Osteoprotegerin, s-RANKL, and selected interleukins in the pathology of bone metabolism in patients with Crohn's disease.
Crohn's disease (CD) promotes the development of osteopaenia/osteoporosis, the cytokine background of which is not fully known. Evaluation of bone mineral density (BMD), the prevalence of osteopaenia and osteoporosis, and the determination of the levels of selected interleukins (IL), osteoprotegerin (OPG), and s-RANKL proteins in patients with CD in relation to a control group and assessment of the relationship between the tested cytokines, OPG, s-RANKL, and BMD. Thirty-seven CD patients and 37 healthy volunteers (control group) were enrolled into the study. Densitometry of the lumbar spine (L2-L4) and of the femoral neck using the DXA technique was carried out. Serum levels of: IL-13, IL-4, IL-17, IL-1β, OPG, and s-RANKL were determined using the ELISA method. Progression-of-disease questionnaires were collected. The prevalence of osteoporosis and osteopaenia in the CD group was: 18.92% and 32.43% in L2-L4; 13.51% and 35.13% in the neck, respectively. The IL-13 and IL-1β concentrations were significantly higher and OPG was significantly lower in CD patients when compared to controls. In the case of all subjects: IL-13 correlated negatively with the BMD of the neck, IL-17 correlated negatively with the Z-score of L2-L4, and OPG correlated negatively with the IL-13. In the case of CD patients, IL-4 correlated negatively with the BMD of L2-L4. The incidence of osteopaenia and osteoporosis in Polish CD patients is high. IL-13, IL-1β, and IL-4 seem to be connected with the pathology of decreased BMD in CD. It can be hypothesised that IL-13 may lower BMD by modulating OPG.


Interactions between the monocyte/macrophage and the vascular smooth muscle cell. Stimulation of mitogenesis by a soluble factor and of prostanoid synthesis by cell-cell contact.
The effect of soluble factors from the monocyte/macrophage (M phi) on cell proliferation and the functional effects of cell-cell contact on the arachidonic acid (AA) cascade were studied with vascular smooth muscle cells (SMCs). Peripheral blood M phi s were isolated by adherence or in a Percoll gradient, and alveolar M phi s were obtained by lavage. Conditioned medium (CM) was prepared by preincubating M phi s with medium alone or by separating SMC and M phi cocultures by a membrane insert. Cell proliferation (image analysis) and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha, radioimmunoassay) were measured in SMCs. Labeled prostanoids and other eicosanoid metabolites were isolated by high-performance liquid chromatography from SMCs prelabeled with 14C-AA. M phi s did not synthesize 6-keto-PGF1 alpha. The CM enhanced proliferation but did not stimulate 6-keto-PGF1 alpha synthesis in SMCs. However, cell-cell contact in cocultures of SMCs with the same concentration of M phi s used to generate CM resulted in increased 6-keto-PGF1 alpha synthesis by SMCs. Since the stimulatory effect of cell contact was not blocked by butylated hydroxytoluene, it could not be attributed to an oxidative burst from M phi s. Functional studies showed that the stimulatory effect of cell contact was enhanced by exogenous free AA and by endogenous AA release through A23187. Release of total radioactivity from prelabeled SMCs was enhanced by cell contact, and this effect was blocked by indomethacin (IM). Cell contact did not increase the release of free AA from prelabeled SMCs, even in the presence of IM. Finally, cell contact only stimulated the formation of prostanoids (IM-sensitive eicosanoid metabolites) from prelabeled SMCs. Lipoxygenase and other products of AA were not formed through cell-cell contact. These data showed that M phi s express a soluble factor that enhances SMC proliferation without affecting prostanoid synthesis. Subsequent cell contact between SMCs and M phi s stimulates prostanoid synthesis, which may possibly serve as a local and focal homeostatic mechanism for the regulation of uncontrolled SMC proliferation in atherogenesis.


Undetectable levels of N6-methyl adenine in mouse DNA: Cloning and analysis of PRED28, a gene coding for a putative mammalian DNA adenine methyltransferase.
Three methylated bases, 5-methylcytosine, N4-methylcytosine and N6-methyladenine (m6A), can be found in DNA. However, to date, only 5-methylcytosine has been detected in mammalian genomes. To reinvestigate the presence of m6A in mammalian DNA, we used a highly sensitive method capable of detecting one N6-methyldeoxyadenosine per million nucleosides. Our results suggest that the total mouse genome contains, if any, less than 10(3) m6A. Experiments were next performed on PRED28, a putative mammalian N6-DNA methyltransferase. The murine PRED28 encodes two alternatively spliced RNA. However, although recombinant PRED28 proteins are found in the nucleus, no evidence for an adenine-methyltransferase activity was detected.


Studies on the carboxyl terminal peptides of human seminal plasma inhibin (HSPI). Chemical synthesis and in vivo biological activity of the disulfide loop peptide 67-94 of HSPI.
Observation of contradictory results with the in vitro assays for inhibin-like activity of the carboxyl terminal 28 amino acid peptide 67-94 with a disulfide loop, of human seminal plasma inhibin (HSPI), prompted us to synthesize both the linear and the cyclic peptides and test their ability to suppress the circulating levels of follicle stimulating hormone (FSH) in vivo in adult male rats. The linear peptide [Cys(Acm)73,87] 67-94 of HSPI was synthesized by solid-phase peptide synthesis using fluorenylmethyloxycarbonyl (Fmoc) chemistry and a continuous-flow technology. The peptide was cyclized by direct iodine oxidation of the S-diacetamidomethyl peptide in dilute solution. In the in vivo assay the linear peptide did not affect the levels of FSH, whereas the cyclic peptide suppressed the levels of FSH significantly. Thus, the carboxyl terminal region of HSPI does have inhibin-like activity and perhaps has the active core of the protein.


Breast cancer patients' experience of external-beam radiotherapy.
Radiotherapy is a critical component of treatment for the majority of women with breast cancer, particularly those who receive breast conserving surgery. Although medically beneficial, radiotherapy can take a physical and psychological toll on patients. However, little is known about the specific thoughts and feelings experienced by women undergoing breast cancer radiotherapy. Therefore, the study aim was to use qualitative research methods to develop an understanding of these thoughts and feelings based on 180 diary entries completed during radiotherapy by 15 women with stage 0 to stage III breast cancer. Thematic analysis identified four primary participant concerns: (a) a preoccupation with time, (b) fantasies (both optimistic and pessimistic) about life following radiotherapy, (c) the toll their side-effect experience takes on their self-esteem, and (d) feeling mystified by radiotherapy. These themes are consistent with previous literature on illness and identity. These findings have implications for the treatment and care of women undergoing breast cancer radiotherapy.


Exploring the role of hydrophilic amino acids in unfolding of protein in aqueous ethanol solution.
Hydrophobic association is the key contributor behind the formation of well packed core of a protein which is often believed to be an important step for folding from an unfolded chain to its compact functional form. While most of the protein folding/unfolding studies have evaluated the changes in the hydrophobic interactions during chemical denaturation, the role of hydrophilic amino acids in such processes are not discussed in detail. Here we report the role of the hydrophilic amino acids behind ethanol induced unfolding of protein. Using free energy simulations, we show that chicken villin head piece (HP-36) protein unfolds gradually in presence of water-ethanol binary mixture with increasing composition of ethanol. However, upon mutation of hydrophilic amino acids by glycine while keeping the hydrophobic amino acids intact, the compact state of the protein is found to be stable at all compositions with gradual flattening of the free energy landscape upon increasing compositions. The local environment around the protein in terms of ethanol/water number significantly differs in wild type protein compared to the mutated protein. The calculated Wyman-Tanford preferential binding coefficient of ethanol for wild type protein reveals that a greater number of cosolutes (here ethanol) bind to the unfolded state compared to its folded state. However, no significant increase in binding coefficient of ethanol at the unfolded state is found for mutated protein. Local-bulk partition coefficient calculation also suggests similar scenarios. Our results reveal that the weakening of hydrophobic interactions in aqueous ethanol solution along with larger preferential binding of ethanol to the unfolded state mediated by hydrophilic amino acids combinedly helps unfolding of protein in aqueous ethanol solution.


Carnitine Palmitoyltransferase 1b Deficiency Protects Mice from Diet-Induced Insulin Resistance.
Carnitine Palmitoyl Transferase 1 (CPT1) is the rate-limiting enzyme governing long-chain fatty acid entry into mitochondria. CPT1 inhibitors have been developed and exhibited beneficial effects against type II diabetes in short-term preclinical animal studies. However, the long-term effects of treatment remain unclear and potential non-specific effects of these CPT1 inhibitors hamper in-depth understanding of the potential molecular mechanisms involved. We investigated the effects of restricting the activity of the muscle isoform CPT1b in mice using heterozygous CPT1b deficient (Cpt1b+/-) and Wild Type (WT) mice fed with a High Fat Diet (HFD) for 22 weeks. Insulin sensitivity was assessed using Glucose Tolerance Test (GTT), insulin tolerance test and hyperinsulinemic euglycemic clamps. We also examined body weight/composition, tissue and systemic metabolism/energetic status, lipid profile, transcript analysis, and changes in insulin signaling pathways. We found that Cpt1b+/- mice were protected from HFD-induced insulin resistance compared to WT littermates. Cpt1b+/- mice exhibited elevated whole body glucose disposal rate and skeletal muscle glucose uptake. Furthermore, Cpt1b+/- skeletal muscle showed diminished ex vivo palmitate oxidative capacity by ~40% and augmented glucose oxidation capacity by ~50% without overt change in whole body energy metabolism. HFD feeding Cpt1b+/- but not WT mice exhibited well-maintained insulin signaling in skeletal muscle, heart, and liver. The present study on a genetic model of CPT1b restriction supports the concept that partial CPT1b inhibition is a potential therapeutic strategy.


