Solution-processed bulk heterojunction photovoltaic cells from gradient pi-conjugated thienylene vinylene dendrimers.
A series of gradient pi-conjugated dendrimers and their corresponding models based on 5,5,10,10,15,15-hexahexyltruxene moieties as nodes and oligo(thienylene vinylene) (OTVs) units with different lengths as branching arms are synthesized in good yields through Wittig-Horner reactions. All new compounds are fully characterized by (1)H and (13)C NMR spectroscopy, elemental analysis, and MALDI-TOF MS or ESI-MS. Investigation of their photophysical properties reveals that the gradient dendritic scaffold not only results in a higher molar absorption coefficient and broader absorption region than those of their corresponding model compounds, but also improves the PL quantum yields relative to the corresponding OTVs. The suitable HOMO and LUMO levels as well as excellent film forming properties make these molecules potential candidates for organic solar cells. Solution-processed bulk heterojunction solar cells using these dendrimers as donor and [6,6]-phenyl-C(61) butyric acid methyl ester as acceptor are prepared and tested. The power conversion efficiency of the devices based on G0-4-2 is 0.40 % under illumination of air mass 1.5 and 100 mW cm(-2). This is the highest record value for OTV-based materials to date. Although the absorption band of dendrimer G0-4-2 is much narrower than that of poly(3-hexylthienylene vinylene) (P3HTV), the efficiency of its solar cell device is almost twice that of the device based on P3HTV. This result shows clearly the advantage of gradient dendritic structures as active materials for photovoltaic cells.


Decision analysis, public health policy, and isoniazid chemoprophylaxis for young adult tuberculin skin reactors.
As part of a plan to eliminate tuberculosis in America, tuberculin skin testing was advised for all US citizens, with isoniazid chemopreventive therapy administered to appropriate positive reactors. Implementation of this plan, however, may be limited by concerns over which skin test reactors should receive isoniazid therapy. Recent decision analyses suggest that, contrary to American Thoracic Society guidelines, asymptomatic skin test reactors under age 35 years with normal chest roentgenograms and no predisposing conditions to tuberculosis reactivation will not benefit from isoniazid chemopreventive therapy. Repeated analysis of these studies reveals that calculated life expectancy depends on estimates of the probability of certain chance outcomes. If the isoniazid-related hepatitis case-fatality rate is below 1%, isoniazid chemopreventive therapy appears to be beneficial. A literature review suggests that this rate is indeed this low. If the tuberculosis case-fatality rate is above 6.7%, also supported by the literature, the advantages of isoniazid therapy are further increased. This repeated analysis should reassure physicians that isoniazid chemoprophylaxis for tuberculin skin test reactors is beneficial to the individual and consonant with public health policies.


Clearing the Smoke Screen: Smoking, Alcohol Consumption, and Stress Management Techniques among Canadian Long-Term Care Workers.
Currently, there is abundant research indicating that smoking and alcohol consumption have significant impacts on morbidity and mortality, though little is known about these behaviors among Canadian health care workers. The objective of this study was to examine health and coping behaviors, such as smoking and alcohol consumption as well as stress management techniques, among health care workers consisting of gendered, racialized, and immigrant employees. Drawing on a single-case, mixed-methods study in Ontario, Canada, this paper presents under-researched data about smoking practices, alcohol consumption, and stress management techniques among health care workers in labor-intensive, high-stress, high-turnover environments. In particular, it identifies the various mechanisms for maintaining health and well-being. The findings suggest that 7.7% of survey respondents reported smoking while 43.4% reported alcohol consumption, which were reported more frequently among immigrants than among non-immigrants. Participants also reported health-promoting activities in face-to-face interviews, such as mindful breathing techniques and drawing upon social support, while a few respondents reported alcohol consumption to specifically cope with sleep disturbances and job stress. Although smoking and alcohol consumption were both connected with coping strategies and leisure, they were predominant in immigrant groups compared to non-immigrant groups.


Development and Validation of MRI Sacroiliac Joint Scoring Methods for the Semiaxial Scan Plane Corresponding to the Berlin and SPARCC MRI Scoring Methods, and of a New Global MRI Sacroiliac Joint Method.
To develop semiaxial magnetic resonance imaging (MRI) scoring methods for assessment of sacroiliac joint (SIJ) bone marrow edema (BME) in patients with axial spondyloarthritis, and to compare the reliability with equivalent semicoronal scoring methods. Two semiaxial SIJ MRI scoring methods were developed based on the principles of the semicoronal Berlin and Spondyloarthritis Research Consortium of Canada (SPARCC) methods. A global quadrant-based method was also developed. Baseline and 12-week MRI of the SIJ from 51 patients participating in a randomized double-blind placebo-controlled trial of adalimumab 40 mg every other week versus placebo were scored by the semiaxial and the corresponding semicoronal methods. Results were compared by linear regression analysis. The reproducibility and sensitivity were evaluated by intraclass correlation coefficients (ICC) and smallest detectable change [SDC, absolute values and percentage of the highest observed score (SDC-HOS)]. Interreader and intrareader ICC were moderate to very high for semiaxial scoring methods (baseline 0.83-0.88 and 0.85-0.97; change 0.33-0.78), while high to very high for semicoronal scoring methods (baseline 0.90-0.92 and 0.93-0.97; change 0.77-0.89). Association between semiaxial and semicoronal scores were high for both the Berlin and SPARCC method (baseline: R2 = 0.93 and 0.88; change: R2 = 0.82 and 0.87, respectively), while lower for the global method (baseline: R2 = 0.79; change: R2 = 0.54). The SDC-HOS were 9.8-18.6% and 5.9-10.7% for the semiaxial and semicoronal methods, respectively. Detection of SIJ BME in the semiaxial scan plane is feasible and reproducible. However, a slightly lower reliability of all 3 semiaxial methods supports the general practice of using the coronal scan-plane in therapeutic studies.


Pleomorphic ichthyosis: proposed name for a heterogeneous group of congenital ichthyoses with phenotypic shifting and mild residual scaling.
Congenital ichthyosis is often associated with typical neonatal phenotypes, "Collodion baby" and "Harlequin foetus", later transforming into severe lamellar or erythrodermic ichthyosis. However, in a minority of cases the skin condition will improve spontaneously after birth, although slight scaling, xerosis, hypohidrosis and keratoderma usually persist. Some of these patients will eventually be diagnosed as suffering from self-improving collodion ichthyosis, ichthyosis prematurity syndrome, or other, even rarer, forms of ichthyosis also characterized by a phenotypic shift in early childhood. This paper summarizes newly described aetiologies for some of these diseases and discusses difficulties encountered when trying to distinguish them clinically from other types of autosomal recessive congenital ichthyosis. To remind health providers about this heterogeneous group of partially transient disorders of cornification, a new umbrella term, "pleomorphic ichthyosis", is proposed.


Immunologic dysregulation in a patient with familial hemophagocytic lymphohistiocytosis.
A 6-year-old Jewish Iranian girl with familial hemophagocytic lymphohistiocytosis (FHLH) is described. The course of the disease fluctuated with partial initial response to antibiotics, steroids, and supportive treatment. Subsequent cytotoxic treatment, including VP-16, Velban (vinblastine sulfate), and methotrexate (MTX) controlled the disease for a few months but the child died with a clinical picture of meningocephalitis 1.5 years later. Benign-looking lymphohistiocytic infiltrates with varying degrees of hemophagocytosis were present in the bone marrow, pleural effusion, cerebrospinal fluid (CSF), liver, and brain. Clinical and laboratory evidence of immunologic dysregulation during the disease could be demonstrated. Frequent and intense viral and bacterial infectious diseases were encountered. The laboratory examination most consistently found was the absence of natural killer (NK) cell activity against K562 target cells. The impaired activity of NK cells persisted during all stages of the disease including remission, although NK cell numbers, determined morphologically and immunophenotypically (by Leu-11, Leu-7), were normal. Natural killer activity could not be restored by interferon. Moreover, the interferon system appeared to be intact. Impaired monokin interleukin 1 (IL-I) production by peripheral blood monocytes was found and could not be restored by indomethacin. Lymphopenia, a mild decrease in T4 numbers, and subsequently, decreased proliferative response to mitogens was noted. Elevated immunoglobulin levels were found during exacerbations and viral episodes, at times accompanied by the presence of auto-antibodies. The exaggerated fatal lymphohistiocytic response typical for FHLH could be attributed to a underlying genetic pathologic dysregulation of the various immunological response pathways.


An observational study on the empiric use of cefpirome in febrile neutropenia.
The objective of this study was to document the clinical experience of cefpirome use in the treatment of febrile neutropenia in everyday medical practice. This was an open, non-controlled multicenter study. Patients with fever and neutropenia were started on cefpirome empirically. Response to therapy was evaluated 72 to 96 h after the beginning of treatment. The primary endpoint, clinical response, was classified as: improvement (disappearance of fever and the other signs and symptoms of infection) or failure (the patient died during the therapy or had no response to the antibiotic regimen; i.e., fever persisted and the patient's clinical condition was not improving, requiring a change in antibiotic therapy). The secondary endpoints were time to the resolution of fever and improvement of neutropenia, and microbiological response evaluated on-treatment or post-treatment. 140 patients were enrolled in this study; clinical response was analyzed on the clinically evaluated population after 72 to 96 h of treatment. Among the 69 evaluated patients, 58 patients (84.1%) were improved and 11 patients (15.9%) failed. Overall, among the enrolled 140 patients, 124 patients' clinical outcomes were improved after treatment and 16 patients failed. The mean time to fever resolution was 3.1 days. Mean temperature reduced from a baseline reading of 38.7 degrees C to 37.2 degrees C (p<0.0001). Moreover, the mean neutrophil count (342.7/mm(3) at baseline) increased significantly to 3664/mm(3) (p<0.0001) after 72 to 96 h of treatment. Twenty five pathogens were isolated from 20 patients (13 Gram-positive and 9 Gram-negative). The eradication rate was 72% on-treatment or post-treatment, and the mean time to eradication was 5 days. Cefpirome improves clinical signs and symptoms of infection and offers improved coverage against some Gram-positive and Gram-negative pathogens in patients with febrile neutropenia. Thus, cefpirome is likely to be a valuable and cost-effective extended-spectrum agent for the empiric treatment of severe infections.


