Serum Phospholipid Fatty Acids and Mammographic Density in Premenopausal Women.
The role of fatty acids (FAs) on mammographic density (MD) is unclear, and available studies are based on self-reported dietary intake. This study assessed the association between specific serum phospholipid fatty acids (PLFAs) and MD in premenopausal women. The cross-sectional study DDM-Madrid recruited 1392 Spanish premenopausal women, aged 39-50 y, who attended a screening in a breast radiodiagnosis unit of Madrid City Council. Women completed lifestyle questionnaires and FFQs. Percentage MD was estimated using a validated computer tool (DM-Scan), and serum PLFA percentages were measured by GC-MS. Multivariable linear regression models were used to quantify the association of FA tertiles with MD. Models were adjusted for age, education, BMI, waist circumference, parity, oral contraceptive use, previous breast biopsies, and energy intake, and they were corrected for multiple testing. Women in the third tertile of SFAs showed significantly higher MD compared with those in the first tertile (βT3vsT1 = 7.53; 95% CI: 5.44, 9.61). Elevated relative concentrations of palmitoleic (βT3vsT1 = 3.12; 95% CI: 0.99, 5.25) and gondoic (βT3vsT1 = 2.67; 95% CI: 0.57, 4.77) MUFAs, as well as high relative concentrations of palmitelaidic (βT3vsT1 = 5.22; 95% CI: 3.15, 7.29) and elaidic (βT3vsT1 = 2.69; 95% CI: 0.59, 4.79) trans FAs, were also associated with higher MD. On the contrary, women with elevated relative concentrations of n-6 (ω-6) linoleic (βT3vsT1 = -5.49; 95% CI; -7.62, -3.35) and arachidonic (βT3vsT1 = -4.68; 95% CI: -6.79, -2.58) PUFAs showed lower MD. Regarding desaturation indices, an elevated palmitoleic to palmitic ratio and a low ratio of oleic to steric and arachidonic to dihomo-γ-linolenic acids were associated with higher MD. Spanish premenopausal women with high relative concentrations of most SFAs and some MUFAs and trans FAs showed an increased MD, whereas those with high relative concentrations of some n-6 PUFAs presented lower density. These results, which should be confirmed in further studies, underscore the importance of analyzing serum FAs individually.


SGLT2 inhibition in a kidney with reduced nephron number: modeling and analysis of solute transport and metabolism.
Sodium-glucose cotransporter 2 (SGLT2) inhibitors enhance urinary glucose, Na+ and fluid excretion, and lower hyperglycemia in diabetes by targeting Na+ and glucose reabsorption along the proximal convoluted tubule. A goal of this study was to predict the effects of SGLT2 inhibitors in diabetic and nondiabetic patients with chronic kidney disease. To that end, we employed computational rat kidney models to explore how SGLT2 inhibition affects renal solute transport and metabolism when nephron populations are normal or reduced. Model simulations suggested that in a nondiabetic rat, acute and chronic SGLT2 inhibition induces glucosuria, diuresis, natriuresis, and kaliuresis. Those effects were stronger with chronic SGLT2 inhibition (due to SGLT1 downregulation) and tempered by nephron loss. In a diabetic rat with normal nephron number, acute SGLT2 inhibition similarly elevated urine fluid, Na+, and K+ excretion, whereas the urinary excretory effects of chronic SGLT2 inhibition were attenuated in proportion to its plasma glucose level lowering effect. Nephron loss in a diabetic kidney was predicted to lower the glucosuric and blood glucose-reducing effect of chronic SGLT2 inhibition, but due to the high luminal glucose delivery in the remaining hyperfiltering nephrons, nephron loss enhanced proximal tubular paracellular Na+ secretion, thereby augmenting the natriuretic, diuretic, and kaliuretic effects. A proposed shift in oxygen-consuming active transport to the outer medulla, which may simulate systemic hypoxia and enhance erythropoiesis, was also preserved with nephron loss. These effects may contribute to the protective effects of SGLT2 inhibitors on blood pressure and heart failure observed in diabetic patients with chronic kidney diseases.


A first near real-time seismology-based landquake monitoring system.
Hazards from gravity-driven instabilities on hillslope (termed 'landquake' in this study) are an important problem facing us today. Rapid detection of landquake events is crucial for hazard mitigation and emergency response. Based on the real-time broadband data in Taiwan, we have developed a near real-time landquake monitoring system, which is a fully automatic process based on waveform inversion that yields source information (e.g., location and mechanism) and identifies the landquake source by examining waveform fitness for different types of source mechanisms. This system has been successfully tested offline using seismic records during the passage of the 2009 Typhoon Morakot in Taiwan and has been in online operation during the typhoon season in 2015. In practice, certain levels of station coverage (station gap < 180°), signal-to-noise ratio (SNR ≥ 5.0), and a threshold of event size (volume >106 m3 and area > 0.20 km2) are required to ensure good performance (fitness > 0.6 for successful source identification) of the system, which can be readily implemented in other places in the world with real-time seismic networks and high landquake activities.


Premature ejaculation: A clinical review for the general physician.
Premature ejaculation is one of the most common sexual dysfunctions in men. Recent epidemiological studies suggest its prevalence in Australia may range from 21-31% This article will discuss the current definition of premature ejaculation from a urological perspective. It will provide an understanding of the pathogenesis of premature ejaculation, as well as assessment and management options. Premature ejaculation can have a significant adverse effect on the quality of life for the patient and his sexual partners. It can potentially lead to psychological distress, diminished self- esteem, anxiety, erectile dysfunction, reduced libido and poor interpersonal relationships. Most men feel reluctant to discuss premature ejaculation with their general practitioner despite its psychological, emotional and relational effects. Effective, evidence-based treatment options are available and physicians should feel confident when exploring ways to improve the quality of life for men with sexual dysfunction.


Compensation of birefringence in active elements with a novel Faraday mirror operating at high average power.
A decrease in the depolarization ratio by more than one order of magnitude by use of a recently proposed Faraday mirror (FM) in comparison with the traditional FM has been demonstrated experimentally. At a high average laser power, the possibility of an increase in the accuracy of compensation of depolarization in the active element by means of a lambda/4 plate with both the traditional and the novel FM is shown.


Long Noncoding RNA lncSHGL Recruits hnRNPA1 to Suppress Hepatic Gluconeogenesis and Lipogenesis.
Mammalian genomes encode a huge number of long noncoding RNAs (lncRNAs) with unknown functions. This study determined the role and mechanism of a new lncRNA, lncRNA suppressor of hepatic gluconeogenesis and lipogenesis (lncSHGL), in regulating hepatic glucose/lipid metabolism. In the livers of obese mice and patients with nonalcoholic fatty liver disease, the expression levels of mouse lncSHGL and its human homologous lncRNA B4GALT1-AS1 were reduced. Hepatic lncSHGL restoration improved hyperglycemia, insulin resistance, and steatosis in obese diabetic mice, whereas hepatic lncSHGL inhibition promoted fasting hyperglycemia and lipid deposition in normal mice. lncSHGL overexpression increased Akt phosphorylation and repressed gluconeogenic and lipogenic gene expression in obese mouse livers, whereas lncSHGL inhibition exerted the opposite effects in normal mouse livers. Mechanistically, lncSHGL recruited heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) to enhance the translation efficiency of CALM mRNAs to increase calmodulin (CaM) protein level without affecting their transcription, leading to the activation of the phosphatidyl inositol 3-kinase (PI3K)/Akt pathway and repression of the mTOR/SREBP-1C pathway independent of insulin and calcium in hepatocytes. Hepatic hnRNPA1 overexpression also activated the CaM/Akt pathway and repressed the mTOR/SREBP-1C pathway to ameliorate hyperglycemia and steatosis in obese mice. In conclusion, lncSHGL is a novel insulin-independent suppressor of hepatic gluconeogenesis and lipogenesis. Activating the lncSHGL/hnRNPA1 axis represents a potential strategy for the treatment of type 2 diabetes and steatosis.


Mutations which affect the structure and activity of colicin E3.
Among 69 ColE3 mutant plasmids selected on the basis of their inability to produce an active colicin, seven (cop-1 to cop-7) were found to bear a mutation affecting the structural gene for colicin. Three of these (cop-1, cop-2 and cop-3) lead to the production of an inactive colicin molecule which has the same molecular weight as wild-type colicin E3 (67,000). These three inactive colicins are still able to interact with the outer membrane receptor. The cop-1 protein retained the ability to inhibit protein synthesis in vitro and therefore seems specifically affected in it ability to penetrate the cell envelope. The cop-2 and cop-3 proteins lost the ability to inhibit protein synthesis in vitro, and activity which is normally associated with the C-terminal part of the colicin molecule. On the basis of this and further evidence, it is suggested that the cop-2 and cop-3 mutations affect the structure of the C-terminal part of the colicin molecule. The other four mutations (cop-4 to cop-7) lead to the production of colicin-related polypeptides of lower molecular weight (29,000 to 45,000) which display a reaction of partial immunological identity with wild-type colicin. These four polypeptides are unable to interact with the cell surface receptor. Three of these mutants are shown to carry a nonsense mutation.


The pivotal role of small non-coding RNAs in the regulation of seed development.
Seeds represent a crucial stage of the seed plants life cycle. It is during seed development that the foundations of the future plant body, and the ability to give rise to a new plant capable of growing under sometimes adverse environmental conditions, are established. Small non-coding RNAs are major regulators of gene expression both at the post-transcriptional and transcriptional levels and, not surprisingly, these elements play major roles in seed development and germination. We review here the current knowledge about small RNA expression and functions in seed development, going from the morphogenesis phase comprehending embryo development and patterning, to the several steps of the maturation phase, ending in the transition to the germination. A special focus is given to the small RNAs for which functional studies have been conducted and their participation in regulatory networks operating in seeds. Many challenges remain ahead for dissecting the complex small RNA landscape in seeds, but this is a highly relevant issue in plant biology and advances in this area will most certainly impact plant breeding.