Constitutive androstane receptor and pregnane X receptor gene expression in human liver: interindividual variability and correlation with CYP2B6 mRNA levels.
The constitutive androstane receptor (CAR) and pregnane X receptor (PXR) mediate the expression of mammalian cytochrome p450 (p450) 2B genes, including CYP2B6 in humans. Large interindividual differences exist in hepatic CYP2B6 expression, but the molecular basis for this variability is not well understood. In the present study, we developed real-time polymerase chain reaction methods to measure CYP2B6, CAR, and PXR mRNA expression and compared the levels in a panel of 12 individual human liver samples. The transcripts of CAR and CYP2B6 were present in all the samples analyzed, whereas those of PXR were detectable in all but one sample. A striking finding was the 240-fold interindividual variability in hepatic CAR mRNA levels, which was similar to the variability (278-fold) in CYP2B6 mRNA levels but greater than the 27-fold variability in PXR mRNA expression. Additional analysis revealed positive and statistically significant correlations between the mRNA levels of CAR and CYP2B6 (r(2) = 0.63, p = 0.002), PXR and CYP2B6 (r(2) = 0.75. p < 0.001), and CAR and PXR (r(2) = 0.86, p < 0.001). In summary, substantial interindividual differences exist in hepatic CAR and, to a lesser extent, PXR gene expression. The variability in the abundance of these transcription factors may contribute to the large interindividual differences in CYP2B6 gene expression in human liver.


p53 abnormalities in different subtypes of human sarcomas.
In this report we examined p53 alterations at the DNA, mRNA, and protein levels on tissue from 39 patients with different subtypes of sarcoma. Loss of heterozygosity for the chromosome 17p region was found in 60, 63, and 33% of 10 informative osteosarcomas, 11 malignant fibrous histiocytomas, and 6 leiomyosarcomas, respectively. In addition, 2 of 10 tumors belonging to a heterogeneous group of soft tissue sarcomas showed loss of heterozygosity. Elevated levels of p53 mRNA were found in six tumors, four had a truncated transcript, and in six patients no mRNA was detected. In most cases, elevated transcript levels were accompanied by overexpression of protein as studied by immunohistochemistry, whereas the presence of truncated transcripts was associated with negative immunostaining. Point mutations in exons 5, 7, or 8 of the TP53 gene were detected in seven tumors. Six of these expressed high levels of mRNA and protein, probably reflecting a point mutation in one of the alleles and loss of the other. Three of the mutations have not previously been described. Taken together, p53 abnormalities were found in approximately 65% of the osteosarcomas, malignant fibrous histiocytomas, and leiomyosarcomas examined and in 30% of the other soft tissue tumors. The results indicate that the TP53 gene is involved in the tumorigenesis of several sarcoma subtypes in a higher fraction of cases than was previously recognized.


An experimental protocol for molecular biology lab at an Amazonian University.
Laboratory-based practical classes are an essential component in teaching molecular biology for undergraduate students. Universidad Regional Amazonica Ikiam is a higher education institution located in the Ecuadorian Amazon rainforest, a high biodiversity place, including amphibians. Based on this, we have established a practical molecular biology program with eight sessions that contextualize the biodiverse surroundings of the University. This program stimulates synchronization of information between theory and practice and improves research skills. During these sessions, students are motivated to identify and characterize antimicrobial peptides from Ecuadorian frog skin secretions, using molecular biology techniques and biochemistry and microbiology knowledge. This practical course was held twice with a total of 56 students from the fifth semester of the biotechnology engineering. The evaluation of the practical program was carried out through a questionnaire applied to students using the Likert scale. Overall, this form of teaching had high receptivity and presented benefits for student learning. Interestingly, 80% of respondents strongly agreed that this course provided tools and knowledge for the development of their undergraduate dissertation. Therefore, practical courses tailored to the student's context can stimulate student learning and interest. Additionally, this experimental methodology is interdisciplinary and can be applied to other research fields and subjects.


PET Imaging and Protein Expression of Prostate-Specific Membrane Antigen in Glioblastoma: A Multicenter Inventory Study.
Upregulation of prostate-specific membrane antigen (PSMA) in neovasculature has been described in glioblastoma multiforme (GBM), whereas vasculature in nonaffected brain shows hardly any expression of PSMA. It is unclear whether PSMA-targeting tracer uptake on PET is based on PSMA-specific binding to neovasculature or aspecific uptake in tumor. Here, we quantified uptake of various PSMA-targeting tracers in GBM and correlated this with PSMA expression in tumor biopsy samples from the same patients. Methods: Fourteen patients diagnosed with de novo (n = 8) or recurrent (n = 6) GBM underwent a preoperative PET scan after injection of 1.5 MBq/kg [68Ga]Ga-PSMA-11 (n = 7), 200 MBq of [18F]DCFpyl (n = 3), or 200 MBq of [18F]PSMA-1007 (n = 4). Uptake in tumor and tumor-to-background ratios, with contralateral nonaffected brain as background, were determined. In a subset of patients, PSMA expression levels from different regions in the tumor tissue samples (n = 40), determined using immunohistochemistry (n = 35) or RNA sequencing (n = 13), were correlated with tracer uptake on PET. Results: Moderate to high (SUVmax, 1.3-20.0) heterogeneous uptake was found in all tumors irrespective of the tracer type used. Uptake in nonaffected brain was low, resulting in high tumor-to-background ratios (6.1-359.0) calculated by dividing SUVmax of tumor by SUVmax of background. Immunohistochemistry showed variable PSMA expression on endothelial cells of tumor microvasculature, as well as on dispersed individual cells (of unknown origin), and granular staining of the neuropil. No correlation was found between in vivo uptake and PSMA expression levels (for immunohistochemistry, r = -0.173, P = 0.320; for RNA, r = -0.033, P = 0.915). Conclusion: Our results indicate the potential use of various PSMA-targeting tracers in GBM. However, we found no correlation between PSMA expression levels on immunohistochemistry and uptake intensity on PET. Whether this may be explained by methodologic reasons, such as the inability to measure functionally active PSMA with immunohistochemistry, tracer pharmacokinetics, or the contribution of a disturbed blood-brain barrier to tracer retention, should still be investigated.


[A case report of cholangiectasis with cholangiocarcinoma].
This is a case report of cholangiectasis with cholangiocarcinoma in a 37-year-old female. Both computed tomography (CT) and endoscopic retrograde cholangio-pancreatography (ERCP) demonstrated gallstone, and intrahepatic bile duct dilatation with the stone. The diagnosis was intrahepatic cholangiectasis without common bile duct-dilatation. Hepatectomy of segment 3 with resection of the extrahepatic bile duct and reconstruction of the biliary tract was performed. Upon pathological examination, an early stage of cholangiocarcinoma was pointed out within the small range of common bile duct without dilatation or stone. Cholangiocarcinoma with cholangiectasis has been reported to be induced by counter flow of pancreas and intestinal juice because of the pancreaticobiliary maljunction. So we usually choose a diversion operation as our tactics to get rid of the counter flow of those digestive juices. Despite the above-mentioned tendency, this is a very rare case of carcinogenesis in common bile duct without dilatation.


[Electoro-surgical device].
Electro-surgical device is an essential instrument for bloodless surgery after the 1st introduction by Harvey Cushing in 1926. Basal mechanisms of electric scalpels (monopolar and bipolar), current waveforms (cut, coagulation and blend), high-frequency currents and electrical shocks were commented. After 1990s, several new electro-surgical devices such as argon beam coagulator, bipolar scissors and vessel sealing system (LigaSure) were developed and introduced in chest surgery. Argon beam coagulator is useful in sealing and hemostasis of bleeding from chest walls after extrapleural dissections. Bipolar scissors can seal small vessels less than diameter 2 mm and is useful in mediastinal lymphnode dissections. Vessel sealing system is able to seal and cut vessels up to diameter 7 mm. LigaSure V is the most suitable instrument for thymic vein handling in thoracoscopic thymectomy. Clinical applications of these new surgical devices in chest surgery are discussed.


Design of Temperature Insurance Index and Risk Zonation for Single-Season Rice in Response to High-Temperature and Low-Temperature Damage: A Case Study of Jiangsu Province, China.
Disaster insurance is an important tool for achieving sustainable development in modern agriculture. However, in China, the design of such insurance indexes is far from sufficient. In this paper, the single-season rice in Jiangsu Province of China is taken as an example to design the high-temperature damage index in summer and the low-temperature damage index in autumn to construct the formula calculating the weather output and single-season rice yield reduction. The daily highest, lowest and average temperatures between 1999 and 2015 are selected as main variables for the temperature disaster index to quantitatively analyze the relationship between the temperature index and the yield reduction rate of the single-season rice. The temperature disaster index can be put into the relevant model to obtain the yield reduction rate of the year and determine whether to pay the indemnity. Then, the burn analysis is used to determine the insurance premium rate for all cities in Jiangsu Province under four-level deductibles, and the insurance premium rate can be used for the risk division of the Province. The research provides some insights for the design of agricultural weather insurance products, and the empirical results provide a reference for the design of similar single-season rice temperature index insurance products.


Gut glutamine metabolism.
The gut plays a key role in interorgan glutamine metabolism in normal and catabolic states. During critical illness, the gut responds to prevailing metabolic pressures that may result in a temporary "reset" in interorgan glutamine flow. As the body recovers from the disease process, the alterations in gut glutamine metabolism revert to normal, which helps restore glutamine homeostasis. Overwhelming stresses, such as severe systemic infection, may lead to permanent organ dysfunction and further adaptive changes in glutamine metabolism.


Metacognition and mathematical problem solving in grade 3.
This article presents an overview of two studies that examined the relationship between metacognition and mathematical problem solving in 165 children with average intelligence in Grade 3 in order to help teachers and therapists gain a better understanding of contributors to successful mathematical performance. Principal components analysis on metacognition revealed that three metacognitive components (global metacognition, off-line metacognition, and attribution to effort) explained 66% to 67% of the common variance. The findings from these studies support the use of the assessment of off-line metacognition (essentially prediction and evaluation) to differentiate between average and above-average mathematical problem solvers and between students with a severe or moderate specific mathematics learning disability.