The biosynthetic pathway of curcuminoid in turmeric (Curcuma longa) as revealed by 13C-labeled precursors.
In order to investigate the biosynthesis of curcuminoid in rhizomes of turmeric (Curcuma longa), we established an in vitro culture system of turmeric plants for feeding (13)C-labeled precursors. Analyses of labeled desmethoxycurcumin (DMC), an unsymmetrical curcuminoid, by (13)C-NMR, revealed that one molecule of acetic acid or malonic acid and two molecules of phenylalanine or phenylpropanoids, but not tyrosine, were incorporated into DMC. The incorporation efficiencies of the same precursors into DMC and curcumin were similar, and were in the order malonic acid > acetic acid, and cinnamic acid > p-coumaric acid >> ferulic acid. These results suggest the possibility that the pathway to curcuminoids utilized two cinnamoyl CoAs and one malonyl CoA, and that hydroxy- and methoxy-functional groups on the aromatic rings were introduced after the formation of the curcuminoid skeleton.


Effects of harmonics on relative pitch discrimination in a musical context.
The contribution of different harmonics to pitch salience in a musical context was examined by requiring subjects to discriminate a small (1/4 semitone) pitch change in one note of a melody that repeated in transposition. In Experiment 1, performance was superior when more harmonics were present (first five vs. fundamental alone) and when the second harmonic (of tones consisting of the first two harmonics) was in tune compared with when it was out of tune. In Experiment 2, the effects of harmonics 6 and 8, which stand in octave-equivalent simple ratios to the fundamental (2:3 and 1:2, respectively) were compared with harmonics 5 and 7, which stand in more complex ratios (4:5 and 4:7, respectively). When the harmonics fused into a single percept (tones consisting of harmonics 1, 2, and one of 5, 6, 7, or 8), performance was higher when harmonics 6 or 8 were present than when harmonics 5 or 7 were present. When the harmonics did not fuse into a single percept (tones consisting of the fundamental and one of 5, 6, 7, or 8), there was no effect of ratio simplicity.


Episcleral and orbital pseudorheumatoid nodules.
Pseudorheumatoid nodules are subcutaneous necrobiotic granulomas that are histopathologically similar or identical to those seen with rheumatoid arthritis, granuloma annulare, necrobiosis lipoidica diabeticorum, and systemic lupus erythematosus. Although these nodules are most common in children, they are also seen in adults and are usually located on the extremities and scalp. Eyelid and eyebrow involvement is seen infrequently. We histopathologically verified episcleral and orbital pseudorheumatoid nodules in an adult with eyelid and eyebrow nodules. Pseudorheumatoid nodules must be included in the differential diagnosis of subconjunctival mass lesions that may concomitantly involve the orbit, episclera, and periocular region.


Toward a model of continuous care: A necessity for caregiving partners.
Caregiving partners constitute a unique group, who provide both physical and emotional care for patients. There has been extensive research conducted on caregivers during either the caregiving or bereavement phase; however, these phases are often treated as separate entities rather than as part of a continuum. In this paper, utilizing relevant literature and clinical observations, we map the emotional journey and lived experience of caregivers moving from disease progression, to the end of life, to the dying process itself, and then through life after the death of a partner. Along this journey, we identify the links between pre-death caregiving and bereavement. Our illustration raises awareness regarding the unmet needs experienced by caregiving partners across the continuum and provides an alternative framework through which clinicians can view this course. of Results We bolster arguments for improved palliative care services and early interventions with distressed caregiving partners by emphasizing continuity of care both before and after a patient's death.


The usefulness of the cervical range of motion device in the ocular motility examination.
To determine if the cervical range of motion (CROM) device, an instrument designed to assess the range of motion in the cervical spine, may be suited for accurately quantifying the magnitude of a patient's abnormal head posture, limitation of ductions, or range of single binocular vision at distance fixation. The CROM device was used to measure abnormal head postures in 10 subjects and limitations of ductions in 12 patients by 2 masked observers. In addition, it was used to test the diplopia field in 17 patients at one third of a meter and 6 m. These findings were compared with a standard diplopia field performed on a Goldmann perimeter. For 10 subjects with abnormal head postures, the findings of the 2 observers had a mean+/-SD difference of 1.0 degrees +/-0.7 degrees (P=.15, paired t test). For the assessment of limitations of ductions, the findings of the 2 observers had a mean+/-SD difference of 1.1 degrees +/-2.6 degrees (P=.17, paired t test). For the 17 patients undergoing diplopia field testing, the results obtained on the Goldmann perimeter and with CROM device at the same test distance were essentially identical (mean+/-SD difference of 1.3 degrees +/-0.95 degrees; P=.88, paired t test); however, there was a significant difference between the results at one third of a meter and 6 m (mean+/-SD difference of 6.0 degrees +/-1.1 degrees for esotropic patients [P=.001]; mean+/-SD difference of 6.0 degrees +/-2.6 degrees for exotropic patients [P=.002]). The CROM device seems to be suitable for testing abnormal head postures, limitations of ductions, and the range of single binocular vision. Arch Ophthalmol. 2000;118:946-950


Seroprevalence of Toxoplasma gondii infection in freerange chickens in Jilin Province, northeastern China.
The prevalence of Toxoplasma gondii infection in free-range chickens in Jilin province, northeastern China was investigated. A total of 1095 serum samples were collected from nine administrative regions from July to October, 2012, and antibodies to T. gondii were examined by an in-house enzyme-linked immunosorbent assay (ELISA) using Toxoplasma lysate antigen (TLA). The detection results were confirmed by Western blot. The overall seroprevalence of T. gondii in free-range chickens was 17.6% (95% confidence interval [CI], 15.4-19.4%), ranging from 13.3% (95% CI, 6.3-20.4%) in Siping to 23.6% (95% CI, 15.7-31.6%) in Liaoyuan. There was no significant difference in T. gondii infection among different regions in Jilin province (P> 0.05). The widespread presence of T. gondii infection in freerange chickens of Jilin province implies the wide contamination with T. gondii oocysts in the living environment of people, and free-range chickens might be an important source of infection for humans.


A token-flow paradigm for verification of rule-based expert systems.
This paper presents a novel approach to the verification of rule-based systems (RBSs). A graph structure, called the rule-dependency graph (RDG), is introduced to describe the dependency relationship among the rules of an RBS, in which each type of improper knowledge forms a specific topological structure. Knowledge verification is then performed by searching for such topological structures through a token-flow paradigm. An algorithm is provided, which automatically generates a minimally sufficient set of literals as test tokens in the detection procedure. The proposed scheme can be applied to rules of non-Horn clause form in both propositional and first-order logic, and restrictions imposed by other graph-based approaches can be avoided. Furthermore, explicit and potential anomalies of RBSs can be correctly found, and efficient run-time validation is made possible.


Temperature-mediated patterns of local adaptation in a natural plant-pathogen metapopulation.
There have been numerous investigations of parasite local adaptation, a phenomenon important from the perspectives of both basic and applied evolutionary ecology. Recent work has demonstrated that temperature has striking effects on parasite performance by mediating trade-offs in parasite life history and through genotype x environment interactions. To test whether parasite local adaptation is mediated by temperature, I measured the performance of sympatric populations against allopatric populations of a fungal pathogen, Podosphaera plantaginis, on its host Plantago lanceolata, across a temperature gradient. I used data on parasite life history and epidemiology to derive fitness estimates to measure local adaptation. The results demonstrate unambiguously that trajectories of host-parasite co-evolution are tightly coupled with parasite adaptation to the abiotic habitat, as the strength, and even direction, of local adaptation varied with temperature. Patterns of local adaptation further depended on how parasite fitness was estimated, highlighting the importance of choosing relevant fitness measures in studies of local adaptation.


Role of laminin receptor in tumor cell migration.
Polyclonal antisera were made against biochemically purified laminin receptor protein as well as against synthetic peptides deduced from a complementary DNA clone corresponding to the COOH-terminal end of the laminin receptor (U.M. Wewer et al., Proc. Natl. Acad. Sci. USA, 83: 7137-7141, 1986). These antisera were used to study the potential role of laminin receptor in laminin-mediated attachment and haptotactic migration of human A2058 melanoma cells. The anti-laminin receptor antisera reacted with the surface of suspended, nonpermeabilized melanoma and carcinoma cells. The anti-laminin receptor antisera blocked the surface interaction of A2058 cells with endogenous laminin, resulting in the inhibition of laminin-mediated cell attachment. The A2058 melanoma cells migrated toward a gradient of solid phase laminin or fibronectin (haptotaxis). Anti-laminin antiserum abolished haptotaxis on laminin but not on fibronectin. Synthetic peptide GRGDS corresponding to the fibronectin cell-binding domain inhibited haptotaxis on fibronectin but not on laminin. Both types of anti-laminin receptor antisera inhibited haptotaxis on laminin but not on fibronectin. Using immunohistochemistry, invading human carcinoma cells in vivo exhibited a marked cytoplasmic immunoreactivity for the receptor antigen. Together these findings indicate a specific role for the laminin receptor in laminin-mediated migration and that the ligand binding of the laminin receptor is encompassed in the COOH-terminal end of the protein.


Exercise of low energy expenditure along with mild energy intake restriction acutely reduces fasting and postprandial triacylglycerolaemia in young women.
A single bout of prolonged, moderate-intensity endurance exercise lowers fasting and postprandial TAG concentrations the next day. However, the TAG-lowering effect of exercise is dose-dependent and does not manifest after light exercise of low energy cost ( < 2 MJ). We aimed to investigate whether superimposing mild energy intake restriction to such exercise, in order to augment total energy deficit, potentiates the hypotriacylglycerolaemic effect. Eight healthy, sedentary, premenopausal women (age 27.1 (sem 1.3) years; BMI 21.8 (sem 0.9) kg/m2) performed two oral fat tolerance tests in the morning on two different occasions: once after a single bout of light exercise (100 min at 30 % of peak oxygen consumption; net energy expenditure 1.04 (sem 0.01) MJ) coupled with mild energy intake restriction (1.39 (sem 0.22) MJ) on the preceding day, and once after resting coupled with isoenergetic feeding on the preceding day (control). Fasting plasma TAG, TAG in the TAG-rich lipoproteins (TRL-TAG) and serum insulin concentrations were 18, 34 and 30 % lower, respectively, after exercise plus diet compared with the control trial (P < 0.05). Postprandial concentrations of plasma TAG and TRL-TAG were 19 and 27 % lower after exercise plus diet compared with the control condition (P < 0.01), whereas postprandial insulin concentrations were not different. It is concluded that a combination of light exercise along with mild hypoenergetic diet may be a practical and feasible intervention to attenuate fasting and postprandial triacylglycerolaemia, especially for people who cannot exercise for prolonged periods of time at moderate-to-high intensities, such as many sedentary individuals.


