Extraction of chitosan and its oligomers from shrimp shell waste, their characterization and antimicrobial effect.
The present study was performed to utilize the shrimp shell waste for chitin and chitosan production, characterization by Fourier transform infrared (FT-IR) technique and to evaluate the antimicrobial effects of chitosan oligomers produced by depolymerization of chitosan by nitrous acid. Chitosan was extracted from the shrimp shell waste by the chemical method and characterized by FT-IR. Chitooligomers were produced by depolymerising chitosan using nitrous acid, and the chitooligomers were tested for antimicrobial effect against four gut pathogenic organisms, i.e., Enterobacter aerogen (National Collection of Dairy Culture [NCDC] 106), Enterococcus faecalis (NCDC 119), Escherichia coli (NCDC 134), and Staphylococcus aureus (NCDC 109) by well diffusion method using Muller-Hinton agar. A pure culture of pathogenic organisms was collected from NCDC, ICAR-National Dairy Research Institute, Karnal. Extracted chitosan characterized by FT-IR and chitooligomers demonstrated antimicrobial effect against four gut pathogenic organisms used in this study. Zone of inhibitions (mm) were observed in E. faecalis (13±0.20), E. coli (11.5±0.4), S. aureus (10.7±0.2), and E. aerogen (10.7±0.3). E. faecalis showed larger inhibition zone as compared to all other organisms and inhibitions zones of E. aerogen and S. aureus were comparable to each other. Shrimp waste can be utilized for chitosan production, and the chitooligomers can be used as feed additive for gut health enhancement and have potential to replace antibiotics from the feed. Along with value addition pollutant load could be reduced by waste utilization.


High dielectric loss in graphite-coated Ti nanocapsules.
Graphite-coated Ti nanocapsules, with Ti nanoparticles as core and onion-like graphite layers as shell, have been prepared by a modified arc-discharge method in ethanol atmosphere, and characterized by means of X-ray diffraction, transmission electron microscopy and Raman spectroscopy. The dielectric properties of the graphite-coated Ti nanocapsules have been investigated in the 2-18 GHz range. An equivalent circuit model was used to interpret the non-linear dielectric resonance behavior of the graphite-coated Ti nanocapsules. The high dielectric loss is mainly attributed to conductance loss and dipole-relaxation loss in the graphite-coated Ti nanocapsules. The graphite-coated Ti nanocapsules exhibit promising properties for application as a new type of shield or absorbent of electromagnetic waves.


Treatment of femoral shaft union disturbances with intramedullary nailing. Treatment failure.
The paper contains an analysis of the treatment outcomes of intramedullary nailing for femoral shaft non-union. Twenty-two patients were treated between 1999 and 2005 with locked intramedullary nailing for femoral shaft non-union. The average age was 38.2 years (range 17-79). The study group comprised 20 males and 2 females. The right femur was affected in 12 patients, and the left in 10 patients. All patients had undergone multiple operations to treat the non-union. At the time of the study, non-union had been present for a period ranging from 9 months to as much as 10 years. Stabilisation with an intramedullary nail was preceded by reaming of the medullary cavity. Nails of different diameter were used (11-16 mm, usually 11 or 13 mm). Both static and dynamic locking was used. Surgery was confined to stabilization with an intramedullary nail in 13 patients, and 9 patients additionally underwent the Judet-Forbes decortication procedure, bone grafting or internal plate fixation and osteomuscular decortication. The non-union healed in 19 patients and was not achieved in the remaining 3. A detailed analysis was performed in 9 cases in which the bone union was not achieved despite reaming the medullary cavity, nailing and additional procedures, which did not lead to bone healing in 3 patients. Despite being an acknowledged method of treatment for delayed union of long-bone shafts, intramedullary nailing following reaming of the medullary cavity did not result in bone healing in all of our patients and additional procedures were often required. Therefore, the use of this procedure for femoral shaft pseudoarthroses should be decided on a case-by-case basis.


Rh(III)-Catalyzed C-H Activation/Cyclization of Benzamides and Diazonaphthalen-2(1H)-ones for Synthesis of Lactones.
A Rh(III)-catalyzed C-H activation/cyclization of benzamides and diazonaphthalen-2(1H)-ones for synthesis of lactones has been developed. In the presence of Rh(III) catalysis, the benzamides would form rhodacycle species and could be trapped by diazonaphthalen-2(1H)-ones for arylation, and the following intramolecular lactonization would rapidly furnish the products. Thus, the diazonaphthalen-2(1H)-ones were first revealed as a lactonization component in Rh(III)-catalysis, while the kinetic isotope effect study was conducted and a plausible reaction mechanism was proposed.


Plasma renin activity, blood uric acid and plasma volume in pregnancy-induced hypertension.
Plasma renin activity (PRA), plasma aldosterone (PA), blood uric acid (BUA), plasma concentrations of catecholamines (Pcat) and plasma volume (PV) were measured simultaneously in 24 patients with pregnancy-induced hypertension (PIH). This hypertensive group was divided into labile (LH) and persistent hypertension (PH) groups according to the response of their blood pressure to home bed rest. Compared to normal theoretical values, PV was decreased in both hypertensive groups (LH = -7%; PH = -14%). Compared to a control group (C) of 16 normotensive pregnant women, PRA was higher in LH and lower in PH whereas PA was lower in both hypertensive groups. BUA was higher than in C in both hypertensive groups. No difference in PCat was found between the three groups. In the PH group negative correlations were found between BUA and PRA, as well as between BUA and PV but no correlation between PRA and PV nor between Pcat and BUA were found. LH and PH are two pathophysiologically different entities in PIH. In PH renin secretion is not appropriate to hypovolaemia and therefore not primarily involved in the pathogenesis of hypertension. Hypovolaemia may play a role in the increase of BUA in PIH.


Hyperspectral-based Estimation of Leaf Nitrogen Content in Corn Using Optimal Selection of Multiple Spectral Variables.
Accurate and dynamic monitoring of crop nitrogen status is the basis of scientific decisions regarding fertilization. In this study, we compared and analyzed three types of spectral variables: Sensitive spectral bands, the position of spectral features, and typical hyperspectral vegetation indices. First, the Savitzky-Golay technique was used to smooth the original spectrum, following which three types of spectral parameters describing crop spectral characteristics were extracted. Next, the successive projections algorithm (SPA) was adopted to screen out the sensitive variable set from each type of parameters. Finally, partial least squares (PLS) regression and random forest (RF) algorithms were used to comprehensively compare and analyze the performance of different types of spectral variables for estimating corn leaf nitrogen content (LNC). The results show that the integrated variable set composed of the optimal ones screened by SPA from three types of variables had the best performance for LNC estimation by the validation data set, with the values of R2, root means square error (RMSE), and normalized root mean square error (NRMSE) of 0.77, 0.31, and 17.1%, and 0.55, 0.43, and 23.9% from PLS and RF, respectively. It indicates that the PLS model with optimally multitype spectral variables can provide better fits and be a more effective tool for evaluating corn LNC.


[Tyrosine kinase inhibitors for the treatment of papillary thyroid cancer].
Since 2005, different types of multitargeted tyrosine kinase inhibitors were used in clinical trials for the treatment of patients with advanced thyroid cancers. Experimental studies have demonstrated that tyrosine kinase inhibitors has both anti-proliferative and anti-angiogenic properties in vitro and in vivo, against thyroid cancer cells. Furthermore, several completed (or ongoing) studies have evaluated the long-term efficacy and tolerability of tyrosine kinase inhibitors in patients with papillary, follicular and medullary aggressive thyroid cancer. The results of the different studies showed good clinical responses and stabilization of the disease and suggested that tyrosine kinase inhibitors are a promising therapeutic option in patients with advanced thyroid cancer that is not responsive to traditional therapeutic strategies (such as radioiodine).


Plasma levels of advanced glycation end products during haemodialysis, haemodiafiltration and haemofiltration: potential importance of dialysate quality.
Advanced glycation end products (AGEs) accumulate in patients with end-stage renal disease (ESRD). The aim of this study was to investigate the potential influence of different modalities of renal replacement therapies on plasma AGE levels. The removal of AGEs by high-flux haemodialysis (HD) using standard and ultrapure dialysis fluid (SDF and UDF), by haemodiafiltration (HDF) and by haemofiltration (HF) was studied by fluorescence spectroscopy and by a carboxymethyllysine (CML)-specific ELISA. In addition, molecular weight distribution of fluorescent AGE products in serum of several patients was analysed by gel filtration. The highest AGE-typical fluorescence was found in the serum of patients on HD using SDF (114,667+/-18,967 arbitrary units (AU)), followed by patients on HDF (86,912+/-24,411 AU, P<0.005), by patients on HD using UDF (74,953+/-21,152 AU, P<0.0001) and by patients on HF (74 039+/-17 027 AU, P<0.0001). Similar results were found for serum CML levels with the highest values in HD patients on SDF (1609+/-504 ng/ml), followed by patients on HF (1354+/-614 ng/ml, P<0.001), then by HD patients on UDF (1310+/-403 ng/ml, P<0.001) and by patients on HDF (1132+/-338 ng/ml, P<0.001). The removal rate of AGEs, as evaluated by the determination of the pre-/post-dialysis AGE differences, was comparable across all groups. These findings suggest that factors other than removal are responsible for the lower pre-dialysis AGE levels found in patients on convective dialysis as well as on HD with UDF. A role of water quality is assumed. This is corroborated by the finding that the high molecular weight AGE-fraction is preferentially lowered in comparison with patients on HD with SDF, as analysed by gel filtration chromatography. These findings could be best explained by a less severe oxidative stress (i.e. resulting in decreased AGE generation) with HF and HDF, as well as with ultrapure HD.


Assessment of quality performance measures for primary percutaneous coronary intervention: A report from a tertiary referral centre in Switzerland.
The present study aimed to document a local pattern of care in consecutive patients undergoing primary percutaneous coronary intervention for ST-elevation myocardial infarction (STEMI) in a tertiary centre in Switzerland. A retrospective study was conducted at the University Hospital of Lausanne, Switzerland. A total of 389 consecutive patients undergoing primary percutaneous coronary intervention for STEMI between 2009 and 2010 were studied. The audit focused on 14 items derived from the American College of Cardiology/American Heart Association 2008 quality performance measures position paper on STEMI management. These indicators all corresponded to a class 1 recommendation at the time of the study period. All patients received aspirin and anticoagulation within 24 hours after admission. Only 31.3% of patients received beta-blocking agents within 24 hours of admission. Left ventricular function was evaluated in 89.2% of cases and referral for cardiac rehabilitation was achieved in 78.5% of eligible patients. Patients subsequently transferred to another facility for further inpatient care had significantly less evaluation of left ventricular function (82.0% vs. 97.5%, P<0.0001). Global adherence to all performance measures was significantly higher among younger patients (45.9% vs. 31.4%, P<0.0075). The present study, which provides a snapshot on quality performance between 2009 and 2010 in a referral centre for primary percutaneous coronary intervention, demonstrates a suboptimal application of the global guidelines on STEMI management. This observation is mainly driven by a low prescription of beta-blocking agents, a class IA indication at that time. This observation should be put in perspective to current practice.