The G protein α chaperone Ric-8 as a potential therapeutic target.
Resistance to inhibitors of cholinesterase (Ric-8)A and Ric-8B are essential genes that encode positive regulators of heterotrimeric G protein α subunits. Controversy persists surrounding the precise way(s) that Ric-8 proteins affect G protein biology and signaling. Ric-8 proteins chaperone nucleotide-free Gα-subunit states during biosynthetic protein folding prior to G protein heterotrimer assembly. In organisms spanning the evolutionary window of Ric-8 expression, experimental perturbation of Ric-8 genes results in reduced functional abundances of G proteins because G protein α subunits are misfolded and degraded rapidly. Ric-8 proteins also act as Gα-subunit guanine nucleotide exchange factors (GEFs) in vitro. However, Ric-8 GEF activity could strictly be an in vitro phenomenon stemming from the ability of Ric-8 to induce partial Gα unfolding, thereby enhancing GDP release. Ric-8 GEF activity clearly differs from the GEF activity of G protein-coupled receptors (GPCRs). G protein βγ is inhibitory to Ric-8 action but obligate for receptors. It remains an open question whether Ric-8 has dual functions in cells and regulates G proteins as both a molecular chaperone and GEF. Clearly, Ric-8 has a profound influence on heterotrimeric G protein function. For this reason, we propose that Ric-8 proteins are as yet untested therapeutic targets in which pharmacological inhibition of the Ric-8/Gα protein-protein interface could serve to attenuate the effects of disease-causing G proteins (constitutively active mutants) and/or GPCR signaling. This minireview will chronicle the understanding of Ric-8 function, provide a comparative discussion of the Ric-8 molecular chaperoning and GEF activities, and support the case for why Ric-8 proteins should be considered potential targets for development of new therapies.


Structure, stability, and folding of ribonuclease H1 from the moderately thermophilic Chlorobium tepidum: comparison with thermophilic and mesophilic homologues.
Proteins from thermophilic organisms are able to function under conditions that render a typical mesophilic protein inactive. Pairwise comparisons of homologous mesophilic and thermophilic proteins can help to identify the energetic features of a protein's energy landscape that lead to such thermostability. Previous studies of bacterial ribonucleases H (RNases H) from the thermophile Thermus thermophilus and the mesophile Escherichia coli revealed that the thermostability arises in part from an unusually low change in heat capacity upon unfolding (DeltaC(p)) for the thermophilic protein [Hollien, J., and Marqusee, S. (1999) Biochemistry 38, 3831-3836]. Here, we have further examined how nearly identical proteins can adapt to different thermal constraints by adding a moderately thermophilic homologue to the previously characterized mesophilic and thermophilic pair. We identified a putative RNase H from Chlorobium. tepidum and demonstrated that it is an active RNase H and adopts the RNase H fold. The moderately thermophilic protein has a melting temperature (T(m)) similar to that of the mesophilic homologue yet also has a surprisingly low DeltaC(p), like the thermophilic homologue. This new RNase H folds through a pathway similar to that of the previously studied RNases H. These results suggest that lowering the DeltaC(p) may be a general strategy for achieving thermophilicity for some protein families and implicate the folding core as the major contributor to this effect. It should now be possible to design RNases H that display the desired thermophilic or mesophilic properties, as defined by their DeltaC(p) values, and therefore fine-tune the energy landscape in a predictable fashion.


Tissue factor-activated coagulation cascade in the tumor microenvironment is critical for tumor progression and an effective target for therapy.
Tissue factor (TF), a rate-limiting enzyme cofactor in activating coagulation, is highly expressed in a wide spectrum of human tumor and tumor stromal cells. Using TF-deficient cancer cells and a conditional TF-knockout mouse model, we show that TF expressed by cancer cells, but not by the host stromal cells, plays a critical role in tumor growth. In the tumor microenvironment, serum coagulation factors are readily extravasated and therefore lead to continuous TF-mediated activation of coagulation proteases. To target this highly specific cascade of serine proteases, we used both a TF:VIIa inhibitor and doxorubicin-based prodrugs that are selectively activated by TF:FVIIa, FXa, and thrombin. Treatment with the TF:FVIIa inhibitor led to growth retardation in breast tumor models. In contrast, treatment with the prodrug eliminated primary tumor cells and lung metastases without apparent toxicity. Our findings offer preclinical proof of principle that targeting the coagulation cascade that is activated in the tumor microenvironment can be a highly effective approach for cancer therapy.


Microsatellite marker analysis in screening for hereditary nonpolyposis colorectal cancer (HNPCC).
Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant cancer predisposition syndrome caused by germ-line mutations in DNA mismatch repair genes. It is relevant to identify HNPCC patients because colonoscopic screening of individuals with HNPCC mutations reduces cancer morbidity and mortality. Microsatellite instability (MSI) is characteristic of HNPCC tumors. A panel of five markers (BAT25, BAT26, D2S123, D5S346, and D17S250, the so-called Bethesda markers) has been proposed for screening for MSI. To test a hypothesis that the use of BAT26 alone is feasible in screening for MLH1/MSH2 mutation-positive HNPCC patients, we compared the MSI results of 494 colorectal cancer patients obtained using BAT26 with results obtained using the Bethesda markers. BAT26 was able to identify all 27 mutation-positive individuals in this series. The marker failed to identify 2 high MSI tumors and 20 low MSI tumors, all of which expressed MLH1, MSH2, and MSH6 when scrutinized by immunohistochemistry.


Amplification of the full-length hepatitis A virus genome by long reverse transcription-PCR and transcription of infectious RNA directly from the amplicon.
The genetic study of RNA viruses is greatly facilitated by the availability of infectious cDNA clones. However, their construction has often been difficult. While exploring ways to simplify the construction of infectious clones, we have successfully modified and applied the newly described technique of "long PCR" to the synthesis of a full-length DNA amplicon from the RNA of a cytopathogenic mutant (HM 175/24a) of the hepatitis A virus (HAV). Primers were synthesized to match the two extremities of the HAV genome. The antisense primer, homologous to the 3' end, was used in both the reverse transcription (RT) and the PCR steps. With these primers we reproducibly obtained a full-length amplicon of approximately 7.5 kb. Further, since we engineered a T7 promoter in the sense primer, RNA could be transcribed directly from the amplicon with T7 RNA polymerase. Following transfection of cultured fetal rhesus kidney cells with the transcription mixture containing both the HAV cDNA and the transcribed RNA, replicating HAV was detected by immunofluorescence microscopy and, following passage to other cell cultures, by focus formation. The recovered virus displayed the cytopathic effect and large plaque phenotype typical of the original virus; this result highlights the fidelity of the modified long reverse transcription-PCR procedure and demonstrates the potential of this method for providing cDNAs of viral genomes and simplifying the construction of infectious clones.


Evaluating census data quality using intensive reinterviews: a comparison of U.S. Census Bureau methods and Rasch methods.
"In this paper, we consider Rasch measurement methodology as an alternative to conventional U.S. Census Bureau methodology for evaluating the quality of data obtained using different measurements of the same characteristic. Rather than assuming, like the Census approach, that respondents have true states corresponding to the categories of a questionnaire item, the Rasch approach assumes that measuring instruments and survey respondents vary continuously on one or more common dimensions called latent traits. Unlike the Census approach, the Rasch approach requires that the properties of measuring instruments be invariant across different subclasses of respondents, generating parameter estimates that are sufficient statistics for elementary discrete sampling models. The different conclusions that can be drawn from the Census and Rasch approaches are illustrated by an evaluation of questionnaire items designed to measure the limitation or prevention of work because of physical or mental disability."


Comparison of ease of swallowing of dietary supplement products for age-related eye disease.
To examine patients' perceptions on the relative importance of the physical characteristics and appearance of dietary supplements, and to evaluate two supplements with the same combination of vitamins and minerals used in the Age-Related Eye Disease Study (AREDS) with respect to ease of swallowing and other features in elderly patients. A single-site, single-visit, crossover design, subject-masked comparison of two dietary supplements (ICaps AREDS Formula--Alcon; Ocuvite PreserVision-Bausch & Lomb). Ophthalmology practice. 50 patients aged 50 years or older. Patients ranked the importance of eight physical characteristics of a vitamin tablet or capsule (ease of swallowing, size, shape, color, smell, coating, texture, and taste) irrespective of the test products used in the study and then took both test products randomly and were asked to indicate which product they preferred based on the same eight characteristics. Overall patient preference and preference for swallowing two tablets at once. The highest rated (most important) characteristic in a vitamin supplement was ease of swallowing, with a median score of 9.0 on a 0-10 visual analogue scale. The characteristic of least importance was tablet color, with the lowest median score of 1.0. Statistically significant differences were detected between the products with regard to preferences for ease of swallowing, swallowing two tablets at once, size, and coating (P < or = .0001). Significantly more patients preferred the ICaps AREDS formula to Ocuvite PreserVision with respect to these characteristics and overall preference (P < .001). Age, gender, and previous vitamin use were contributing factors in the rating of physical characteristics and tablet preferences. Based on the results of this study, ease of swallowing is the most important characteristic of dietary supplement tablets for elderly patients, followed by taste, size, and smell. Significant differences in preference exist between the study products, which contain similar formulations but have different physical characteristics.


Use of zebrafish larvae lateral line to study protection against cisplatin-induced ototoxicity: A scoping review.
The present review aimed to consolidate and analyze the recent information about the use of zebrafish in studies concerning cisplatin-induced ototoxicity and otoprotection. The PubMed, Web of Science, and Scopus databanks were searched using the following MESH terms: zebrafish, cisplatin, ototoxicity. The identified publications were screened according to inclusion and exclusion criteria and the 26 qualifying manuscripts were included in the full-text analysis. The experimental protocols, including cisplatin concentrations, the exposure duration and the outcome measurements used in zebrafish larvae studies, were evaluated and the reported knowledge was summarized. Twenty-six substances protecting from cisplatin-induced toxicity were identified with the use of zebrafish larvae. These substances include quinine, salvianolic acid B, berbamine 6, benzamil, quercetin, dexmedetomidine, dexamethsanone, quinoxaline, edaravone, apocynin, dimethyl sulfoxide, KR-22335, SRT1720, ORC-13661, 3-MA, D-methionine, mdivi-1, FUT-175, rapamycin, Z-LLF-CHO, ATX, NAC, CYM-5478, CHCP1, CHCP2 and leupeptin. The otoprotective effects of compounds were attributed to their anti-ROS, anti-apoptotic and cisplatin uptake-blocking properties. The broadest range of protection was achieved when the experimental flow used preconditioning with an otoprotective compound and later a co-incubation with cisplatin. Protection against a high concentration of cisplatin was observed only in protocols using short exposure times (4 and 6 h). The data extracted from the selected papers confirm that despite the differences between the human and the zebra fish hearing thresholds (as affected by cisplatin), the sensory cells of zebrafish and larval zebrafish are a valuable tool which could be used: (i) for the discovery of novel otoprotective substances and compounds; (ii) to screen their side effects and (iii) to extend the knowledge on the mechanisms of cisplatin-induced inner ear damage. For future studies, the development of a consensus experimental protocol is highly recommended.