Soft Electronic Materials with Combinatorial Properties Generated via Mussel-Inspired Chemistry and Halloysite Nanotube Reinforcement.
Soft and electrically active materials are currently being utilized for intelligent systems, including electronic skin, cybernetics, soft robotics, and wearable devices. However, fabricating materials that fulfill the complex requirements of such advanced applications remains a challenge. These attributes include electronic, adhesive, self-healing, flexible, moldable, printable, and strong mechanical properties. Inspired by the recent interest in transforming monofunctional materials into multifunctional ones through nanoreinforcement and mussel-inspired chemistry, we have designed a simple two-step methodology based on halloysite nanotube (HNT) and polydopamine (PDA) to address the grand challenges in the field. In brief, HNTs were coated with PDA and embedded within a poly(vinyl alcohol) (PVA)-based polymeric matrix in combination with ferric ions (Fe3+). The final composite displayed a 3-fold increase in electrical conductivity, a 20-fold increase in mechanical stiffness, and a 7-fold increase in energy dissipation in comparison to their nonfunctional counterparts, which arose from a combination of nanotube alignment and mussel-inspired chemistry. Moreover, the developed composite could elongate up to 30000% of its original length, maintain its electrical properties after 600% strain, self-heal within seconds (both electrically and mechanically), and display strain-sensitivity. Finally, it was 3D-printable and thus amenable for engineering of customized wearable electronics.


Urinary excretion of arsenic species after exposure to arsenic present in drinking water.
The water from some drilled wells in southwest Finland contains high arsenic concentrations (min-max: 17-980 microg/L). We analyzed inorganic arsenic (As-i) and organic arsenic (monomethylarsonate [MMA] and dimethylarsinate [DMA]) species in urine and conducted a clinical examination of current users (n = 35) and ex-users (n = 12) of such wells. Ex-users had ceased to use the water from the wells 2-4 months previously. Urinary arsenic species were also analyzed from persons whose drinking water contained less than 1 microg/L of arsenic (controls, n = 9). The geometric means of the concentrations of total arsenic in urine were 58 microg/L for current users, 17 microg/L for ex-users, and 5 microg/L for controls. The excreted arsenic was associated with the calculated arsenic doses, and on average 63% of the ingested arsenic dose was excreted in urine. The ratios of MMA/DMA and As-i/As-tot (As-tot = As-i + MMA + DMA) in urine tended to be lower among the current users and in the higher exposure levels than in controls, suggesting that As-i was better methylated in current users. However, the differences were mainly explained by age; older persons were better methylators of inorganic arsenic than younger individuals. The arsenic content of hair correlated well with the past and chronic arsenic exposure; an increase of 10 microg/L in the arsenic concentration of the drinking water or an increase of 10-20 microg/day of the arsenic exposure corresponded to a 0.1 mg/kg increase in hair arsenic. The individuals were interviewed and complained of muscle cramps, mainly in the legs, and this was associated with elevated arsenic exposure. The present study demonstrates that arsenic methylation has no threshold at these exposure levels.


Incidence of arrhythmias and impact of permanent pacemaker implantation in hospitalizations with transcatheter aortic valve replacement.
This study sought to analyze in-hospital outcomes associated with preexisting and newly implanted permanent pacemaker (PPM) in patients who underwent transcatheter aortic valve replacement (TAVR). PPM implantation following the development of conduction abnormalities is a common adverse event following TAVR. Furthermore, PPM implantation rates are higher in TAVR hospitalizations compared with the surgical alternative, thus we have analyzed the predictors of pacing post-TAVR. We hypothesize that incidence of arrhythmias are high post-TAVR and have worse adverse outcomes after receiving PPM. The study population was identified from the National Inpatient Sample database between 2012 and 2014. TAVR population was identified using ICD-9-CM procedure codes 35.05 and 35.06. Hospitalizations were divided into 3 group: (1) with preexisting PPM, (2) with newly implanted PPM, and (3) without any PPM. Overall, 0.8% of hospitalizations presented with preexisting PPM and 23.7% of hospitalizations received new PPM. The overall incidence of atrial fibrillation was 44.5%, left bundle branch block 8.9%, complete atrioventricular block 9.5%, and right bundle branch block 2.7%. In-hospital mortality was higher in hospitalizations receiving PPM compared with those without (4.9% vs 4.0%; P = 0.05). Length of stay and cost were higher in the group receiving new PPM. Female sex, atrial fibrillation, left bundle branch block, and second-degree and complete atrioventricular block were significant predictors for receiving PPM after TAVR. A risk stratification for hospitalizations with conduction disorders is necessary to avoid longer hospital stays, added costs, and mortality. Further research is warranted to investigate additional predictors for PPM after TAVR.


Particulate matter composition and respiratory health: the PIAMA Birth Cohort study.
Ambient particulate matter (PM) exposure is associated with children's respiratory health. Little is known about the importance of different PM constituents. We investigated the effects of PM constituents on asthma, allergy, and lung function until the age of 11-12 years. For 3,702 participants of a prospective birth cohort study, questionnaire-reported asthma and hay fever and measurements of allergic sensitization and lung function were linked with annual average concentrations of copper, iron, potassium, nickel, sulfur, silicon, vanadium, and zinc in particles with diameters of less than 2.5 and 10 μm (PM2.5 and PM10) at birth addresses and current addresses from land-use regression models. Exposure-health relations were analyzed by multiple (repeated measures) logistic and linear regressions. Asthma incidence and prevalence of asthma symptoms and rhinitis were positively associated with zinc in PM10 at the birth address (odds ratio [95% confidence interval] per interquartile range increase in exposure 1.13 [1.02, 1.25], 1.08 [1.00, 1.17], and 1.16 [1.04, 1.30], respectively). Moreover, asthma symptoms were positively associated with copper in PM10 at the current address (1.06 [1.00, 1.12]). Allergic sensitization was positively associated with copper and iron in PM10 at the birth address (relative risk [95% confidence interval] 1.07 [1.01, 1.14] and 1.10 [1.03, 1.18]) and current address. Forced expiratory volume in 1 second was negatively associated with copper and iron in PM2.5 (change [95% confidence interval] -2.1% [-1.1, -0.1%] and -1.0% [-2.0, -0.0%]) and FEF75-50 with copper in PM10 at the current address (-2.3% [-4.3, -0.3%]). PM constituents, in particular iron, copper, and zinc, reflecting poorly regulated non-tailpipe road traffic emissions, may increase the risk of asthma and allergy in schoolchildren.


Genetic polymorphisms of CYP2D6*10 and the effectiveness of combined tamoxifen citrate and testosterone undecanoate treatment in infertile men with idiopathic oligozoospermia.
Tamoxifen citrate, as the first line of treatment for infertile men with idiopathic oligozoospermia, was proposed by the World Health Organization (WHO), and testosterone undecanoate has shown benefits in semen values. Our objective was to assess the effectiveness of treatment with tamoxifen citrate and testosterone undecanoate in infertile men with idiopathic oligozoospermia, and whether the results would be affected by polymorphisms of CYP2D6*10. A total of 230 infertile men and 147 controls were included in the study. Patients were treated with tamoxifen citrate and testosterone undecanoate. Sex hormone, sperm parameters, and incidence of spontaneous pregnancy were detected. There were no significant differences between the control and patient groups with respect to CYP2D6*10 genotype frequencies (P>0.05). The follicle-stimulation hormone (FSH), luteinizing hormone (LH), and testosterone (T) levels were raised, and sperm concentration and motility were increased at 3 months and became significant at 6 months, and they were higher in the wild-type allele (C/C) than in the heterozygous variant allele (C/T) or homozygous variant allele (T/T) subgroups (P<0.05). In addition, the percentage of normal morphology was raised at 6 months, and represented the highest percentage in the C/C subgroup (P<0.05). The incidence of spontaneous pregnancy in the C/C subgroup was higher than that in the C/T or T/T subgroups (P<0.01). This study showed that the CYP2D6*10 variant genotype demonstrated worse clinical effects in infertile men with idiopathic oligozoospermia.


A cluster randomized clinical trial comparing fit-tested and non-fit-tested N95 respirators to medical masks to prevent respiratory virus infection in health care workers.
We compared the efficacy of medical masks, N95 respirators (fit tested and non fit tested), in health care workers (HCWs). A cluster randomized clinical trial (RCT) of 1441 HCWs in 15 Beijing hospitals was performed during the 2008/2009 winter. Participants wore masks or respirators during the entire work shift for 4 weeks. Outcomes included clinical respiratory illness (CRI), influenza-like illness (ILI), laboratory-confirmed respiratory virus infection and influenza. A convenience no-mask/respirator group of 481 health workers from nine hospitals was compared. The rates of CRI (3·9% versus 6·7%), ILI (0·3% versus 0·6%), laboratory-confirmed respiratory virus (1·4% versus 2·6%) and influenza (0·3% versus 1%) infection were consistently lower for the N95 group compared to medical masks. By intention-to-treat analysis, when P values were adjusted for clustering, non-fit-tested N95 respirators were significantly more protective than medical masks against CRI, but no other outcomes were significant. The rates of all outcomes were higher in the convenience no-mask group compared to the intervention arms. There was no significant difference in outcomes between the N95 arms with and without fit testing. Rates of fit test failure were low. In a post hoc analysis adjusted for potential confounders, N95 masks and hospital level were significant, but medical masks, vaccination, handwashing and high-risk procedures were not. Rates of infection in the medical mask group were double that in the N95 group. A benefit of respirators is suggested but would need to be confirmed by a larger trial, as this study may have been underpowered. The finding on fit testing is specific to the type of respirator used in the study and cannot be generalized to other respirators. Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN: ACTRN12609000257268 (http://www.anzctr.org.au).


Selective Temporary Stent-Assisted Coil Embolization for Intracranial Wide-Necked Small Aneurysms Using Solitaire AB Retrievable Stent.
Stent-assisted coil embolization of intracranial wide-necked aneurysm requires long-term postoperative antiplatelet therapy to prevent in-stent thrombosis. This study aimed to demonstrate results of temporary stent placement for coiling wide necked small intracranial aneurysms, which eliminated need for antiplatelet agents, and to discuss its feasibility and safety. Data of 156 patients who underwent stent-assisted coil embolization between 2011 and 2014 were retrospectively analyzed. Thirteen cases of temporary stent-assisted coil embolization were included, and their clinical and radiological results were evaluated. The aneurysms treated were all unruptured except one case. All of them had wide neck with mean dome-to-neck ratio of 0.96 and were small-sized aneurysms with mean maximal diameter of 4.2 mm. There was no technical failure in retrieval of stent after completion of embolization of the target aneurysm. Immediate angiography revealed 11 complete and two partial embolization (one residual neck and one residual aneurysm). Two cases encountered thrombosis complication, and they were managed without neurological sequelae. The mean follow-up period was 43 months, angiographic follow-up revealed two cases with minor recurrence, and clinical outcome was good with modified Rankin scale score of 0. Temporary stent-assisted coil embolization of small wide-necked intracranial aneurysm using fully retrievable stent appears safe and effective. Further application and evaluation of this technique in more cases with larger size aneurysm is warranted.