Sub-inhibitory concentrations of gentamicin triggers the expression of aac(6')Ie-aph(2″)Ia, chaperons and biofilm related genes in Lactobacillus plantarum MCC 3011.
The study aimed to analyze the effects of sub-inhibitory concentrations of gentamicin on the expressions of high level aminoglycoside resistant (HLAR) bifunctional aac(6')Ie-aph(2″)Ia, biofilm and chaperone genes in Lactobacillus plantarum. The analysis of the biofilm formation in five isolates obtained from chicken sausages indicated their role in exhibiting phenotypic resistance based on the varied MIC values despite carrying the bifunctional gene. The biofilm formation significantly increased when L. plantarum MCC 3011 was grown in sub-inhibitory concentrations of gentamicin (4 μg/ml), kanamycin (8 μg/ml) and streptomycin (2 μg/ml). Thirty day gentamicin selection increased minimum inhibitory concentration (MIC) values from 4 to 64 and 2 to 256 fold for gentamicin and kanamycin, respectively when compared to the parental cultures. Expression studies revealed that constant exposure to gentamicin had induced chaperon [groEL] and the bifunctional gene, aac(6')Ie-aph(2″)Ia upto nine fold. Induction of groEL, groES and lamC genes in gentamicin (4 μg/ml) preincubated MCC 3011 indicated their significant role in aminoglycoside mediated response. Our study indicates that constant exposure to sub inhibitory concentrations of gentamicin allows L. plantarum to adapt against higher doses of aminoglycosides. This highlights the risks and food safety issues associated with the use of aminoglycosides in livestock and consumption of farm oriented fermented food products.


Cardiovascular recovery following bariatric surgery in extremely obese adolescents: preliminary results using Cardiac Magnetic Resonance (CMR) Imaging.
Baseline cardiovascular characteristics and longitudinal changes following weight loss surgery (WLS) in adolescents are not well defined. Recent data suggest that the use of transthoracic echocardiography (TTE) for preoperative cardiac assessment may provide suboptimal imaging fidelity secondary to excessive upper body adiposity. High fidelity imaging using cardiac magnetic resonance (CMR) is an extremely useful diagnostic tool. We report the use of CMR in a cohort of extremely obese adolescents undergoing WLS. A retrospective analysis of adolescent WLS patients at a single institution was conducted. Data collection included mean age, sex, body mass index (BMI), and CMR measurements of left ventricular (LV) mass, LV end-diastolic volume (LVEDV), ejection fraction (EF), and myocardial perfusion reserve index (MPRI). Comparison of CMR results to normative data derived from lean subjects was performed. Ten subjects (9 female), with a mean age and BMI of 17.4 ± 1.9 years and 50.33 ± 10.21 kg/m(2) respectively, were studied. When compared to age, gender, and height matched normal weight (NW) controls, the obese (OB) subjects had evidence of increased LV mass (122 ± 25 g vs. 101 ± 10 g, OB vs. NW respectively, p<0.05), and increased LVEDV (156 ± 25 mL vs. 109 ± 9 mL, p<0.05), with an average EF of 61.5% ± 5% (range 52% to 67% vs. 71% to 74% expected EF for males and females, respectively, p=0.003). In addition, 60% of the OB subjects (6/10) demonstrated adenosine-induced sub-endocardial ischemia at baseline, the majority of whom underwent WLS (n=5) resulting in complete normalization of ischemia in 60% (3/5) and partial improvement in 40% (2/5). A reduction in mean LV mass (range 2 to 12 g) following WLS was observed. Extreme adolescent obesity is associated with significant cardiovascular abnormalities that include LV hypertrophy (i.e. increased LV mass) and LV dilatation. These findings, considered to be well-recognized cardiovascular disease risk factors in adults, were shown to be reversible after WLS in the small group of subjects studied here. Additional large-scale investigations designed to examine obesity-related cardiovascular disease in severely obese adolescents are required.


[A case of carcinoma associated with anal fistula effectively treated with preoperative chemoradiotherapy].
A 60-year-old man presented with anal pain. He was diagnosed as having perianal abscess and carcinoma associated with anal fistula. We performed chemoradiotherapy (radiation, total 50.4 Gy; capecitabine 2,000 mg/m2) followed by chemotherapy( XELOX, 2 courses: capecitabine 2,000 mg/m2, oxaliplatin 130 mg/m2). After chemoradiotherapy, the tumor significantly reduced in size. Laparoscopic abdominoperineal resection of the rectum, extended resection of the perianal region, and reconstruction of the perianal skin defect using a rectus abdominis musculocutaneous flap were performed. Histopathologically, the tumor was classified as tub2, pMP, ly0, v0, pN0 (0/3), pStage I, and the therapeutic efficacy was classified as Grade 2. Chemoradiation appears to be effective for the treatment of carcinomas associated with anal fistula.


Thermal stability of porcine circovirus type 2 in cell culture.
International trade in pig meat has resulted in some countries placing restrictions on the importation of pig meat, with requirements for cooking of imported meat to destroy viral agents. This study investigated the in vitro resistance of an Australian strain of porcine circovirus type 2 (PCV2), the causative agent of post-weaning multisystemic wasting syndrome (PMWS), to heat treatment. The viability of the virus in cell cultures was determined by a combination of reverse transcriptase polymerase chain reaction (RT-PCR) to detect viral transcripts, and immunohistochemistry (IHC) to visualize viral capsid antigen. PCV2 retained infectivity when heated at 75 degrees C for 15 min but was inactivated by heating at 80 degrees C and above for 15 min. The results provide important information on the thermal tolerance of PCV2, which can be taken into account in risk assessments for trade in pig meat and porcine-derived biological products.


Modification of TiO2 by Bimetallic Au-Cu Nanoparticles for Wastewater Treatment.
Au, Cu and bimetallic Au-Cu nanoparticles were synthesized on the surface of commercial TiO2 compounds (P25) by reduction of the metal precursors with tetrakis (hydroxymethyl) phosphonium chloride (THPC) (0.5 % in weight). The alloyed structure of Au-Cu NPs was confirmed by HAADF-STEM, EDS, HRTEM and XPS techniques. The photocatalytic properties of the modified TiO2 have been studied for phenol photodegradation in aqueous suspensions under UV-visible irradiation. The modification by the metal nanoparticles induces an increase in the photocatalytic activity. The highest photocatalytic activity is obtained with Au-Cu/TiO2 (Au/Cu 1:3). Their electronic properties have been studied by time resolved microwave conductivity (TRMC) to follow the charge-carrier dynamics. TRMC measurements show that the TiO2 modification with Au, Cu and Au-Cu nanoparticles plays a role in charge-carrier separations increasing the activity under UV-light. Indeed, the metal nanoparticles act as a sink for electron, decreasing the charge carrier recombination. The TRMC measurements show also that the bimetallic Au-Cu nanoparticles are more efficient in electron scavenging than the monometallic Au and Cu ones.


Surgical Outcomes Post Neoadjuvant Chemotherapy in Stage IV cancers of Oral Cavity.
To know the effect of neoadjuvant chemotherapy on surgical outcomes (R1 resections, post-operative complications, recurrence and follow up) in Stage IV borderline operable cancers of oral cavity. Patients in group A (n=45) were those who were referred for neoadjuvant chemotherapy (NACT) with an intention to operate at a later date. These were compared with 45 patients of group B who were operated upfront. All 90 patients have stage IV squamous cell carcinoma of oral cavity. Details of patients were studied retrospectively from hospital records of surgical, medical, radiotherapy and pathology departments. All patients referred for NACT were wet lesions with perilesional edema and diffuse margins of lesions where the demarcation from normal tissue was not clear. Treatment response was assessed clinically and radiologically. Any reduction in tumor size on CT scan, MRI or clinically was considered response to chemotherapy. Various chemotherapy regimens were given in different patients - TPF (Taxol- Docetaxel or Paclitaxel, Cisplatin, 5 Fluoro Uracil), PMF (Cisplatin, Mitomycin C, 5 Fluoro Uracil), Cisplatin + Methotrexate and Cisplatin with 5 Fluoro Uracil. Inoperability was defined as involvement of the upper infratemporal fossa where R0 resection was difficult. Patients were followed up monthly after completion of treatment for one year and three monthly thereafter. Survival was calculated from the day of surgery to the death of the patient or last patient contact. The time of recurrence was also calculated from the day of surgery. Statistical methods used in the study were simple frequencies and proportion. Test of significance was Z test. Z = 2 was considered significant. Kaplan Meir survival analysis was used through SPSS software for disease free survival Results: Total 39 patients were operated in group A as remaining six progressed to inoperability while on chemotherapy. There were 3 R1 resections in group A and 9 R1 resections in group B (Z= 1.67). Eleven and three postoperative complications in group A and B respectively (Z= 2.67). There were nine and 16 recurrences so far in group A and B respectively (Z=1.27). DFS at one year was 90% and 55% respectively (p= 0.017). Though the study shows a trend in favor of NACT when R1 resections, recurrences and survival at one year are considered but this was at the cost of those six patients who progressed on NACT and could have been operated initially. Such patients were present in each and every subset of chemotherapy used.


Prospective investigation of the effects of socioeconomic disadvantage, life stress, and social support on early adolescent adjustment.
In this prospective study, we investigated the effects of socioenvironmental conditions on adjustment during early adolescence. Participants (N = 339) were assessed at the beginning of the school year and at follow-up approximately 7 months later. Both stressful events and social support made significant contributions to the prediction of psychological distress and conduct problems at follow-up, controlling for initial levels of adjustment in each of these areas. Conditions related to socioeconomic disadvantage predicted poorer academic performance and higher levels of absences and disciplinary problems at school. Youths who experienced multiple conditions of socioeconomic disadvantage were found to demonstrate heightened vulnerability to stressful events (daily hassles) as well as a greater potential to benefit from social support received from adults in the school setting.


Investigating conformational stability of bovine pancreatic phospholipase A2: a novel concept in evaluating the contribution of the 'native-framework' of disulphides to the global conformational stability of proteins.
Bovine pancreatic PLA(2) (phospholipase A(2)) is a 14 kDa protein whose structure is highly cross-linked by seven disulphide bonds. We investigated the structural stability of this enzyme by the method of 'disulphide-scrambling' with denaturants such as urea, GdmCl (guanidine hydrochloride), GdmSCN (guanidine thiocyanate) and at high temperatures in the presence of 2-mercaptoethanol (0.2 mM) as thiol initiator. Reverse-phase HPLC was used to follow denaturation. To denature 50% of the native protein, 1.25 M GdmSCN, approx. 3 M GdmCl and higher than 8 M urea were required. Only 20% of the protein was denatured after 2 h at 60 degrees C, whereas complete denaturation was seen after 2 h at 70 degrees C and within 30 min at 80 degrees C. A distinct enhancement of stability was observed when denaturation was conducted in the presence of 10 mM calcium chloride, which has not been reported previously. CD studies of GdmCl denaturation of bovine PLA(2) showed that 2.5 M GdmCl was required to denature 50% of the protein in the presence of 0.2 mM 2-mercaptoethanol (in agreement with the HPLC analysis), whereas 6.4 M GdmCl was necessary to denature 50% of the protein in the absence of a thiol initiator. Conformational stability (Delta G (water)) was estimated to be 8.7 kcal/mol (1 cal=4.184 J) by 'disulphide-intact' denaturation (where 'native' disulphide framework was unaffected) and 2.5 kcal/mol by 'disulphide-scrambling' denaturation (involved breaking of native disulphides and formation of 'non-native' ones). The difference, Delta(Delta G (water)), of 6.2 kcal/mol was the conformational stability contributed by the 'native-framework' of seven disulphides. Using bovine PLA(2) as an example, we have demonstrated a novel comparative technique, where the conformational stability study of a disulphide-containing protein, with a common denaturant, in both the presence and absence of catalytic amounts of a thiol initiator can be used as a convenient method to estimate selectively and quantitatively the actual contribution of the 'native disulphide bond network' towards the global conformational stability of the protein.