1[alpha],25-dihydroxyvitamin D(3) enhances annexin II dependent proliferation of osteoblasts.
Cells experience a variety of physiological and non-physiological stresses and consequently have appropriate mechanisms to deal with such deviations from homeostasis. Particularly subject to mechanical stress and shear forces are the cells that make up the bones. Osteoblastic cells can interpret this stress as a stimulus for proliferation; however, the molecular mechanisms underlying this phenomenon are poorly understood. We have identified annexin II as being specifically upregulated in mechanically stressed osteoblasts and found that increased levels of this protein are necessary for 1[alpha],25-dihydroxyvitamin D(3) mediated augmentation of the proliferative response of osteoblasts after mechanical stress. Our data demonstrate a novel interaction between 1[alpha],25-dihydroxyvitamin D(3) and annexin II in the proliferative response of osteoblasts as well as a novel function for annexin II in the stress response. These findings may offer new therapeutic opportunities for conditions that require regenerative osteoblastic activity such as osteoporosis.


Extremely low genetic diversity in a circumpolar dragonfly species, Somatochlora sahlbergi (Insecta: Odonata: Anisoptera).
We present the first empirical treatment of the northernmost breeding dragonfly, Somatochlora sahlbergi. We sequenced populations from United States, Canada, Finland, Sweden and Norway for cytochrome oxidase I (COI) and D2 region of 28s. We found that, despite geographic barriers across its vast arctic range, S. sahlbergi is a single species. Not only does it appear to interbreed across its entire range, there also seems to be almost no variation among European and North American populations in their COI gene fragment (the barcode gene), which is usually extremely variable. We further found that characters thought to be diagnostic for the larvae of S. sahlbergi were absent in our European samples. We review and re-describe the habitat of this species based on new findings from recent field observations. Finally, we report for the first time the likely presence of this species in Japan. We hope our findings will encourage further study of this species and other under-studied insect taxa that inhabit the remote Arctic.


Chromosome-plasmid interaction in Escherichia coli K-12 carrying a thermosensitive plasmid, Rts1, in autonomous and in integrated states.
An Hfr strain of Escherichia coli K-12 was obtained by integrative suppression with a thermosensitive plasmid, Rts1. The R plasmid was integrated into the chromosome between rif and thr, and transfer of the chromosome occurred counterclockwise. The thermosensitivity of host cell growth due to the dnaA mutation was markedly but not completely reduced in this integratively suppressed Hfr strain. When the dnaA mutation was removed by transducing the dnaA+ genome to this Hfr, the thermosensitivity of cell growth due to existence of Rts1 was suppressed in contrast to strains carrying it autonomously. Thermosensitivity of cell growth appeared again when the plasmid was detached from the chromosome to exist autonomously. Contrary to the effect on cell growth, the transfer of the chromosome and the plasmid itself and the ability to "restrict" T-even phages were still thermosensitive in all of these strains carrying Rts1, irrespective of its state of existence. The detached plasmid as well as the original Rts1 were segregated upon growth at 42 C. These data are discussed in relation to chromosome-plasmid interaction. One of the most important conculusions is that some plasmid genes, related to their replication, are phenotypically suppressed by the chromosome when it is integrated.


Chylous ascites after retroperitoneal lymphadenectomy: successful management with peritoneovenous shunt.
A case of chylous ascites occurring after retroperitoneal lymphadenectomy for testicular carcinoma is described. After failure of conservative therapy, the patient was successfully treated with peritoneovenous shunt. The pathophysiological and therapeutic aspects of this rare complication are described; in the world literature only 7 cases of chylous ascites following retroperitoneal lymphadenectomy are reported.


Advance in plasma SEPT9 gene methylation assay for colorectal cancer early detection.
This review article summarizes the research advances of the plasma-based SEPT9 gene methylation assay for the clinical detection of colorectal cancer and its limitations. Colorectal cancer is a common malignancy with a poor prognosis and a high mortality, for which early detection and diagnosis are particularly crucial for the high-risk groups. Increasing evidence supported that SEPT9 gene methylation is associated with the pathogenesis of colorectal cancer and that detecting the level of methylation of SEPT9 in the peripheral blood can be used for screening of colorectal cancer in susceptible populations. In recent years, the data obtained in clinical studies demonstrated that the SEPT9 gene methylation assay has a good diagnostic performance with regard to both sensitivity and specificity with the advantage of better acceptability, convenience and compliance with serological testing compared with fecal occult blood tests and carcinoembryonic antigen for colorectal cancer (CRC). Furthermore, the combination of multiple methods or markers has become a growing trend for CRC detection and screening. Nevertheless, the clinical availability of the methylated SEPT9 assay is still limited because of the large degree of sample heterogeneity caused by demographic characteristics, pathological features, comorbidities and/or technique selection. Another factor is the cost-effectiveness of colorectal cancer screening strategies that hinders its large-scale application. In addition, improvements in its accuracy in detecting adenomas and premalignant polyps are required.


Assessment of the Naso-Maxilla and Related Dentoalveolar Region with Cone Beam Computed Tomography.
To evaluate via CBCT the anatomical variations of the maxillary teeth and associated major anatomical cavities, the maxillary sinus and nasal fossa. CBCT scans of 221 patients were used to examine maxillary sinus variations, the posterior superior alveolar artery (PSAA) course, nasal septum variations, middle and inferior concha-meatus variations, canalis sinuosus, infraorbital ethmoid cell, infraorbital canal, anterior nasal spina, and nasopalatine canal. The incidence of anatomical variations was 32.6% for maxillary sinus septa, 50.9% for PSAA, 23.1% for nasal septum deviation, 6.3% for nasal septum spur and pneumatization, 3.6% for paradoxical middle concha, 14.9% for middle concha hypertrophy, 39.6% for middle concha bullosa, 0.45% for bifid inferior concha, 0.9% for paradoxical inferior concha, 60.1% for inferior conch hypertrophy, 1.8% for inferior concha bullosa, and 40.3% for the infraorbital ethmoid cell. The study mainly observed group 2 anterior nasal spina with a rate of 35.7%, group 1 nasopalatine canal with a rate of 37.1%, and infraorbital duct type 2 with a rate of 70%. In 20.4% and 47% of cases, canalis sinuosus was located in the right and left sides of the maxilla, respectively. Maxillary sinus variations, PSAA prevalence and localization, nasal septum and concha variations, anterior nasal spina subgroups, nasopalatine canal subgroups, canalis sinuosus prevalence, and localization and infraorbital ethmoid cell prevalence were found to be consistent with the literature. Moreover, a rare case of the lower bifid concha was identified. The nasomaxillary complex and related dental structures, which are a multidisciplinary study area, should be carefully examined in the presence of pain of unknown origin and the planning of surgical procedures.


Impulsivity moderates the relationship between implicit associations about alcohol and alcohol use.
Implicit associations about alcohol are strong predictors of alcohol use, as is the personality trait of impulsivity. This study examines the role of impulsivity as a moderator of the association between implicit associations about alcohol and alcohol use. Two hundred and 19 participants completed measures of positive and negative implicit associations, as measured by the Implicit Association Test (IAT) and self-report questionnaires of impulsivity and alcohol use in the past month. Trait impulsivity was broken down into five facets identified in previous research. All facets of impulsivity and positive implicit associations about alcohol were positively correlated with past month alcohol use. The urgency facets (positive and negative) of impulsivity (acting rashly in response to strong positive or negative mood) moderated the relationship between positive implicit associations about alcohol and alcohol use. Compared to individuals low on positive or negative urgency, individuals high on positive or negative urgency tended to report acting more in line with their positive implicit associations by reporting more drinking in the past month.


Profulla Kumar Sen: his contributions to cardiovascular surgery.
One of the most eminent cardiothoracic surgeons of India, Profulla Kumar Sen (1915-1982) had a keen interest in research and in the subsequent clinical application of knowledge gained in the laboratory. His most significant contributions are his pioneering work on a transmyocardial acupuncture technique for treatment of ischemic myocardium, on heart transplantation in canine models and later in human beings, and on a new technique for aortic arch replacement. Transmyocardial laser revascularization of the 1990s was but an extension of his mechanical myocardial acupuncture for the treatment of ischemic heart disease, which he introduced 30 years earlier. On 16 February 1968, after many years of preparation through work with animal models, P.K. Sen and his team performed the 1st cardiac transplantation in India and the 6th in the world.


Real-life effectiveness of MP-AzeFlu in Irish patients with persistent allergic rhinitis, assessed by visual analogue scale and endoscopy.
Most allergic rhinitis (AR) patients have moderate-to-severe, persistent disease. Meda Pharma's AzeFlu (MP-AzeFlu) combines intranasal azelastine hydrochloride (AZE) and fluticasone propionate (FP) in a novel formulation in a single device to treat AR. This prospective, noninterventional study sought to assess the effectiveness of MP-AzeFlu (one spray/nostril twice daily; 548 µg AZE/200 µg FP daily dose) in relieving AR symptom severity. A visual analogue scale (VAS) was used prior to MP-AzeFlu treatment on days 0, 1, 3, 7, 14, 21, 28, 35, and 42 by 53 persistent AR (PER) patients seen in routine clinical practice in Ireland. An endoscopy was performed on days 0 and 28, and symptoms of edema, discharge, and redness were scored on a three-point scale (for both nostrils). Patients using MP-AzeFlu experienced rapid VAS score reduction from 73.4 mm (standard deviation [SD], 20.3) at Day 0 to 31.5 mm (SD, 25.0) at day 28 (P < 0.0001) to 28.1 mm (SD, 24.1) at day 42 (P < 0.0001), a 45.3-mm reduction. On average, patients achieved a clinically relevant VAS score cutoff of 50 mm before Day 7. Total endoscopy score decreased from 7.5 mm (SD, 3.1) at baseline to 3.5 mm (SD, 2.5) at Day 28. The incidence of severe edema on endoscopy decreased from 53.1% at baseline to 3.8% at Day 28. A similar reduction in the incidence of thick/mucousy discharge (from 28.3% to 4.8%) and severe redness (from 34.9% to 0%) was also observed. MP-AzeFlu provided effective, rapid control of PER as assessed by VAS in a real-world clinical setting in Ireland. Symptom improvement was observed at Day 1, sustained for 42 days, and associated with improved mucosal appearance after 28 days. These results confirm the safety of MP-AzeFlu and exceed the efficacy demonstrated in phase 3 clinical studies for controlling AR in PER patients.