Enhancing Interpretability of Gene Signatures with Prior Biological Knowledge.
Biological interpretability is a key requirement for the output of microarray data analysis pipelines. The most used pipeline first identifies a gene signature from the acquired measurements and then uses gene enrichment analysis as a tool for functionally characterizing the obtained results. Recently Knowledge Driven Variable Selection (KDVS), an alternative approach which performs both steps at the same time, has been proposed. In this paper, we assess the effectiveness of KDVS against standard approaches on a Parkinson's Disease (PD) dataset. The presented quantitative analysis is made possible by the construction of a reference list of genes and gene groups associated to PD. Our work shows that KDVS is much more effective than the standard approach in enhancing the interpretability of the obtained results.


Alternative approaches to abdominal wound closure in severely injured patients with massive visceral edema.
Excessive tension in an abdominal incision line may lead to fascial necrosis and wound sepsis. We utilized two alternative approaches to wound closure in 13 patients with severe abdominal trauma (2 blunt, 11 penetrating) whose midline incision could not be closed primarily without excessive tension at the initial operation because of massive visceral edema. In five patients synthetic mesh was used to bridge the fascial defect. Four patients survived the early postoperative period but had large open midline wounds that required one or more delayed procedures to close the wound or cover the visceral mass with skin graft. Two patients currently have large abdominal wall hernias. In the other eight patients the skin was reapproximated over the visceral mass utilizing towel clips at the initial operation. Six patients survived to be reexplored within 48-96 hours. Acute hemorrhage had stopped, the edema of the bowel and retroperitoneum had largely resolved, and the fascia could be closed primarily without excessive tension. All wounds went on to heal satisfactorily. When massive edema makes fascial closure at the initial operation difficult or impossible, closure of the skin over the visceral mass promotes resolution of the edema and often allows satisfactory primary closure within 48-96 hours. Synthetic mesh should be reserved for cases of abdominal wall tissue loss or dehiscence associated with wound sepsis.


Post-menopausal hormone therapy reduces autoantibodies to oxidized apolipoprotein B100.
The aim of the study was to verify whether post-menopausal hormone replacement therapy (HRT) modifies autoantibody titers against oxidized low-density lipoprotein (LDL) (anti-LDLoxi), against epitopes of oxidized apolipoprotein B100 and common carotid intima-media thickness (IMT) in these women. Sixty-eight women in pre-menopause (PMW) and 216 in post-menopause (POMW) were recruited; eighty-three had undergone HRT for at least 12 months, where 48 received conjugated estrogens alone (EHRT) and 35 received conjugated estrogen and medroxyprogesterone acetate (CHRT). ELISA was used to determine autoantibodies. Lipoprotein lipase (LPL), hepatic lipase (HL), cholesterol ester transfer protein (CETP) and phospholipid transfer protein (PLTP) activities were assayed by radiometric methods. IMT was measured using Doppler ultrasound. Anti-oxidized LDL and anti-D antibodies increased by 40% (p ≤ 0.003) and 42% (p ≤ 0.006), respectively, with menopause. There was a surprising and significant 7% reduction in anti-D2 antibody titers with HRT (p ≤ 0.050), indicating a positive effect of treatment on the immune response to oxidized LDL. Combined HRT decreased activities of HL and LPL. HRT did not change common carotid IMT, which was increased by 32% as expected after menopause (p ≤ 0.030). This study describes, for the first time, the protective effect of HRT on decreasing autoantibody titers against oxidized apolipoprotein B in LDL.


The future of long-term and permanent contraceptive methods. Developments in technology.
The Association for Voluntary Surgical Contraception (AVSC) does not expect dramatic advances in female sterilization during the decade. Minilaparotomy and laparoscopy will endure as the standard surgical approaches, but programs will continue to shift toward the use of local anesthesia for these procedures because of greater safety and lower costs. No-scalpel vasectomy demonstrated by AVSC to be popular, effective, and safe holds greater potential for expanding the vast, and largely ignored, male market. The injection methods of vasectomy now being tested in China and elsewhere may make male sterilization even more acceptable. Markets for IUDs, implants, and injectables will continue to expand as more clients seek safe and effective long term contraception, and as national family planning programs (particularly in Asia) realize the ethical and programmatic importance of offering choices. Norplant is expensive and requires a skilled network of providers to both insert and remove the implants. For these reasons, AVSC expects Norplant to remain a niche method, mostly for urban clients who are not interested in sterilization or who are ill-suited for IUDs or injectables. Injectables, already popular in many parts of the world, will become increasingly available and used now that the US food and Drug Administration has approved Depo-Provera. New types of injectables, currently being developed, will be brought to market. The potential for IUDs is vast, particularly the low-cost, highly-effective Copper T 380A, which is expected to be approved as a 10-year method. However, poor quality service delivery and the high prevalence of sexually transmitted diseases could limit the potential of this method.


Organochlorine pollutants [corrected] in California sea lions revisited.
Dichlorodiphenyltrichloroethane (DDT) and polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants that have been banned in most countries, but considerable amounts continue to cycle the ecosphere. Top trophic level predators, like sea birds and marine mammals, bioaccumulate these lipophilic compounds, reflecting their presence in the environment. We measured concentrations of tDDT (p,p' - DDT + p,p' - DDD + p,p' - DDE) and PCBs in the blubber of dead California sea lions stranded along the California coast. tDDT and PCB concentrations were 150 +/- 257 ug/g lipid weight (mean +/- SD) and 44 +/- 78 ug/g lipid weight, respectively. There were no differences in tDDT or PCB concentrations between animal categories varying in sex or age. There was a trend towards a decrease in tDDT and PCB concentrations from northern to southern California. The lipid content of the blubber was negatively correlated with levels of tDDT and PCBs. tDDT concentrations were approximately 3 times higher than PCB concentrations. tDDT levels in the blubber of California sea lions decreased by over one order of magnitude from 1970 to 2000. PCB level changes over time were unclear owing to a paucity of data and analytical differences over the years. Current levels of these pollutants in California sea lions are among the highest among marine mammals and exceed those reported to cause immunotoxicity or endocrine disruption.


[Upper segmental hydronephrosis in incomplete duplex system (a subtype of Fraley's syndrome)].
We present a case of upper segmental hydronephrosis in the incomplete duplex system due to vascular obstruction of superior ureteropelvic junction. This case appears to be a subtype of Fraley's syndrome in the incomplete duplex system.


Multi-function indoor light sources based on light-emitting diodes-a solution for healthy lighting.
A solution for multi-functional indoor light sources is proposed to achieve the new concept of healthy lighting. A remotely controllable light source that embodies a quadruple-chip light-emitting diode and driven by pulse-width-modulation currents is designed. Therefore, spectral power distributions (SPDs) of the light source can be readily controlled. An algorithm, namely the optical power ratio algorithm, is developed to select all suitable SPDs adapted for various applications. Principles of selection are based on those traditional visual indices, as well as on some non-visual parameters such as circadian action factor, circadian efficacy of radiation and circadian illuminance. We investigate in detail the correlation among these parameters and provide SPDs with both decent visual and non-visual performances for three typical cases. The study suggests some fundamental principles for designing healthy light sources, and can be regarded as a guide for designing indoor light sources of the next generation.


Hospital costs, resource characteristics, and the dynamics of death for surgical patients.
This article details data that suggest significant inequities in the current DRG prospective payment system vis-à-vis surgical mortalities. Important health policy issues, in addition to the ability of outcome data to function as a proxy for quality, involve the usefulness of stratifying DRGs vis-à-vis outcome or severity of illness in the future. Much interest has emerged in outcome data--especially with regard to its ability to function as a risk-adjusted quality-of-care screen for hospitals. A study of hospital resource consumption comparing survivors and mortalities demonstrated that surgical mortalities had a much greater intensity of hospital resource utilization and a substantial financial risk under Medicare's DRG prospective payment pricing system, as compared to surgical survivors. Hospital length of stay for mortalities proved very unprofitable. Emergency-admitted patients who died tended to have shorter hospital stays and less financial risk under DRGs than nonemergency mortalities. Mortalities referred to surgery from other clinical services tended to have greater resource utilization and financial risk under DRGs than nonreferred mortalities.


Endothelin-1 and -3 induce choleresis in the rat through ETB receptors coupled to nitric oxide and vagovagal reflexes.
We have reported previously that centrally applied ET (endothelin)-1 and ET-3 induce either choleresis or cholestasis depending on the dose. In the present study, we sought to establish the role of these endothelins in the short-term peripheral regulation of bile secretion in the rat. Intravenously infused endothelins induced significant choleresis in a dose-dependent fashion, ET-1 being more potent than ET-3. Endothelins (with the exception of a higher dose of ET-1) did not affect BP (blood pressure), portal venous pressure or portal blood flow. ET-1 and ET-3 augmented the biliary excretion of bile salts, glutathione and electrolytes, suggesting enhanced bile acid-dependent and -independent bile flows. ET-induced choleresis was mediated by ET(B) receptors coupled to NO and inhibited by truncal vagotomy, atropine administration and capsaicin perivagal application, supporting the participation of vagovagal reflexes. RT (reverse transcription)-PCR and Western blot analysis revealed ETA and ET(B) receptor expression in the vagus nerve. Endothelins, through ET(B) receptors, augmented the hepatocyte plasma membrane expression of Ntcp (Na⁺/taurocholate co-transporting polypeptide; Slc10a1), Bsep (bile-salt export pump; Abcb11), Mrp2 (multidrug resistance protein-2; Abcc2) and Aqp8 (aquaporin 8). Endothelins also increased the mRNAs of these transporters. ET-1 and ET-3 induced choleresis mediated by ET(B) receptors coupled to NO release and vagovagal reflexes without involving haemodynamic changes. Endothelin-induced choleresis seems to be caused by increased plasma membrane translocation and transcriptional expression of key bile transporters. These findings indicate that endothelins are able to elicit haemodynamic-independent biological effects in the liver and suggest that these peptides may play a beneficial role in pathophysiological situations where bile secretion is impaired.