Comparative computational analysis of prion proteins reveals two fragments with unusual structural properties and a pattern of increase in hydrophobicity associated with disease-promoting mutations.
Prion diseases are a group of neurodegenerative disorders associated with conversion of a normal prion protein, PrPC, into a pathogenic conformation, PrPSc. The PrPSc is thought to promote the conversion of PrPC. The structure and stability of PrPC are well characterized, whereas little is known about the structure of PrPSc, what parts of PrPC undergo conformational transition, or how mutations facilitate this transition. We use a computational knowledge-based approach to analyze the intrinsic structural propensities of the C-terminal domain of PrP and gain insights into possible mechanisms of structural conversion. We compare the properties of PrP sequences to those of a PrP paralog, Doppel, and to the distributions of structural propensities observed in known protein structures from the Protein Data Bank. We show that the prion protein contains at least two sequence fragments with highly unusual intrinsic propensities, PrP(114-125) and helix B. No segments with unusual properties were found in Doppel protein, which is topologically identical to PrP but does not undergo structural rearrangements. Known disease-promoting PrP mutations form a statistically significant cluster in the region comprising helices B and C. Due to their unusual properties, PrP(114-125) and the C terminus of helix B may be considered as primary candidates for sites involved in conformational transition from PrPC to PrPSc. The results of our study also show that most PrP mutations associated with neurodegenerative disorders increase local hydrophobicity. We suggest that the observed increase in hydrophobicity may facilitate PrP-to-PrP or/and PrP-to-cofactor interactions, and thus promote structural conversion.


Crystal growth of La2/3-x Li3x TiO3 by the TSFZ method.
Double-perovskite-type La2/3-x Li3x TiO3 (LLT) crystals were grown by the travelling solvent floating zone (TSFZ) method. When the floating zone (FZ) crystal growth method was applied, the La2Ti2O7 phase was deposited as an inclusion in the initial growth region. Using the TSFZ crystal growth method, however, inclusion-free LLT crystals were obtained for a 10 mol% La2Ti2O7-poor composition solvent relative to the stoichiometric LLT crystals. The molten zone was initially unstable as a result of habit plane formation during the crystal growth; however, the molten zone was stably maintained for a long period of time by decreasing the feed rate compared with the growth rate. Hence, LLT crystals of approximately 5 mmφ and 37 mm in length were obtained. The anisotropic ionic conductivity of the crystals annealed in air was σ[110]/σ[001] ≈ 3, with σ[110] = 1.64 × 10-3 S cm-1 and σ[001] = 5.26 × 10-4 S cm-1. LLT single crystals are candidates for high-performance solid-state electrolytes in all-solid-state Li ion batteries.


Advances in antimicrobial hydrogels for dental tissue engineering: regenerative strategies for endodontics and periodontics.
Dental tissue infections have been affecting millions of patients globally leading to pain, severe tissue damage, or even tooth loss. Commercial sterilizers may not be adequate to prevent frequent dental infections. Antimicrobial hydrogels have been introduced as an effective therapeutic strategy for endodontics and periodontics since they have the capability of imitating the native extracellular matrix of soft tissues. Hydrogel networks are considered excellent drug delivery platforms due to their high-water retention capacity. In this regard, drugs or nanoparticles can be incorporated into the hydrogels to endow antimicrobial properties as well as to improve their regenerative potential, once biocompatibility criteria are met avoiding high dosages. Herein, novel antimicrobial hydrogel formulations were discussed for the first time in the scope of endodontics and periodontics. Such hydrogels seem outstanding candidates especially when designed not only as simple volume fillers but also as smart biomaterials with condition-specific adaptability within the dynamic microenvironment of the defect site. Multifunctional hydrogels play a pivotal role against infections, inflammation, oxidative stress, etc. along the way of dental regeneration. Modern techniques (e.g., 3D and 4D-printing) hold promise to develop the next generation of antimicrobial hydrogels together with their limitations such as infeasibility of implantation.


SIFT web server: predicting effects of amino acid substitutions on proteins.
The Sorting Intolerant from Tolerant (SIFT) algorithm predicts the effect of coding variants on protein function. It was first introduced in 2001, with a corresponding website that provides users with predictions on their variants. Since its release, SIFT has become one of the standard tools for characterizing missense variation. We have updated SIFT's genome-wide prediction tool since our last publication in 2009, and added new features to the insertion/deletion (indel) tool. We also show accuracy metrics on independent data sets. The original developers have hosted the SIFT web server at FHCRC, JCVI and the web server is currently located at BII. The URL is http://sift-dna.org (24 May 2012, date last accessed).


Gastrointestinal symptoms associated with enteric-coated sulfasalazine (Azulfidine EN tablets).
Abstract To investigate both the incidence and the dosage used to treat gastrointestinal (GI) symptoms associated with enteric-coated sulfasalazine (Azulfidine EN, AZL) in patients with rheumatoid arthritis (RA), we studied the clinical history of 153 RA patients, and any available data on GI symptoms that might have been associated with AZL. GI symptoms appeared in 64 (42.5%) of the 153 cases. There were 19 events of nausea, vomiting, or dyspepsia, 14 events each of epigastric discomfort and reduction or loss of appetite, 10 events of epigastric, stomach, or abdominal pain, 9 events of heartburn, 8 events of mouth ulcer, 3 events each of loss of taste and abdominal bloating or borborygmus, 2 events each of diarrhea or loose stools, hematemesis or melanemia, and gastric or esophageal ulcer, and 1 event of stomatitis. These results indicate that GI symptoms associated with AZL are usually mild and treatment can continue, with almost all cases responding to a reduction in dose or drug cessation. In some cases, a histamine receptor-2 blocker or proton pump inhibitor is also required.


Transcatheter Aortic Valve Implantation Versus Surgical Aortic Valve Replacement: A Systematic Review and Meta-analysis.
The comparative benefits and harms of transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) for patients with aortic stenosis are unclear. To compare clinical outcomes, including early (≤30-day) and midterm (≤1-year) mortality, in adults with severe aortic stenosis undergoing either TAVI or SAVR. MEDLINE, Cochrane, and Scopus databases (without language restrictions) from April 2002 to 5 April 2016; multiple registries and Web sites; scientific meeting presentations. Five randomized trials and 31 observational matched studies comparing mortality outcomes after TAVI or SAVR. Two investigators independently extracted study data and rated risk of bias. 16 638 patients were analyzed. Overall, there was no statistically significant difference between TAVI and SAVR in early (odds ratio [OR], 1.01 [95% CI, 0.81 to 1.26]) or midterm (OR, 0.96 [CI, 0.81 to 1.14]) all-cause mortality. Analyses restricted to trials (early: OR, 0.80 [CI, 0.51 to 1.25]; midterm: OR, 0.90 [CI, 0.64 to 1.26]) were inconclusive, with wide CIs, whereas analyses of matched studies were similar to the overall results. Transfemoral TAVI provided mortality benefits over SAVR in trials. Analyses restricted to studies of patients at low to intermediate risk showed statistically nonsignificant reductions in early (OR, 0.67 [CI, 0.42 to 1.07]) and midterm (OR, 0.91 [CI, 0.67 to 1.23]) mortality with TAVI. Incidence of periprocedural myocardial infarction, major bleeding, acute kidney injury, and new-onset atrial fibrillation was lower with TAVI, but risk for pacemaker implantation, vascular complications, and paravalvular leak increased. Overall, there was a statistically nonsignificant increased risk in long-term (2- to 5-year) all-cause mortality with TAVI (OR, 1.28 [CI, 0.97 to 1.69]), whereas long-term mortality outcomes in patients at low to intermediate risk were inconclusive, with wide CIs (OR, 1.06 [CI, 0.59 to 1.91]). The number of trials was limited, and study designs and patient characteristics were heterogeneous. Compared with SAVR, TAVI may have similar or better early and midterm outcomes for adults with aortic stenosis, including those at low to intermediate risk. None.


The unwary purchaser: consumer psychology and the regulation of commerce in America.
Starting in the 1870s, American jurists deciding cases of trademark infringement began advancing arguments that the ordinary purchaser was an unwary one, easily deceived by imitations. Embedded within their legal decisions was a vision of the typical consumers' habitual behavior and cognitive ability. In response to legal critics who argued that the presumed psychology of the consumer was unevenly deployed, applied psychologists developed laboratory-based experiments and scales for determining the likelihood that the "average" purchaser would be confused. Although these psychologists failed in their goal of securing regular legal patronage, this commercial context and the resulting experiments were constitutive of the delineation of "recognition" as a distinct mental process. Furthermore, this case study complicates the scholarly consensus about the role of standardization and personal responsibility in the liberal administration of mass society.