Cytokines in dementias.
Knowledge regarding putative inflammatory component(s) participating in Alzheimer's disease (AD) and in vascular dementia (VAD) remains scarce. Recently, we have demonstrated the presence of inflammatory components, such as cytokines, in the CSF of demented patients. Although the initial events triggering the neurodegenerative processes in AD versus VAD may be different and thus lead to different neuropathological outcome, they may initiate a similar cascade of cytokine production in response to neuronal injury. The cytokines released in the CNS may in turn, act in a similar manner in both diseases, amplifying certain pathological changes such as amyloidogenesis and amyloid accumulation in the blood vessels, white matter lesions and angiogenesis. This hypothesis is supported by clinical studies demonstrating the presence of white matter infarcts and cerebrovascular pathology in patients with AD as well as the presence of senile plaques in patients with VAD. This review will focus on the production of pro-inflammatory and anti-inflammatory cytokines in dementia, and their putative role for glia cell activation, amyloidogenesis, vascular changes, white matter damage and neurodegeneration.


Global control of aberrant splice-site activation by auxiliary splicing sequences: evidence for a gradient in exon and intron definition.
Auxiliary splicing signals play a major role in the regulation of constitutive and alternative pre-mRNA splicing, but their relative importance in selection of mutation-induced cryptic or de novo splice sites is poorly understood. Here, we show that exonic sequences between authentic and aberrant splice sites that were activated by splice-site mutations in human disease genes have lower frequencies of splicing enhancers and higher frequencies of splicing silencers than average exons. Conversely, sequences between authentic and intronic aberrant splice sites have more enhancers and less silencers than average introns. Exons that were skipped as a result of splice-site mutations were smaller, had lower SF2/ASF motif scores, a decreased availability of decoy splice sites and a higher density of silencers than exons in which splice-site mutation activated cryptic splice sites. These four variables were the strongest predictors of the two aberrant splicing events in a logistic regression model. Elimination or weakening of predicted silencers in two reporters consistently promoted use of intron-proximal splice sites if these elements were maintained at their original positions, with their modular combinations producing expected modification of splicing. Together, these results show the existence of a gradient in exon and intron definition at the level of pre-mRNA splicing and provide a basis for the development of computational tools that predict aberrant splicing outcomes.


Functional and molecular characterization of nucleobase transport by recombinant human and rat equilibrative nucleoside transporters 1 and 2. Chimeric constructs reveal a role for the ENT2 helix 5-6 region in nucleobase translocation.
The human (h) and rat (r) equilibrative (Na(+)-independent) nucleoside transporters (ENTs) hENT1, rENT1, hENT2, and rENT2 belong to a family of integral membrane proteins with 11 transmembrane domains (TMs) and are distinguished functionally by differences in sensitivity to inhibition by nitrobenzylthioinosine and coronary vasoactive drugs. Structurally, the proteins have a large glycosylated loop between TMs 1 and 2 and a large cytoplasmic loop between TMs 6 and 7. In the present study, hENT1, rENT1, hENT2, and rENT2 were produced in Xenopus laevis oocytes and investigated for their ability to transport pyrimidine and purine nucleobases. hENT2 and rENT2 efficiently transported radiolabeled hypoxanthine, adenine, guanine, uracil, and thymine (apparent K(m) values 0.7-2.6 mm), and hENT2, but not rENT2, also transported cytosine. These findings were independently confirmed by hypoxanthine transport experiments with recombinant hENT2 produced in purine-cytosine permease (FCY2)-deficient Saccharomyces cerevisiae and provide the first direct demonstration that the ENT2 isoform is a dual mechanism for the cellular uptake of nucleosides and nucleobases, both of which are physiologically important salvage metabolites. In contrast, recombinant hENT1 and rENT1 mediated negligible oocyte fluxes of hypoxanthine relative to hENT2 and rENT2. Chimeric experiments between rENT1 and rENT2 using splice sites at rENT1 residues 99 (end of TM 2), 171 (between TMs 4 and 5), and 231 (end of TM 6) identified TMs 5-6 of rENT2 (amino acid residues 172-231) as a determinant of nucleobase transport activity, suggesting that this domain forms part(s) of the ENT2 substrate translocation channel.


Evolving role of toremifene in the adjuvant setting.
The Finnish Breast Cancer Group (FBCG) started the first multicenter trial of toremifene (Fareston) in the adjuvant setting in 1992. The primary aim of the trial is to compare the efficacy and side effects of toremifene and tamoxifen (Nolvadex) as adjuvant therapies for postmenopausal node-positive breast cancer patients. About 830 patients have been enrolled in the trial to date. An interim analysis of the first 500 patients, performed after a mean follow-up of 18 months, showed no significant difference between toremifene and tamoxifen with regard to efficacy or side effects. The study includes additional protocols aimed at examining some side effects, including ocular problems and the formation of DNA adducts in the endometrium and leukocytes, as well as possible additional benefits, such as effects on lipid levels and bone density. Toremifene also is being studied in two other trials in Europe. These studies, which are being coordinated by the International Breast Cancer Study Group (IBCSG), have enrolled approximately 600 patients to date.


[Bortezomib-induced tumor lysis syndrome with a remarkable elevation of LDH in a case of relapsed and therapy-resistant multiple myeloma].
A 60-year-old female patient with a therapy-resistant Bence-Jones (BJ) lambda-type multiple myeloma was treated with bortezomib. She had been treated with tandem autologous stem cell transplantations and achieved complete remission before her disease relapsed. Sixteen hours after the first administration of bortezomib, an episode of fever, slight consciousness disturbance and vomiting occurred, which was accompanied by a remarkable elevation of LDH (3608 IU/l). Serum levels of creatinine, uric acid, and AST were also transiently elevated. Serum interleukin-6 level was also increased after the administration of bortezomib. The symptoms disappeared rapidly within 48 hours. Bortezomib at a 25%-reduced dose was administered again along with dexamethasone 26 days later, which caused a moderate increase in LDH levels, but no other symptoms. Further treatment caused no increase in LDH. The treatment was very effective and eradicated both urinary BJ protein and bone marrow myeloma cells after 8 sessions of bortezomib administration. These findings suggest that a bortezomib-induced rapid reduction in tumor burden led to tumor lysis syndrome, for which caution is needed when treating myeloma patients with this very effective agent.


Ability of General Dentists and Prosthodontists to Discern and Identify Incremental Increases in Occlusal Vertical Dimension in Dentate Subjects.
The aim of this study was to determine whether dentists are able to discern and identify increases in occlusal vertical dimension (OVD) in dentate subjects without apparent loss of OVD. A total of 10 dentate subjects had mandibular overlays fabricated at 2-, 3-, 4-, and 5-mm openings of the anterior guide pin (AGP) of a semiadjustable articulator. Standardized frontal and profile photographs with subjects wearing each of the overlays were made. Photographs were presented in random order to 40 judges comprising 20 prosthodontists and 20 general dentists who were informed about the purpose of the study. Judges first rated the degree of facial naturalness on a visual analog scale (VAS) and then took a discriminatory sensory analysis test (triangle test) where they were required to correctly identify the image with no increase in OVD from a set of three images. Mean VAS ratings for facial naturalness were inversely correlated with incremental increases in OVD, irrespective of the judge's background. Though subjects were rated less natural with incremental increases in OVD, only a 5-mm increase from baseline was clinically significant (P < .05). For the triangle test, judges correctly identified the image with a 3-mm increase in OVD 57% of the time (P < .582), irrespective of the judge's profession, sex, race, and years in practice, which were clinically insignificant. Increasing OVD by a 5-mm opening of the AGP of the articulator significantly decreased the judge's evaluation of facial naturalness. The ratings were more pronounced in female subjects than in male subjects. However, an increase in OVD of 3 mm was visually indistinguishable by the judges.


Impact of Spectators on a Two-Qubit Gate in a Tunable Coupling Superconducting Circuit.
Cross-resonance (CR) gates have emerged as a promising scheme for fault-tolerant quantum computation with fixed-frequency qubits. We experimentally implement an entangling CR gate by using a microwave-only control in a tunable coupling superconducting circuit, where the tunable coupler provides extra degrees of freedom to verify optimal conditions for constructing a CR gate. By developing a three-qubit Hamiltonian tomography protocol, we systematically investigate the dependency of gate fidelities on spurious qubit interactions and present the first experimental approach to the evaluation of the perturbation impact arising from spectator qubits. Our results reveal that the spectator qubits lead to reductions in CR gate fidelity dependent on ZZ interactions and particular frequency detunings between spectator and gate qubits. The target spectator demonstrates a more serious impact than the control spectator under a standard echo pulse scheme, whereas the degradation of gate fidelity is observed up to 22.5% as both the spectators are present with a modest ZZ coupling to the computational qubits. Our experiments uncover an optimal CR operation regime, and the method we develop here can readily be applied to improving other kinds of two-qubit gates in large-scale quantum circuits.


[A case of myocardial infarction with ventricular tachycardia, which had discrepancy of defect size between 123I-MIBG and 201TlCl myocardial imaging].
123I-MIBG and 201TaCl myocardial imaging were carried out in 69 years-old man who had anterior myocardial infarction with ventricular tachycardia. In planar and SPECT imaging, the defect size of 123I-MIBG was larger compared to that of 201TlCl. The zone of fractionated activity was corresponded with the defect of 123I-MIBG. Thus, the denervated but viable myocardium could be detected by 123I-MIBG and 201TlCl myocardial imaging. 123I-MIBG may give a useful clinical information, since denervation may play a role in causing ventricular arrhythmia after myocardial infarction.


Inhibition of HIV-1 in the central nervous system by IFN-alpha2 delivered by an SV40 vector.
In human immunodeficiency virus type 1 (HIV-1)-infected individuals, virus-induced production of interferon alpha (IFN-alpha) is impaired. In order to obtain regulated expression of IFN-alpha that responds to HIV-1 infection, a recombinant SV40 vector was designed that carries the human IFN-alpha2 cDNA under the control of the HIV-1 long terminal repeat (LTR) (SV[HIVLTR]IFN). Thus, the IFN-alpha2 gene would be trans-activated on infection with HIV-1. This vector was tested to determine if central nervous system (CNS) cell types that may be potential HIV-1 targets could be transduced and protected from HIV. SV[HIVLTR]IFN transduced NT2 cells, a human neuronal precursor cell line, mature neurons derived from NT2 precursor cells, and human primary monocyte-derived macrophages. IFN-alpha2 expression was retained in mature neurons after SV[HIVLTR]IFN-transduced NT2 precursor cells were induced to differentiate using retinoic acid. IFN-alpha expression was detected only after exposing transduced cells to HIV. Furthermore, SV[HIVLTR]IFN-delivered IFN-alpha2 expression significantly inhibited replication of multiple strains of HIV in both NT2 and NT2-derived mature neurons. SV[HIVLTR]IFN transduction also inhibited HIV-1(BaL) replication in human primary monocyte-derived macrophages. Therefore, we have demonstrated the effectiveness of IFN-alpha2, delivered by an SV40 vector driven by HIV-1 LTR as a promoter, to protect several CNS-based, potentially HIV-susceptible cell types. These findings may have implications for therapy of HIV-1 infection in the CNS.