Alcohol consumption, serum gamma-glutamyltransferase, and helicobacter pylori infection in a population-based study among 9733 older adults.
Moderate alcohol consumption has been suggested to facilitate the elimination of Helicobacter pylori infection as the result of its antibacterial effect. We aimed to assess the associations of current and lifetime alcohol consumption as well as serum gamma-glutamyltransferase (GGT), an established biomarker of alcohol consumption, with H. pylori infection in a large population-based study. In the baseline examination of the ESTHER study, serological measurements of antibodies against H. pylori and GGT measurements were taken in 9733 subjects ages 50 to 74 years. Information on lifestyle factors and medical history were obtained by self-administered standardized questionnaire. A significant inverse association, in dose-response manner, was observed between both current and lifetime alcohol consumption and H. pylori seropositivity. The estimates based on lifetime consumption were more pronounced than the results for current consumption, and such inverse associations were found both for men and women. Stronger relations were observed for those who only drank wine or mixed drinkers compare with those who only drank beer. Furthermore, there was a significant inverse dose-response relationship between serum GGT levels and H. pylori seropositivity, which was selectively observed among alcohol drinkers. In conclusion, our results support the hypothesis that moderate alcohol consumption may facilitate elimination of H. pylori.


Slow-fast dynamics in a model of population and resource growth.
"Models of the interaction of population, the economy, and the environment often contain nonlinear functional relationships and variables that move at different speeds. These properties foster apparent unpredictabilities in system behaviour. Using a simple deterministic model of demographic, economic and environmental interactions we illustrate the usefulness of geometric singular perturbation theory in environmental population economics. In contrast to local stability analysis, the theory of slow-fast dynamics helps to gain new insights into the global behaviour of the system. In particular, the knowledge of the basins of attraction of the stationary states enables one to determine the regions of sustainable future paths of resources and population." (SUMMARY IN FRE)


Effects of gallbladder function on human bile: compositional and structural changes.
Water and electrolyte absorption leading to increased intraluminal concentrations of lipids and other solutes comprise the primary physiologic effect of the gallbladder. The dynamics of enterohepatic circulation can lead to confinement of up to 60% of the bile acid pool within the gallbladder during prolonged fasting. This bile acid sequestration markedly reduces both the bile salt secretory rate and total solute concentration in comparison with the nonfasting state producing hepatic bile that is more than normally dilute especially in comparison with gallbladder bile. These conditions favor formation of small low-density vesicles in hepatic bile which are more buoyant than the concentrated biliary micelles found in anatomically dependent regions of the gallbladder. Vesicle formation in hepatic bile may explain the "stratification" phenomenon often noted within the gallbladder. This observation could be accounted for by inhomogeneous mixing of the dissimilar lipid particles, i.e., vesicles and micelles. If vesicles are present and stratified as presumed, the overall cholesterol transporting capability of the total lipid particles, including these regionalized vesicles, would be considerably enhanced. The net effect of this process would lead to an overestimation of the true degree of metastable cholesterol supersaturation for the biliary micellar system within the gallbladder on the incorrect assumption of homogeneous mixing of lipids.


[Considerations about the endovascular treatment of infrarenal aortic aneurysms].
The introduction of the endovascular repair of aortic aneurysm (EVAR) in the clinical practice by Parodi was a milestone in the development of aortic surgery. This minimal invasive procedure promised a significant lower postoperative mortality and complications rate. Despite numerous controversies, the endovascular technique was wide accepted and fast implemented in the clinical practice. But the first prospective randomized trials showed that the benefit of the patients was limited and this innovative approach leads to particular postoperative problems. Due to a continuous improvement of the endovascular devices and increasing experience in endovascular treatment a lot of early problems have been resolved. The new generation of endografts makes possible the endovascular approach of aneurysm with shorter or angulated proximal neck. However, the anatomical suitability is still the most important limited factor of the endovascular treatment. An accurate analysis of suitability, the proper choice of the device and correct implantation allows good postoperative results. The significance of specific complications must be recognized in order to make the right surgical decision.


Serious Games for Health: Features, Challenges, Next Steps.
As articles in this journal have demonstrated over the past 3 years, serious game development continues to flourish as a vehicle for formal and informal health education. How best to characterize a "serious" game remains somewhat elusive in the literature. Many researchers and practitioners view serious games as capitalizing on computer technology and state-of-the-art video graphics as an enjoyable means by which to provide and promote instruction and training, or to facilitate attitude change among its players. We invited four distinguished researchers and practitioners to further discuss with us how they view the characteristics of serious games for health, how those characteristics differ from those for academic purposes, the challenges posed for serious game development among players of different ages, and next steps for the development and empirical examination of the effectiveness of serious games for players' psychological and physical well-being.


Gravitational effects on body composition in birds.
Gallinaceous birds, presenting a wide range of body size, were adapted physiologically to hyperdynamic environments, provided by chronic centrifugation. Chemical composition was measured directly on prepared carcasses, which were anatomically comparable, and more amenable to analysis than the intact body. Body mass and body fat decreased arithmetically with increasing field strength and also with increasing body mass. Water content of lean tissue increased in hyperdynamic environments, but irrespectively of body size.


[Neuronal growth-associated proteins in neural plasticity and brain aging].
This review summarizes current issues on neuronal structural plasticity and its molecular marker genes in the aged brain. Neuronal growth-associated proteins (nGAPs) are introduced as potential markers of neuronal structural plasticity in the brain. The expression of genes encoding nGAPs such as GAP-43, SCG10 and stathmin is increased following striatal and hippocampal neuronal deafferentation lesions in the adult rat brain. In aged brains, the magnitude of neuronal plasticity is reduced and nGAP gene induction is limited at least in part, while the kinetics of the response remains unchanged in comparison to young brains. These results suggest that nGAPs serve as molecular markers of neuronal structural plasticity in the aging brain and that neuronal plasticity decreases, at least in certain neuronal circuits, during aging. The expression of genes encoding SCG10, stathmin and GAP-43 is also altered in age-related neurodegenerative conditions such as Alzheimer's disease in humans. Thus, studies of nGAPs are important for the elucidation of the mechanisms of the reduction of neuronal structural plasticity in aged brains.


Whole and Purified Aqueous Extracts of Nigella sativa L. Seeds Attenuate Apoptosis and the Overproduction of Reactive Oxygen Species Triggered by p53 Over-Expression in the Yeast Saccharomyces cerevisiae.
Plants are an important source of pharmacologically active compounds. In the present work, we characterize the impact of black cumin (Nigella sativa L.) aqueous extracts on a yeast model of p53-dependent apoptosis. To this end, the Saccharomyces cerevisiae recombinant strain over-expressing p53 was used. The over-expression of p53 triggers the expression of apoptotic markers: the externalization of phosphatidylserine, mitochondrial defect associated with cytochrome-c release and the induction of DNA strand breaks. These different effects were attenuated by Nigella sativa L. aqueous extracts, whereas these extracts have no effect on the level of p53 expression. Thus, we focus on the anti-apoptotic molecules present in the aqueous extract of Nigella sativa L. These extracts were purified and characterized by complementary chromatographic methods. Specific fluorescent probes were used to determine the effect of the extracts on yeast apoptosis. Yeast cells over-expressing p53 decrease in relative size and have lower mitochondrial content. The decrease in cell size was proportional to the decrease in mitochondrial content and of mitochondrial membrane potential (ΔΨm). These effects were prevented by the purified aqueous fraction obtained by fractionation with different columns, named C4 fraction. Yeast cell death was also characterized by reactive oxygen species (ROS) overproduction. In the presence of the C4 fraction, ROS overproduction was strongly reduced. We also noted that the C4 fraction promotes the cell growth of control yeast cells, which do not express p53, supporting the fact that this purified extract acts on cellular mediators activating cell proliferation independently of p53. Altogether, our data obtained on yeast cells over-expressing p53 demonstrate that anti-apoptotic molecules targeting p53-induced apoptosis associated with mitochondrial dysfunction and ROS overproduction are present in the aqueous extracts of Nigella seeds and in the purified aqueous C4 fraction.


Subphrenic versus nonsubphrenic hepatocellular carcinoma: combined therapy with chemoembolization and radiofrequency ablation.
This retrospective study was conducted to evaluate the clinical utility of the combination of chemoembolization and real-time CT fluoroscopically guided radiofrequency ablation in the treatment of patients with subphrenic hepatocellular carcinoma (HCC). Patients who had a single HCC with a maximum diameter of 5 cm or less were included in the study. None of the patients was a candidate for surgery, and all underwent combination therapy as initial treatment. The patients were divided into two groups based on tumor location. In all, the 93 men and 38 women (mean age, 67.9 +/- 9.4 years; range, 43-83 years) had 46 subphrenic HCCs and 85 nonsubphrenic HCCs. No differences were found in the pretreatment baseline characteristics of the two patient groups. Safety profiles, local tumor progression rates, and prognoses were compared. Tumor enhancement disappeared after 58 radiofrequency sessions (1.3 sessions/tumor) in patients with subphrenic HCC and after 104 radiofrequency sessions (1.2 sessions/tumor) in patients with nonsubphrenic HCC. The 5-year local tumor progression rates (subphrenic, 3% [95% CI, 0.2-12%]; nonsubphrenic, 9% [95% CI, 3-20%]; p = 0.31) and survival rates (subphrenic, 63% [95% CI, 36-81%]; nonsubphrenic, 69% [95% CI, 53-81%]; p = 0.55) were similar for the two patient groups. Although the incidence of self-limited pneumothorax was significantly higher among the patients with subphrenic HCC (13.8% vs 3.85%; p < 0.03), other complication rates were similar for the two patient groups. Combination therapy with chemoembolization and real-time CT-guided radiofrequency ablation is safe and useful even when HCC is in the subphrenic region.


Overexpression of GSK3betaS9A resulted in tau hyperphosphorylation and morphology reminiscent of pretangle-like neurons in the brain of PDGSK3beta transgenic mice.
It has been demonstrated that GSK3beta is involved in Alzheimer Disease (AD) pathogenesis. In order to understand the underlying mechanism, we have generated and characterized transgenic mice in which the constitutively active human GSK3beta (with S9A mutation) was overexpressed in the brain under the control of the platelet-derived growth factor (PDGF) B-chain promoter. Varying levels of human GSK3betaS9A transgene protein expression was observed in six of the seven founders generated. Line 3083, 3107, 3112 and 3125 displayed higher GSK3betaS9A protein expression levels. Immunostaining analysis demonstrated that transgene expression was observed mainly in cortex and hippocampus of transgenic brain. Expression of human GSK3beta transgene did not significantly change the brain total GSK3beta protein levels in any of the generated mouse lines, as comparing to age matched wild type mice. Although significant kinase activity was detected in human GSK3betaS9A transgene protein extracted from brains of all six expressing lines, significant increase in total GSK3betaS9A kinase activity was observed only in the offspring of line 3083 and 3107. By analyzing the offspring from several transgenic mouse lines, including lines other than 3083 and 3107, it was found that overexpressed constitutively active human GSK3betaS9A resulted in hyperphosphorylation of tau and morphology reminiscent of pretangle-like neurons in cortex and hippocampus.