Functional anatomy of pelvic floor.
Generally, descriptions of the pelvic floor are discordant, since its complex structures and the complexity of pathological disorders of such structures; commonly the descriptions are sectorial, concerning muscles, fascial developments, ligaments and so on. On the contrary to understand completely nature and function of the pelvic floor it is necessary to study it in the most unitary view and in the most global aspect, considering embriology, philogenesy, anthropologic development and its multiple activities others than urological, gynaecological and intestinal ones. Recent acquirements succeeded in clarifying many aspects of pelvic floor activity, whose musculature has been investigated through electromyography, sonography, magnetic resonance, histology, histochemistry, molecular research. Utilizing recent research concerning not only urinary and gynecologic aspects but also those regarding statics and dynamics of pelvis and its floor, it is now possible to study this important body part as a unit; that means to consider it in the whole body economy to which maintaining upright position, walking and behavior or physical conduct do not share less than urinary, genital, and intestinal functions. It is today possible to consider the pelvic floor as a musclefascial unit with synergic and antagonistic activity of muscular bundles, among them more or less interlaced, with multiple functions and not only the function of pelvic cup closure.


Time to achieving therapeutic international normalized ratio increases hospital length of stay after heart valve replacement surgery.
Achieving a therapeutic international normalized ratio (INR) before hospital discharge is an important inpatient goal for patients undergoing mechanical cardiac valve replacement (MCVR). The use of clinical algorithms has reduced the time to achieve therapeutic INR (TTI) with warfarin therapy. Whether TTI prolongs length of stay (LOS) is unknown. Patients who underwent MCVR over a consecutive 42-month period were included. Clinical data were obtained from the Society of Thoracic Surgeons Adult Cardiac Surgery database and electronic medical records. Therapeutic INR was defined as per standard guidelines. Warfarin dose was prescribed using an inpatient pharmacy-managed algorithm and computer-based dosing tool. International normalized ratio trajectory, procedural needs, and drug interactions were included in warfarin dose determination. There were 708 patients who underwent MCVR, of which 159 were excluded for reasons that would preclude or interrupt warfarin use. Among the remainder of 549 patients, the average LOS was 6.4days and mean TTI was 3.5days. Landmark analysis showed that subjects in hospital on day 4 (n=542) who achieved therapeutic INR were more likely to be discharged by day 6 compared with those who did not achieve therapeutic INR (75% vs 59%, P<.001). Multivariable proportional hazards regression with TTI as a time-dependent effect showed a strong association with discharge (P=.0096, hazard ratio1.3) after adjustment for other significant clinical covariates. Time to achieve therapeutic INR is an independent predictor of LOS in patients requiring anticoagulation with warfarin after MCVR surgery. Alternative dosing and anticoagulation strategies will need to be adopted to reduce LOS in these patients.


Intestinal mucosal damage caused by non-steroidal anti-inflammatory drugs: role of bile salts.
The strong analgesic, anti-inflammatory effects of non-steroidal anti-inflammatory drugs (NSAIDs) are hampered by high occurrence of gastrointestinal side effects. Therapeutic actions of NSAIDs result from cyclooxygenase (COX) enzymes inhibition with reduced synthesis of prostaglandins, major modulators of inflammation. Since prostaglandins also regulate key events in gut homeostasis -mucosal secretion, blood flow, epithelial regeneration - COX inhibition has been accepted as the reason for NSAID gastrointestinal toxicity. Several findings challenge this theory: first, intestinal damage by NSAIDs occurs also in COX-1 knockout mice, demonstrating that topical (non-prostaglandin mediated) mechanisms are involved; second, no correlation is found in vivo between the extent of intestinal injury and the degree of inhibition of prostaglandin synthesis; third, bile flow interruption in animal models completely prevents intestinal damage by parenterally administered NSAIDs. What is in bile that could play a role in NSAID toxicity? This timely review will critically discuss the role of bile salts in NSAID-dependent gut damage.


Aroclor 1254 pretreatment effects on DNA repair in rat hepatocytes elicited by in vivo or in vitro exposure to various chemicals.
Inducers of liver mixed function oxidase (MFO) activities have profound effects on the genotoxicity of substances that undergo metabolic activation by the MFO system. The polychlorinated biphenyl mixture Aroclor 1254 is a broad-spectrum inducer of liver MFO activities that has been employed as a pretreatment to augment the metabolic activation capabilities of rat liver fractions used in a number of short-term tests for genotoxicity, including the Ames Salmonella/bacterial mutagenicity assay. The present study was designed to characterize the effects of Aroclor pretreatment of rats on the DNA repair responses elicited by various chemicals in the in vitro hepatocyte primary culture/DNA repair (HPC/DR) assay as well as the in vivo/in vitro HPC/DR assay. The amount of DNA repair produced in vitro by diethylnitrosamine (DEN), benzo(a)pyrene (B(a)P), 3-methylcholanthrene (3-MC), 2-acetylaminofluorene (2-AAF), o-aminoazotoluene (o-AT), and aflatoxin B1 (AFB1) was significantly greater in hepatocytes derived from Aroclor-pretreated rats than in control rat hepatocytes; in vitro responses to dimethylnitrosamine (DMN), 7,12-dimethylbenzanthracene (DMBA), benzidine (BZ), and 2-naphthylamine (2-NA) were not significantly affected by Aroclor pretreatment. DNA repair elicited by the direct-acting alkylating agents methyl methanesulfonate and N-methyl-N'-nitro-N-nitrosoguanidine was also not increased by Aroclor pretreatment, which indicated that Aroclor does not exert a general stimulatory effect on the hepatocellular DNA repair capacity. Therefore, the pretreatment-related potentiation of DNA repair observed for 6 out of 12 compounds tested in vitro was considered to be due to enhanced metabolic activation. These results suggested that pretreatment with Aroclor may increase the sensitivity of the in vitro HPC/DR assay to certain compounds. In contrast, Aroclor pretreatment had little effect on the amount of hepatocellular DNA repair elicited by in vivo administration of DMN, DEN, o-AT, 2-AAF, 3-MC, or AFB1, which indicated that this pretreatment regimen may have little utility for improving the sensitivity of the in vivo/in vitro HPC/DR assay.


Semax, a Synthetic Regulatory Peptide, Affects Copper-Induced Abeta Aggregation and Amyloid Formation in Artificial Membrane Models.
Alzheimer's disease, the most common form of dementia, is characterized by the aggregation of amyloid beta protein (Aβ). The aggregation and toxicity of Aβ are strongly modulated by metal ions and phospholipidic membranes. In particular, Cu2+ ions play a pivotal role in modulating Aβ aggregation. Although in the last decades several natural or synthetic compounds were evaluated as candidate drugs, to date, no treatments are available for the pathology. Multifunctional compounds able to both inhibit fibrillogenesis, and in particular the formation of oligomeric species, and prevent the formation of the Aβ:Cu2+ complex are of particular interest. Here we tested the anti-aggregating properties of a heptapeptide, Semax, an ACTH-like peptide, which is known to form a stable complex with Cu2+ ions and has been proven to have neuroprotective and nootropic effects. We demonstrated through a combination of spectrofluorometric, calorimetric, and MTT assays that Semax not only is able to prevent the formation of Aβ:Cu2+ complexes but also has anti-aggregating and protective properties especially in the presence of Cu2+. The results suggest that Semax inhibits fiber formation by interfering with the fibrillogenesis of Aβ:Cu2+ complexes.


Pretreatment with helium does not attenuate liver injury after warm ischemia-reperfusion.
Preconditioning with noble gases serves as an effective strategy to diminish tissue injury in different organs. The aim of this study was to investigate the influence of pretreatment with the nonanesthetic noble gas helium on hepatic injury after warm ischemia and reperfusion (IR) in comparison to ischemic preconditioning (IPC). Anesthetized and ventilated rats were randomized into six groups (n = 8/group): sham: after laparotomy, the portal triad was exposed without clamping; IPC was performed with 10 min of partial liver ischemia and 10 min of reperfusion; HePC: three cycles of 5 min with inhalation of helium 70 vol% and intermittent washout; IR: 45 min of ischemia followed by 240 min of reperfusion; IPC-IR: IPC followed by hepatic IR; HePC-IR: pretreatment with helium 70 vol% followed by hepatic IR. Hepatic injury was evaluated by measurement of serum enzymes aspartate aminotransferase and alanine aminotransferase. Hepatic mRNA expression and serum levels of tumor necrosis factor α (TNF-α) and interleukin 10 (IL-10) were measured with real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. Myeloperoxidase in liver tissue was assessed spectrophotometrically as a marker of neutrophil accumulation. mRNA levels of heme oxygenase 1 in liver tissue were assessed to investigate a protein of the most abundant protective system in the liver. Aspartate aminotransferase and alanine aminotransferase serum activities increased after hepatic IR (sham vs. IR; P < 0.05). The serum levels of liver enzymes after IR were significantly diminished with IPC (P < 0.05), whereas helium pretreatment had no effect. mRNA expression of TNF-α increased in all groups except IPC-IR compared with sham, whereas mRNA expression of IL-10 increased only after helium pretreatment. Serum levels of IL-10 were not affected by any intervention, whereas serum levels of TNF-α and liver myeloperoxidase were increased after IR, but not after HePC-IR. In conclusion, pretreatment with inhaled helium does not attenuate hepatic injury after warm IR of the liver, although there is evidence for a modulation of the inflammatory response.


Length of stay and economic consequences with rivaroxaban vs enoxaparin/vitamin K antagonist in patients with DVT and PE: findings from the North American EINSTEIN clinical trial program.
Venous thromboembolism (VTE) (deep vein thrombosis [DVT] and pulmonary embolism [(PE]) represents a substantial economic burden to the healthcare system. Using data from the randomized EINSTEIN DVT and PE trials, this North American sub-group analysis investigated the potential of rivaroxaban to reduce the length of initial hospitalization in patients with acute symptomatic DVT or PE. A post-hoc analysis of hospitalization and length-of-stay (LOS) data was conducted in the North American sub-set of patients from the randomized, open-label EINSTEIN trial program. Patients received either rivaroxaban (15 mg twice daily for 3 weeks followed by 20 mg once daily; n = 405) or dose-adjusted subcutaneous enoxaparin overlapping with (guideline-recommended 'bridging' therapy) and followed by a vitamin K antagonist (VKA) (international normalized ratio = 2.0-3.0; n = 401). The open-label study design allowed for the comparison of LOS between treatment arms under conditions reflecting normal clinical practice. LOS was evaluated using investigator records of dates of admission and discharge. Analyses were carried out in the intention-to-treat population using parametric tests. Costs were applied to the LOS based on weighted mean cost per day for DVT and PE diagnoses obtained from the Healthcare Cost and Utilization Project dataset. Of 382 patients hospitalized, 321 (84%), had acute symptomatic PE; few DVT patients required hospitalization. Similar rates of VTE patients were hospitalized in the rivaroxaban and enoxaparin/VKA treatment groups, 189/405 (47%) and 193/401 (48%), respectively. In hospitalized VTE patients, rivaroxaban treatment produced a 1.6-day mean reduction in LOS (median = 1 day) compared with enoxaparin/VKA (mean = 4.5 vs 6.1; median = 3 vs 4), translating to total costs that were $3419 lower in rivaroxaban-treated patients. In hospitalized North American patients with VTE, treatment with rivaroxaban produced a statistically significant reduction in LOS. When treating DVT and PE patients, clinicians should consider newer anti-coagulants with less complex treatment regimens.


