Creating Appropriate Training Environments to Improve Technical, Decision-Making, and Physical Skills in Field Hockey.
The purpose of this study was to determine the influence of eight different small-sided games (SSG) on physical, technical, and decision-making demands of training environments in U14 field hockey. A total of 13 participants played eight different training games consisting of two 7.5-minute halves, where number of players (three per side or six per side) and/or field characteristics (normal game, cage hockey game, possession game, and two-goals game) was manipulated. Match performance was determined by using notational analysis, and physical demands were determined by using GPS analyses. Findings revealed that lowering the number of players increased the number of technical actions performed per player and the physical demands of the SSG. Findings of the field characteristics manipulation revealed that the possession game forced players to control the ball more as a team, which resulted in more passes (+4.82 passes) and fewer dribbles (-1.48 dribbles) and tackles (-0.69 tackles) compared to the normal game. The two-goals game led to players scoring more goals (+0.61 goals) compared to the normal game, while the cage hockey game increased passing (+1.46 passes) and physical demands (+7.32 meters per minute) compared to the normal game. It can be concluded from these findings that coaches and trainers are able to promote a change in playing behavior, and in turn the development of skills, by manipulating specific constraints of the training environment.


Management of open chest wounds in tactical emergency casualty care: application of vented versus nonvented chest seals.
The 2014 midyear, full meeting of the Committee for Tactical Emergency Combat Care (C-TECC) was hosted by the Johns Hopkins University Center for Law Enforcement Medicine on June 9 and 10 in Baltimore, Maryland. As the C-TECC guidelines are increasingly recognized as the best-practice recommendations for civilian, high-threat, prehospital trauma response, a focused guidelines discussion occurred to develop best-practice recommendations for the management of open chest wounds, specifically regarding the application of vented and nonvented chest seals.


Biochemical and Proteomic Studies of Human Pyridoxal 5'-Phosphate-Binding Protein (PLPBP).
The pyridoxal 5'-phosphate-binding protein (PLPBP) is an evolutionarily conserved protein linked to pyridoxal 5'-phosphate-binding. Although mutations in PLPBP were shown to cause vitamin B6-dependent epilepsy, its cellular role and function remain elusive. We here report a detailed biochemical investigation of human PLPBP and its epilepsy-causing mutants by evaluating stability, cofactor binding, and oligomerization. In this context, chemical cross-linking combined with mass spectrometry unraveled an unexpected dimeric assembly of PLPBP. Furthermore, the interaction network of PLPBP was elucidated by chemical cross-linking paired with co-immunoprecipitation. A mass spectrometric analysis in a PLPBP knockout cell line resulted in distinct proteomic changes compared to wild type cells, including upregulation of several cytoskeleton- and cell division-associated proteins. Finally, transfection experiments with vitamin B6-dependent epilepsy-causing PLPBP variants indicate a potential role of PLPBP in cell division as well as proper muscle function. Taken together, our studies on the structure and cellular role of human PLPBP enable a better understanding of the physiological and pathological mechanism of this important protein.


Biphasic aggregation of a perylene bisimide dye identified by exciton-vibrational spectra.
The quantum efficiency of light emission is a crucial parameter of supramolecular aggregates that can be tuned by the molecular design of the monomeric species. Here, we report on a strong variation of the fluorescence quantum yield due to different phases of aggregation for the case of a perylene bisimide dye. In particular, a change of the dominant aggregation character from H- to J-type within the first aggregation steps is found, explaining the observed dramatic change in quantum yield. This behaviour is rationalised by means of a systematic study of the intermolecular potential energy surfaces using the time-dependent density functional based tight-binding (TD-DFTB) method. This provides a correlation between structural changes and a coupling strength and supports the notion of H-type stacked dimers and J-type stack-slipped dimers. The exciton-vibrational level structure is modelled by means of an excitonic dimer model including two effective vibrational modes per monomer. Calculated absorption and fluorescence spectra are found to be in reasonable agreement with experimental ones, thus supporting the conclusion on the aggregation behaviour.