The D-type cyclin CYCD4;1 modulates lateral root density in Arabidopsis by affecting the basal meristem region.
Root cell division occurs primarily in the apical meristem, from which cells are displaced into the basal meristem, where division decreases and cell length increases before the final differentiation zone. The organization of the root in concentric files implies coordinated division and differentiation of cell types, including the xylem pole pericycle cells, which uniquely can resume division to initiate lateral roots (LR). Here, we show that D-type cyclin CYCD4;1 is expressed in meristematic pericycle protoxylem poles and is required for normal LR density. Cycd4;1 mutants also show a displacement of the apical/basal meristem boundary in the pericycle and longer pericycle basal meristem cells, whereas other cell layers and overall meristem size and root growth are unaffected. Auxin is proposed to separately prepattern and stimulate LR initiation. Stimulation is unimpaired in cycd4;1, suggesting CYCD4;1 requirement for normal spacing but not initiation. Both pericycle cell length and LR density phenotypes of cycd4;1 are rescued by low concentrations of applied auxin, suggesting that the basal meristem has a role in determining LR density. We further show CYCD4;1 is rate-limiting for sucrose-dependent LR formation, since CYCD4;1 expression is sucrose-dependent and wild-type roots fully phenocopy cycd4;1 in sucrose absence. We conclude that CYCD4;1 links meristem pericycle cell behavior to LR density consistent with a basal meristem prepatterning model and that D-type cyclins can confer division potential of defined cell types through cell-specific expression patterns.


A portable digital speech-rate converter for hearing impairment.
A real-time hand-sized portable device that slows speech speed without changing the pitch is proposed for hearing impairment. By using this device, people can listen to fast speech at a comfortable speed. A combination of solid-state memory recording and real-time digital signal processing with a single chip processor enables this unique function. A simplified pitchsynchronous, time-scale-modification algorithm is proposed to minimize the complexity of the DSP operation. Unlike the traditional algorithm, this dynamic-processing algorithm reduces distortion even when the expansion rate is only just above 1. Seven out of 10 elderly hearing-impaired listeners showed improvement in a sentence recognition test when using speech-rate conversion with the largest expansion rate, although no improvement was observed in a word recognition test. Some subjects who showed large improvement had limited auditory temporal resolution, but the correlation was not significant. The results suggest that, unlike conventional hearing aids, this device can be used to overcome the deterioration of auditory ability by improving the transfer of information from short-term (echoic) memory into a more stable memory trace in the human auditory system.


Nonionic surfactant adsorption at the ethylammonium nitrate surface: a neutron reflectivity and vibrational sum frequency spectroscopy study.
The adsorbed layers of polyoxyethylene n-alkyl ether surfactants C(12)E(4), C(14)E(4), and C(16)E(4) at the EAN surface have a headgroup layer that is thin and compact (only approximately 30 vol % EAN). The headgroups do not adopt a preferred orientation and are disordered within the ethylene oxide layer. Alkyl tails contain a significant number of gauche defects indicating a high degree of conformational disorder. The thickness of the tail layer increases with increasing alkyl chain length, while the headgroup layer shows little change. Lowering the C(12)E(4) concentration from 1 to 0.1 wt % decreases the adsorbed amount, and the headgroup layer becomes thinner and less solvated, whereas C(14)E(4) and C(16)E(4) adsorbed layers are unaffected by dilution over the same concentration range. The C(16)E(4) layer thickness increases and area per molecule decreases on warming to 60 degrees C, but the adsorbed layer structures of C(12)E(4) and C(14)E(4) are unchanged. Both effects are attributed to surfactant solubility.


Synthesis of enhanced corrosion resistant Fe-B-C-Ti amorphous ribbons and evaluation of their photodegradation efficiency under light irradiation.
Fe-based amorphous alloys have been found to be very efficient in the degradation of water pollutants due to their unique atomic arrangements with long-range disordered structure. In this work, Fe-B-C-Ti amorphous ribbons were successfully synthesized and showed high catalytic efficiency in the degradation of methylene blue (MB) under simulated sunlight and across a wide pH range. The catalytic efficiency was evaluated under different conditions to optimize the degradation performance. The amorphous ribbon Fe75B10C10Ti5 was found to exhibit the highest photocatalytic activity as explained by its optical and photoelectrochemical properties. It can degrade MB completely with low Fe-leaching and significant recyclability at pH close to a neutral range (pH 5). The degradation mechanisms can be explained in terms of photocatalytic activity along with the galvanic cell effect which contributed to the efficient MB degradation. This work provides a comprehensive idea for the synthesis of amorphous alloys by optimizing their elemental composition and also explains the catalytic activity of partially crystallized regions on the ribbon surface. The significant corrosion resistance and the quick degradation of MB in a wide pH range in a recyclable manner by these easily separable and highly efficient catalysts indicate great potential for their practical application.


Object-recognition and spatial learning and memory in rats prenatally exposed to ethanol.
Prenatal ethanol exposure can produce cognitive and behavioral impairments. In the present study, rats from prenatal ethanol (E), pair-fed (PF), and ad libitum-fed control (C) treatment conditions were tested on the object-recognition delayed-nonmatching-to-sample (DNMS) task with nonrecurring items and on the spatial-navigation Morris water maze task. In Experiment 1, there were no significant differences among groups in object-recognition learning and memory, distractibility, or response perseveration on the DNMS task. In Experiment 2, the same rats were tested in the water maze; E rats took significantly longer to learn the task than did the PF or C rats. These data suggest that the mechanisms underlying spatial cognitive abilities are more vulnerable to the teratogenic effects of prenatal ethanol exposure than those underlying object-recognition abilities.


Should nonsuicidal self-injury be a putative obsessive-compulsive-related condition? A critical appraisal.
Nonsuicidal self-injury (NSSI) has many behavioral and cognitive features that would make it appear to be closely tied to obsessive-compulsive disorder (OCD). Obsessive-compulsive-related disorders (OCRDs) have been described in the literature as conditions that share a common phenomenology, neurobiology, and treatment response. The authors reviewed the literature describing the degree that NSSI is similar to, and distinct from, OCRDs based on these hypothesized common areas. They conclude with recommendations for conceptualization that draws partly from the OCRD literature and from cognitive-behavioral models of rumination.


Evaluation of the aldosterone synthase (CYP11B2) gene polymorphism in patients with myocardial infarction.
Left ventricular remodeling after myocardial infarction involves activation of the renin-angiotensin-aldosterone system. Recently, the biallelic -344T/C polymorphism of the aldosterone synthase gene was associated with increased aldosterone levels, arterial hypertension, diastolic dysfunction, and left ventricular dilatation. We hypothesized that this polymorphism may also affect left ventricular geometry and function after myocardial infarction. By using a standardized questionnaire, as well as anthropometric and echocardiographic measurements, we thus studied 606 patients (533 men and 73 women) who had a myocardial infarction before the age of 60 years. The aldosterone synthase gene polymorphism was analyzed after polymerase chain reaction amplification and restriction enzyme digestion. The results demonstrated that there was no association of the aldosterone synthase gene polymorphism with echocardiographically determined left ventricular dimensions, wall thicknesses, or indexes of systolic or diastolic function. Furthermore, anthropometric data, including blood pressure levels, were balanced between the different genotypes. Finally, the allele frequency was similar for patients with myocardial infarction and a sample group from the normal population (n=1675). The data indicate that the allele status of the aldosterone synthase gene polymorphism is not useful for the identification of patients with myocardial infarction who have impaired left ventricular function or unfavorable remodeling.


"Stress knocks hard on your immune system": asthma and the discourse on stress.
Stress has been described by anthropologists and other scholars as a problematic concept, a discourse, a modern metaphor, a collective representation, and a cultural resource. The vast array of academic work in the arena of stress research belies the historical reality of stress as an object of inquiry; rather, stress is presented as new, the story of its emergence intermingled with processes of industrialization, individualism, and perceptions of modern life. This article traces the uses to which the concept of stress is put in the illness narratives of persons with asthma. It argues that multiple invocations of stress not only make visible the workings of personal responsibility and individualism regarding chronic illness management in the contemporary United States but also gesture toward the social relations of sickness that lie beyond individual control.


RELATIONSHIP BETWEEN ORPHANHOOD STATUS, LIVING ARRANGEMENTS AND SEXUAL DEBUT: EVIDENCE FROM FEMALES IN MIDDLE ADOLESCENCE IN SOUTHERN AFRICA.
This study examined the relationship between orphanhood status, living arrangements and sexual debut. The study is important in the context of southern Africa, where a substantial number of children live apart from their parents because the parent is dead or living elsewhere, and where female adolescents face disproportionate sexual and reproductive health risks. Data for female adolescents were taken from Demographic and Health Surveys conducted in seven southern African countries. Unadjusted and adjusted hazard ratios of sexual debut were estimated using Cox Proportional Hazard models. The results from multivariate analyses showed that non-co-residence with biological parents was significantly associated with higher risk of sexual debut in five of the seven countries. Using pooled data, the results showed that father absence was associated with higher risk of sexual debut - whether the father was deceased or living elsewhere. Interventions to delay sexual debut among female adolescents should seek to promote father-adolescent co-residence and improve access to education.


Association of intestinal bacteria with immune activation in a cohort of healthy adults.
Chronic inflammation may develop over time in healthy adults as a result of a variety of factors, such as poor diet directly affecting the composition of the intestinal microbiome, or by causing obesity, which may also affect the intestinal microbiome. These effects may trigger the activation of an immune response that could eventually lead to an inflammation-related disease, such as colon cancer. Before disease develops it may be possible to identify subclinical inflammation or immune activation attributable to specific intestinal bacteria normally found in the gut that could result in future adverse health impacts. In the present study, we examined a group of healthy men and women across a wide age range with and without obesity to determine which bacteria were associated with particular types of immune activation to identify potential preclinical markers of inflammatory disease risk. Several associations were found that may help develop dietary interventions to lower disease risk.


