame under pentobarbital sodium anesthesia. For compression of the trigeminal ganglion, a 4% agar solution (8μl) was injected into the trigeminal ganglion through a stainless steel injector (24 gauge), which extended 2mm beyond the end of a guide cannula (21 gauge). Following agar injection, the injector and guide cannula were removed. In the control group, rats were sham operated without agar injection. Air-puff thresholds (mechanical allodynia), pin prick responses (mechanical hyperalgesia), and spontaneous scratching behavior were examined 3 days before surgery and at 3, 7, 10, 14, 17, 21, 24, 30, and 40 days after surgery. Data were analyzed using a repeated measures ANOVA followed by multiple group comparisons using the LSD post-hoc test. Air-puff thresholds significantly decreased after compression of the trigeminal ganglion. Mechanical allodynia was established within 3 days and lasted beyond postoperative day 24. Mechanical hyperalgesia was also evident 3 days after compression and persisted until the 40th postoperative day. Although mechanical allodynia and hyperalgesia appeared bilaterally, the ipsilateral side was significantly more sensitive. Intraperitoneal treatment with carbamazepine significantly blocked mechanical allodynia produced by compression of the trigeminal ganglion. These findings suggest that prolonged nociceptive behavior following compression of the trigeminal ganglion may mimic trigeminal neuralgia in this animal model. [Copyright &y& Elsevier]

Withania sominifera (Indian ginseng) was transformed by Agrobacterium rhizogenes. Explants from seedling roots, stems, hypocotyls, cotyledonary nodal segments, cotyledons and young leaves were inoculated with A. rhizogenes strain R1601. Hairy (transformed) roots were induced from cotyledons and leaf explants. The transgenic status of hairy roots was confirmed by polymerase chain reaction using nptII and rolB specific primers and, subsequently, by Southern analysis for the presence of nptII and rolB genes in the genomes of transformed roots. Four clones of hairy roots were established; these differed in their morphology. The doubling time of faster growing cultures was 8–14 d with a fivefold increase in biomass after 28 d compared with cultured, non-transformed seedling roots. MS-based liquid medium was superior for the growth of transformed roots compared with other culture media evaluated (SH, LS and N6), with MS-based medium supplemented with 40 g/L sucrose being optimal for biomass production. Cultured hairy roots synthesized withanolide A, a steroidal lactone of medicinal and therapeutic value. The concentration of withanolide A in transformed roots (157.4 μg/g dry weight) was 2.7-fold more than in non-transformed cultured roots (57.9 μg/g dry weight). [ABSTRACT FROM AUTHOR]

CpG island methylator phenotype (CIMP) is a recently described subset of colorectal cancers (CRC) with widespread methylation of multiple promoter CpG islands. But the prognostic implication of CIMP in CRC has not been clarified. Thus, the aim of the present study was to differentiate the unique characteristics of CIMP from those of microsatellite instability (MSI)-high CRC, especially with regard to prognosis. CIMP, MSI, and mutations of KRAS codons 12 and 13 and of BRAF codon 600 were evaluated in 134 sporadic CRC. Patient survival and other clinicopathological variables were correlated with CIMP or genetic changes. High CIMP, high MSI, and mutations in KRAS or BRAF were detected in 31.3%, 14.2%, 33.6%, and 4.5% of overall CRC, respectively. High CIMP was closely associated with MSI and BRAF mutation but not with KRAS mutation. CIMP-high, microsatellite-stable (MSS) CRC were significantly associated with proximal location and nodal metastasis and had close but non-significant associations with liver metastasis. A worse clinical outcome was found for CIMP-high, MSS CRC with KRAS/BRAF mutation but not for those lacking KRAS/BRAF mutation. The findings support the contention that CIMP-high CRC have distinct clinicopathological and epidemiological features and suggest that the alleged poor clinical outcome of CIMP-high CRC patients is closely associated with the presence of KRAS/BRAF mutation. [ABSTRACT FROM AUTHOR]

Skin findings in childhood sarcoidosis vary greatly, but only a few occurrences have been published in which the histopathology has been characterized well. We describe a child with sarcoidosis in whom the cutaneous findings were atypical, resembling granuloma annulare. Histologic examination of these cutaneous lesions, however, revealed areas of sarcoid-like epithelioid cell granulomas, a palisading granulomatous process with features of granuloma annulare, as well as palisading neutrophilic and granulomatous dermatitis and interstitial granulomatous dermatitis. This underscores the variability of skin findings in childhood sarcoidosis—even within the same patient—and suggests that sarcoidosis should be considered in the differential diagnosis of children initially diagnosed with granulomatous skin lesions, such as granuloma annulare, palisading neutrophilic, and granulomatous dermatitis or interstitial granulomatous dermatitis, who demonstrate associated signs of systemic disease. [ABSTRACT FROM AUTHOR]