Identification of paired immunoglobulin-like type 2 receptor α as hepatitis B virus DNA polymerase transactivated protein 1 interacting proteins.
Hepatitis B Virus (HBV) DNA polymerase transactivated protein 1 (HBVDNAPTP1) is a novel protein transfected by HBV DNA polymerase, which has been screened by a suppression subtractive hybridization technique. In the present study, a yeast two-hybrid system was used to screen the proteins interacting with HBVDNAPTP1 in leukocytes in order to investigate the biological function of HBVDNAPTP1. The HBVDNAPTP1 coding sequence was cloned into a pGEM-T vector. Subsequent to sequencing, the HBVDNAPTP1 was subcloned into the bait plasmid pGBKT7 and transformed into yeast AH109. Western blotting confirmed the presence of HBVDNAPTP1 expression in the AH109 yeast strains. The transformed yeast AH109 cells were mated with Y187 yeast cells containing the leucocyte cDNA library pACT2 plasmids in 2X yeast extract peptone D-glucose adenine (YPDA) medium. For selection and screening, diploid yeast was plated on synthetic dropout medium (SD/-Trp-Leu-His-Ade) containing X-α-gal. Following sequencing and the verification of the open reading frames of positive colonies, four different proteins were obtained. To further confirm the interaction between HBVDNAPTP1 and the screened proteins, paired immunoglobulin-like type 2 receptor α (PILRA), one of the positive colonies, was cloned. The glutathione S-transferase pull-down in vitro assay and a co-immunoprecipitation in vivo assay were used to examine the interaction between HBVDNAPTP1 and PILRA, respectively. HBVDNAPTP1 may be involved in the negative regulation of the PILRA‑mediated Janus-activated kinase/signal tranducer and activator of transcription signaling pathway, and exert a positive effect on the initiation of monocyte apoptosis. These results contribute our knowledge of the biological functions of HBVDNAPTP1 and provide novel data to aid in the further analysis of the regulatory mechanism of this protein.


Topically Applied Epsilon-Aminocaproic Acid Reduces Blood Loss and Length of Hospital Stay After Total Knee Arthroplasty.
Perioperative blood loss after total knee arthroplasty (TKA) affects postoperative recovery. Tranexamic acid is safe and efficient in reducing blood loss without increasing thromboembolic events. Epsilon-aminocaproic acid (ε-ACA) is less expensive than and as safe as tranexamic acid. Its efficiency when locally applied in TKA is unknown. The authors retrospectively followed 240 consecutive patients treated by 1 surgeon with TKA from January 2012 to August 2016. From January 2013 to May 2015, the authors topically applied 5 g of ε-ACA to the open wound after tourniquet release and before closure (ε-ACA-after-tourniquet-release group). From August 2015 to August 2016, the authors topically applied 5 g of ε-ACA intraoperatively to the open wound 3 minutes before tourniquet release (ε-ACA-before-tourniquet-release group). The last 80 patients not receiving ε-ACA (control group), the 80 patients in the ε-ACA-after-tourniquet-release group, and the 80 patients in the ε-ACA-before-tourniquet-release group were compared regarding blood loss, treatment costs, and thromboembolic complications. The mean±SD calculated blood loss was 1478.8±367.1 mL for the control group, 1424.0±249.3 mL for the ε-ACA-after-tourniquet-release group, and 1052.3±419.1 mL for the ε-ACA-before-tourniquet-release group (P<.05). Using ε-ACA before tourniquet release reduced the length of hospital stay by 0.7 days (P<.05) compared with not using ε-ACA, leading to cost savings of $1547.37 per patient. One patient in the ε-ACA-before-tourniquet-release group and 1 patient in the control group developed a venous thromboembolism in the postoperative period. Epsilon-aminocaproic acid significantly reduces blood loss after TKA when topically applied before tourniquet release. Its application reduced costs by decreasing the length of hospital stay and did not increase thromboembolic events. [Orthopedics. 2017; 40(6):e1044-e1049.].


The Drosophila Claudin Kune-kune is required for septate junction organization and tracheal tube size control.
The vertebrate tight junction is a critical claudin-based cell-cell junction that functions to prevent free paracellular diffusion between epithelial cells. In Drosophila, this barrier is provided by the septate junction, which, despite being ultrastructurally distinct from the vertebrate tight junction, also contains the claudin-family proteins Megatrachea and Sinuous. Here we identify a third Drosophila claudin, Kune-kune, that localizes to septate junctions and is required for junction organization and paracellular barrier function, but not for apical-basal polarity. In the tracheal system, septate junctions have a barrier-independent function that promotes lumenal secretion of Vermiform and Serpentine, extracellular matrix modifier proteins that are required to restrict tube length. As with Sinuous and Megatrachea, loss of Kune-kune prevents this secretion and results in overly elongated tubes. Embryos lacking all three characterized claudins have tracheal phenotypes similar to any single mutant, indicating that these claudins act in the same pathway controlling tracheal tube length. However, we find that there are distinct requirements for these claudins in epithelial septate junction formation. Megatrachea is predominantly required for correct localization of septate junction components, while Sinuous is predominantly required for maintaining normal levels of septate junction proteins. Kune-kune is required for both localization and levels. Double- and triple-mutant combinations of Sinuous and Megatrachea with Kune-kune resemble the Kune-kune single mutant, suggesting that Kune-kune has a more central role in septate junction formation than either Sinuous or Megatrachea.


Muscle-Splitting Augmentation-Mastopexy: Implant Protection With an Inferior Dermoglandular Flap.
Simultaneous augmentation-mastopexy can achieve excellent patient and surgeon satisfaction but continues to pose a challenge, with revision rates of up to 25%. Recurrent ptosis and poor overall breast shape are 2 common reasons for reoperation, whereas some of the most feared complications is breast implant exposure, infection, and loss secondary to wound breakdown; excessively large implants or too much tension during closure are possible contributing factors. We describe a technique for augmentation-mastopexy combining a muscle-splitting pocket for implant placement along with an inferior flap, which helps secure the implant in place and provides coverage in case of wound dehiscence. A retrospective chart review was performed (January 2015 to December 2017) of women who underwent augmentation-mastopexy with round, textured silicone gel implants using a muscle-splitting technique combined with an inferior de-epithelialized dermoglandular flap. A total of 118 patients (236 breasts) were operated on. Mean follow-up was 13 months (10-42 months). Mean patient age was 33.3 years (24-55 years). Mean operative time was 102.9 minutes (80-135 minutes), and implant size ranged from 175 to 350 mL (mode, 275 mL). There were no cases of implant extrusion, nipple-areola complex ischemia, or surgical site infection; however, 1 patient required revision surgery for implant malposition, and 2 had a postoperative hematoma. In summary, the technique we describe combines 2 established mammaplasty techniques, ensuring upper pole fullness with good cleavage, implant protection in case of wound breakdown, and good patient satisfaction as evidenced by a low revision rate and minimal complications. LEVEL OF EVIDENCE: IV, therapeutic. Evidence obtained from multiple time series with or without the intervention, such as case studies.


[Pyogenic sacroiliitis in children].
Pyogenic sacroiliitis is a rarely occurring disease. In recent years more reports have been published about this topic. We report on a case of infectious sacroiliitis in a young female patient. The multivarious clinical symptoms, the problems of diagnosis, differential diagnosis, treatment and prognosis of this disease will be described.


Citrus Physiological and Molecular Response to Boron Stresses.
Since the essentiality of boron (B) to plant growth was reported nearly one century ago, the implication of B in physiological performance, productivity and quality of agricultural products, and the morphogenesis of apical meristem in plants has widely been studied. B stresses (B deficiency and toxicity), which lead to atrophy of canopy and deterioration of Citrus fruits, have long been discovered in citrus orchards. This paper reviews the research progress of B stresses on Citrus growth, photosynthesis, light use efficiency, nutrient absorption, organic acid metabolism, sugar metabolism and relocation, and antioxidant system. Moreover, the beneficial effects of B on plant stress tolerance and further research in this area were also discussed.


Pancreatic effects of ethionine: blockade of exocytosis and appearance of crinophagy and autophagy precede cellular necrosis.
Young female mice fed a choline-deficient, ethionine-supplemented (CDE) diet for 24 h develop hemorrhagic pancreatic necrosis with a 5-day mortality rate of approximately 50%. At the end of the diet administration, the in vivo discharge of digestive enzymes is blocked, images of exocytosis and luminal membrane recycling disappear, and zymogen granules accumulate within acinar cells. The general ultrastructure, however, remains well preserved, protein synthesis is normal, and intracellular transport of secretory proteins is only slightly retarded. Thus, the CDE diet does not affect the general phenomenon of membrane fusion-fission but specifically inhibits that associated with exocytosis. Twenty-four hours after withdrawal of the CDE diet, discharge of zymogen granules into lysosomes (crinophagy) can be observed, and, 24 h latr, autophagocytosis is noted. Finally, shortly before the onset of pancreatic necrosis, cells of nearly normal appearance are noted to be scattered among cells showing varying degrees of lesion up to complete disruption. Thus, the CDE-induced pancreatic necrosis results from a sequence of events: blockade of exocytosis evolves to crinophagy and autophagy, which might lead to lysosomal activation of zymogens.