Unique digital skin lesions associated with systemic sclerosis.
A 40-year-old woman with systemic sclerosis presented with multiple, large soft skin lesions with a cystic appearance over the interphalangeal joints of both hands. Aspiration of one of these lesions revealed the presence of a yellowish mucoid material which rapidly reappeared. Surgical dissection and excision of the masses was followed by recurrence a few months later. Pre-operative diagnosis was that of myxoid cysts, but the histological picture was reminiscent of cutaneous focal mucinosis, another form of primary mucinosis. The origin of these unique skin lesions is unclear, but speculation on a possible aetiological relationship between them and systemic sclerosis is presented.


Properties of brodimoprim as an inhibitor of dihydrofolate reductases.
Based on both IC50 and Ki values, brodimoprim (BDP) was often found to be two- to threefold more effective than trimethoprim (TMP) against a great variety of different bacterial dihydrofolate reductases (DHFR). In all cases BDP was found to be a reversible, tight-binding inhibitor. The higher affinity for enzymes relatively insensitive to TMP, like those of Nocardia, which is paralleled by higher in vitro activity, may be therapeutically useful. BDP also often inhibited plasmid-coded, TMP-resistant DHFRs, as well as altered chromosomal TMP-resistant DHFRs at lower concentrations than TMP did, this property, however, being therapeutically irrelevant. A higher affinity was also observed for eucaryotic DHFRs, the specificity, however, remaining similar to that of TMP.


Smart Human-Serum-Albumin-As2 O3 Nanodrug with Self-Amplified Folate Receptor-Targeting Ability for Chronic Myeloid Leukemia Treatment.
Arsenic trioxide (ATO, As2 O3 ) is currently used to treat acute promyelocytic leukemia. However, expanding its use to include high-dose treatment of other cancers is severely hampered by serious side effects on healthy organs. To address these limitations, we loaded ATO onto folate (FA)-labeled human serum albumin (HSA) pretreated with glutathione (GSH) based on the low pH- and GSH-sensitive arsenic-sulfur bond, and we termed the resulting smart nanodrug as FA-HSA-ATO. FA-HSA-ATO could specifically recognize folate receptor-β-positive (FRβ+) chronic myeloid leukemia (CML) cells, resulting in more intracellular accumulation of ATO. Furthermore, the nanodrug could upregulate FRβ expression in CML cancer cells and xenograft tumor model, facilitating even more recruitment and uptake of FRβ-targeting drugs. In vitro and in vivo experiments indicate that the nanodrug significantly alleviates side effects and improves therapeutic efficacy of ATO on CML and xenograft tumor model.


Health in all policies as a priority in Finnish health policy: a case study on national health policy development.
This article describes national level development towards a Health in All Policies approach in Finland over the past four decades. In the early 1970s, improving public health became a political priority, and the need to influence key determinants of health through sectors beyond the health sector became evident. The work began with policy on nutrition, smoking and accident prevention. Intersectoral health policy was developed together with the World Health Organization (WHO). When Finland joined the European Union in 1995, some competencies were delegated to the EU which complicated national intersectoral work. The priority in the EU is economy, but the Constitution's requirement to protect health in all policies gives legal backing for including health consideration in the EU-level work. To promote that, Finland adopted 'Health in All Policies' (HiAP) as the health theme for its EU Presidency in 2006. The intersectoral work on health has developed from tackling single health problems, through large-scale programmes, further to systematic work based on legislation and permanent structures. In the 2000s, work at local level was strengthened by introducing more focused and tighter legislation and by providing expert support for implementation. Recently, emphasis has been on broad objectives and Governmental intersectoral programmes, and actors outside the administrative machinery. Great improvements in the population health have been gained over the past few decades. However, health inequalities across social groups have remained unacceptably large. Major decisions on economic policy with varying impacts by the social groups have been made without health impact assessment, or ignoring assessments conducted.


Metanephric osteopontin regulates nephrogenesis in vitro.
Renal expression of osteopontin is enhanced in the setting of acute ischemic injury. Because of the parallels that exist between recovery from renal ischemia and renal development, we characterized the role that osteopontin plays during metanephrogenesis in the rat. Osteopontin mRNA is present in kidneys obtained from rat embryos as early as embryonic day 13 (E13). Immunohistochemical staining of metanephroi obtained from E16 rat embryos and metanephroi obtained from E13 embryos and cultured for 3 days in vitro demonstrated that osteopontin is expressed both in the developing nephron and in the ureteric bud. Addition of anti-osteopontin antibodies to metanephric organ cultures results in failure of the metanephric blastema to undergo normal tubulogenesis. Addition of the arginine-glycine-aspartic acid-containing peptide, cyclo-RGDfV, or the anti-alpha(v)beta3-integrin antibody, LM609, to cultures has a similar effect. These findings establish that osteopontin is produced within the rat metanephros during development in vivo and suggest that the binding of osteopontin to the alpha(v)beta3-integrin is required for tubulogenesis to occur in vitro. Blastemal cells within metanephroi cultured in the presence of OP199 manifest increased apoptosis compared with controls. It is possible that osteopontin plays an important anti-apoptotic role during the process of metanephric blastema condensation that is a prerequisite for the formation of nephrons in vivo.


Epidemiology of metabolic disorders in the periparturient dairy cow.
The descriptive epidemiology and risk factors were reviewed for six clinical disorders: milk fever, downer cow syndrome, hypomagnesemic tetany, udder edema, left displaced abomasum, and ketosis. Data were included also from preliminary analyses of a data set from approximately 61,000 Finnish Ayrshire cows. A web of postulated associations among the metabolic disorders and other risks factors (previous lactation diseases and milk yield, calf factors, certain dry period nutritional factors, dystocia, retained placenta, and metritis) was diagrammed.


Radioimmunoassay of sisomicin.
An antibody induced in rabbits against a gentamicin-bovine serum albumin conjugate cross-reacted with the chemically related aminoglycoside, sisomicin, facilitating the development of a sisomicin radioimmunoassay. Sisomicin was labeled with (125)I using an acylating agent [3-(4-hydroxyphenyl)propionic acid-N-hydroxy-succinimide ester]. The resulting assay produced a linear standard curve on a logit-log plot with a sensitivity of 140 pg. Comparison with a microbiological assay showed no significant difference (P < 0.001) in the measurement of sisomicin by these two methods.


Can axillary surgery be omitted in patients with breast pathologic complete response after neoadjuvant systemic therapy for breast cancer? A real-world retrospective study in China.
Studies show that axillary surgery can be potentially omitted in certain breast cancer patients who achieve breast pathologic complete response (pCR) after neoadjuvant systemic therapy (NST). However, potential differences between the ypT0 and ypTis subgroups remain to be explored. Furthermore, whether axillary surgery can be omitted in patients with clinically assessed positive axillary lymph nodes (cN+) remains unknown. This study was to evaluate the status of axillary lymph nodes for patients who achieved breast pCR after NST in the real-world study. This retrospective cohort study included 258 patients with early or locally advanced breast cancer who underwent breast and axillary surgery after NST. Clinical and pathologic data were compared between patients with breast pCR (ypT0/is) and those without breast pCR. The rate of breast pCR after NST was 27.1% (70/258). Among the patients with initial cN0, the rate of axillary pCR was similar between the breast pCR and breast non-pCR groups (100% vs. 85.7%, P = 0.1543). Among those with breast pCR, the rate of axillary pCR was 100% in both the ypT0 and ypTis subgroups. Furthermore, among those with initial cN+, the rate of axillary pCR was higher in the breast pCR group than in the breast non-pCR group (82.7% vs. 22.9%, P < 0.0001). Among the patients with breast pCR, the rate of axillary pCR was higher in the ypT0 subgroup than in the ypTis subgroup (94.3% vs. 58.8%, P = 0.0034). Axillary surgery may potentially be omitted in patients with initial cN0 who achieve breast pCR (ypT0/is), and may also be considered for omission in patients with initial cN+ who achieve ypT0 (not ypTis).


Detection of iso-α-acids to confirm beer consumption in postmortem specimens.
Iso-α-acids (IAAs) can be used as markers for the consumption of beer. Postmortem specimens from a range of coronial cases were analyzed for IAAs in order to determine the prevalence of beer consumption and any correlation to blood alcohol concentrations (BAC). A total of 130 cases were included in this study including those where beer was mentioned in the case circumstances, cases where beer was not mentioned specifically but alcohol was detected, and cases where neither beer was mentioned nor a positive BAC was present. Available blood, serum, vitreous humour and urine specimens were analyzed. Of the 50 cases where beer was mentioned, 86% had one or more IAAs detected. In cases that only had a positive BAC (n = 60), 57% of these cases also showed the presence of these beer markers. IAAs were detected in specimens obtained from traumatized, burnt, and decomposed cases with a mention of beer consumption or where BAC was positive in blood. No IAAs were detected in cases where BAC was negative. There was little or no correlation between blood IAA concentrations and BAC. This study demonstrates the possible detection of IAAs as a marker for beer consumption.


Lipopolysaccharide-Stimulated Transglutaminase 2 Expression Enhances Endocytosis Activity in the Mouse Microglial Cell Line BV-2.
In peripheral macrophages, tissue-type transglutaminase (TG2) is reported to be involved in phagocytosis of apoptotic cells. However, the contribution of TG2 to microglial phagocytosis has not been investigated. In this study, using a microglial cell line, BV-2, we examined the changes in TG2 expression, phagocytosis and pinocytosis in cells stimulated by lipopolysaccharide (LPS). Cells of the mouse microglial cell line BV-2 were stimulated by LPS with or without cystamine, an inhibitor of TG enzyme activity, for 24 h. TG2 expression was measured by real-time RT-PCR and Western blotting. TG activity was evaluated using biotinylated pentylamine as a substrate. Pinocytosis was determined by uptake of 1-µm fluorescent microbeads. Phagocytosis was assessed by uptake of dead cells, human neuroblastoma SH-SY5Y cells, which were pretreated with H2O2 for 24 h. Phagocytosis of dead cells and pinocytosis of fluorescent microbeads were up-regulated by LPS stimulation together with TG2 expression. Blockade of TG enzyme activity by cystamine suppressed TG2 expression, phagocytosis and pinocytosis. These results suggested that LPS-induced TG2 was involved in the mechanism of pinocytosis and phagocytosis in microglia.