It has recently been shown that thin polymer films in the nanometer thickness range exhibit anomalous swelling maxima in supercritical CO2 (Sc‐Co2) in the vicinity of the critical point of CO2. The adsorption isotherm of CO2 on carbon black, silica surfaces, porous zeolites, and other surfaces, is known to exhibit anomalous maxima under similar CO2 conditions. It is believed that because CO2 possesses a low cohesive energy density, there would be an excess amount of CO2 at the surfaces of these materials and hence the CO2/polymer interface. This might cause excess CO2 in the polymer films near the free surface, and hence the swelling anomaly. In addition, an excess of CO2 would reside at the polymer/substrate and polymer/CO2 interfaces for entropic reasons. These interfacial effects, as have been suggested, should account for an overall excess of CO2 in a thin polymer film compared to the bulk, and would be responsible for the anomalous swelling. In this study, we use in situ spectroscopic ellipsometry to investigate the role of interfaces on the anomalous swelling of polymer thin films of varying initial thicknesses, h0, exposed to Sc‐CO2. We examined three homopolymers, poly(1,1′‐dihydroperflurooctyl methacrylate) (PFOMA), polystyrene (PS), poly(ethylene oxide) (PEO), that exhibit very different interactions with Sc‐CO2, and the diblock copolymer of PS‐b‐PFOMA. We show that the anomalous swelling cannot be solely explained by the excess adsorption of CO2 at interfaces. © 2007 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 45: 1313–1324, 2007 [ABSTRACT FROM AUTHOR]

CD14 is a high-affinity receptor protein for the complex of bacterial LPS (LPS) and LPS binding protein in animals. Binding of the soluble form of CD14 (sCD14) to LPS, found in the outer membrane of Escherichia colt and other Gram-negative bacteria, enhances host innate immune responses, reduces the severity of mastitis, and facilitates clearance and neutralization of LPS, thus protecting against an excessive immune response to LPS and development of endotoxic shock. A truncated form of sCD14, carrying a histidine residue affinity tag for purification, was incorporated into Potato virus X for transient expression in Nicotiana benthamiana plants. Western blots probed with CD14-specific antibodies demonstrated that crude plant extracts and affinity-purified samples contained immunoreactive sCD14. Biological activity of plant-derived recombinant bovine sCD14 (PrbosCD14) was demonstrated in vitro by LPS-induced apoptosis and interleukin (IL) -8 production in bovine endothelial cells, and in viva by enhancement of LPS-induced neutrophil recruitment. Finally, in PrbosCD14-infused glands subsequently infected with E. coli, lower numbers of viable bacteria were recovered and there was an absence of clinical symptoms, demonstrating prophylactic efficacy of PrbosCD14. This is the first report of a functionally active animal receptor protein made in plants and the prophylactic use of a plant-derived protein to reduce the severity of bacterial infections in animals. [ABSTRACT FROM AUTHOR]

Background/Purpose: Seborrheic keratoses (SKs) are common epidermal tumors in the white population over 40 years. The etiology of SKs is not well known; however, exposure to sunlight was suggested to play a role in the development of them. To our knowledge, no well-designed study has been undertaken in order to investigate the clinical characteristics of SKs in a brown-skinned Korean population. The aim of this study was to assess the prevalence and clinical features of SKs in the Korean males and to investigate the possible relationship of SKs with sun exposure and possible risk factors of developing SKs. Methods: A total of consecutive 303 male volunteers, aged 40–70 years, were recruited from general community and public health centres. Each volunteer was interviewed regarding demographic data, sunlight sensitivity, lifetime cumulative sun exposure and smoking history. Skin examination was performed except for scalp, buttocks and genitals. All SKs were recorded about the anatomical distribution, the size of each lesion measured with a caliber, color and morphology. Results: The mean overall prevalence of SKs in the Korean males, aged 40–70 years was 88.1%. A considerable increase in the prevalence of SKs was shown from 78.9% at 40 years to 93.9% at 50 years and 98.7% in those over 60 years. The mean number of lesions per person was 5.5 at 40 years, 9.2 at 50 years and 13.4 at 60 years. Seborrheic keratoses were considerably more frequent on exposed areas (0.47 ± 0.06/percentage of body surface area, BSA) than partly exposed areas (0.04 ± 0.01/percentage of BSA). The majority of lesions were concentrated on the face (0.98 ± 0.09/ percentage of BSA) and on the dorsum of each hand (0.51 ± 0.08/percentage of BSA). The size of each lesion on exposed areas also became significantly larger by decade significantly (P < 0.01). The estimated area covered by SKs per percentage of BSA on exposed areas was 5.7-fold larger than that on partly exposed areas at 40 years, 11.2-fold larger at 50 years and 18.3-fold larger at 60 years. Aging by decade showed a 2.08-fold increased risk for SKs (n ≥ 6) (95% CI, 1.07–4.08) at 50 years and a 3.47-fold risk (95% CI, 1.67–7.20) at 60 years on exposed areas compared with the 40-year age group, for developing many SKs (n ≥ 6). Lifetime cumulative sunlight exposure of more than 6 h per day was associated with a 2.28-fold higher risk of SKs than a sun exposure of less than 3 h per day. A tendency for an odds ratio value reduction was found on increasing Fitzpatrick skin types I–III to VI, V; however, this was without statistical significance. Conclusions: Seborrheic keratoses are common in the Korean males, aged 40–70 years, and may be a major pigmentary problem. Both aging and cumulative sunlight exposure were found to be independent contributory factors. [ABSTRACT FROM AUTHOR]