Leukoencephalopathy with vanishing white matter: from magnetic resonance imaging pattern to five genes.
Leukoencephalopathy with vanishing white matter can be diagnosed on the basis of distinct clinical and magnetic resonance imaging (MRI) findings. It is a recessively inherited disorder, most often presenting in young children. The clinical symptoms include a slowly progressive cerebellar ataxia, spasticity, variable optic atrophy, and relatively preserved mental capacities. In addition, there are episodes of rapid and major deterioration following infections with fever and minor head trauma. These episodes can end in unexplained coma. MRI findings suggest that over time there is a progressive vanishing of the abnormal white matter, which is replaced by cerebrospinal fluid. We performed a genome-wide search and localized a gene for vanishing white matter on chromosome 3q27. We demonstrated that mutations in the gene EIF2B5 cause the disease. This gene encodes one of the five subunits of the translation factor eIF2B. Patients without mutations in the EIF2B5 gene were found to be mutated in one of the other genes that encode eIF2B subunits: EIF2B1 to EIF2B4.


Down regulation of macrophage mannose/N-acetylglucosamine receptors by elevated glucose concentrations.
The binding of the 125I-induced neoglycoprotein mannosyl-bovine serum albumin (Man-albumin) to peptone-elicited murine peritoneal macrophages was examined. Binding studies demonstrated that the extent of receptor activity for Man-albumin depended upon the glucose concentration of the medium in which the cells were cultured following peritoneal lavage and prior to the binding assay. Macrophages cultured in a medium containing a high glucose concentration (25 mM or greater) prior to the binding assay, consistently showed a reduced capacity for binding Man-albumin as compared to cells cultured in the presence of low glucose (5 mM). These results were obtained in a variety of tissue culture media or when the same medium was employed with differing amounts of added glucose (5, 25 and 50 mM). Cell toxicity and/or death was not the cause of the reduced receptor activity of macrophages cultured in high glucose as determined by morphology. Trypan blue exclusion, and the ability of these cells to actively phagocytose IgG-coated sheep red blood cells to an extent identical with those cells cultured in low glucose. Saturation binding studies and Scatchard analysis of the data demonstrated that the decreased level of binding observed with cells cultured in high glucose was the result of a reduced number of receptors and not altered receptor affinity. These studies suggest that an increased glucose concentration, such as in diabetes mellitus, can downshift the expression of the mannose/N-acetylglucosamine receptor on murine peritoneal macrophages.


Clinicopathological models for predicting lymph node metastasis in patients with early-stage lung adenocarcinoma: the application of machine learning algorithms.
Lymph node metastasis (LNM) status can be a critical decisive factor for clinical management of lung cancer. Accurately evaluating the risk of LNM during or after the surgery can be helpful for making clinical decisions. This study aims to incorporate clinicopathological characteristics to develop reliable machine learning (ML)-based models for predicting LNM in patients with early-stage lung adenocarcinoma. A total of 709 lung adenocarcinoma patients with tumor size ≤2 cm were enrolled for analysis and modeling by multiple ML algorithms. The receiver operating characteristic (ROC) curve and decision curve were used for evaluating model's predictive performance and clinical usefulness. Feature selection based on potential models was performed to identify most-contributed predictive factors. LNM occurred in 11.3% (80/709) of patients with lung adenocarcinoma. Most models reached high areas under the ROC curve (AUCs) >0.9. In the decision curve, all models performed better than the treat-all and treat-none lines. The random forest classifier (RFC) model, with a minimal number of five variables introduced (including carcinoembryonic antigen, solid component, micropapillary component, lymphovascular invasion and pleural invasion), was identified as the optimal model for predicting LNM, because of its excellent performance in both ROC and decision curves. The cost-efficient application of RFC model could precisely predict LNM during or after the operation of early-stage adenocarcinomas (sensitivity: 87.5%; specificity: 82.2%). Incorporating clinicopathological characteristics, it is feasible to predict LNM intraoperatively or postoperatively by ML algorithms.


Outcome in schizophrenia: beyond symptom reduction.
Although some patients with schizophrenia may have a single episode and recover, the vast majority remain ill and unable to work for life. In the United States, patients with schizophrenia use 2.5% of the annual total health care allocations. The atypical antipsychotics, particularly when combined with psychosocial treatment, hold the promise of improving outcome and reducing the economic burden on society. Both clinical outcome and cost effectiveness are best evaluated in the context of a comprehensive assessment of a range of meaningful outcome measures studied in clinical situations. Evidence exists that the atypical antipsychotics not only reduce positive and negative symptoms and cause fewer side effects than conventional neuroleptics, but also lessen cognitive impairment, lead to a better quality of life, and have antidepressant effects, all of which should result in improved outcome in patients with schizophrenia. Increasing the availability of the atypical agents should be cost effective for society by restoring productivity in some patients with schizophrenia.


Dichlorocarbene Addition to
In contrast to the terminal phosphinidene complex PhPW(CO)(5) (2), which adds to [5]metacyclophane (1) in a 1,4-fashion, dichlorocarbene preferentially adds in a 1,2-fashion to the formal "anti-Bredt" type double bond of the aromatic ring of 1 to afford the norcaradiene 11b, which immediately rearranges to the bridged cycloheptatriene 12b and further by a [1,5] sigmatropic chlorine migration to the isomeric 13b as the first observable product. More slowly, the latter isomerizes via a dissociative mechanism to give 15b. A computational study supports the notion that the [1,5] chlorine migration in the rearrangement 12b --> 13b, for which an activation barrier of 70.2 kJ mol(-)(1) was calculated, is essentially concerted with minor charge separation. In contrast, the analogous [1,5] chlorine migration in the flat model compound 7,7-dichlorocycloheptatriene (12a) displays features of a dissociative pathway.


Cervical spinal motion during intubation: efficacy of stabilization maneuvers in the setting of complete segmental instability.
The purpose of this study was to characterize and compare segmental cervical motion during orotracheal intubation in cadavers with and without a complete subaxial injury, as well as to examine the efficacy of commonly used stabilization techniques in limiting that motion. Intubation procedures were performed in 10 fresh human cadavers in which cervical spines were intact and following the creation of a complete C4-5 ligamentous injury. Movement of the cervical spine during direct laryngoscopy and intubation was recorded using video fluoroscopy and examined under the following conditions: 1) without stabilization; 2) with manual in-line cervical immobilization; and 3) with Gardner-Wells traction. Subsequently, segmental angular rotation, subluxation, and distraction at the injured C4-5 level were measured from digitized frames of the recorded video fluoroscopy. After complete C4-5 destabilization, the effects of attempted stabilization on distraction, angulation, and subluxation were analyzed. Immobilization effectively eliminated distraction, and diminished angulation, but increased subluxation. Traction significantly increased distraction, but decreased angular rotation and effectively eliminated subluxation. Orotracheal intubation without stabilization had intermediate results, causing less distraction than traction, less subluxation than immobilization, but increased angulation compared with either intervention. These results are discussed in terms of both statistical and clinical significance and recommendations are made.


MyD88-dependent and independent pathways of Toll-Like Receptors are engaged in biological activity of Triptolide in ligand-stimulated macrophages.
Triptolide is a diterpene triepoxide from the Chinese medicinal plant Tripterygium wilfordii Hook F., with known anti-inflammatory, immunosuppressive and anti-cancer properties. Here we report the expression profile of immune signaling genes modulated by triptolide in LPS induced mouse macrophages. In an array study triptolide treatment modulated expression of 22.5% of one hundred and ninety five immune signaling genes that included Toll-like receptors (TLRs). TLRs elicit immune responses through their coupling with intracellular adaptor molecules, MyD88 and TRIF. Although it is known that triptolide inhibits NFkappaB activation and other signaling pathways downstream of TLRs, involvement of TLR cascade in triptolide activity was not reported. In this study, we show that triptolide suppresses expression of proinflammatory downstream effectors induced specifically by different TLR agonists. Also, the suppressive effect of triptolide on TLR-induced NFkappaB activation was observed when either MyD88 or TRIF was knocked out, confirming that both MyD88 and TRIF mediated NFkappaB activation may be inhibited by triptolide. Within the TLR cascade triptolide downregulates TLR4 and TRIF proteins. This study reveals involvement of TLR signaling in triptolide activity and further increases understanding of how triptolide activity may downregulate NFkappaB activation during inflammatory conditions.


New therapeutic strategy for mood disorders.
The development of new treatments for mood disorders, as anxiety and depression, is based on identification of neural substrates and the mechanisms underlying their etiology and pathophysiology. The heterogeneity of mood disorders indicates that its origin may lie in dysfunction of multiple brain regions (amygdala, nucleus accumbens, hippocampus, prefrontal cortex and cingulate cortex). The hippocampus of patients with depression show signs of atrophy and neuronal loss. This suggests the contribute of new neurons to the biology of mood disorders that is still under debate. The production of new neurons, referred to as neurogenesis, occurs throughout life in discrete brain areas such as the dentate gyrus (DG) of the hippocampus and the subventricular zone/olfactory bulb. Findings describing that neurogenesis process in DG is increased by antidepressants, like fluoxetine, and it is required for the behavioral effect of antidepressants, lead to a new strategy and drugs for the treatment of mood disorders. As many patients display poor response to therapy, research on depression and antidepressant drugs is necessary. In this regard, focusing on neurogenesis and neuroplasticity processes in experimental models is particularly interesting for the understanding of the pathophysiology of mood disorders and should define the role of adult-born neurons in hippocampal physiology. Different classes of drugs are currently prescribed for the treatment of mood disorders. Among them selective serotonin reuptake (SSRIs), monoamine oxidase inhibitors (MAOIs), specific norepinephrine reuptake inhibitors (SNRIs) and tricyclic acids (TCA) alleviate symptoms of mood disorders. Here we review different strategies that may be adopted for impairing mood disorders and that may be further developed for innovative therapeutic approaches.


A urethral afferent mediated excitatory bladder reflex exists in humans.
An excitatory reflex between urethral flow receptors and the bladder has been established in animals, but attempts to demonstrate this reflex in humans using urethral fluid flow have been inconclusive. Intraurethral electrical stimulation has recently been shown to generate bladder contractions in animals and was applied to study the presence of an excitatory urethra to bladder reflex in humans. The prostatic urethra was stimulated electrically via a catheter-based electrode in five men with complete spinal cord injury. Bladder contractions were generated in four of five individuals, however, only when the bladder volume was sufficiently large. These results demonstrate the presence of a volume dependent excitatory bladder reflex mediated by urethral afferent nerve fibers and the lumbosacral spinal cord.