Noncompetitive homogeneous immunodetection of small molecules based on beta-glucuronidase complementation.
In this study, a novel noncompetitive homogeneous immunoassay for antigen detection was developed. We utilized β-glucuronidase (GUS), a homotetrameric enzyme, the assembly of all of whose subunits is necessary to attain its activity. By using a mutant GUS (GUSm), wherein the dimerization of dimers, which is a rate-limiting step, can be effectively inhibited by a set of interface mutations, we attempted to create a biosensor for detecting various molecules. Usually, the affinity between the two variable region domains (VH and VL) of an antibody, especially for a small molecule, is relatively low. However, in the presence of an antigen, the affinity increases so that they bind tighter to each other. A pair of fusion proteins, comprising the VH and VL regions of the antibody as the detector tethered to a GUSm subunit as the reporter, was constructed to detect antigen 4-hydroxy-3-nitrophenylacetyl (NP) and bone Gla protein (BGP) through GUS activity measurement. Colorimetric and fluorescence assays could detect NP, 5-iodo-NP, and BGP within 1 h without separation steps and with a higher signal/background ratio than conventional ELISA. The instantaneous response after simple mixing of the components makes this system convenient and high-throughput. The system could be effective for the analyses of various small molecules in environmental and clinical settings.


Vigorous physical activity in relation to family affluence: time trends in Europe and North America.
The aim of the study was to determine secular trends in vigorous physical activity (VPA) among adolescents in relation to family affluence across 34 countries. This study used data from the Health Behaviour in School-aged Children (HBSC) study from 34 countries in Europe and North America. Adolescents (N = 501,647) aged 11, 13 and 15 years across three survey cycles (2006, 2010, 2014) self-reported data on VPA and a family affluence scale (FAS) using standardized questionnaires. A significant increase in VPA was found in low-FAS boys (girls) in four (10) countries and a decrease in four (three) countries. In high-FAS boys (girls), a significant increase was observed in nine (11) countries and a decrease in two(three) countries. An overall significant increase in meeting the VPA recommendations was found in high-FAS boys (OR 1.11; 95% CI 1.06-1.16) and in all FAS groups in girls, with the largest effect being found among high-FAS girls (OR 1.24; 95% CI 1.18-1.30). A country-specific increase in VPA was observed primarily in the medium- and high-FAS categories. This study suggests a need to focus on increasing VPA efforts, especially in low- and medium-FAS boys.


Systemic anti-tumour effects of local thermally sensitive liposome therapy.
There were two primary objectives of this study: (1) to determine whether treatment of a tumour site with systemically administered thermally sensitive liposomes and local hyperthermia (HT) for triggered release would have dual anti-tumour effect on the primary heated tumour as well as an unheated secondary tumour in a distant site, and (2) to determine the ability of non-invasive optical spectroscopy to predict treatment outcome. The optical end points studied included drug levels, metabolic markers flavin adenine dinucleotide (FAD), nicotinamide adenine dinucleotide phosphate (NAD(P)H), and physiological markers (total haemoglobin (Hb) and Hb oxygen saturation) before and after treatment. Mice were inoculated with SKOV3 human ovarian carcinoma in both hind legs. One tumour was selected for local hyperthermia and subsequent systemic treatment. There were four treatment groups: control, DOXIL (non-thermally sensitive liposomes containing doxorubicin), and two different thermally sensitive liposome formulations containing doxorubicin. Optical spectroscopy was performed prior to therapy, immediately after treatment, and 6, 12, and 24 h post therapy. Tumour growth delay was seen with DOXIL and the thermally sensitive liposomes in the tumours that were heated, similar to previous studies. Tumour growth delay was also seen in the opposing tumour in the thermally sensitive liposome-treated groups. Optical spectroscopy demonstrated correlation between growth delay, doxorubicin (DOX) levels, and changes of NAD(P)H from baseline levels. Hb and Hb saturation were not correlated with growth delay. The study demonstrated that thermally sensitive liposomes affect the primary heated tumour as well as systemic efficacy. Non-invasive optical spectroscopy methods were shown to be useful in predicting efficacy at early time points post-treatment.