Condensing non-Abelian quasiparticles.
A most interesting feature of certain fractional quantum Hall states is that their quasiparticles obey non-Abelian fractional statistics. So far, candidate non-Abelian wave functions have been constructed from conformal blocks in cleverly chosen conformal field theories. In this work we present a hierarchy scheme by which we can construct daughter states by condensing non-Abelian quasiparticles (as opposed to quasiholes) in a parent state, and show that the daughters have a non-Abelian statistics that differs from the parent. In particular, we discuss the daughter of the bosonic, spin-polarized Moore-Read state at nu=4/3 as an explicit example.


Competition and health cost containment: cautions and conjectures.
Market approaches based on reformed incentives and newly vigorous competition are increasingly proposed as reliable, preferable alternatives to public regulation in the quest for health care cost containment. Health maintenance organizations (HMOs) are often said to provide both theoretical and empirical support for market approaches and are expected to be important vehicles for the exercise of market forces in a "reformed" health care system. Yet experience in the 1970s with federal efforts to increase the number and enrollment of HMOs suggests that serious problems of organization, expectations, and political interest will arise even in a reformed marketplace.


Successful use of the cell separator hemonetics multicomponent collection system+ for therapeutic thrombocytapheresis in a low body weight child of essential thrombocythemia.
In children, essential thrombocythemia (ET) is extremely rare with an incidence of 1/million. Since thromboembolic complications are more common than hemorrhagic manifestation, immediate thromboctyapheresis by an automated cell separator can prevent untoward consequences in the form of cerebrovascular, coronary or peripheral vascular occlusive events. Due to varied options of automated cell separators, selecting an appropriate cell separator in such acute emergency situation can be confusing for a treating physician, especially if the patient is a child of low body weight. We present here the successful use of hemonetics multicomponent collection system (MCS+) for therapeutic platelet reduction (TPR) in a 12-year-old male child of 28 kg with extreme thrombocytosis (TS) (3072 × 10(9)/l) due to ET. A total of three procedures were performed without priming of the machine with allogenic blood. We observed hemonetics MCS+, best suited for TPR even in children with low body weight.


Breaking the silence: integration of facial disfigurement after surgical treatment for cancer.
Little is known about the psychosocial effects of facial disfigurement. We present the results of a qualitative study following 15 patients who had been surgically treated for head, neck, or eye cancer over the course of their first postoperative year. Taped nurse-patient conversations and individual interviews were analyzed using the grounded theory method. The findings revealed that the main concern of the patients was feeling isolated, which was resolved using a process of interactional integration. Interactional integration begins by breaking the silence to enable the progression from a disfigured person to a person with a disfigurement. The model explains the process of adjustment and demonstrates various elements that could be used in interventions targeting patients who experience psychosocial problems.


Annular elastolytic giant cell granuloma.
Annular elastolytic giant cell granuloma is a granulomatous process that presents as slowly growing annular papules and plaques on sun-exposed skin. It was first described in patients in the fourth and fifth decades of life. These lesions are primarily distributed on the head and neck. A review of the literature shows a preponderance of cases in adults. We report two cases of annular elastolytic giant cell granuloma developing in children under the age of 11 years.


Determination of essential oils composition of blanket-leaf (Stachys byzantina C. Koch.) by microwave assisted extraction coupled to headspace single-drop microextraction.
The composition of essential oils from Stachys byzantina was studied by simple method based on gas chromatography-mass spectrophotometry (GC-MS) following microwave assisted headspace single-drop microextraction (MA-HS-SDME) method. Several parameters affecting MA-HS-SDME such as sample mass, solvent volume, extraction time, microwave power and the nature of extracting solvent were optimised. The MA-HS-SDME method was compared with traditional hydrodistillation (HD) method. Within the study elaborated, thirty-eight components were extracted and identified. Compared with HD, MA-HS-SDME is an easy, rapid and efficient method for the analysis of essential oils in S. byzantina.


Seed Germination and Seed Bank Dynamics of Eruca sativa (Brassicaceae): A Weed on the Northeastern Edge of Tibetan Plateau.
As a versatile cruciferous species, Eruca sativa is widely cultivated, but in some areas, it has become an invasive weed. There are few studies on its seed dormancy and soil seed bank. This research examined seed dormancy, germination, and dynamics of the soil seed bank of E. sativa, with a view to provide support for its prevention and control. We tested the effects of temperature, light, storage, water, and salinity stress on seed germination and burial depth on seedling emergence of E. sativa. Dynamics of the soil seed bank were determined with a 24 month in situ seed-burial study. Seeds of E. sativa can germinate in a temperature range of 5-35°C; moreover, they exhibited non-deep physiological dormancy (NDPD) at maturity, which can be broken by dry storage or exposure to low temperature in winter. Germination of E. sativa seeds was sensitive to water and salinity stress, and most seeds did not germinate at -0.3 MPa. When buried in soil in the field, seeds exhibited an annual dormancy/non-dormancy cycle and formed at least a short-term persistent soil seed bank. Seeds buried deeper than 5 cm can hardly emerge. Seeds of E. sativa have a wide germination temperature range and exhibited dormancy cycling, which promotes the formation of a persistent soil seed bank and enables it to better adapt to the harsh low-temperature climate of the Qinghai-Tibet Plateau. No-tillage would be a good management strategy for this species.


Type IA topoisomerases can be "magicians" for both DNA and RNA in all domains of life.
Topoisomerases solve critical topological problems in DNA metabolism and have long been regarded as the "magicians" of the DNA world. Here we present views from 2 of our recent studies indicating that Type IA topoisomerases from all domains of life often possess dual topoisomerase activities for both DNA and RNA. In animals, one of the 2 Type IA topoisomerases, Top3β, contains an RNA-binding domain, possesses RNA topoisomerase activity, binds mRNAs, interacts with mRNA-binding proteins, and associates with active mRNA translation machinery. The RNA-binding domain is required for Top3β to bind mRNAs and promote normal neurodevelopment. Top3β forms a highly conserved complex with Tudor-domain-containing 3 (TDRD3), a protein known to interact with translation factors, histones, RNA polymerase II, single stranded DNA and RNA. Top3β requires TDRD3 for its association with the mRNA translation machinery. We suggest that Type IA topoisomerases can be "magicians" for not only DNA, but also RNA; and they may solve topological problems for both nucleic acids in all domains of life. In animals, Top3β-TDRD3 is a dual-activity topoisomerase complex that can act on DNA to stimulate transcription, and on mRNA to promote translation.


Self-reported Male Infertility and Metabolic Disturbance: A Cross-Sectional Study.
Male infertility is a growing health problem. It is proposed that infertility is associated with some metabolic abnormalities. This study aimed to examine the prevalence of self-reported male infertility and related metabolic disturbances. This is a cross-sectional analysis of the Tehran Lipid and Glucose Study (TLGS). A total of 1526 males participated in the study. Logistic regression was used to examine metabolic factors associated with self-reported male infertility. The total prevalence of self-reported male infertility was 6.42%. The mean (SD) body mass index (BMI) of participants among fertile and infertile males was 26.80 (3.93) and 26.92 (4.36), respectively. The majority of participants in both groups were in the age group of 40-50 years old. In the fully adjusted model, the odds of infertility were significantly increased by each unit increase in total cholesterol [TC; odds ratio (OR), 1.01; 95% CI, 1.01 - 1.01; P = 0.03] and hip circumference (HC; OR, 1.06; 95% CI, 1.00 - 1.12; P = 0.02), respectively. The prevalence of self-reported male infertility was 6.42%. Male infertility was positively associated with TC and HC, indicating that knowledge about these risks might assist health care professionals and governments in developing and executing measures to change the status quo.


Rhenium-catalyzed insertion of terminal acetylenes into a C-H bond of active methylene compounds.
[reaction: see text] A rhenium complex, [ReBr(CO)(3)(thf)](2), catalyzed the intermolecular reactions of 1,3-dicarbonyl compounds with terminal acetylenes and gave the corresponding alkenyl derivatives in excellent yields. These reactions could apply to an intramolecular version and gave the corresponding cyclic compounds quantitatively.


[Generalized gas gangrene infection with rhabdomyloysis following cholecystectomy].
We report a rare case of spontaneously developing generalised gas gangrene with massive rhabdomyolysis after a cholecystectomy and drainage of a hepatic abscess. On preoperative physical examination the patient appeared severely ill and was icteric and oliguric. Laboratory evaluation showed signs of systemic inflammation, elevated lactate levels, evidence of disseminated intravascular coagulation (DIC), and increased levels of serum creatine kinase (CK) activity. Abdominal ultrasound and endoscopic retrograde cholangiography showed a gallbladder perforation and a hepatic abscess. Cholecystectomy and drainage of the abscess was performed immediately and without technical problems. After postoperative admission to the intensive care unit, the patient showed evidence of generalised myonecrosis with subcutaneous gas formation and acute renal failure. Initially, there were few other signs of systemic toxicity; the patient was not hypotensive and the pulmonary gas exchange was normal. Within hours diffuse swelling of his right leg developed with cutaneous gangrene and a compartment syndrome. After fasciectomy and extensive surgical debridement, uncontrollable bleeding due to DIC developed from the fasciectomy site, which finally required exarticulation of the leg at the hip joint. At this point, multiple organ failure including severe adult respiratory distress syndrome was present. Two days after cholecystectomy, the patient died from hypoxic cardiocirculatory failure. Clostridium perfringens was repeatedly isolated from the wounds. Besides gas gangrene, the differential diagnosis of such infections includes localised clostridial cellulitis, nonclostridial anaerobic cellulitis caused by mixed aerobes and anaerobes, and type I or type II necrotising fasciitis. Patients with systemic necrotising infections should be treated with broad-spectrum antimicrobial regimens (penicillin G, 3rd generation cephalosporins, clindamycin, and aminoglycosides). An otherwise unexplained elevation of serum CK activity in the presence of acute cholecystitis may suggest haematologic spread of an aggressive myolytic agent and the beginning of myonecrosis. This should prompt immediate surgical exploration after establishing broad-spectrum antibiotic coverage. The role of hyperbaric oxygen treatment in this situation remains to be established. If hyperbaric oxygen is to be employed, it should neither delay surgical exploration nor jeopardize the patient with the hazards of an interhospital transport.