Measurement of specific heat and thermal conductivity of supported and suspended graphene by a comprehensive Raman optothermal method.
The last decade has seen the rapid growth of research on two-dimensional (2D) materials, represented by graphene, but research on their thermophysical properties is still far from sufficient owing to the experimental challenges. Herein, we report the first measurement of the specific heat of multilayer and monolayer graphene in both supported and suspended geometries. Their thermal conductivities were also simultaneously measured using a comprehensive Raman optothermal method without needing to know the laser absorption. Both continuous-wave (CW) and pulsed lasers were used to heat the samples, based on consideration of the variable laser spot radius and pulse duration as well as the heat conduction within the substrate. The error from the laser absorption was eliminated by comparing the Raman-measured temperature rises for different spot radii and pulse durations. The thermal conductivity and specific heat were extracted by analytically fitting the temperature rise ratios as a function of spot size and pulse duration, respectively. The measured specific heat was about 700 J (kg K)-1 at room temperature, which is in accordance with theoretical predictions, and the measured thermal conductivities were in the range of 0.84-1.5 × 103 W (m K)-1. The measurement method demonstrated here can be used to investigate in situ and comprehensively the thermophysical properties of many other emerging 2D materials.


Gut Microbiota Profiles in Early- and Late-Onset Colorectal Cancer: A Potential Diagnostic Biomarker in the Future.
Researchers believe the role of gut microbiota dysbiosis in the raised incidence of early-onset colorectal cancer (EOCRC). The development of EOCRC may be associated with microbiota dysbiosis either dependently or independently (combined with other risk factors). Recently, the rising of incidence and mortality of EOCRC have been noted. Some researchers are looking for risk factors influencing this fact. They hypothesize that it may be because of microbiota dysbiosis. Microbiota dysbiosis has been known to promote cancer development through immunity dysregulation and chronic inflammation. Microbiomes profile in late-onset colorectal cancer (LOCRC) among older patients has been documented, but there is still lack of data about microbial profiles among younger colorectal cancer (CRC) patients. This review tries to explain microbial profiles differences between EOCRC and LOCRC as a potential diagnostic biomarker in the future, and whether microbiota can have a role in EOCRC genesis. Key Messages: Microbiota does vary with age, and EOCRC may be associated with colonization of some specific bacteria. Further studies about gut microbiota profiles in EOCRC and LOCRC may provide a new insight on diagnostic biomarker of CRC.


Prostate-specific antigen-based serial screening may decrease prostate cancer-specific mortality.
To compare the preoperative characteristics, postoperative prostate-specific antigen (PSA) doubling time (DT), and prostate cancer-specific mortality (PCSM) estimates after PSA failure in men diagnosed during a screening study versus a community referral population. A PSA-DT of less than 3 months is a surrogate endpoint for PCSM. From 1988 to 2002, 1492 of 9637 patients with clinically localized prostate cancer underwent radical prostatectomy and experienced PSA failure. They were either participating in a screening study (n = 841) or attended 1 of 44 community-based practices (n = 611). The distributions of PSA, Gleason score, tumor stage, and PSA-DT were compared using chi-square metric. The estimates of PCSM after PSA failure were compared using Gray's P value. Compared with the community population, the annually screened men experiencing PSA failure had a lower PSA level at diagnosis (5.1 versus 9.5 ng/mL, P <0.0001), were less likely to have Gleason score 7 to 10 cancer (25.1% versus 42.1%, P <0.0001), and were more likely to have low-risk disease (64.5% versus 23.8%, P <0.0001). Furthermore, the screened cohort had a reduction (P <0.0001) in the proportion with a PSA-DT of less than 3, 3 to 5.99, and 6 to 11.99 months and a significant increase in the proportion with a PSA-DT of 12 months or longer. After a median follow-up of 4.5 and 4.1 years after PSA failure in the screened and community cohorts, respectively, the PCSM estimates were lower (P = 0.0002) in the screened cohort (10-year estimate 3.6% [95% confidence interval 1.3 to 5.8] versus 11.3% [95% confidence interval 5.9 to 17.4]). Patients diagnosed by annual prostate cancer screening appeared more likely to experience an indolent PSA recurrence and less likely to die of prostate cancer after PSA recurrence compared with patients referred from the community.


Prospective, high-throughput molecular profiling of human gliomas.
Gliomas consist of multiple histologic and molecular subtypes with different clinical phenotypes and responsiveness to treatment. However, enrollment criteria for clinical trials still largely do not take into account these underlying molecular differences. We have incorporated a high-throughput tumor genotyping program based on the ABI SNaPshot platform as well as other molecular diagnostic tests into the standard evaluation of glioma patients in order to assess whether prospective molecular profiling would allow rational patient selection onto clinical trials. From 218 gliomas we prospectively collected SNaPshot genotyping data on 68 mutated loci from 15 key cancer genes along with data from clinical assays for gene amplification (EGFR, PDGFRA, MET), 1p/19q co-deletion and MGMT promoter methylation. SNaPshot mutations and focal gene amplifications were detected in 38.5 and 47.1 % of glioblastomas, respectively. Genetic alterations in EGFR, IDH1 and PIK3CA closely matched frequencies reported in recent studies. In addition, we identified events that are rare in gliomas although are known driver mutations in other cancer types, such as mutations of AKT1, BRAF and KRAS. Patients with genetic alterations that activate signaling pathways were enrolled onto genetically selective clinical trials for malignant glioma as well as for other solid cancers. High-throughput molecular profiling incorporated into the routine clinical evaluation of glioma patients may enable the rational selection of patients for targeted therapy clinical trials and thereby improve the likelihood that such trials succeed.


Pregnancy blocking in the vole, Microtus agrestis. I. Effect of the social environment.
Pregnancy failed in a high proportion of newly mated Microtus agrestis females when they were exposed to a strange male between 48 and 72 hr after mating with a stud male. This effect of the strange male was testosterone dependent. Direct contact with the strange male was normally necessary, and even a single barrier of wire mesh between the female and strange male prevented the male from exerting his pregnancy-blocking effect. The results suggest that the stimuli mediating pregnancy blocking in the vole may differ from those operative in the mouse.


Effort-reward imbalance and long-term benzodiazepine use: longitudinal findings from the CONSTANCES cohort.
To examine the association between effort-reward imbalance and incident long-term benzodiazepine use (LTBU). We included 31 077 employed participants enrolled in the French population-based CONSTANCES cohort between 2012 and 2014 who had not undergone LTBU in the 2 years before enrolment. LTBU was examined using drug reimbursement administrative databases. The effort-reward imbalance was calculated in quartiles. We computed ORs (95% CIs) for LTBU according to effort-reward imbalance over a 2-year follow-up period. We adjusted for age, gender, education, occupational grade, income, marital status, tobacco smoking, risk of alcohol use disorder, depressive symptoms and self-rated health. Over the 2-year follow-up, 294 (0.9%) participants experienced incident LTBU. In the univariable analysis, effort-reward imbalance was associated with subsequent LTBU with ORs of 1.79 (95% CI 1.23 to 2.62) and 2.73 (95% CI 1.89 to 3.95) for the third and fourth quartiles, respectively, compared with the first quartile. There was no interaction between effort-reward imbalance and any of the considered variables other than tobacco smoking (p=0.033). The association remained significant in both smokers and non-smokers, with higher odds for smokers (p=0.031). In the fully adjusted model, the association remained significant for the third and fourth quartiles, with ORs of 1.74 (95% CI 1.17 to 2.57) and 2.18 (95% CI 1.50 to 3.16), respectively. These associations were dose dependent (p for trend <0.001). Effort-reward imbalance was linked with incident LTBU over a 2-year follow-up period after adjustment for sociodemographic and health-related factors. Thus, screening and prevention of the risk of LTBU should be systematised among individuals experiencing effort-reward imbalance, with special attention paid to smokers.


Coaches' perspectives on implementing an evidence-informed injury prevention programme in junior community netball.
For effective sports injury prevention, information is needed about the implementation context for interventions. This study describes coaches' feedback on the implementation of an evidence-informed injury prevention programme in community junior netball using coaches' perceptions and the RE-AIM framework. A lower-limb injury prevention programme (Down to Earth; D2E), for teaching safe-landing techniques, was delivered to 31 coaches from 31 junior community netball teams in a 1-h workshop. Coaches then delivered a 6-week programme at team training sessions starting in the week before the competition season commenced. 65% of coaches completed a feedback survey 17 weeks after they had delivered the programme. Most (88%) coaches believed that D2E improved their players' ability to perform correct landing techniques in games and that players had retained these improvements over the season. The majority (83%) indicated that an improvement in player athletic attributes was the greatest advantage of D2E, followed by a reduction in injury risk. Identified barriers to implementing D2E were running out of time and very young players finding the drills too difficult. Coaches reported that they needed more ideas for training drills that could be incorporated into their programmes and believed that their own coaching training did not adequately prepare them to implement an injury prevention programme. Although coaches believed that D2E was effective in developing correct landing techniques, some modifications are needed to make it more suitable for younger players and coach education by accreditation courses could be improved to support the implementation of injury prevention programmes.


The WRKY Transcription Factor GmWRKY12 Confers Drought and Salt Tolerance in Soybean.
WRKYs are important regulators in plant development and stress responses. However, knowledge of this superfamily in soybean is limited. In this study, we characterized the drought- and salt-induced gene GmWRKY12 based on RNA-Seq and qRT-PCR. GmWRKY12, which is 714 bp in length, encoded 237 amino acids and grouped into WRKY II. The promoter region of GmWRKY12 included ABER4, MYB, MYC, GT-1, W-box and DPBF cis-elements, which possibly participate in abscisic acid (ABA), drought and salt stress responses. GmWRKY12 was minimally expressed in different tissues under normal conditions but highly expressed under drought and salt treatments. As a nucleus protein, GmWRKY12 was responsive to drought, salt, ABA and salicylic acid (SA) stresses. Using a transgenic hairy root assay, we further characterized the roles of GmWRKY12 in abiotic stress tolerance. Compared with control (Williams 82), overexpression of GmWRKY12 enhanced drought and salt tolerance, increased proline (Pro) content and decreased malondialdehyde (MDA) content under drought and salt treatment in transgenic soybean seedlings. These results may provide a basis to understand the functions of GmWRKY12 in abiotic stress responses in soybean.


Leiothecium cristatum sp. nov. and Aspergillus posadasensis sp. nov., two species of Eurotiales from rainforest soils in South America.
We describe two novel fungi isolated from soil samples collected in Northern Argentina and belonging to the family Aspergillaceae of the order Eurotiales: Leiothecium cristatum sp. nov. and Aspergillus posadasensis sp. nov. Leiothecium cristatum sp. nov., represented by the ex-type strain FMR 11998(T) ( = CBS 134260(T) = NBRC 109843(T)), is distinguishable morphologically from the type species of the genus, Leiothecium ellipsoideum, by the presence of irregular reticulate ascospores with two prominent equatorial crests, and Aspergillus posadasensis sp. nov., represented by the ex-type strain FMR 12168(T) ( = CBS 134259(T) = NBRC 109845(T)), is differentiated from Aspergillus acanthosporus, the nearest species phylogenetically, by its non-sclerotioid ascomata and a lack of an asexual stage on all culture media tested. The taxonomic proposals are supported by the analysis of the sequences of the internal transcribed spacer region, the D1-D2 domains of the 28S rRNA gene, the fragments of the RNA polymerase II largest subunit, and the putative chaperonin complex related to TCP-1, β-tubulin and calmodulin genes.