Predictions of middle-ear and passive cochlear mechanics using a finite element model of the pediatric ear.
A finite element (FE) model was developed based on histological sections of a temporal bone of a 4-year-old child to simulate middle-ear and cochlear function in ears with normal hearing and otitis media. This pediatric model of the normal ear, consisting of an ear canal, middle ear, and spiral cochlea, was first validated with published energy absorbance (EA) measurements in young children with normal ears. The model was used to simulate EA in an ear with middle-ear effusion, whose results were compared to clinical EA measurements. The spiral cochlea component of the model was constructed under the assumption that the mechanics were passive. The FE model predicted middle-ear transfer functions between the ear canal and cochlea. Effects of ear structure and mechanical properties of soft tissues were compared in model predictions for the pediatric and adult ears. EA responses are predicted to differ between adult and pediatric ears due to differences in the stiffness and damping of soft tissues within the ear, and any residual geometrical differences between the adult ear and pediatric ear at age 4 years. The results have significance for predicting effects of otitis media in children.


Ethnicity and the first diagnosis of a wide range of cardiovascular diseases: Associations in a linked electronic health record cohort of 1 million patients.
While the association of ethnic group with individual cardiovascular diseases has been studied, little is known about ethnic differences in the initial lifetime presentation of clinical cardiovascular disease in contemporary populations. We studied 1,068,318 people, aged ≥30 years and free from diagnosed CVD at baseline (90.9% White, 3.6% South Asian and 2.9% Black), using English linked electronic health records covering primary care, hospital admissions, acute coronary syndrome registry and mortality registry (CALIBER platform). During 5.7 years median follow-up between 1997-2010, 95,224 people experienced an incident cardiovascular diagnosis. 69.9% (67.2%-72.4%) of initial presentation in South Asian <60 yrs were coronary heart disease presentations compared to 47.8% (47.3%-48.3%) in White and 40.1% (36.3%-43.9%) in Black patients. Compared to White patients, Black patients had significantly lower age-sex adjusted hazard ratios (HRs) for initial lifetime presentation of all the coronary disease diagnoses (stable angina HR 0.80 (95% CI 0.68-0.93); unstable angina- 0.75 (0.59-0.97); myocardial infarction 0.49 (0.40-0.62)) while South Asian patients had significantly higher HRs (stable angina- 1.67 (1.52-1.84); unstable angina 1.82 (1.56-2.13); myocardial infarction- 1.67 (1.49-1.87). We found no ethnic differences in initial presentation with heart failure (Black 0.97 (0.79-1.20); S Asian 1.04(0.87-1.26)). Compared to White patients, Black patients were more likely to present with ischaemic stroke (1.24 (0.97-1.58)) and intracerebral haemorrhage (1.44 (0.97-2.12)). Presentation with peripheral arterial disease was less likely for Black (0.63 (0.50-0.80)) and South Asian patients (0.70 (0.57-0.86)) compared with White patients. While we found the anticipated substantial predominance of coronary heart disease presentations in South Asian and predominance of stroke presentations in Black patients, we found no ethnic differences in presentation with heart failure. We consider the public health and research implications of our findings. NCT02176174, www.clinicaltrials.gov.