Long-term safety and efficacy of veverimer in patients with metabolic acidosis in chronic kidney disease: a multicentre, randomised, blinded, placebo-controlled, 40-week extension.
Metabolic acidosis, a complication of chronic kidney disease, causes protein catabolism and bone demineralisation and is associated with adverse kidney outcomes and mortality. Veverimer, a non-absorbed, counterion-free, polymeric drug candidate selectively binds and removes hydrochloric acid from the gastrointestinal lumen. We did a multicentre, randomised, blinded, placebo-controlled, 40-week extension of a 12-week parent study at 29 sites (hospitals and specialty clinics) in seven countries (Bulgaria, Georgia, Hungary, Serbia, Slovenia, Ukraine, and the USA). Eligible patients were those with chronic kidney disease (estimated glomerular filtration rate 20-40 mL/min per 1·73 m2) and metabolic acidosis (serum bicarbonate 12-20 mmol/L), who had completed the 12-week parent study, for which they were randomly assigned (4:3) to veverimer (6 g/day) or placebo as oral suspensions in water with food. Participants in the extension continued with the same treatment assignment as in the parent study. The primary endpoint was safety; the four secondary endpoints assessed the long-term effects of veverimer on serum bicarbonate concentration and physical functioning. The safety analysis set was defined as all patients who received any amount of study drug. This trial is registered at ClinicalTrials.gov, number NCT03390842, and has now completed. Participants entered the study between Dec 20, 2017, and May 4, 2018. Of the 217 patients randomly assigned to treatment in the parent study (124 to veverimer and 93 to placebo), 196 patients (114 veverimer and 82 placebo) continued on their blinded randomised treatment assignment into this 40-week extension study. Compared with placebo, fewer patients on veverimer discontinued treatment prematurely (3% vs 10%, respectively), and no patients on veverimer discontinued because of an adverse event. Serious adverse events occurred in 2% of veverimer-treated patients and in 5% of placebo patients (two of whom died). Renal system adverse events were reported in 8% and 15% in the veverimer and placebo groups, respectively. More patients on veverimer than placebo had an increase in bicarbonate (≥4 mmol/L or normalisation) at week 52 (63% vs 38%, p=0·0015) and higher bicarbonate concentrations were observed with veverimer than placebo at all timepoints starting at week 1 (p<0·001). Veverimer resulted in improved patient-reported physical functioning (Kidney Disease and Quality of Life-Physical Function Domain) versus placebo with a mean placebo-subtracted change at end of treatment of 12·1 points (SE 3·3; p<0·0001). Time to do the repeat chair stand test improved by 4·3 s (1·2) on veverimer versus 1·4 s (1·2) on placebo (p<0·0001). In patients with chronic kidney disease and metabolic acidosis, veverimer safely and effectively corrected metabolic acidosis and improved subjective and objective measures of physical function. Tricida.


Semantic Retrieval of Remote Sensing Images Based on the Bag-of-Words Association Mapping Method.
With the increasing demand for remote sensing image applications, extracting the required images from a huge set of remote sensing images has become a hot topic. The previous retrieval methods cannot guarantee the efficiency, accuracy, and interpretability in the retrieval process. Therefore, we propose a bag-of-words association mapping method that can explain the semantic derivation process of remote sensing images. The method constructs associations between low-level features and high-level semantics through visual feature word packets. An improved FP-Growth method is proposed to achieve the construction of strong association rules to semantics. A feedback mechanism is established to improve the accuracy of subsequent retrievals by reducing the semantic probability of incorrect retrieval results. The public datasets AID and NWPU-RESISC45 were used to validate these experiments. The experimental results show that the average accuracies of the two datasets reach 87.5% and 90.8%, which are 22.5% and 20.3% higher than VGG16, and 17.6% and 15.6% higher than ResNet18, respectively. The experimental results were able to validate the effectiveness of our proposed method.


Bone propeller flap: a staged procedure.
The ideal reconstruction technique for complex defects of the lower limb consists of replacing tissue with similar tissue in an attempt to achieve a good functional result. A 23-year-old white male sustained a crush injury with a grade IIIB open ankle dislocation. After open reduction and fixation, the patient developed severe osteomyelitis at the tibiotalar joint requiring a staged and radical debridement with a substantial combined soft tissue and bony defect over the distal tibia, fibula, and talus area. The reconstructive approach consisted of a modified model of the propeller flap, implementing the spare part concept in a 2-stage procedure using a prefabricated and vascularized "double-barrel" fibular graft. At 17 months postoperatively, a plain radiograph showed bony union with complete and stable coverage of the soft tissue defect. The patient was fully weightbearing. In conclusion, there is evidence to suggest that the established concept of a soft tissue propeller flap can be implemented on bone.


Malaria treatment-seeking behaviour and recovery from malaria in a highland area of Kenya.
Malaria epidemics in highland areas of Kenya cause significant morbidity and mortality. To assess treatment-seeking behaviour for malaria in these areas, a questionnaire was administered to 117 randomly selected households in the highland area of Kipsamoite, Kenya. Self-reported episodes of malaria occurred in 100 adults and 66 children. The most frequent initial sources of treatment for malaria in adults and children were medical facilities (66.0% and 66.7%) and local shops (19.0% and 30.3%). Adults and children who initially visited a medical facility for treatment were significantly more likely to recover and require no further treatment than those who initially went to a local shop (adults, 84.9% v. 36.8%, P < 0.0001, and children, 79.6% v. 40.0%, P = 0.002, respectively). Individuals who attended medical facilities recalled receiving anti-malarial medication significantly more frequently than those who visited shops (adults, 100% vs. 29.4%, and children, 100% v. 5.0%, respectively, both P < 0.0001). A significant proportion of this highland population chooses local shops for initial malaria treatment and receives inappropriate medication at these localshops, reslting in delay of effective treatment. Shopkeeper education has the potential to be a component of prevention or containment strategies for malaria epidemics in highland areas.


Role of phospholipid head groups in ethanol tolerance of Saccharomyces cerevisiae.
Pre-incubation of cells of Saccharomyces cerevisiae with 2 M-ethanol led to decreased rates of L-alanine uptake, H+ efflux and fermentation rate. However, these responses were modified in yeast cells with altered phospholipid composition. Using L-alanine transport and H+ efflux as indices of ethanol tolerance, it was observed that cells enriched with phosphatidylserine had greater tolerance to ethanol. This resulted from altered charge of membrane phospholipids rather than changes in membrane fluidity. It is suggested that the anion:zwitterion ratio of phospholipids may be one of the important determinants of ethanol tolerance in S. cerevisiae.


[A case of neurolymphomatosis that was diagnosed by acoustic nerve biopsy].
A 58-year-old female was admitted to our hospital because of recurrent multiple cranial neuropathy (right facial palsy followed by involvement of the left trigeminal, facial, acoustic, pharyngeal, and vagal nerves and the right abducens nerve). Brain MRI showed gadolinium enhancement of the right abducens, bilateral facial/acoustic, and left pharyngeal/vagal nerves, and 18F-Fluorodeoxyglucose (FDG)-positron emission tomography revealed abnormal FDG uptake in the right facial, acoustic, pharyngeal, and vagal nerves and the left cervical lymph nodes. Blood and biochemical analyses did not show any abnormalities, including in the patient's lactate dehydrogenase and soluble interleukin-2 receptor (sIL2R) levels. A cerebrospinal fluid (CSF) examination showed gradual increases in the patient's cell counts and protein, β2-microglobulin, and sIL2R levels, but no malignant cells were detected. A thorough investigation involving repeated CSF examinations, whole-body computed tomography, bone marrow aspiration, random skin biopsies, and cervical lymph node aspiration biopsy examinations did not result in any definitive conclusions. Steroid therapy was ineffective, and the patient developed deafness in her left ear. Therefore, we performed a biopsy examination of the left acoustic nerve, which resulted in the patient being diagnosed with diffuse large B-cell lymphoma. High-dose MTX following the intrathecal administration of MTX, cytarabine, and prednisolone partially improved her symptoms, but she died after several episodes of clinical recurrence. Acoustic nerve biopsy may help diagnose neurolymphomatosis in carefully selected cases.


The possible role of c-fos expression in rheumatoid joint destruction.
Abstract At present, although the etiology of rheumatoid arthritis (RA) remains unknown, most investigators believe that it is primarily an inflammatory disease of the synovial membrane of the joints. However, we have recently focused on the pathology of the early changes in articular cartilage and subchondral bone in RA patients, and have shown that RA involves articular cartilage and subchondral bone, not synovia. This research direction may lead to the development of a new specific treatment for the disease.


Intrathecal administration of proteinase-activated receptor-2 agonists produces hyperalgesia by exciting the cell bodies of primary sensory neurons.
Proteinase-activated receptors (PARs) are a family of G-protein-coupled receptors that are activated by endogenous serine proteinases that cleave the N-terminal domain of the receptor unmasking a "tethered ligand" sequence. Trypsin and other agonists at PAR(2) act on peripheral nerves to augment the transfer of nociceptive information. We tested whether PAR(2) agonists also exert a spinal pronociceptive effect by i.t. administering the selective ligand, Ser-Leu-Ile-Gly-Arg-Leu-NH(2) (SLI-GRL). This produced thermal and mechanical hyperalgesia in rats and mice and augmented mechanical and thermal hyperalgesia seen in the formalin inflammatory pain test. Effects of SLIGRL were abrogated in PAR(2)-deficient mice and were not seen with the inactive control peptide, Leu-Arg-Gly-Ile-Leu-Ser-NH(2). Surprisingly, electrophysiological studies, using whole-cell recording from rat substantia gelatinosa neurons, failed to demonstrate an increase in excitatory transmission or neuronal excitability following treatment with SLIGRL or trypsin. In fact, the actions of trypsin were consistent with a decrease in dorsal horn excitability. SLIGRL and trypsin did, however, depolarize and increase the excitability of large, medium and small primary afferent, dorsal root ganglion neurons. The effects were associated with an increase in conductance at hyperpolarized potentials and a decrease in conductance at depolarized potentials. PAR(2)-like immunoreactivity was found in DRG but not in spinal dorsal horn. These results suggest that activation of DRG neuron cell bodies may account for the pronociceptive actions of i.t. applied PAR(2) agonists. They also imply that pathophysiological release of PAR(2)-activating proteases in the vicinity of DRG neurons may produce profound effects on nociceptive processing in vivo.


The human TLR innate immune gene family is differentially influenced by DNA stress and p53 status in cancer cells.
The transcription factor p53 regulates genes associated with a wide range of functions, including the Toll-like receptor (TLR) set of innate immunity genes, suggesting that p53 also modulates the human immune response. The TLR family comprises membrane glycoproteins that recognize pathogen-associated molecular patterns (PAMP) and mediate innate immune responses, and TLR agonists are being used as adjuvants in cancer treatments. Here, we show that doxorubicin, 5-fluorouracil, and UV and ionizing radiation elicit changes in TLR expression that are cell line- and damage-specific. Specifically, treatment-induced expression changes led to increased downstream cytokine expression in response to ligand stimulation. The effect of DNA stressors on TLR expression was mainly mediated by p53, and several p53 cancer-associated mutants dramatically altered the pattern of TLR gene expression. In all cell lines tested, TLR3 induction was p53-dependent, whereas induction of TLR9, the most stress-responsive family member, was less dependent on status of p53. In addition, each of the 10 members of the innate immune TLR gene family tested was differentially inducible. Our findings therefore show that the matrix of p53 status, chromosome stress, and responsiveness of individual TLRs should be considered in TLR-based cancer therapies.