Recognizing spoken words: the neighborhood activation model.
A fundamental problem in the study of human spoken word recognition concerns the structural relations among the sound patterns of words in memory and the effects these relations have on spoken word recognition. In the present investigation, computational and experimental methods were employed to address a number of fundamental issues related to the representation and structural organization of spoken words in the mental lexicon and to lay the groundwork for a model of spoken word recognition. Using a computerized lexicon consisting of transcriptions of 20,000 words, similarity neighborhoods for each of the transcriptions were computed. Among the variables of interest in the computation of the similarity neighborhoods were: 1) the number of words occurring in a neighborhood, 2) the degree of phonetic similarity among the words, and 3) the frequencies of occurrence of the words in the language. The effects of these variables on auditory word recognition were examined in a series of behavioral experiments employing three experimental paradigms: perceptual identification of words in noise, auditory lexical decision, and auditory word naming. The results of each of these experiments demonstrated that the number and nature of words in a similarity neighborhood affect the speed and accuracy of word recognition. A neighborhood probability rule was developed that adequately predicted identification performance. This rule, based on Luce's (1959) choice rule, combines stimulus word intelligibility, neighborhood confusability, and frequency into a single expression. Based on this rule, a model of auditory word recognition, the neighborhood activation model, was proposed. This model describes the effects of similarity neighborhood structure on the process of discriminating among the acoustic-phonetic representations of words in memory. The results of these experiments have important implications for current conceptions of auditory word recognition in normal and hearing impaired populations of children and adults.


Epigenetics of colorectal cancer: emerging circulating diagnostic and prognostic biomarkers.
Colorectal cancer (CRC) is one of the most common cancers worldwide and the second leading cause of cancer-related mortality in western countries. Despite the high incidence, treatment options for advanced CRC remain limited and unsuccessful, resulting in a poor prognosis. Therefore, novel accurate diagnostic, prognostic and predictive biomarkers are clearly and urgently needed to detect advanced colon polyps and early stage CRC and to identify the most effective treatments for specific CRC patients. CRC is known to develop from early premalignant lesions to full blown cancer via a multi-step process involving a series of genetic mutations that accumulate over time. Recent improvement of our understanding of CRC biology and advances in genomic technologies has led to the identification of a variety of epigenetic alterations strongly involved in cancer initiation and progression. Among the epigenetic marks implicated in CRC the most widely studied are the global DNA hypomethylation, the promoter hypermethylation and the miRNAs dysregulations. Many evidence exist that such tumour associated alterations may serve as new potential biomarkers. Moreover, due the non-invasive, objective, and potential reproducible assessment, circulating epigenetic biomarkers have reached increasing attentions in the last few years. In this review, we attempt to analyze the existing most recent literature on the role of circulating DNA methylations and miRNAs alterations in CRC diagnosis and prognosis.


Boronate-containing polymer brushes: characterization, interaction with saccharides and mammalian cancer cells.
Boronate-containing polymer brushes were synthesized by free radical copolymerization of N,N-dimethylacrylamide (DMAA) and N-acryloyl-m-phenylboronic acid (NAAPBA) (9:1) on the surface of 3-mercaptopropyl-silylated glass plates and capillaries. The brushes were characterized with time-of-flight secondary ion mass-spectrometry (ToF SIMS), atomic force microscopy and contact angle measurements. Fructose caused a well-expressed drop spreading on the surface of copolymer-grafted glass, due to the strong interaction with the boronate groups. Sedimentation of murine hybridoma cells M2139 or human myeloid leukemia cells KG1 onto the DMAA-NAAPBA copolymer-grafted glass plates from 10 mM phosphate buffer solution (pH 8.0) resulted in the cell adhesion. The adhered M2139 and KG1 cells could be quantitatively detached from the grafted plates with 0.1 M fructose, which competed with cell surface carbohydrates for binding to the boronates. Evaluation of the binding strength between M2139 cells and the copolymer brush was performed by exposure of the adhered cells to a shear stress. Detachment of a fraction of 18% of the adhered M2139 cells was obtained at a shear force of 1400-2800 pN/cell generated by the running phosphate buffer (pH 8.0), whereas the remaining adhered cells (70%) could be detached with 0.1 M fructose dissolved in the same buffer. Possible applications of the boronate-containing polymer brushes to affinity cell separation can be based upon the facile recovery of the attached cells.


Do steroids increase lymphoma risk? A case-control study of lymphoma risk in polymyalgia rheumatica/giant cell arteritis.
Recent studies indicate increased risks of malignant lymphomas among individuals treated with corticosteroids, but have not taken into account the underlying reasons for steroid use, so the increased risks might be attributable to the underlying disease or concomitant treatments other than steroids. Polymyalgia rheumatica (PMR) and temporal arteritis (giant cell arteritis, GCA) are common inflammatory conditions treated with steroids as single immunosuppressive therapy, but data on lymphoma risk in GCA/PMR are limited. To assess the risk of lymphoma associated with steroid treatment of GCA/PMR. The association between GCA/PMR and malignant lymphomas (overall, and separately for non-Hodgkin lymphoma, Hodgkin lymphoma, and chronic lymphatic leukaemia) was examined in a nationwide, population based, case-control study of 42,676 lymphoma cases and 78,487 matched population controls, using prospectively recorded data on lymphomas from the Swedish cancer register 1964-2000 and data on pre-lymphoma hospital admissions for GCA/PMR from the Swedish inpatient register 1964-2000. Odds ratios (OR) associated with a pre-lymphoma hospital admission for GCA/PMR were calculated using conditional logistic regression. 153 lymphoma cases and 345 population controls had a history of GCA/PMR, resulting in an overall OR for malignant lymphomas of 0.81 (95% confidence interval, 0.67 to 0.98). The OR varied little with lymphoma type, sex, age, and calendar period. The OR for GCA was 0.67 (0.48 to 0.98) and for PMR, 0.83 (0.67 to 1.04). Treated GCA is not associated with increased lymphoma risks, which suggests that even at considerable cumulative doses, steroids may not appreciably increase lymphoma risk.


Lineage-specific genes are clustered with HET-domain genes and respond to environmental and genetic manipulations regulating reproduction in Neurospora.
Lineage-specific genes (LSGs) have long been postulated to play roles in the establishment of genetic barriers to intercrossing and speciation. In the genome of Neurospora crassa, most of the 670 Neurospora LSGs that are aggregated adjacent to the telomeres are clustered with 61% of the HET-domain genes, some of which regulate self-recognition and define vegetative incompatibility groups. In contrast, the LSG-encoding proteins possess few to no domains that would help to identify potential functional roles. Possible functional roles of LSGs were further assessed by performing transcriptomic profiling in genetic mutants and in response to environmental alterations, as well as examining gene knockouts for phenotypes. Among the 342 LSGs that are dynamically expressed during both asexual and sexual phases, 64% were detectable on unusual carbon sources such as furfural, a wildfire-produced chemical that is a strong inducer of sexual development, and the structurally-related furan 5-hydroxymethyl furfural (HMF). Expression of a significant portion of the LSGs was sensitive to light and temperature, factors that also regulate the switch from asexual to sexual reproduction. Furthermore, expression of the LSGs was significantly affected in the knockouts of adv-1 and pp-1 that regulate hyphal communication, and expression of more than one quarter of the LSGs was affected by perturbation of the mating locus. These observations encouraged further investigation of the roles of clustered lineage-specific and HET-domain genes in ecology and reproduction regulation in Neurospora, especially the regulation of the switch from the asexual growth to sexual reproduction, in response to dramatic environmental conditions changes.


Validation of the 2HELPS2B Seizure Risk Score in Acute Brain Injury Patients.
Seizures are common after traumatic brain injury (TBI), aneurysmal subarachnoid hemorrhage (aSAH), subdural hematoma (SDH), and non-traumatic intraparenchymal hemorrhage (IPH)-collectively defined herein as acute brain injury (ABI). Most seizures in ABI are subclinical, meaning that they are only detectable with EEG. A method is required to identify patients at greatest risk of seizures and thereby in need of prolonged continuous EEG monitoring. 2HELPS2B is a simple point system developed to address this need. 2HELPS2B estimates seizure risk for hospitalized patients using five EEG findings and one clinical finding (pre-EEG seizure). The initial 2HELPS2B study did not specifically assess the ABI subpopulation. In this study, we aim to validate the 2HELPS2B score in ABI and determine its relative predictive accuracy compared to a broader set of clinical and electrographic factors. We queried the Critical Care EEG Monitoring Research Consortium database for ABI patients age ≥ 18 with > 6 h of continuous EEG monitoring; data were collected between February 2013 and November 2018. The primary outcome was electrographic seizure. Clinical factors considered were age, coma, encephalopathy, ABI subtype, and acute suspected or confirmed pre-EEG clinical seizure. Electrographic factors included 18 EEG findings. Predictive accuracy was assessed using a machine-learning paradigm with area under the receiver operator characteristic (ROC) curve as the primary outcome metric. Three models (clinical factors alone, EEG factors alone, EEG and clinical factors combined) were generated using elastic-net logistic regression. Models were compared to each other and to the 2HELPS2B model. All models were evaluated by calculating the area under the curve (AUC) of a ROC analysis and then compared using permutation testing of AUC with bootstrapping to generate confidence intervals. A total of 1528 ABI patients were included. Total seizure incidence was 13.9%. Seizure incidence among ABI subtype varied: IPH 17.2%, SDH 19.1%, aSAH 7.6%, TBI 9.2%. Age ≥ 65 (p = 0.015) and pre-cEEG acute clinical seizure (p < 0.001) positively affected seizure incidence. Clinical factors AUC = 0.65 [95% CI 0.60-0.71], EEG factors AUC = 0.82 [95% CI 0.77-0.87], and EEG and clinical factors combined AUC = 0.84 [95% CI 0.80-0.88]. 2HELPS2B AUC = 0.81 [95% CI 0.76-0.85]. The 2HELPS2B AUC did not differ from EEG factors (p = 0.51), or EEG and clinical factors combined (p = 0.23), but was superior to clinical factors alone (p < 0.001). Accurate seizure risk forecasting in ABI requires the assessment of EEG markers of pathologic electro-cerebral activity (e.g., sporadic epileptiform discharges and lateralized periodic discharges). The 2HELPS2B score is a reliable and simple method to quantify these EEG findings and their associated risk of seizure.