[Self-rated health among climacteric women affiliated with the Instituto Mexicano del Seguro Social].
To evaluate self-rated health (SRH) in climacteric women and to identify the factors associated with negative SRH. Information from 9 248 women aged 40 to 59 years was analyzed. SRH was the dependent variable. Independent variables were demographic characteristics, history of reproductive and chronic diseases, physical activity, and participation in screening and health education programs. Data were analyzed using descriptive statistics, bivariate analysis, and logistic regression modeling. Forty-two percent of women reported positive SRH and 58% reported negative SRH. Factors associated with negative SRH were: low literacy level (OR 1.78, CI95% 1.62-1.95), unemployment (OR 1.20, CI95% 1.09-1.33), menopause (OR 1.22, CI95% 1.11-1.33), type 2 diabetes (OR 1.88, CI95% 1.65-2.13) hypertension (OR 2.01, CI95% 1.82-2.22), irregular physical exercise (OR 1.30, CI95% 1.12-1.50), sedentarism (OR 1.395, CI95% 1.23-1.57), lack of information about climacteric (OR 1.17, CI95% 1.07-1.28) and lack of screening for chronic diseases (OR 0.82, CI95% 0.75-0.89). Factors associated with negative SRH such as lack of information and physical activity should be strengthened.


A randomised placebo-controlled trial of the efficacy of beta-sitosterol and its glucoside as adjuvants in the treatment of pulmonary tuberculosis.
To evaluate the adjuvant effect of beta-sitosterol and its glucoside in the treatment of culture proven pulmonary tuberculosis (PTB). A blinded randomised placebo-controlled trial in culture proven drug sensitive PTB. Patients were hospitalised for the duration of treatment and evaluated at monthly intervals with regard to sputum culture positivity, chest radiography, weight gain, Mantoux test response, routine haematology and liver functions. STATISTICAL EVALUATION: General linear models for repeated measures (SAS GLM package) compared the interaction effects, group effects and time effects of findings in 19 patients receiving sitosterols with those in 18 patients receiving a placebo (talcum powder). Absolute values and change from baseline values were evaluated, although only the latter are reported. Weight gain was significantly greater in the sitosterol group (mean weight gain 8.9 kg) than the placebo group (mean gain 6.1 kg) (P = 0.0023 group effects; P = 0.0001 for time effects). Speed of achieving culture negativity, radiological improvement and induration on Mantoux testing was similar in the two groups. Change in lymphocyte counts from baseline was significantly higher in the sitosterol group (P = 0.0001 and P = 0.0001 for group and time effects) as was the increase in eosinophil counts (P = 0.0001 and P = 0.0137 for group and time effects). The study has shown significantly improved weight gain and higher lymphocyte and eosinophil counts in PTB patients receiving sitosterols in addition to an efficacious antituberculosis regimen. Sitosterols and their possible mode of action should now be evaluated in larger numbers of tuberculosis patients and in diseases with a similar immunopathogenesis.


Regulation of DNA repair fidelity by molecular checkpoints: "gates" in DNA polymerase beta's substrate selection.
With an increasing number of structural, kinetic, and modeling studies of diverse DNA polymerases in various contexts, a complex dynamical view of how atomic motions might define molecular "gates" or checkpoints that contribute to polymerase specificity and efficiency is emerging. Such atomic-level information can offer insights into rate-limiting conformational and chemical steps to help piece together mechanistic views of polymerases in action. With recent advances, modeling and dynamics simulations, subject to the well-appreciated limitations, can access transition states and transient intermediates along a reaction pathway, both conformational and chemical, and such information can help bridge the gap between experimentally determined equilibrium structures and mechanistic enzymology data. Focusing on DNA polymerase beta (pol beta), we present an emerging view of the geometric, energetic, and dynamic selection criteria governing insertion rate and fidelity mechanisms of DNA polymerases, as gleaned from various computational studies and based on the large body of existing kinetic and structural data. The landscape of nucleotide insertion for pol beta includes conformational changes, prechemistry, and chemistry "avenues", each with a unique deterministic or stochastic pathway that includes checkpoints for selective control of nucleotide insertion efficiency. For both correct and incorrect incoming nucleotides, pol beta's conformational rearrangements before chemistry include a cascade of slow and subtle side chain rearrangements, followed by active site adjustments to overcome higher chemical barriers, which include critical ion-polymerase geometries; this latter notion of a prechemistry avenue fits well with recent structural and NMR data. The chemical step involves an associative mechanism with several possibilities for the initial proton transfer and for the interaction among the active site residues and bridging water molecules. The conformational and chemical events and associated barriers define checkpoints that control enzymatic efficiency and fidelity. Understanding the nature of such active site rearrangements can facilitate interpretation of existing data and stimulate new experiments that aim to probe enzyme features that contribute to fidelity discrimination across various polymerases via such geometric, dynamic, and energetic selection criteria.