Stereospecificity and requirements for activity of the respiratory NADH dehydrogenase of Escherichia coli.
The respiratory NADH dehydrogenase of Escherichia coli has been further amplified in vivo by genetic methods. The enzyme, a single polypeptide of Mr 47 200 of known amino acid sequence [Young, I. G., Rogers, B. L., Campbell, H. D., Jaworowski, A., & Shaw, D. C. (1981) Eur. J. Biochem. 116, 165-170], constitutes 10-15% of the total protein in the amplified membranes. In situ in the membrane, the enzyme contains 1 mol of FAD/mol of subunit and has a specific NADH:ubiquinone-1 oxidoreductase activity of approximately 1100-1200 units mg-1 at 30 degrees C, pH 7.5. The purified enzyme contains phospholipid, which remains closely associated with it during gel filtration on Sephacryl S-300 in the presence of 0.1% (w/v) cholate at low ionic strength. Under these conditions the enzyme is extensively aggregated (apparent Mr greater than 10(6]. This procedure yielded enzyme with a specific activity of 980 units mg-1, similar to the value observed in the membrane. This preparation contained less than 0.1 mol of Fe/mol of enzyme, confirming that Fe is not involved in reduction of ubiquinone 1 catalyzed by the enzyme. Neutron activation analysis of purified enzyme has demonstrated the absence of 35 trace elements including Se, Zn, Mn, Co, W, Cu, and Fe. The enzyme polypeptide, prepared completely free of phospholipid, FAD, and ubiquinone by gel filtration in the presence of sodium dodecyl sulfate, has been reactivated. The results show that the only components necessary for catalysis of ubiquinone-1 reduction by NADH in this system are the enzyme polypeptide, FAD, and phospholipid.(ABSTRACT TRUNCATED AT 250 WORDS)


Evaluation of analytic and clinical performance of thrombin-antithrombin complex and D-dimer assay in prognosis of acute ischemic stroke.
: To evaluate analytic and clinical performance of plasma thrombin-antithrombin complex (TAT) and D-dimer assay in assessing the severity and outcome of acute ischemic stroke. The prospective study was conducted and extended from January 2018 to December 2018. A total of 236 patients admitted within 24 h after neurologic symptoms onset were recruited. The median TAT and D-dimer levels were significantly higher in the acute ischemic stroke patients than in the controls. The average TAT levels in patients with mild, moderately severe and severe stroke were 1.75 [interquartile ranges (IQR), 1.1-2.6], 3.3 (IQR, 1.8-4.5) and 13.5 (IQR, 7.2-15.3) ng/ml. The D-dimer levels of respective patient groups were 0.39 (IQR, 0.22-0.73), 0.58 (IQR, 0.39-1.25) and 3.59 (IQR, 1.73-4.74) mg/l. With the optimal cut-off TAT level (1.75 ng/ml) determined from receiver operating characteristic analysis, the Area under the curve (AUC), the sensitivity and specificity of TAT for stroke diagnosis were 0.763, 58.1 and 87.8%. The cut-off D-dimer level was 0.38 mg/l and the AUC, the sensitivity and specificity were 0.772, 60.2 and 88.9%. The Area under the receiver operating characteristic curves (AUROCs) and sensitivity in the moderate to severe stroke increased to 0.903 and 86.9% for TAT, and 0.880 and 80.3% for D-dimer, respectively. Age and high TAT level were significant independent risk factors for stroke severity. Age, high initial National Institutes of Health Stroke Scale score and high TAT level were significant independent poor prognostic factors on multivariate analysis. TAT and D-dimer were superior in separating the moderate-to-severe stroke than mild stroke. A high TAT plasma level is an independent predictor for stroke severity and poor prognosis during 1-month follow-up.


Comparative first-principles structural and vibrational properties of rutile and anatase TiO2.
The structural and vibrational properties of two polymorphs of TiO2, rutile and anatase, have been investigated by first-principles methods at different levels of exchange-correlational (XC) energy functionals in density functional theory (DFT). Reports in the literature to date are contradictory regarding the stability of the rutile phase using DFT XC-functionals more sophisticated than simple local-density approximation. Here the PBEsol generalized gradient approximation (GGA), TPSS meta-GGA, and HSE06 hybrid functionals have been employed to demonstrate the XC-functional effects on the calculated structural, phonon and thermodynamic properties of rutile and anatase TiO2. Lattice and elastic parameters correctly calculated with these XC-functionals show good agreement with the experimental values. Calculated phonon frequencies generated stable phonon dispersion relations for both rutile and anatase TiO2when correctly converged, in agreement with the experimental observations. The phonon frequencies along high symmetry Brillouin zone paths and their corresponding phonon density of states showed sensitivity to different levels of XC-functional employed in phonon dispersion prediction. Nevertheless, the thermodynamic properties of rutile and anatase TiO2estimated by harmonic approximations are in excellent experimental agreement and are effectively invariant to the level of theory employed in the DFT XC-functional.


The effect of parecoxib sodium combined with perioperative psychological care on postoperative pain in elderly patients with hip fractures.
This study aimed to investigate the effect of parecoxib sodium combined with perioperative psychological nursing on postoperative pain in elderly patients with hip fractures. 80 elderly patients with hip fractures who received surgical treatment in our hospital were selected as the research subjects. According to the different interventions received by the patients, they were divided into a control group (CG) (n=40) who received intravenous parecoxib sodium intervention before surgery, and an observation group (OG) (n=40) who received perioperative psychological nursing intervention in addition to the intervention received by the CG. The pain status, psychological status, hip joint function, daily living ability level, and quality of life of the two groups were compared. After surgery, the VAS score, SAS score and SDS score of the OG were lower than those of the CG (p < 0.05). After surgery, the Harris score of the OG was higher than that of the CG (p < 0.05). Before surgery, there was no significant difference in the Barthel index and SF-36 score between the two groups (p > 0.05). After surgery, the Barthel index and SF-36 scores of both groups showed a significant improvement compared to before surgery, and the scores in the OG were higher than those in the CG (p < 0.05). Perioperative psychological nursing combined with preemptive analgesia of parecoxib sodium has a significant positive effect on elderly patients with hip fractures after surgery. The combined nursing intervention can further alleviate postoperative pain, improve patients' psychological status, promote the recovery of hip joint function, and significantly improve the daily living ability and quality of life of patients. The combined intervention plan is worthy of clinical promotion and application.


Incarcerated native orthotopic kidney through an inguinal hernia: a case report and literature review.
This is a case report of a 66-year-old male with an incarcerated inguinal hernia that contained native orthotopic kidney causing obstructive uropathy. The patient presented to the hospital due to intractable right groin pain, and CT imaging showed herniation of the right kidney in the right inguinal hernia with the upper pole squeezed in the inguinal canal. The patient underwent surgery to reduce the hernia contents and hernia repair with mesh. He was discharged on postoperative day 3 without complication. To the best of our knowledge, this is the first reported case of an incarcerated native orthotopic kidney without anatomic abnormality that had to undergo surgical intervention.


Complete transcriptional map of yeast chromosome XI in different life conditions.
Systematic sequencing of the genome of Saccharomyces cerevisiae has demonstrated the existence of many novel genes, whose functions need to be studied. Entire chromosome sequences also offer the possibility to examine functional properties of the genome at a higher hierarchical level than the genes themselves. We used ordered DNA fragments of chromosome XI to systematically probe yeast DNA and total RNA extracted from MAT a, MAT alpha and diploid cells grown under three different conditions. Taking into account transcript sizes and uniqueness of probes, we attributed 94 transcripts to sequence-predicted open reading frames (ORFs) or tRNA genes; another 83 being tentatively assigned. The remaining 187 ORFs on chromosome XI do not correspond to transcripts detected under our conditions. More than 80% of transcripts are constitutively expressed, others are regulated by medium composition or cell type, the most frequent regulations being determined by carbon source (glycerol/glucose) or rich versus synthetic medium. Moreover, we show that transcript levels and regulation patterns are not statistically different between ORFs of unknown function, which constitute ca. 40% of the total, and previously identified genes (ca. 30%) or their structural homologues.


Relationship of the BCR gene breakpoint and the type of BCR/ABL transcript to clinical course, prognostic indexes and survival in patients with chronic myeloid leukemia.
Chronic myeloid leukemia is characterized by the presence of the Philadelphia chromosome. At the molecular level a fusion of part of the ABL and BCR genes is observed. The breakpoint locations in the BCR gene fall between exons b2a2 or b3a2 (5' and 3', respectively). Depending on the BCR gene breakpoint two types of mRNA are created. Differences in the types of transcripts and/or the breakpoint site may have an influence on the clinical course of the disease. This prompted the present author to separate subtypes of chronic myeloid leukemia on the molecular level. 71 patients diagnosed with chronic myeloid leukemia in the chronic phase were enrolled in the study. In 61 patients the type of BCR/ABL transcript was determined, and in 27 patients BCR breakpoints were established. Possible correlations between the clinical course, prognostic indexes, survival and the type of transcript and breakpoint were examined. No correlation between the clinical course, prognostic index, or survival was observed in patients with 5' and 3' breakpoints. The patients with b3a2 transcript experienced longer survival than the patients expressing b2a2 transcript. However, no significant differences were observed in the duration of the chronic phase between the two groups. The type of BCR gene breakpoint seems to have no prognostic value in patients with chronic myeloid leukemia. The longer survival of patients expressing the b3a2 transcript may be caused by the less aggressive course of the accelerated or blastic phase.


Monitoring galenical process development by near infrared chemical imaging: one case study.
The objective of this study is to evaluate by NIR imaging the homogeneity of process intermediates obtained with different process parameters during the development of a new pharmaceutical solid form. The process under investigation is a solid dosage form based on extrusion. The parameters are two kinds of crystallizations, two sizes of particle of API, two screw speeds during the extrusion and two milling screens used to reduce the extrudates into a granulate form. Two kinds of intermediates are evaluated: the extrudates and the cores. Two approaches are used to analyze the data: the univariate NIR analysis which consists in wavelength selection and multivariate analysis, i.e., Classical Least Squares (CLS), which takes into account the whole spectra. The univariate method reveals good chemical homogeneity of the extrudates but differences in their physical aspect. CLS shows well-distributed excipients for all the cores; differences in the sizes of the granules have also been revealed. The univariate method can be applied on simple chemical systems such as binary mixtures. When complex samples are analyzed, multivariate analysis is the method of choice. This study demonstrates that NIR imaging can be a useful tool for the optimization of the process and for the selection of the final parameters of the process.


Multi-Trajectory Models of Chronic Kidney Disease Progression.
An ever increasing number of people are affected by chronic kidney disease (CKD). A better understanding of the progression ofCKD and its complications is needed to address what is becoming a major burden for health-care systems worldwide. Utilizing a rich data set consisting of the Electronic Health Records (EHRs) of more than 33,000 patients from a leading community nephrology practice in Western Pennsylvania, we applied group-based trajectory modeling (GBTM) in order to detect patient risk groups and uncover typical progressions of CKD and related comorbidities and complications. We have found distinct risk groups with differing trajectories and are able to classify new patients into these groups with high accuracy (up to ≈ 90%). Our results suggest that multitrajectory modeling via GBTM can shed light on the developmental course ofCKD and the interactions between related complications.