Molecular method for typing Mycobacterium ulcerans.
A cluster of Mycobacterium ulcerans infections has recently occurred on Phillip Island, Victoria, Australia. Previous cases of infection have generally been located around Bairnsdale in southeast Gippsland. The aim of this study was to determine the epidemiological relationship between these strains and other strains originating in Australia and Africa. The previously described plasmid pTBN12 was used as a probe with restriction enzyme-digested chromosomal DNA to differentiate the strains of M. ulcerans. The probe was able to distinguish 11 restriction fragment length polymorphisms (RFLPs). Forty-three strains originating in Victoria were divided into three types, i.e., V1, V2, and V3. The majority of strains (40) yielded a type V1 pattern, including strains from southeast Gippsland. Fourteen strains from Queensland yielded three additional RFLP types, i.e., Q1, Q2, and Q3. Five strains from Benin and seven strains from Zaire yielded five additional RFLP types. It is envisaged that molecular typing of M. ulcerans strains from around the world may have a great impact on understanding of the epidemiology of infection with this organism.


Transcriptomic Reprogramming, Alternative Splicing and RNA Methylation in Potato (Solanum tuberosum L.) Plants in Response to Potato Virus Y Infection.
Plant-virus interactions are greatly influenced by environmental factors such as temperatures. In virus-infected plants, enhanced temperature is frequently associated with more severe symptoms and higher virus content. However, the mechanisms involved in controlling the temperature regulation of plant-virus interactions are poorly characterised. To elucidate these further, we analysed the responses of potato plants cv Chicago to infection by potato virus Y (PVY) at normal (22 °C) and elevated temperature (28 °C), the latter of which is known to significantly increase plant susceptibility to PVY. Using RNAseq analysis, we showed that single and combined PVY and heat-stress treatments caused dramatic changes in gene expression, affecting the transcription of both protein-coding and non-coding RNAs. Among the newly identified genes responsive to PVY infection, we found genes encoding enzymes involved in the catalysis of polyamine formation and poly ADP-ribosylation. We also identified a range of novel non-coding RNAs which were differentially produced in response to single or combined PVY and heat stress, that consisted of antisense RNAs and RNAs with miRNA binding sites. Finally, to gain more insights into the potential role of alternative splicing and epitranscriptomic RNA methylation during combined stress conditions, direct RNA nanopore sequencing was performed. Our findings offer insights for future studies of functional links between virus infections and transcriptome reprogramming, RNA methylation and alternative splicing.


[Changes in lymph circulation in rats with experimental disseminated intravascular coagulation].
To explore changes in lymph circulation in rats with experimental disseminated intravascular coagulation (DIC). Thirty-two male Wistar rats were randomly divided into two groups: DIC group and sham-operation group, with 16 rats in each group.In each group, 8 rats were used to observe the lymphatic circulation of intestinal mesentery, and the others were used to observe lymphatic dynamics. Experimental DIC model was replicated by injecting dextran 500 via jugular vein in Wistar rats. The changes in lymph circulation were observed in these rats with lymphology methods. During the phase of DIC, the contractility of mesenteric micro-lymphatic (ML), the intestinal lymph flux, lymphocytes output were obviously decreased, and there was a few monocytes in the lymph fluid, but the lymph fluid viscosity was increased. After treatment with normal saline (NS), the contractility of ML, the intestinal lymph flux, lymphocytes output were obviously increased, and there was a large amount of monocytes in the lymph fluid, with significant difference compared with sham-operation group (all P<0.05). Moreover, the lymph fluid viscosity was decreased compared with sham-operation group (P<0.05). The disturbance in lymph circulation mainly includes depression of contractility of lymphatics, the transport function of lymph circulation, and increased lymph fluid viscosity.


Aging-dependent proteolysis of NF-kappaB in human fibroblasts.
We investigated the NF-kappaB-like factor induced in the late-passage human oral mucosal fibroblasts stimulated with interleukin-1 (IL-1). Compared with the NF-kappaBs of HeLa cells and early-passage fibroblasts, the NF-kappaB-like factor of late-passage (passage 15) fibroblasts migrated faster in the electrophoretic mobility shift assay (EMSA) and behaved like a 70-80 kDa protein in the gel filtration chromatography. Both antibodies against p50 and p65 subunits of NF-kappaB could supershift the small NF-kappaB-like factor of late-passage cells in the EMSAs. A 47-kDa band was detected in late-passage fibroblasts by immunoblotting against p50. The mobility of the trypsin-degraded NF-kappaB of HeLa cells corresponded to that of the small NF-kappaB-like factor of late-passage fibroblasts in the EMSAs. Furthermore, when the nuclear extracts of the IL-1-stimulated HeLa cells were incubated with those of the IL-1-stimulated old fibroblasts, the p65-p50 NF-kappaB band disappeared, leaving behind a small NF-kappaB-like band. This reduction of NF-kappaB was prevented by the addition of a cysteine protease inhibitor leupeptin. These results suggest that the small NF-kappaB-like factor of late-passage fibroblasts is a part of the NF-kappaB truncated by aging-induced protease(s).


CT evaluation of chondromatosis of the temporomandibular joint.
The CT findings in two cases of chondromatosis of the temporomandibular joint are described. The distinctive feature of the first case was the presence of ossified loose bodies surrounding the head of the condyle, whereas in the second there was clear evidence of arthrosis. Three-dimensional image reconstruction was also used in the first case to obtain a better overall visualization of the changes.


Control of an outbreak of respiratory syncytial virus infection in immunocompromised adults.
Respiratory syncytial virus (RSV) is increasingly recognized as an important pathogen in immunocompromised adults, particularly those receiving bone marrow transplants, and, given the ease with which it spreads, represents a significant nosocomial problem. We describe an outbreak of RSV infection involving eight patients on a haematology/oncology ward which was controlled by early screening of patients and staff. Positive patients were cohort nursed on a separate ward and basic infection control measures including use of gowns and gloves were enforced. Children under age 12 were denied ward access. All patients with lower respiratory tract infection, and bone marrow transplant recipients with upper respiratory symptoms, were treated with nebulized ribavirin. There were no deaths. We conclude that awareness of the risk of RSV infection in immunocompromised patients coupled with rapid diagnosis and treatment, screening of symptomatic patients and staff, cohort nursing of cases and basic infection control procedures can prevent spread of RSV infection and reduce morbidity.


Overrides of medication-related clinical decision support alerts in outpatients.
Electronic prescribing is increasingly used, in part because of government incentives for its use. Many of its benefits come from clinical decision support (CDS), but often too many alerts are displayed, resulting in alert fatigue. To characterize the override rates for medication-related CDS alerts in the outpatient setting, the reasons cited for overrides at the time of prescribing, and the appropriateness of overrides. We measured CDS alert override rates and the coded reasons for overrides cited by providers at the time of prescribing. Our primary outcome was the rate of CDS alert overrides; our secondary outcomes were the rate of overrides by alert type, reasons cited for overrides at the time of prescribing, and override appropriateness for a subset of 600 alert overrides. Through detailed chart reviews of alert override cases, and selective literature review, we developed appropriateness criteria for each alert type, which were modified iteratively as necessary until consensus was reached on all criteria. We reviewed 157,483 CDS alerts (7.9% alert rate) on 2,004,069 medication orders during the study period. 82,889 (52.6%) of alerts were overridden. The most common alerts were duplicate drug (33.1%), patient allergy (16.8%), and drug-drug interactions (15.8%). The most likely alerts to be overridden were formulary substitutions (85.0%), age-based recommendations (79.0%), renal recommendations (78.0%), and patient allergies (77.4%). An average of 53% of overrides were classified as appropriate, and rates of appropriateness varied by alert type (p<0.0001) from 12% for renal recommendations to 92% for patient allergies. About half of CDS alerts were overridden by providers and about half of the overrides were classified as appropriate, but the likelihood of overriding an alert varied widely by alert type. Refinement of these alerts has the potential to improve the relevance of alerts and reduce alert fatigue.


Cell Wall and Extensin mRNA Changes during Cold Acclimation of Pea Seedlings.
During exposure to 2 degrees C, pea (Pisum sativum) seedlings cold acclimated to a killing temperature of -6 degrees C. Associated with this increase in freezing resistance was an increase in the weight of cell walls and changes in wall composition. Arabinosyl content increased by 100%, while other cell wall glycosyl residues and cellulose increased by about 20%. The cell wall hydroxyproline content increased by 80%. Arabinose and hydroxyproline are both major components of the structural cell wall glycoprotein, extensin. The increase in these components indicates that the level of extensin in the cell wall increases during cold acclimation. Northern blot analysis, using the pDC5A1 genomic clone as a probe, revealed a more than three-fold increase in total extensin mRNA during exposure to cold temperature. Specific extensin transcripts of 6.0, 4.5, 3.5, 2.6, 2.3, 1.8, and 1.5 kilobases were identified. Those at 6.0, 2.6, and 1.5 kilobases were especially promoted by low temperature treatment. The rise in extensin during cold acclimation may be regulated, at least in part, at the gene level. The possible structural role of this protein in freezing protection is discussed.


Probing infants' sensitivity to pupil size when viewing eyes.
Sensitive responding to eye cues plays a key role in human social interactions. Pupil size provides subtle cues regarding a social interaction partner's arousal states. The current study assessed infants' sensitivity to and preference for differences in pupil size. Specifically, we examined White 14-month-old infants' pupillary responses when viewing own-race and other-race (Asian) eyes with dilating, constricting, and static medium-sized pupils. Our results show that, independent of race, infants' pupils dilated more when viewing eyes with dynamically changing (dilating and constricting) pupils than when viewing eyes with non-changing, static, and medium-sized pupils. We also measured infants' looking preferences, showing that, independent of race, infants preferentially attended to eyes with dilated pupils. Moreover, our results show that infants orient more quickly to pupillary changes in own-race eyes than in other-race eyes. These findings demonstrate that infants detect, but do not mimic, changes in pupil size in others and show a preference for eyes with dilated pupils.