The role of cysteine 116 in the active site of the antitumor enzyme L-methionine gamma-lyase from Pseudomonas putida.
The cysteinyl residue at the active site of L-methionine gamma-lyase from Pseudomonas putida (MGL_Pp) is highly conserved among the heterologous MGLs. To determine the role of Cys116, we constructed 19 variants of C116X MGL_Pp by saturation mutagenesis. The Cys116 mutants possessed little catalytic activity, while their affinity for each substrate was almost the same as that of the wild type. Especially, the C116S, C116A, and C116H variants composed active site catalytic function as measured by the kinetic parameter k(cat) toward L-methionine. Furthermore, the mutagenesis of Cys116 also affected the substrate specificity of MGL_Pp at the active center. Substitution of Cys116 for His led to a marked increase in activity toward L-cysteine and a decrease in that toward L-methionine. Propargylglycine inactivated the WT MGL, C116S, and C116A mutants. Based on these results, we postulate that Cys116 plays an important role in the gamma-elimination reaction of L-methionine and in substrate recognition in the MGLs.


[Effects of different nasotracheal intubations in obstructive sleep apnea hypopnea syndrome patients with uvulopalatopharyngoplasty].
To explore the safe and effective way of nasotracheal intubations in obstructive sleep apnea hypopnea syndrome patients with uvulopalatopharyngoplasty. Upon the approval of the Ethics Committee at Second Affiliated Hospital of Fujian Medical University, from August 2008 to November 2011, 90 sleep apnea hypopnea syndrome patients were randomly divided into 3 groups (n=30 each): GlideScope (G), fiberoptic bronchoscope (F) and combination of Glidescope with fiberoptic bronchoscope (G+F). The parameters of tracheal intubation time, placement of endotracheal intubation, tracheal injury and complications were recorded. Also systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and heart rate (HR) were recorded at post-induction, the moment of tracheal intubation and post-intubation 1, 3, 5 min. Rate pressure product (RPP) was calculated at all time points as the product of heart rate and SBP during observation. All of them underwent successful endotracheal intubation. There were 24 successful cases of intubation during the first attempt in Group G with a success rate of 80%; 27 patients successful during the first attempt in group F with a success rate of 90%; all in group G+F successful during the first attempt with a success rate of 100%. The rates were significantly different in 3 groups (P<0.05). Groups G and F patients with failed intubation during the first attempt were of Mallampati III/IV. After induction, SBP, DBP, MAP and RPP were lower in 3 groups (P<0.05) while HR change was not obvious. Compared with the after induction, the moment of tracheal intubation and after intubation 1 min, 3 groups of patients with SBP, DBP, MAP, HR and RPP increased (P<0.05). Groups F and G+F after intubation in intubated patients and 1 min of SBP, DBP, MAP, HR, RPP were higher than G group (P<0.05). No difference existed between groups F and G+F. Three groups showed no serious tracheal injury, laryngeal edema, hoarseness or other complications. During nasotracheal intubation for Mallampati I/II patients, GlideScope offers better overall glottic views. For those of Mallampati III and IV, the combination of Glidescope with fiberoptic bronchoscope may achieve a higher success rate and shorter intubation time than the latter alone.


[Diagnostic errors and mortality in those suffering in road traffic accidents].
The paper deals with the analysis of diagnostic errors and lethality causes among the victims of traffic accidents. It was found that 40.75% of cases died from craniocerebral injuries, 32.5%-from traumatic shock and blood loss. Complete coincidence of clinical and medicolegal diagnosis was in 47.05% of cases, and complete discrepancy in 8.13%. The greatest number of errors are concerned with the diagnosis and treatment of chest and abdomen injuries. The least number of errors were made in big multiprofile clinics with well organized reanimation service. Some recommendations on the improvement of the organization of the treatment of traffic accident cases, ways of preventing diagnostic errors and the decrease of lethality are suggested.


The inflammation and coagulation cross-talk in patients with systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is a chronic inflammatory disorder with a high prevalence of cardiovascular disease due to accelerated atherosclerosis, as well as an increased risk of venous thromboembolism. Many of these clinical features have been attributed to the high prevalence of autoantibodies that are directed against phospholipid-bound antigens and that induce prothrombotic effects and disturb endothelial cell function. We conducted a case-control study in a cohort of female patients with SLE and in age-matched and sex-matched normal individuals. Patients had significantly higher levels of plasma inflammatory markers, but their overall coagulation status assessed by prothrombin fragment 1 + 2 and D-dimer plasma levels was not different from controls. Resistance against activated protein C (APC), assessed by a thrombin generation-based as well as an activated partial thromboplastin time-based method, however, was increased in patients. This defect was neither due to factor V Leiden carriership or to the use of oral contraceptives. This acquired form of APC resistance was due to proinflammatory changes associated with lower plasma levels of free protein S. In conclusion, acquired APC resistance may be an important determinant of the risk of thrombosis in patients with SLE, probably due to an active cross-talk between inflammation and coagulation systems.


Top-down heating for low substrate temperature synthesis of carbon nanotubes.
A top-down heating method to allow for low-temperature large area synthesis of carbon nanotubes using plasma-enhanced chemical vapour deposition is introduced in this paper. The approach utilizes top-down electromagnetic heating rather than conventional heating from a substrate heater under the electrode. A temperature gradient is created between the Ni catalyst surface and the substrate using a metal thermal control barrier layer, on which carbon nanotubes are grown as a function of the bias voltage, hydrocarbon concentrations and growth conditions. The heat during growth is provided by the plasma or energy coupling to the catalyst via top-down heating, which based on the coupled power density and the cooling of the substrate, in addition to the thermal 'barrier layer' properties will dictate the temperature of the growth surface. This unique approach of top-down heating with suitable cooling schemes, coupled with thermal barriers allows for the low substrate temperature synthesis of carbon nanotubes, scalable to large areas.


Families, brain death, and traditional medical excellence.
Staff neurosurgeons and residents at a tertiary care hospital designated as a transplant center were surveyed regarding personal opinions concerning brain death and family conferences. Compared to an extensive survey done in 1976, the responses indicated that, while a professional consensus regarding the definition and meaning of brain death has emerged in the past 10 years, a range of personal beliefs and opinions regarding the concept still exists. In spite of the professional consensus, it is still difficult for the physician to communicate gently, yet firmly, to families both the scientific groundwork that validates the determination of brain death, the concept, and the finality of the information.


Rac1 Promotes Cell Motility by Controlling Cell Mechanics in Human Glioblastoma.
The failure of existing therapies in treating human glioblastoma (GBM) mostly is due to the ability of GBM to infiltrate into healthy regions of the brain; however, the relationship between cell motility and cell mechanics is not well understood. Here, we used atomic force microscopy (AFM), live-cell imaging, and biochemical tools to study the connection between motility and mechanics in human GBM cells. It was found thatRac1 inactivation by genomic silencing and inhibition with EHT 1864 reduced cell motility, inhibited cell ruffles, and disrupted the dynamics of cytoskeleton organization and cell adhesion. These changes were correlated with abnormal localization of myosin IIa and a rapid suppression of the phosphorylation of Erk1/2. At the same time, AFM measurements of the GBM cells revealed a significant increase in cell elasticity and viscosity following Rac1 inhibition. These results indicate that mechanical properties profoundly affect cell motility and may play an important role in the infiltration of GBM. It is conceivable that the mechanical characters might be used as markers for further surgical and therapeutical interventions.


A Novel Reconstructive Procedure for the Divided Nevus of the Eyelids Using a Tissue Expander.
Expanded local flaps and skin grafts (expanded/nonexpanded) are a common approach for reconstructing medium (1.5-20 cm) and large (>20 cm) divided nevi of the eyelids. However, this approach does not often provide a satisfactory cosmetic result, particularly in Asian patients, because of different skin types. We recently devised a new surgical procedure using an extended cheek flap and tissue expander for the medium-sized divided nevus of the eyelids. The upper and lower eyelids are concurrently reconstructed by divided flaps. This method is an effective treatment method for the medium-sized divided nevus of the eyelids and can be applied in total reconstruction of the eyelids in the future. This article presents our novel technique and is illustrated using a brief case report.


Impact of Fungal MAPK Pathway Targets on the Cell Wall.
The fungal cell wall is an extracellular organelle that provides structure and protection to cells. The cell wall also influences the interactions of cells with each other and surfaces. The cell wall can be reorganized in response to changing environmental conditions and different types of stress. Signaling pathways control the remodeling of the cell wall through target proteins that are in many cases not well defined. The Mitogen Activated Protein Kinase pathway that controls filamentous growth in yeast (fMAPK) was required for normal growth in media containing the cell wall perturbing agent Calcofluor White (CFW). A mass spectrometry (MASS-SPEC) approach and analysis of expression profiling data identified cell wall proteins and modifying enzymes whose levels were influenced by the fMAPK pathway. These include Flo11p, Flo10p, Tip1p, Pry2p and the mannosyltransferase, Och1p. Cells lacking Flo11p or Och1p were sensitive to CFW. The identification of cell wall proteins controlled by a MAPK pathway may provide insights into how signaling pathways regulate the cell wall.


Adolescent transitions: a nursing concern.
Adolescents with chronic conditions face unique challenges as they approach adulthood. Statistics on adults with disabilities indicate high rates of unemployment, few with college degrees, and limited options for community living. Until recently, efforts to facilitate successful transitions for adolescents with chronic conditions to adulthood have been limited. An awareness of some of the pertinent issues pertaining to adolescent transitions, especially those pertaining to health care, can assist the pediatric nurse in facilitating the transition to adult health care, career, employment, and community living.


Impact of caries and dental fluorosis on oral health-related quality of life: a cross-sectional study in schoolchildren receiving water naturally fluoridated at above-optimal levels.
The purpose of this study was to evaluate the impact of caries and fluorosis on oral health-related quality of life (OHRQoL) among schoolchildren living in areas with high concentrations of fluoride in water. Five hundred and twenty-four schoolchildren (8-12 year olds) residing in rural communities in central Mexico were examined for oral hygiene, caries (International Caries Detection and Assessment System, ICDAS II), and fluorosis (Thylstrup and Fejerskov Index, TFI). OHRQoL was evaluated with the Child Perceptions Questionnaire for two age groups (CPQ8-10 and CPQ11-14). Generalized structural equation models were constructed for data analysis. Overall prevalence of caries was 88.5% and fluorosis 46.9%. In the group of 8-10 year olds, 48% of the children had advanced carious lesions in primary or permanent teeth (ICDAS ≥4), 22.6% had moderate/severe fluorosis, and 59.9% of children had an impact on OHRQoL. Schoolchildren with ICDAS ≥4 were more likely [OR = 1.75, (95% CI 1.34-2.28)] to suffer a negative impact on OHRQoL. In the group of 11-12 year olds, 19.9% of children had advanced carious lesions and 23.2% showed moderate/severe fluorosis; 67.3% of children reported had an impact on OHRQoL. Children 11-12 year olds with fluorosis (TFI ≥4) [OR = 2.39 (95% CI 2.12-2.69)], caries (ICDAS ≥4) [OR = 2.18 (95% CI 2.13-2.24)], and low brushing frequency [OR = 2.04 (95% CI 1.21-3.44)] were more likely to have deterioration on OHRQoL. A negative impact on OHRQoL was observed in children with caries and fluorosis. Deterioration on OHRQoL found in children as a sequel of caries and fluorosis should be considered when designing health policies leading to prevention and effective health promotion programs and incorporated to clinical guidelines for timely dental treatment.