Antihypertensives. N-1H-Pyrrol-1-yl-3-pyridazinamines.
The hypothesis that the side effects of hydralazine, such as mutagenicity and lupus erythematosus like syndrome, might be due to the NHNH2 group prompted us to incorporate part of this moiety into a pyrrole ring. Therefore, we prepared a series of N-1H-pyrrol-1-yl-3-pyridazinamines and a limited number of N-1H-pyrrol-1-yl-1-phthalazinamines by reaction of 3-hydrazinopyridazines and 1-hydrazinophthalazines with gamma-diketones. Most of these compounds, especially in the pyridazine series, showed moderate to strong antihypertensive activity in spontaneously hypertensive rats. The decrease in blood pressure generally had a slow onset after either oral or intravenous administration. N-(2,5-Dimethyl-1H-pyrrol-1-yl)-6-(4-morpholinyl)-3-pyridazinamine hydrochloride (30) (MDL 899) showed no mutagenic activity in several tests and is now in clinical trials in patients.


Synthesis and Antiproliferative Activity of Triphenylphosphonium Derivatives of Natural Allylpolyalkoxybenzenes.
Derivatives of natural allylpolyalkoxybenzenes conjugated to triphenylphosphonium (TPP) cations by aliphatic linkers of three, six, seven, and eight atoms were synthesized to examine the role of the polyalkoxybenzene pharmacophore, TPP fragment, and linker length in antiproliferative activities. The key synthetic procedures included (i) hydroboration-oxidation of apiol, dillapiol, myristicin, and allyltetramethoxybenzene; (ii) acylation of polyalkoxybenzyl alcohols or amines; and (iii) condensation of polyalkoxybenzaldehydes followed by hydrogenation and cyclopropyl-homoallyl rearrangement. The targeted TPP conjugates as well as the starting allylbenzenes, the corresponding alkylpolyalkoxybenzenes, and the respective alkyl-TPP salts were evaluated for cytotoxicity in a panel of human cancer cell lines using MTT and Click-iT-EdU assays and in a sea urchin embryo model. The linker of three carbon atoms was identified as favorable for selective cancer cell growth inhibition. Although the propyl-TPP salt was cytotoxic at low micromolar concentrations, the introduction of a polyalkoxybenzene moiety significantly potentiated inhibition of both cell growth and de novo DNA synthesis in several human cancer cell lines, HST-116 colon cancer, A375 melanoma, PC-3 prostate cancer, and T-47D breast carcinoma cells, while it failed to produce any developmental abnormalities in the sea urchin embryos.


Prevalence, clinical characteristics and morbidity of the Asthma-COPD overlap in a general population sample.
Although asthma and chronic obstructive pulmonary disease (COPD) have been regarded as distinct conditions, emerging literature suggests that overlapping phenotypes, called asthma-COPD overlap (ACO), exists. The aim of this study was to describe prevalence, patient characteristics and morbidity of ACO. From a cross-sectional population sample, the West Sweden Asthma Study, subjects with suspected asthma, chronic bronchitis or COPD, and a random sample, were invited to clinical examinations. ACO was defined as doctor-diagnosed asthma, or clear clinical signs of asthma at examination, with a FEV1/FVC < 0.7. Subjects were categorized as ACO (N = 181), COPD only (N = 89), asthma only (N = 651) or healthy (n = 1036) based on clinical examinations. Prevalence of ACO was 3.4% in the random sample (N = 1172) and 18.1% among asthmatics (N = 138) in the random sample. Subjects with ACO (mean age 59 years, 54% women) had an age and gender distribution in between asthma only (45 years, 63% women) and COPD only (62 years, 41% women). Ever-smoking was reported by 71%, 48% and 74% in the ACO, asthma only and COPD only groups, respectively. Subjects with ACO had worse lung function (mean FEV1% of predicted normal 76%) than asthma only (100%) and COPD only (87%) and reported more respiratory symptoms. Also respiratory related emergency visits were more common in ACO compared to asthma only and COPD only, respectively. ACO is present in 3.4% of the population and common among subjects with both asthma and COPD. Subjects with ACO had worse lung function and more symptoms than subjects with asthma or COPD only.


Lithography-Free Planar Band-Pass Reflective Color Filter Using A Series Connection of Cavities.
In this article, a lithography-free multilayer based color filter is realized using a proper series connection of two cavities that shows relatively high efficiency, high color purity, and a wide view angle. The proposed structure is a metal-insulator-metal-insulator-semiconductor (MIMIS) design. To optimize the device performance, at the first step, transfer matrix method (TMM) modeling is utilized to find the right choices of materials for each layer. Simulations are carried out later on to optimize the geometries of the layers to obtain our desired colors. Finally, the optimized devices are fabricated and experimentally characterized to evaluate our modelling findings. The characterization results of the fabricated samples prove the successful formation of efficient and wide view angle color filters. Unlike previously reported FP based designs that act as a band-stop filter in reflection mode (absorbing a narrow frequency range and reflecting the rest of the spectrum), this design generates a specific color by reflecting a narrow spectral range and absorbing the rest of the spectrum. The findings of this work can be extended to other multilayer structures where an efficient connection of cavities in a tandem scheme can propose functionalities that cannot be realized with conventional FP resonators.


Regucalcin expression in bovine tissues and its regulation by sex steroid hormones in accessory sex glands.
Regucalcin (RGN) is a mammalian Ca2+-binding protein that plays an important role in intracellular Ca2+ homeostasis. Recently, RGN has been identified as a target gene for sex steroid hormones in the prostate glands and testis of rats and humans, but no studies have focused on RGN expression in bovine tissues. Thus, in the present study, we examined RGN mRNA and protein expression in the different tissues and organs of veal calves and beef cattle. Moreover, we investigated whether RGN expression is controlled through sex steroid hormones in bovine target tissues, namely the bulbo-urethral and prostate glands and the testis. Sex steroid hormones are still illegally used in bovine husbandry to increase muscle mass. The screening of the regulation and function of anabolic sex steroids via modified gene expression levels in various tissues represents a new approach for the detection of illicit drug treatments. Herein, we used quantitative PCR, western blot and immunohistochemistry analyses to demonstrate RGN mRNA and protein expression in bovine tissues. In addition, estrogen administration down-regulated RGN gene expression in the accessory sex glands of veal calves and beef cattle, while androgen treatment reduced RGN gene expression only in the testis. The confirmation of the regulation of RGN gene expression through sex steroid hormones might facilitate the potential detection of hormone abuse in bovine husbandry. Particularly, the specific response in the testis suggests that this tissue is ideal for the detection of illicit androgen administration in veal calves and beef cattle.


Continuous heart murmur in a 26-year-old woman.
In this report, we describe a continuous murmur heard in a young woman at the beginning of her lactation period, which illustrates a typical example of 'Mammary Souffle', described one century ago. Colour Doppler and pulsed-wave mode echocardiogram allowed to precise, for the first time, the arterial nature of increased systolic and diastolic blood flow in tortuous branches of internal mammary artery, most probably responsible of the murmur, after ruling out any other origin of continuous murmur.


[Cutaneous complications of anti-hypertensive drugs].
Anti-hypertensive drugs are prescribed frequently and can cause cutaneous adverse drug reactions. The extent of this side effect accounts for about 10-60% of the total adverse drug reactions due to antihypertensive drugs. This review analyses anti-hypertensive drugs by class and examines various cutaneous pathologies that could be related to these treatments. We also call attention to the serious and potentially lethal cutaneous complications linked to these drugs.


'I went back to being myself': acceptability of a culturally adapted task-shifted cognitive-behavioural therapy (CBT) treatment for depression (Ziphamandla) for South African HIV care settings.
There is a need for a culturally adapted, evidence-based, psychotherapy treatment that is effective, acceptable, and feasible for integration into primary care in South Africa. This qualitative study used exit interviews to examine participants' experiences of an adapted cognitive-behavioural therapy treatment for adherence and depression, task-shifted and delivered by nurses in two peri-urban HIV clinics near Cape Town. Nine semi-structured exit interviews were conducted with isiXhosa-speaking females and analysed using thematic analysis. Overall, participants responded positively to the treatment, viewing it as acceptable and beneficial and as a catalyst to returning to normalcy. Results indicated that participants viewed the treatment as being effective in ameliorating their depressive symptoms and improving their adherence to ART . Additional benefits described included improvements in subjective wellbeing and social and occupational functioning. Several began or resumed employment, an important behavioural indicator of the treatment's capacity to facilitate positive change and cost saving. Recommendations to improve the treatment included using video material and educating others about depression. These findings have positive implications regarding the acceptability and cultural applicability of the treatment for use in South Africa.


Voltametric determination of vancomycin in dosage forms through treatment with nitrous acid.
Two methods are described for the determination of vancomycin (vancomycin hydrochloride, CAS 1404-93-9) in its dosage forms. The two methods involve a prior treatment with nitrous acid then measuring the formed nitroso derivative, either spectrophotometrically or polarographically. In the spectrophotometric method, the absorbance-concentration plot is rectilinear over the range of 4-32 micrograms/ml with minimum detectability of 2.7 micrograms/ml (1.8 x 10(-6) mol/l). The apparent molar absorptivity is 4.084 x 10(-4)l.mol-1.cm-1 and A (1%, 1 cm) is 275. The reaction product was also found to be polarographically reducible at the Dropping Mercury Electrode (DME) with E1/2 of-0.9 V vs. Ag/AgCl electrode and a diffusion current constant (Id) of 0.85 +/- 0.02. The cathodic current produced was found to be diffusion controlled with some adsorption contribution. The calibration plot was linear over the range of 0.015-0.06 mmol l-1 for direct current (DCt) mode and from 0.005-0.05 mmol l-1 for differential pulse polarography (DPP) mode with minimum detectability of 2.4 x 10(-7) mol l-1 using the latter technique. The results obtained were statistically compared with those given with the official B.P. method and were in good agreement.


What Is the Predictive Value of Animal Models for Vaccine Efficacy in Humans? The Importance of Bridging Studies and Species-Independent Correlates of Protection.
Animal models have played a pivotal role in all stages of vaccine development. Their predictive value for vaccine effectiveness depends on the pathogen, the robustness of the animal challenge model, and the correlates of protection (if known). This article will cover key questions regarding bridging animal studies to efficacy trials in humans. Examples include human papillomavirus (HPV) vaccine in which animal protection after vaccination with heterologous prototype virus-like particles (VLPs) predicted successful efficacy trials in humans, and a recent approval of anthrax vaccine in accordance with the "Animal Rule." The establishment of animal models predictive of vaccine effectiveness in humans has been fraught with difficulties with low success rate to date. Challenges facing the use of animal models for vaccine development against Ebola and HIV will be discussed.