The article presents a study which underscores the controversy and dilemma of using sentinel lymph node (SLN) biopsy for diagnostically difficult melanocytic proliferations. It states that an article by K. J. Busam and M. Pulitzer explores the literature surrounding this medical concern. Relative to this, it is also observed that the practice of designating histopathologically ambigous Spitzoid lesions as malignant based SLN positivity is widely reported in surgical literature.

Our limited ability to predict genotype–phenotype relationships has called for strategies that allow testing of thousands of hypotheses in parallel. Deep scanning mutagenesis has been successfully implemented to map genotype–phenotype relationships at a single‐protein scale, allowing scientists to elucidate properties that are difficult to predict. However, most phenotypes are dictated by several proteins that are interconnected through complex and robust regulatory and metabolic networks. These sophisticated networks hinder our understanding of the phenotype of interest and limit our capabilities to rewire cellular functions. Here, we leveraged CRISPR‐EnAbled Trackable genome Engineering to attempt a parallel and high‐resolution interrogation of complex networks, deep scanning multiple proteins associated with lysine metabolism in Escherichia coli. We designed over 16,000 mutations to perturb this pathway and mapped their contribution toward resistance to an amino acid analog. By doing so, we identified different routes that can alter pathway function and flux, uncovering mechanisms that would be difficult to rationally design. This approach sets a framework for forward investigation of complex multigenic phenotypes. Synopsis: Genotype—phenotype mapping is used to allow a high‐resolution interrogation of different routes that alter lysine metabolism and confer resistance to an antimetabolite analog. This approach narrows the search space down to specific targets to guide engineering efforts. 19 genes affecting lysine metabolism are investigated for their contribution toward resistance to the antimetabolite AEC in E. coli, totaling 16,300 mutations in the pathway.Loss‐of‐function mutations in the transporter are found to be the dominant selection winner.CRISPR‐EnAbled Trackable genome Engineering (CREATE) allowed exploring beyond the dominant selection winner, identifying mutations in biosynthetic genes and regulatory proteins that confer resistance by overproduction of lysine. Genotype—phenotype mapping is used to allow a high‐resolution interrogation of different routes that alter lysine metabolism and confer resistance to an antimetabolite analog. This approach narrows the search space down to specific targets to guide engineering efforts. [ABSTRACT FROM AUTHOR]

Atypical fibroxanthoma ( AFX) is a histologic mimicker of a variety of spindle cell neoplasms, and careful microscopic and immunohistochemical evaluation is critical in establishing the correct diagnosis. Here we report the histologic and immunohistochemical work up of a 1 cm nodule involving the left dorsal hand of a 66-year-old patient. Light microscopy revealed fascicles of spindled and pleomorphic cells within the dermis showing increased mitotic activity occurring in the background of sun-damaged skin. There were numerous multinucleated cells with hyperchromatic nuclei and ample finely vacuolated or foamy cytoplasms. There was strong and diffuse CD10 and patchy CD68 expression among the spindled cells and multinucleated cells. The neoplastic cells did not show immunoreactivity against S100, p75- NGFR, HMB-45 or a panel of keratinocytic, vascular and smooth muscle markers. Tyrosinase and Melan-A were not expressed within the spindle cell component of this neoplasm; however, there was tyrosinase expression among numerous multinucleated giant cells. Melan-A expression was also observed among rare multinucleated giant cells. Tyrosinase expression has not previously been reported in AFX. [ABSTRACT FROM AUTHOR]