Surface-Charge Anisotropy of Scheelite Crystals.
Atomic force microscopy was employed to measure the colloidal interactions between silicon nitride cantilever tips and scheelite crystal surfaces in 1 mM KCl solutions of varying pH. By fitting the Derjguin-Landau-Verwey-Overbeek (DLVO) theoretical model to the recorded force-distance curves, the surface-charge density and surface-potential values were calculated for three crystallographic surfaces including {112}, {101}, and {001}. The calculated surface-potential values were negative in both acidic and basic solutions and varied among crystallographic surfaces. The determined surface-potential values were within zeta-potential values reported in the literature for powdered scheelite minerals. The surface {101} was the most negatively charged surface, followed by {112} and {001}. The surface potential for {001} was only slightly affected by pH, whereas the surface potential for both {112} and {101} increased with increasing pH. Anisotropy in surface-charge density was analyzed in relation to the surface density of active oxygen atoms, that is, the density of oxygen atoms with one or two broken bond(s) within tungstate ions located in the topmost surface layer. On a surface with a higher surface density of active oxygen atoms, a larger number of OH(-) are expected to adsorb through hydrogen bonding, leading to a more negatively charged surface.


[On the English translation of TCM pulse picture terms].
At present, the English translation of TCM terms of pulse picture are various, which would bring confusion to the study and research on TCM diagnostics. In this paper, four principles for the translation are suggested by the authors: to distinguish the nomenclature of term with its connotative explanation, to translate with commonly used words in general, to create new word with common affix and to differentiate the terms similar in meaning. The authors tried to make choice the best translation for each kind pulse picture, and explained the reasons for selection.


Induction of endothelial iNOS by 4-hydroxyhexenal through NF-kappaB activation.
Lipid peroxidation and its end-product, 4-hydroxyhexenal (HHE), are known to affect redox balance during aging, which causes various degenerative processes including vascular alterations from endothelial cell deterioration. To better understand the molecular action of HHE in the development of vascular abnormalities during the aging process, we investigated whether the upregulation of inducible endothelial nitric oxide synthase (iNOS) by HHE is mediated through nuclear factor kappaB (NF-kappaB) activation. Results indicate that HHE stimulates iNOS by the transcriptional regulation of NF-kappaB activation through cytosolic kappaB degradation inhibitors (IkappaB). Pretreatment with NF-kappaB inhibitors Bay 11-7082 and N-acetyl cysteine (NAC) suppressed the upregulation of iNOS by blunting IkappaB degradation and NF-kappaB binding activity. Because inflammatory stimuli induce iNOS to generate large amounts of nitric oxide (NO), intracellular NO levels in the presence of Bay 11-7082, NAC, and caffeic acid methyl ester were estimated. These inhibitors significantly suppressed the HHE-induced NO levels to a basal level. These findings strongly suggest that in endothelial cells, HHE induces iNOS gene expression through NF-kappaB activation, which can lead to vascular dysfunction by the activation of various proinflammatory genes.


Ex vivo activation of CD56(+) immune cells that eradicate neuroblastoma.
Despite the use of intensive contemporary multimodal therapy, the overall survival of patients with high-risk neuroblastoma is still less than 50%. Therefore, immunotherapy without cross-resistance and overlapping toxicity has been proposed. In this study, we report the development of a novel strategy to specifically activate and expand human CD56(+) (NCAM1) natural killer (NK) immune cells from normal donors and patients with neuroblastoma. Enriched CD56(+) cells from peripheral blood were mixed with CD56(-) fraction at 1:1 ratio and cultured in the presence of OKT3, interleukin (IL)-2, and -15 for five days and then without OKT3 for 16 more days. The final products contained more than 90% CD56(+) cells and could kill neuroblastoma cells effectively that were originally highly resistant to nonprocessed NK cells. Mechanistically, cytolysis of neuroblastoma was mediated through natural cytotoxicity receptor (NCR), DNAX accessory molecule-1 (DNAM-1; CD226), perforin, and granzyme B. Successful clinical scale-up in a good manufacturing practices (GMP)-compliant bioreactor yielded effector cells that in a neuroblastoma xenograft model slowed tumor growth and extended survival without GVHD. Investigation of CD56(+) cells from patients with neuroblastoma revealed a similar postactivation phenotype and lytic activity. Our findings establish a novel and clinically expedient strategy to generate allogeneic or autologous CD56(+) cells that are highly cytotoxic against neuroblastoma with minimal risk of GVHD.


Informatics Solutions for Driving an Effective and Efficient Radiology Practice.
Radiologists are facing increasing workplace pressures that can lead to decreased job satisfaction and burnout. The increasing complexity and volumes of cases and increasing numbers of noninterpretive tasks, compounded by decreasing reimbursements and visibility in this digital age, have created a critical need to develop innovations that optimize workflow, increase radiologist engagement, and enhance patient care. During their workday, radiologists often must navigate through multiple software programs, including picture archiving and communication systems, electronic health records, and dictation software. Furthermore, additional noninterpretive duties can interrupt image review. Fragmented data and frequent task switching can create frustration and potentially affect patient care. Despite the current successful technological advancements across industries, radiology software systems often remain nonintegrated and not leveraged to their full potential. Each step of the imaging process can be enhanced with use of information technology (IT). Successful implementation of IT innovations requires a collaborative team of radiologists, IT professionals, and software programmers to develop customized solutions. This article includes a discussion of how IT tools are used to improve many steps of the imaging process, including examination protocoling, image interpretation, reporting, communication, and radiologist feedback. ©RSNA, 2018.


[Cutaneous localization of multiple myeloma on the tract of a central venous catheter].
Extramedullary plasmocytoma are plasmocytic tumours developing outside of the bone marrow. Cutaneous localization of extramedullary plasmocytoma are rare and can be primitive or secondary. We report two cases of secondary extramedullary plasmocytoma occurring on central venous catheterization sites. A 68 year-old woman and a 69 year-old man presented with subcutaneous metastases located along the tracts of central venous catheters or implantable ports, which were either still on site or removed recently. Although the patients initially responded to melphalan therapy, they eventually died of multiple myeloma a few weeks following the diagnosis of the cutaneous localizations. Extramedullary plasmocytoma are most commonly found in the upper respiratory tract, the gut and the lymph, but cutaneous localization is rare. We report two cases of cutaneous extramedullary plasmocytoma located on the tract of central intravenous infusion sites. Both patients were treated with melphalan with initial improvement, followed by an early relapse. Two cases of myeloma metastases occurring on the tract of central venous catheters have previously been published. This localization seems to occur late in the course of this disease and to be associated with a poor prognosis.


Protein synthesis in tissues and in the whole body of laying hens during egg formation.
The present study was conducted to investigate whether or not protein synthesis in tissues and in the whole body of laying hens would be affected by the position of an ovum passing along the oviduct during egg formation. Protein synthesis in tissues was measured in vivo by a primed-continuous infusion of [15N]methionine for 3 h, finishing at the time when an ovum would have stayed at one of the segments within the oviduct, i.e., infundibulum, magnum, isthmus, uterus, or vagina. The dissection of the entire oviduct immediately after the isotope infusion confirmed whether or not the ovum was in the expected position. Whole-body protein synthesis, estimated from plateau enrichment of free [15N]methionine in plasma at the end of the infusion, was not significantly affected by the position of an ovum along the various segments of the oviduct. The highest values were observed in the entire oviduct when an ovum was in the magnum portion, both for protein synthesis and protein synthesis per unit of RNA. Protein synthesis per unit of RNA in the sum of tissues other than the liver and oviduct was highest when an ovum was in the isthmus. The synthesis of liver protein was relatively constant and was not significantly affected by the position of the ovum passing along the oviduct.


Progress on extending the light absorption spectra of photocatalysts.
Photocatalysis has attracted a lot of attention owing to its great potential to solving energy and environmental problems. Although great efforts have been made in the last few decades, the poor efficiency still fails to meet the requirement of practical applications. With the aim to improve further the photocatalytic efficiency and promote their practical applications, in this work we reviewed briefly the progress of the strategies on extending the light absorption spectra of photocatalysts from the aspect of solar energy harvesting. Based on the analyses and discussions of photocatalytic performances, and the mechanisms, advantages and disadvantages of these strategies, some perspectives and interpretations of the future development of photocatalysis were proposed based on our own understanding and experience. We hope it will be helpful for our colleagues that work in the field of photocatalysis.


Use of Medicare services before and after introduction of the prospective payment system.
The case mix-adjusted pattern of use of health care services, especially posthospital care, is compared before and after the introduction of Medicare's Prospective Payment System (PPS). The 1982 and 1984 National Long Term Care Surveys (NLTCS) linked to Medicare administrative records 1982-1986 provide health and health service use data for 12-month periods before and after the introduction of PPS. Case-mix differences between pre- and post-periods are controlled by using the Grade of Membership model to identify health groups from the NLTCS data. Differences in timing (e.g., hospital length of stay) were controlled using life table models estimated for each health group, that is, service use patterns pre- and post-PPS are compared within groups. Hospital LOS and admission rates declined post-PPS. Changes in the timing and location of death occurred but, overall, mortality did not increase. Changes in post-acute care service use by elderly, chronically disabled Medicare beneficiaries were observed: home health service use increased overall and among the unmarried disabled population. PPS did not adversely affect quality of care as reflected in mortality or in hospital readmissions. Moreover, the differential use of post-acute care, and changes in hospital LOS by health group, indicate that the system responded, specific to marital status and age, to the severity of needs of chronically disabled persons.