Dynamic contrast-enhanced MR imaging in a phase Ⅱ study on neoadjuvant chemotherapy combining Rh-endostatin with docetaxel and epirubicin for locally advanced breast cancer.
Anti-angiogenesis is a promising therapeutic strategy for locally advanced breast cancer. We performed this phase II trial to evaluate the anti-angiogenesis and anti-tumor effect of rh-endostatin combined with docetaxel and epirubicin in patients with locally advanced breast cancer by dynamic contrast-enhanced magnetic resonance imaging in 70 previously untreated locally advanced breast cancer patients. The study population was randomly assigned to neoadjuvant chemotherapy with docetaxel and epirubicin (neoadjuvant chemotherapy group) or neoadjuvant chemotherapy combining rh-endostatin with docetaxel and epirubicin (neoadjuvant chemotherapy+rh-endostatin group). The anti-angiogenic and anti-tumor effects of both regimens were evaluated by serial dynamic contrast-enhanced magnetic resonance imaging and microvessel density measurements after final surgery. The results suggested a higher clinical objective response (90.9% vs. 67.7%, P = 0.021) and greater reductions in tumor size (67.2% vs. 55.9%, P = 0.000), Ki-67 proliferation index (32.79% vs. 12.47%, P = 0.000), tumor signal enhanced ratio (64% vs. 48%, P = 0.018), and K(trans) (67% vs. 39%, P = 0.026) in neoadjuvant chemotherapy+rh-endostatin group than those in neoadjuvant chemotherapy group. In addition, the microvessel density value in the neoadjuvant chemotherapy+rh-endostatin group was significantly lower than in the neoadjuvant chemotherapy group (18.67 ± 6.53 vs. 36.05 ± 9.64, P = 0.000). Moreover, the microvessel density value was significantly correlated with K(trans) after neoadjuvant chemotherapy+rh-endostatin treatment (r=0.88, P = 0.00). The neoadjuvant chemotherapy+rh-endostatin treatment significantly repressed angiogenesis in locally advanced breast cancer and synergistically enhanced the anti-tumor effect of neoadjuvant chemotherapy. Serial dynamic contrast-enhanced magnetic resonance imaging data including reductions in tumor size and K(trans), could provide non-invasive evaluation for chemotherapeutic efficacy and, consequently, optimization of individual chemotherapy for locally advanced breast cancer patients.


Helicobacter pylori and microRNAs: Relation with innate immunity and progression of preneoplastic conditions.
The accepted paradigm for intestinal-type gastric cancer pathogenesis is a multistep progression from chronic gastritis induced by Helicobacter pylori (H. pylori) to gastric atrophy, intestinal metaplasia, dysplasia and ultimately gastric cancer. The genetic and molecular mechanisms underlying disease progression are still not completely understood as only a fraction of colonized individuals ever develop neoplasia suggesting that bacterial, host and environmental factors are involved. MicroRNAs are noncoding RNAs that may influence H. pylori-related pathology through the regulation of the transcription and expression of various genes, playing an important role in inflammation, cell proliferation, apoptosis and differentiation. Indeed, H. pylori have been shown to modify microRNA expression in the gastric mucosa and microRNAs are involved in the immune host response to the bacteria and in the regulation of the inflammatory response. MicroRNAs have a key role in the regulation of inflammatory pathways and H. pylori may influence inflammation-mediated gastric carcinogenesis possibly through DNA methylation and epigenetic silencing of tumor suppressor microRNAs. Furthermore, microRNAs influenced by H. pylori also have been found to be involved in cell cycle regulation, apoptosis and epithelial-mesenchymal transition. Altogether, microRNAs seem to have an important role in the progression from gastritis to preneoplastic conditions and neoplastic lesions and since each microRNA can control the expression of hundreds to thousands of genes, knowledge of microRNAs target genes and their functions are of paramount importance. In this article we present a comprehensive review about the role of microRNAs in H. pylori gastric carcinogenesis, identifying the microRNAs downregulated and upregulated in the infection and clarifying their biological role in the link between immune host response, inflammation, DNA methylation and gastric carcinogenesis.


Separate and unequal: Structural racism and infant mortality in the US.
We examined associations between state-level measures of structural racism and infant mortality among black and white populations across the US. Overall and race-specific infant mortality rates in each state were calculated from national linked birth and infant death records from 2010 to 2013. Structural racism in each state was characterized by racial inequity (ratio of black to white population estimates) in educational attainment, median household income, employment, imprisonment, and juvenile custody. Poisson regression with robust standard errors estimated infant mortality rate ratios (RR) and 95% confidence intervals (CI) associated with an IQR increase in indicators of structural racism overall and separately within black and white populations. Across all states, increasing racial inequity in unemployment was associated with a 5% increase in black infant mortality (RR=1.05, 95% CI=1.01, 1.10). Decreasing racial inequity in education was associated with an almost 10% reduction in the black infant mortality rate (RR=0.92, 95% CI=0.85, 0.99). None of the structural racism measures were significantly associated with infant mortality among whites. Structural racism may contribute to the persisting racial inequity in infant mortality.


Clausius inequality beyond the weak-coupling limit: the quantum Brownian oscillator.
We consider a quantum linear oscillator coupled at an arbitrary strength to a bath at an arbitrary temperature. We find an exact closed expression for the oscillator density operator. This state is noncanonical but can be shown to be equivalent to that of an uncoupled linear oscillator at an effective temperature T*(eff) with an effective mass and an effective spring constant. We derive an effective Clausius inequality deltaQ*(eff)< or =T*(eff)dS , where deltaQ*(eff) is the heat exchanged between the effective (weakly coupled) oscillator and the bath, and S represents a thermal entropy of the effective oscillator, being identical to the von-Neumann entropy of the coupled oscillator. Using this inequality (for a cyclic process in terms of a variation of the coupling strength) we confirm the validity of the second law. For a fixed coupling strength this inequality can also be tested for a process in terms of a variation of either the oscillator mass or its spring constant. Then it is never violated. The properly defined Clausius inequality is thus more robust than assumed previously.


MRPS17 promotes invasion and metastasis through PI3K/AKT signal pathway and could be potential prognostic marker for gastric cancer.
In this study, the molecular mechanisms through which Mitochondrial Ribosomal Protein S17 (MRPS17) contributes to gastric cancer (GC) and its prognostic significance in GC have been explored. As a protein encoding gene, MRPS17 encodes a 28s proteins belonging the ribosomal protein S17P family. The specific roles and molecular mechanisms of MRPS17 in cancers remain ambiguous. It was revealed by analyzing data from TCGA and GEO that elevated expression of MRPS17 was significantly associated with invasion of GC and poor survival of GC patients. Then through univariate and multivariate Cox regression analyses it was demonstrated that MRPS17 an independent prognostic factor for GC patients (P<0.001). It was demonstrated by differentially expressed gene analysis and functional enrichment analysis that MPRS17 is related to PI3K/AKT pathway and Cell adhesion molecules (CAMs), while its function is mediated by collagen-containing extracellular matrix and receptor ligand/regulator activity. Then it was proven by in-vitro experiments that knocking down of MRPS17 gene in AGS and SGC7901 cells would significantly inhibit proliferation and invasion capability of these cells. Furthermore, it was revealed by cell immunofluorescence assay that as a ribosomalprotein, MRPS17 was mainly distributed in the cytoplasmic surface of cell membrane. Additionally, activation of PI3K/AKT pathway is responsible for malignant progression of glioma that was promoted by MRPS17. In conclusion, it was revealed in the present study that MRPS17 promoted invasion and metastasis of GC and potential molecular mechanisms through which it exerted its influences on GC were explored, suggesting its potential as a novel prognostic biomarker for GC.


Measurement Invariance of the Internet Addiction Test Among Hong Kong, Japanese, and Malaysian Adolescents.
There has been increased research examining the psychometric properties on the Internet Addiction Test (IAT) in different populations. This population-based study examined the psychometric properties and measurement invariance of the IAT in adolescents from three Asian countries. In the Asian Adolescent Risk Behavior Survey (AARBS), 2,535 secondary school students (55.9% girls) aged 12-18 years from Hong Kong (n=844), Japan (n=744), and Malaysia (n=947) completed a survey in 2012-2013 school year. A nested hierarchy of hypotheses concerning the IAT cross-country invariance was tested using multigroup confirmatory factor analyses. Replicating past findings in Hong Kong adolescents, the construct of the IAT is best represented by a second-order three-factor structure in Malaysian and Japanese adolescents. Configural, metric, scalar, and partial strict factorial invariance was established across the three samples. No cross-country differences on Internet addiction were detected at the latent mean level. This study provided empirical support for the IAT as a reliable and factorially stable instrument, and valid to be used across Asian adolescent populations.


Balanced and unbalanced translocations in a multicentric series of 2843 patients with chronic lymphocytic leukemia.
Chromosomal translocations in chronic lymphocytic leukemia (CLL) are very rare, and therefore systematic analysis of large series of cases is needed to allow the identification of recurrent rearrangements, breakpoints involved, and target genes. The aims of the present study were to identify new translocations and their clinical impact and to establish their frequency in a large cohort of 2843 CLL patients. By conventional cytogenetics 250 translocations were identified in 215 (7.5%) patients, 186 (74%) were apparently balanced and 64 (26%) were unbalanced. All chromosomes were involved in translocations, except Y chromosome. The chromosomes more frequently translocated were in decreasing frequency chromosomes 14, 18, 13, 17, 1, 6, 2, 3, 8, and 11. Translocations were found in the karyotypes either as the unique chromosomal abnormality (27%), associated with another alteration (24%), or as a part of a complex karyotype (CK, 48%). A large proportion of rearranged breakpoints involved genes related to CLL such as IGH (14q32), RB1, MIR15A, MIR16-1 (13q14), BCL2 (18q21), IGL (22q11.2), TP53 (17p13), IRF4 (6p25-p23), ATM (11q22), and CDK6 (7q21). Overall, 76 novel CLL translocations were identified, including a recurrent t(8;11)(p21;q21-23). Whole-genome sequencing and/or copy-number microarray data of 24 cases with translocations confirmed all rearrangements, enabled refinement of 3 karyotypes and all breakpoints at gene level. The projected survival and time to first treatment significantly decreased linearly with the number of translocations. In summary, this study allowed to establish the frequency of translocations (7.5%) and to identify new translocations in a cohort of 2843 CLL patients.