Leukocytapheresis in Chronic Myeloid Leukemia With Leukostasis.
Leukostasis in acute and chronic leukemias leads to increased cell burden and increased blood viscosity. Therapeutic leukocytapheresis is an automated procedure aimed at white blood cell depletion, and it thereby reduces the complications associated with increased blood viscosity, such as thrombotic events and mortality. In this report, we present the case of a 25-year-old patient with leukostasis and splenic laceration who was treated with therapeutic leukocytapheresis with symptomatic relief in leukostasis.


Magneto-plasmonics in graphene-dielectric sandwich.
In this paper, dispersion properties and field distributions of surface magneto plasmons (SMPs) in double-layer graphene structures at room temperature are studied. It is found that, the dispersion curves of both symmetric and antisymmetric SMPs modes split into several branches/bands when a magnetic field is applied perpendicularly to the graphene surface. Surprisingly, the lowest energy SMP band has anomalous dependence on the applied magnetic field, different to the other higher bands. In addition, the symmetric and antisymmetric modes can be decoupled if the two graphene layers possess different properties, such as different Fermi energies. Furthermore, electric components of the surface modes which are parallel to the graphene surfaces but perpendicular to the propagation direction (i.e. the transverse-electric mode) are no longer zero caused by the Lorentz force on the free electrons.


Conditional reasoning difficulties in polysubstance-dependent patients.
Polysubstance dependence has been associated with many neurocognitive impairments. The present study explored one of these deficits, namely conditional reasoning, using the Wason selection task. In healthy individuals, social contract and precautionary content improve conditional reasoning performance compared with descriptive or abstract content. Twenty-two recently detoxified polysubstance-dependent patients were compared with 22 controls matched for sex, age, and education level on their performance on the Wason selection task across problems involving social contract, precautionary, and descriptive conditional rules, controlling for depression, anxiety levels, and verbal intelligence. Conditional reasoning on descriptive and social contract rules was severely impaired in polysubstance-dependent patients. Precautionary reasoning was also impaired, but to a lesser degree than the other modalities of conditional reasoning. These results may reflect a toxic effect of chronic multiple-drug consumption on the prefrontal areas of the brain. Alternatively, conditional reasoning difficulties could be present, at least partially, before polysubstance dependence onset. This population may have difficulties properly understanding social contracts in real-life settings, suggesting a potential target for clinical intervention.


USP28 contributes to the proliferation and metastasis of gastric cancer.
USP28, a member of the deubiquitinating enzymes family, plays a vital role in the physiological process of cell proliferation, differentiation and apoptosis, DNA repair, immune response, and stress response. USP28 has been reported to be overexpressed in bladder cancer, colon cancer, breast carcinomas, and so on. Nevertheless, the role of USP28 in gastric cancer has not yet been investigated. In our study, we examined the USP28 expression in 87 paired samples of gastric cancer and normal gastric tissues. We found that USP28 was overexpressed in gastric cancer compared with normal gastric tissues (P < 0.01), and its overexpression was related to the degree of differentiation and metastases. Inhibiting USP28 expression in vitro suppressed the proliferation and invasion of gastric cancer cells by downregulating lysine specific demethylase 1. On the basis of our data, it can be concluded that USP28 may be a novel therapeutic target for gastric cancer.


Effect of interleukin-17 on receptor-interacting protein 4 expression and keratinocyte proliferation.
The aim of the present study was to investigate the effect of receptor-interacting protein 4 (RIP4) on keratinocyte proliferation and its role in the pathogenesis of psoriasis vulgaris. The expression of RIP4 and Ki-67 in fixed sections from 30 patients with psoriasis vulgaris and 30 gender- and age-matched healthy controls was detected by two-step immunohistochemistry, prior to the correlation being examined with Pearson's analysis. Reverse transcription-semi-quantitative polymerase chain reaction and western blot analyses were carried out to detect the mRNA and protein expression of RIP4 in an immortalized human keratinocyte line, HaCaT, stimulated by different concentrations of interleukin-17 (IL-17), in order to analyze the change in RIP4 expression following IL-17 stimulation. The cell proliferation rate was measured using the cell counting kit-8 assay simultaneously. RIP4 was mainly present in the cytoplasm of the keratinocytes. Compared with its expression in the healthy control skin, RIP4 exhibited a significant upregulation in the psoriatic lesions (P<0.05). Pearson's correlation analysis revealed a positive correlation between the expression level of RIP4 and the proliferation index. Both RIP4 mRNA and protein levels were significantly increased following IL-17 stimulation. Exposure to IL-17 additionally increased the proliferation rate of the HaCaT cells. In conclusion, RIP4 may play a role in the pathogenesis of psoriasis vulgaris as a potential target of IL-17.


External fields in conceptual density functional theory.
The necessity of the recent incorporation of new external variables in the context of conceptual DFT (CDFT) is discussed based on the ever-increasing portfolio of experimental reaction conditions in the endeavor of experimentalists to synthesize new molecules with unprecedented properties. Electric and magnetic fields (ε and B), mechanical forces (F), and confinement are proposed as valuable new variables, extending conventional CDFT and its associated response functions. A finite field approach is used to calculate the evolution of both global and local descriptors in a selected series of atomic and molecular applications, and from it derive new response function involving, with one exception, the first derivative to the field considered. The electric field results, displaying, for example, a case of a field-induced enantioselectivity in the Fukui function, may be instrumental in the recent upsurge of chemistry in oriented external electric fields. The study of atomic electronegativity and hardness in magnetic fields displays a piecewise behavior, associated to configurational jumps upon increasing field strength and reveals an overall compression of their ranges for stronger fields, which may be guiding upon investigating chemistry in extremely high fields like in white dwarfs. The evolution of the electronegativity and hardness of diatomics under mechanical force can elegantly be traced back to differences in their equilibrium distance in the neutral, cationic, and anionic state. The well-known reduction of the polarizability under confinement can be seen as a fore-runner of the increasing hardness of atoms under pressure, presently under investigation. Periodicity showing up in a spontaneous way in the variety of properties is a leitmotiv in this study, as well as the interconnections/analogies between the different response functions.


Effects of dietary taurine on egg production, egg quality and cholesterol levels in Japanese quail.
Taurine is a semi-essential amino acid and has many biological properties. The objective of this study was to determine the effect of dietary supplementation with taurine on egg production, egg quality, and cholesterol level in serum and egg yolk of quails. A total of 108 quails aged 6 weeks were randomly allocated to three dietary treatments. Each treatment consisted of four replicates of nine quails. The diets were supplemented with 0, 100, and 500 mg kg(-1) of taurine for 8 weeks. Dietary 500 mg kg(-1) taurine significantly affected egg production rate and feed conversion ratio, but had no significant effects on body weight gain, feed consumption, or egg weight. Dietary taurine had no significant effect on egg quality parameters studied. Serum triglyceride concentration was reduced significantly with supplementation of taurine at 100 and 500 mg kg(-1). Egg yolk cholesterol content was reduced significantly, and the contents of serum taurine and egg yolk taurine were increased significantly with taurine supplementation at 500 mg kg(-1). Results of the present study indicated that adding 500 mg kg(-1) taurine reduced yolk cholesterol concentration and increased yolk taurine content without adverse effects on performance and egg quality of laying quails.


Intra-articular treatment with hyaluronic acid in osteoarthritis of the knee joint: a controlled clinical trial versus mucopolysaccharide polysulfuric acid ester.
In a single-blind, randomized clinical trial, both the efficacy and safety of hyaluronic acid (HA) were compared with that of mucopolysaccharide polysulfuric acid ester (MPA) in patients with osteoarthritis of the knee joint. Both agents were administered intra-articularly over six weeks. Patients received either seven injections of HA or 13 injections of MPA. Joint function, range of motion, severity of pain, the general condition of the bony structure and soft tissue of the joint area, and the global clinical efficacy and safety of the medication were assessed. The mean improvement in the modified total Larson rating score was 22% (SD = 28) after HA treatment and 7% (SD = 17) after treatment with MPA (analysis of variance: p = 0.02). This change was mainly caused by a reduction of pain. The onset of pain relief was more rapid in the HA group. The therapeutic effect increased in both treatment groups during the follow-up period. During this interval, lasting six months after the start of treatment, a further reduction of pain and an improvement of knee joint function could be observed. At the end of the study, 25 out of 33 (76%) patients in the HA group and 11 out of 24 (46%) patients in the MPA group were symptom-free or markedly improved (Chi-square test: p = 0.02). Both agents were tolerated very well.


A Two-Dimensional Biodegradable Niobium Carbide (MXene) for Photothermal Tumor Eradication in NIR-I and NIR-II Biowindows.
Conventionally, ceramics-based materials, fabricated by high-temperature solid-phase reaction and sintering, are preferred as bone scaffolds in hard-tissue engineering because of their tunable biocompatibility and mechanical properties. However, their possible biomedical applications have rarely been considered, especially the cancer phototherapeutic applications in both the first and second near-infrared light (NIR-I and NIR-II) biowindows. In this work, we explore, for the first time as far as we know, a novel kind of 2D niobium carbide (Nb2C), MXene, with highly efficient in vivo photothermal ablation of mouse tumor xenografts in both NIR-I and NIR-II windows. The 2D Nb2C nanosheets (NSs) were fabricated by a facile and scalable two-step liquid exfoliation method combining stepwise delamination and intercalation procedures. The ultrathin, lateral-nanosized Nb2C NSs exhibited extraordinarily high photothermal conversion efficiency (36.4% at NIR-I and 45.65% at NIR-II), as well as high photothermal stability. The Nb2C NSs intrinsically feature unique enzyme-responsive biodegradability to human myeloperoxidase, low phototoxicity, and high biocompatibility. Especially, these surface-engineered Nb2C NSs present highly efficient in vivo photothermal ablation and eradication of tumor in both NIR-I and NIR-II biowindows. This work significantly broadens the application prospects of 2D MXenes by rationally designing their compositions and exploring related physiochemical properties, especially on phototherapy of cancer.


Wrinkly skin syndrome: phenotype and additional manifestations.
The wrinkly skin syndrome is an autosomal recessive disorder characterized by wrinkling of the skin of the dorsum of the hands and feet, decreased elastic recoil of the skin, an increased number of palmar and plantar creases, multiple musculoskeletal abnormalities, microcephaly, and mental retardation. Our patient is characteristic of the syndrome as previously described, and confirms the presence of mental retardation and microcephaly as component manifestations, with the additional findings of connective tissue abnormalities evidenced by an atrial septal aneurysm.