Intraspecific hybridization as a mitigation strategy of ocean acidification in marine bivalve noble scallop Chlamys nobilis.
The driving factors of climate change, especially ocean acidification (OA), have many detrimental impacts on marine bivalves. Hybridization is one of the important methods to improve environmental tolerance of animals and plants. In this study, we explored the feasibility of intraspecific hybridization as an OA mitigation strategy in noble scallop Chlamys nobilis (ecologically and economically important bivalve species). The results of this study revealed that exposure of C. nobilis to OA condition significantly reduced the hatching rate, survival rate, growth rate (shell height, shell length, shell width and shell weight), and total carotenoid content (TCC), as well as increased the deformity rate of C. nobilis larvae. Interestingly, under both ambient water and OA condition, the intraspecific hybridization of C. nobilis exhibited heterosis in terms of hatching rate, survival rate and growth rate (excepted for growth in shell length under OA). Transcriptome sequencing of C. nobilis (inbreed and hybrid under ambient and OA conditions) identified four main differentially expressed genes involved in signal transduction, biological process maintenances, nucleic acid binding and post-translational modification. In addition, the expression of these four genes in hybrid C. nobilis was significantly higher than that in inbreed C. nobilis. In conclusion, hybrid C. nobilis showed heterosis in growth rate and survival rate under both ambient water and acidified seawater condition, which may be the result of enhanced expression of genes related to signal transduction, DNA replication and post-translational modification.


Eradication of pathogens from the nasopharynx after therapy of acute maxillary sinusitis with low- or high-dose amoxicillin/clavulanic acid.
The growing resistance of Streptococcus pneumoniae to penicillin can be overcome by increasing the dose of the penicillin administered. This generated the recommendation that the adult dose of amoxicillin for the treatment of acute maxillary sinusitis (AMS) be increased from 1.5 g/day to 4.0 g/day. The objective of this study was to investigate whether the higher dose of amoxicillin is more effective than the previously recommended dose in eradicating S. pneumoniae from the nasopharynx of patients who present with AMS. Nasopharyngeal cultures obtained from 58 patients with AMS were studied: 30 received amoxicillin 1.5 g/day given in divided doses three times a day for 10 days (amoxicillin/clavulanic acid 4:1 formulation) and 28 were treated with amoxicillin 4.0 g/day given in divided doses twice a day for 10 days (amoxicillin/clavulanic acid 16:1 formulation). Seventy-one potentially pathogenic organisms were isolated: S. pneumoniae (27 isolates), Haemophilus influenzae non-type b (25), Moraxella catarrhalis (5), Streptococcus pyogenes (5) and Staphylococcus aureus (9). The number of S. pneumoniae isolates in the 1.5 g/day group was reduced from 14 to 9 (2 intermediately resistant and 3 highly resistant). In contrast, the number of S. pneumoniae isolates in the 4.0 g/day group was reduced from 13 to 2 (1 highly resistant) (P<0.05). No differences were noted in the eradication rate of other groups of isolates, which were all susceptible to amoxicillin/clavulanic acid. These data illustrate the superiority of 4.0 g/day amoxicillin/clavulanic acid compared with 1.5 g/day amoxicillin/clavulanic acid in the eradication of S. pneumoniae from the nasopharynx.


Crop Rotational Effects on Yield Formation in Current Sugar Beet Production - Results From a Farm Survey and Field Trials.
In Europe, the framework for sugar beet (Beta vulgaris L.) production was subject to considerable changes and for the future it is expected that sugar beet cultivation might concentrate around the sugar factories for economic reasons. Based on data from a national sugar beet farmers' survey and multi-year crop rotation trials, the effects of cropping interval (number of years in between two subsequent sugar beet crops) and of preceding crops on sugar yield were elucidated under current Central European management conditions. The dominating sugar beet cropping interval was ≥4 years in the farm survey with pronounced differences between regions. However, the cropping intervals 2, 3, and ≥4 years did not affect the sugar yield. Therefore, significant differences in sugar yield between regions were assumed to be caused by multiple interactions between year, site, and farmers' skills. Throughout Germany, the dominating preceding crops in sugar beet cultivation were winter wheat (Triticum aestivum L.) and winter barley (Hordeum vulgare L.). In the field trials, the sugar yield was 5% higher after pea (Pisum sativum L.) compared to maize (Zea mays L.) as preceding crop, while differences between the preceding crops pea and winter wheat, and wheat and maize were not significant. Repeated measurements of canopy development and leaf color during the growing season revealed a higher N-availability after pea as preceding crop. However, decreased growth after maize was not completely compensated for by high N-fertilizer doses. Overall, the causes for the differences in sugar yield between the preceding crops remained open. The results do not support concerns about substantial yield losses in sugar beet production due to a reduction in the cropping interval from 3 to 2 years. Nevertheless, short rotations with maize and sugar beet might increase the risk of Rhizoctonia solani crown and root rot infestation. Leguminous crops such as pea offer the potential for higher sugar beet yield with lower N-fertilizer doses.


Towards Identifying and Reducing the Bias of Disease Information Extracted from Search Engine Data.
The estimation of disease prevalence in online search engine data (e.g., Google Flu Trends (GFT)) has received a considerable amount of scholarly and public attention in recent years. While the utility of search engine data for disease surveillance has been demonstrated, the scientific community still seeks ways to identify and reduce biases that are embedded in search engine data. The primary goal of this study is to explore new ways of improving the accuracy of disease prevalence estimations by combining traditional disease data with search engine data. A novel method, Biased Sentinel Hospital-based Area Disease Estimation (B-SHADE), is introduced to reduce search engine data bias from a geographical perspective. To monitor search trends on Hand, Foot and Mouth Disease (HFMD) in Guangdong Province, China, we tested our approach by selecting 11 keywords from the Baidu index platform, a Chinese big data analyst similar to GFT. The correlation between the number of real cases and the composite index was 0.8. After decomposing the composite index at the city level, we found that only 10 cities presented a correlation of close to 0.8 or higher. These cities were found to be more stable with respect to search volume, and they were selected as sample cities in order to estimate the search volume of the entire province. After the estimation, the correlation improved from 0.8 to 0.864. After fitting the revised search volume with historical cases, the mean absolute error was 11.19% lower than it was when the original search volume and historical cases were combined. To our knowledge, this is the first study to reduce search engine data bias levels through the use of rigorous spatial sampling strategies.


Monoclonal antibody sandwich immunoassay detection of coproantigen to evaluate the efficacy of treatment in natural ovine fasciolosis.
The monoclonal antibody-based sandwich immunoassay (mAb Sandwich ELISA) was used to evaluate the effectiveness of triclabendazole treatment by the detection of coproantigens in Fasciola hepatica naturally infected sheep. Twelve sheep (2 to 5 years of age) were separated into two groups. The first group (three sheep) remained untreated; the other group (nine sheep) was treated with a single dose of 5% triclabendazole at 10 mg kg-1 of body weight. All but one of the treated group had negative optical density values (OD492) after two weeks of treatment, while seven sheep intermittently shed eggs during the course of the study. In all but one of the treated sheep, no F. hepatica infection; the one positive ELISA in 5th week after treatment according to the mAb Sandwich, had one fluke in the liver. The results of the parasitological examinations, as well as OD492 values obtained by the mAb Sandwich ELISA for the detection of coproantigens are described. The findings at necropsy, of the treated group in comparison to the untreated group are shown. The mAb Sandwich ELISA could be a useful and accurate method with which to monitor the efficacy of flukicides in F. hepatica natural infections.


Selective targeting and therapy of metastatic and multidrug resistant tumors using a long circulating podophyllotoxin nanoparticle.
Treatment options for metastatic and multidrug resistant (MDR) tumors are limited, and most of the chemotherapeutic drugs exhibit low efficacy against MDR cancers. An anti-tubulin agent podophyllotoxin (PPT) displays high potency against MDR tumor cells. However, due to its poor solubility and non-specificity, PPT cannot be used systemically. We have developed a self-assembling nanoparticle dosage form for PPT (named Celludo) by covalently conjugating PPT and polyethylene glycol (PEG) to acetylated carboxymethyl cellulose (CMC-Ac) via ester linkages. Celludo displayed extended blood circulation with an 18-fold prolonged half-life (t1/2), 9000-fold higher area under the curve (AUC), and 1000-fold reduced clearance compared to free PPT. Tumor delivery was 500-fold higher in the Cellduo group compared to free PPT. Against the lung metastatic model of EMT6-AR1, Celludo showed selective localization in the metastatic nodules and increased the median survival to 20 d compared to 6-8 d with docetaxel and PPT treatment. In the intraperitoneal metastatic model of human ovarian NCI-ADR/RES tumor, Celludo prolonged the median survival from 50 d to 70 d, whereas the standard therapy PEGylated liposomal doxorubicin showed no effect. No major toxicity was detected with the Celludo treatment. These results demonstrate that Celludo is effective against metastatic and MDR tumors.


Better prediction of protein contact number using a support vector regression analysis of amino acid sequence.
Protein tertiary structure can be partly characterized via each amino acid's contact number measuring how residues are spatially arranged. The contact number of a residue in a folded protein is a measure of its exposure to the local environment, and is defined as the number of Cbeta atoms in other residues within a sphere around the Cbeta atom of the residue of interest. Contact number is partly conserved between protein folds and thus is useful for protein fold and structure prediction. In turn, each residue's contact number can be partially predicted from primary amino acid sequence, assisting tertiary fold analysis from sequence data. In this study, we provide a more accurate contact number prediction method from protein primary sequence. We predict contact number from protein sequence using a novel support vector regression algorithm. Using protein local sequences with multiple sequence alignments (PSI-BLAST profiles), we demonstrate a correlation coefficient between predicted and observed contact numbers of 0.70, which outperforms previously achieved accuracies. Including additional information about sequence weight and amino acid composition further improves prediction accuracies significantly with the correlation coefficient reaching 0.73. If residues are classified as being either "contacted" or "non-contacted", the prediction accuracies are all greater than 77%, regardless of the choice of classification thresholds. The successful application of support vector regression to the prediction of protein contact number reported here, together with previous applications of this approach to the prediction of protein accessible surface area and B-factor profile, suggests that a support vector regression approach may be very useful for determining the structure-function relation between primary protein sequence and higher order consecutive protein structural and functional properties.


Novel salicylic acid-based chemically crosslinked pH-sensitive hydrogels as potential drug delivery systems.
In this work, salicylic acid (SA), a non-steroidal anti-inflammatory, was chemically incorporated into hydrogel systems to achieve sustained SA release profiles. With its anti-inflammatory properties, sustained release of SA would be relevant for treating diseases such as diabetes and cancer. In this work, SA was chemically incorporated into hydrogel systems via covalent attachment to an itaconate moiety followed by UV-initiated crosslinking using acrylic acid and poly(ethylene glycol) diacrylate. The chemical composition of the hydrogel system was confirmed using FT-IR spectroscopy. The SA-based hydrogels were designed as pH-responsive hydrogels, collapsing at acidic pH (1.2) values and swelling at higher pH (7.4) values for gastrointestinal-specific delivery. The hydrogel systems exhibited a pH-dependent SA release profile: SA release was much slower at pH 1.2 compared to pH 7.4. Under acidic pH conditions, 30wt% SA was released after 24h, whereas 100wt% SA was released in a sustained manner within 24h in pH 7.4 PBS buffer. The pore structure of the gel networks were studied using SEM and exhibit appropriate pore sizes (15-60μm) for physically encapsulating drugs. In addition, rheological studies of the hydrogels proved that these systems are mechanically strong and robust. Mucoadhesive behaviors were confirmed using a Texture Analyzer, the work of adhesion for the hydrogels was around 290 g·mm and the maximum detachment force was around 135g. The SA-based hydrogels demonstrate great potential for oral delivery of bioactives in combination with SA to treat serious diseases such as cancer and diabetes.


Negative regulation of CDC42 expression and cell cycle progression by miR-29a in breast cancer.
The inhibitory role of microRNA-29a (miR-29a) has been assessed in breast cancer cells. Herein, we analyze the underlying mechanisms of its role in cell cycle progression in breast cancer cells. We applied real-time polymerase chain reaction (PCR) to detect the expression of miR-29 in breast cancer cell lines. Then one of the cell lines, MDA-MB-453, was transfected with mimics of miR-29a. The cell cycle was analyzed by fluorescence-activated cell sorting after staining the cells with propidium iodide. Real-time PCR, luciferase assay and western blot were used together to verify the regulation of the predicted target, cell division cycle 42 (CDC42) by miR-29a. MiR-29s were decreased in our selected mammary cell lines, among which miR-29a was the dominant isoform. Overexpression of miR-29a caused cell cycle arrest at the G0/G1 phase. We further found that miR-29a could target the expression of CDC42, which is a small GTPase associated with cell cycle progression. We suggest that miR-29a exerts its tumor suppressor role in breast cancer cells partially by arresting the cell cycle through negative regulation of CDC42.


Possible biochemical implications of the crystal structure of biotin.
An examination of the molecular architecture of biotin, as determined by x-ray crystallographic analysis, has indicated that biotin may be capable of forming an intramolecular hydrogen bond in solution. A review of various chemical analogs of the vitamin has shown a close correlation between the possibility of forming such a hydrogen bond and biotin-like activity.


Calibration of a versatile multi-energy soft x-ray diagnostic for WEST long pulse plasmas.
A compact multi-energy soft x-ray diagnostic is being installed on the W Environment in Steady-state Tokamak (WEST), which was designed and built to test ITER-like tungsten plasma facing components in a long pulse (∼1000 s) scenario. The diagnostic consists of a pinhole camera fielded with the PILATUS3 photon-counting Si-based detector (≲100 kpixel). The detector has sensitivity in the range 1.6-30 keV and enables energy discrimination, providing a higher energy resolution than conventional systems with metal foils and diodes with adequate space and time resolution (≲1 cm and 2 ms). The lower-absorption cut-off energy is set independently on each one of the ∼100 kpixels, providing a unique opportunity to measure simultaneously the plasma emissivity in multiple energy ranges and deduce a variety of plasma parameters (e.g., Te, nZ, and ΔZeff). The energy dependence of each pixel is calibrated here over the range 3-22 keV. The detector is exposed to a variety of monochromatic sources-fluorescence emission from metallic targets-and for each pixel, the lower energy threshold is scanned to calibrate the energy dependence. The data are fit to a responsivity curve ("S-curve") that determines the mapping between the possible detector settings and the energy response for each pixel. Here, the calibration is performed for three energy ranges: low (2.3-6 keV), medium (4.5-13.5 keV), and high (5.4-21 keV). We determine the achievable energy resolutions for the low, medium, and high energy ranges as 330 eV, 640 eV, and 950 eV, respectively. The main limitation for the energy resolution is found to be the finite width of the S-curve.


Metabolism of 2-naphthylamine and benzidine by rat and human bladder organ cultures.
The metabolism of benzidine and 2-naphthylamine, two aromatic amines which are carcinogenic for the human, was investigated in human and rat bladder organ cultures. There was little oxidative metabolism of either carcinogen in either species. In particular, N-hydroxy-2-naphthylamine, a proximate carcinogen of 2-naphthylamine could not be detected. In contrast, large amounts of the acetylated metabolites, N-acetylbenzidine, N,N-diacetylbenzidine and N-acetyl-2-naphthylamine were formed both in rat and human bladder cultures. The results suggest that metabolism of these carcinogens in situ in the bladder is unlikely to contribute to their carcinogenic effect but instead may have a positive protective role.


Binary Quadratic Programing for Online Tracking of Hundreds of People in Extremely Crowded Scenes.
Multi-object tracking has been studied for decades. However, when it comes to tracking pedestrians in extremely crowded scenes, we are limited to only few works. This is an important problem which gives rise to several challenges. Pre-trained object detectors fail to localize targets in crowded sequences. This consequently limits the use of data-association based multi-target tracking methods which rely on the outcome of an object detector. Additionally, the small apparent target size makes it challenging to extract features to discriminate targets from their surroundings. Finally, the large number of targets greatly increases computational complexity which in turn makes it hard to extend existing multi-target tracking approaches to high-density crowd scenarios. In this paper, we propose a tracker that addresses the aforementioned problems and is capable of tracking hundreds of people efficiently. We formulate online crowd tracking as Binary Quadratic Programing. Our formulation employs target's individual information in the form of appearance and motion as well as contextual cues in the form of neighborhood motion, spatial proximity and grouping, and solves detection and data association simultaneously. In order to solve the proposed quadratic optimization efficiently, where state-of art commercial quadratic programing solvers fail to find the solution in a reasonable amount of time, we propose to use the most recent version of the Modified Frank Wolfe algorithm, which takes advantage of SWAP-steps to speed up the optimization. We show that the proposed formulation can track hundreds of targets efficiently and improves state-of-art results by significant margins on eleven challenging high density crowd sequences.


Use of platelet rich plasma for the treatment of bicipital tendinopathy in spinal cord injury:: a pilot study.
The purpose of study is to explore the efficacy and safety of platelet rich plasma (PRP) in the nonoperative management of shoulder tendinopathy amongst individuals with spinal cord injury. This objective was met by completing a pilot study on the effectiveness and safety of a PRP injection into the biceps tendon demonstrating clinical and ultrasonagraphic pathology. Recent analysis of the preliminary pilot data has demonstrated remarkably convincing results demonstrating both the safety and efficacy of this novel intervention.


Identification and gene mapping of a novel mutant supernumerary lodicules (snl) in rice.
In order to gain a better understanding of rice flower development, a rice flower mutant supernumerary lodicules (snl), which was identified from ethyl methane sulfonate (EMS)-treated Jinhui10 (Oryza sativa L. ssp. indica) was used in the present study. In the snl mutant, the palea obtained lemma identity, additional glume-like organs formed, lodicules increased and elongated, stamens decreased, and a few aberrant carpels formed. These phenotypes suggest that SNL is involved in the entire rice flower development. SNL was mapped between two simple sequence repeat markers RM3512 and RM1342 on chromosome 2, an approximate 800 kb region, and it co-segregated with SSR215. We conclude that SNL is a novel gene involved in flower development in rice. The present study will be useful for further cloning of the SNL gene, which will contribute to the elucidation of rice flower development.


[A comparative study of voxel-based morphometry in patients with paranoid schizophrenia and bipolar mania].
To assess volumetric abnormalities of grey matter in the brains of patients with paranoid schizophrenia and bipolar disorder (mania). 3D T1 weighted images were acquired by magnetic resonance imaging from 20 patients with paranoid schizophrenia, 20 patients with bipolar disorder (mania) and 20 control subjects. Regional deviation in gray matter volume was assessed using optimized volumetric voxel-based morphometry. ANOVA was performed to test the difference of the gray matter volume (GMV). Compared with controls, the patients with paranoid schizophrenia showed decreased gray matter volume in left superior temporal gyrus, right middle temporal gyrus and inferior temporal gyrus, and increased gray matter volume in bilateral inferior frontal gyrus and bilateral claustrum. Whereas, the patients with bipolar disorder (mania) showed decreased gray matter volume in right superior temporal gyrus, middle temporal gyrus, inferior temporal gyrus and bilateral caudate, and increased gray matter volume in bilateral precuneus, left postcentral gyrus, right superior frontal gyrus and left cingulated gyrus. The patients with paranoid schizophrenic patients had greater gray matter volume in left inferior frontal gyrus, left superior temporal gyrus and right caudate than the patients with bipolar disorder. Patients with schizophrenic and bipolar disorder have different changes in brain structure. However, they also share the same reduction of GDV in right temporal gyrus.


Influence of water flow rate on shear bond strength of resin composite to Er:YAG cavity preparation.
To evaluate in vitro the influence of water flow rate on shear bond strength of a resin composite to enamel and dentin after Er:YAG cavity preparation. Ten bovine incisors were selected and roots removed. Crowns were sectioned in four pieces, resulting in 40 samples that were individually embedded in polyester resin (n = 10), and ground to plane the enamel and expose the dentin. The bonding site was delimited and samples were randomly assigned according to cavity preparation: (1) Er:YAG/1.0 mL/minute; (2) Er:YAG/1.5 mL/minute; (3) Er:YAG/2.0 mL/minute and (4) High speed handpiece/bur (control group). Samples were fixed to a metallic device, where composite resin cylinders were prepared. Subsequently, they were stored for 24 hours and subjected to a shear bond strength test (500N at 0.5 mm/minute). Means (MPa) were: enamel: 1: 12.8; 2: 16.8; 3: 17.5; 4: 36.0 and Dentin: 1: 13.6; 2: 18.7; 3: 12.1; 4: 21.3. Data were submitted to ANOVA and Tukey's test. Adhesion to enamel was more efficient than for dentin. The cavities prepared with conventional bur (control) presented higher statistically significant bond strength values (P < 0.05) than for Er:YAG laser for both enamel and dentin. No significant differences were observed between water flow rates employed during enamel ablation. For dentin, the shear bond strength of 2.0 mL/minute water flow rate was lower than for 1.5 mL/minute and 1.0 mL/minute rates. The Er:YAG laser adversely affected shear bond strength of resin composite to both enamel and dentin, regardless of the water flow rate used.