Staphylococcus aureus helicase but not Escherichia coli helicase stimulates S. aureus primase activity and maintains initiation specificity.
Bacterial primases are essential for DNA replication due to their role in polymerizing the formation of short RNA primers repeatedly on the lagging-strand template and at least once on the leading-strand template. The ability of recombinant Staphylococcus aureus DnaG primase to utilize different single-stranded DNA templates was tested using oligonucleotides of the sequence 5'-CAGA (CA)5 XYZ (CA)3-3', where XYZ represented the variable trinucleotide. These experiments demonstrated that S. aureus primase synthesized RNA primers predominately on templates containing 5'-d(CTA)-3' or TTA and to a much lesser degree on GTA-containing templates, in contrast to results seen with the Escherichia coli DnaG primase recognition sequence 5'-d(CTG)-3'. Primer synthesis was initiated complementarily to the middle nucleotide of the recognition sequence, while the third nucleotide, an adenosine, was required to support primer synthesis but was not copied into the RNA primer. The replicative helicases from both S. aureus and E. coli were tested for their ability to stimulate either S. aureus or E. coli primase. Results showed that each bacterial helicase could only stimulate the cognate bacterial primase. In addition, S. aureus helicase stimulated the production of full-length primers, whereas E. coli helicase increased the synthesis of only short RNA polymers. These studies identified important differences between E. coli and S. aureus related to DNA replication and suggest that each bacterial primase and helicase may have adapted unique properties optimized for replication.


Prediction of mono- and di-nucleotide-specific DNA-binding sites in proteins using neural networks.
DNA recognition by proteins is one of the most important processes in living systems. Therefore, understanding the recognition process in general, and identifying mutual recognition sites in proteins and DNA in particular, carries great significance. The sequence and structural dependence of DNA-binding sites in proteins has led to the development of successful machine learning methods for their prediction. However, all existing machine learning methods predict DNA-binding sites, irrespective of their target sequence and hence, none of them is helpful in identifying specific protein-DNA contacts. In this work, we formulate the problem of predicting specific DNA-binding sites in terms of contacts between the residue environments of proteins and the identity of a mononucleotide or a dinucleotide step in DNA. The aim of this work is to take a protein sequence or structural features as inputs and predict for each amino acid residue if it binds to DNA at locations identified by one of the four possible mononucleotides or one of the 10 unique dinucleotide steps. Contact predictions are made at various levels of resolution viz. in terms of side chain, backbone and major or minor groove atoms of DNA. Significant differences in residue preferences for specific contacts are observed, which combined with other features, lead to promising levels of prediction. In general, PSSM-based predictions, supported by secondary structure and solvent accessibility, achieve a good predictability of approximately 70-80%, measured by the area under the curve (AUC) of ROC graphs. The major and minor groove contact predictions stood out in terms of their poor predictability from sequences or PSSM, which was very strongly (>20 percentage points) compensated by the addition of secondary structure and solvent accessibility information, revealing a predominant role of local protein structure in the major/minor groove DNA-recognition. Following a detailed analysis of results, a web server to predict mononucleotide and dinucleotide-step contacts using PSSM was developed and made available at http://sdcpred.netasa.org/ or http://tardis.nibio.go.jp/netasa/sdcpred/. Most residue-nucleotide contacts can be predicted with high accuracy using only sequence and evolutionary information. Major and minor groove contacts, however, depend profoundly on the local structure. Overall, this study takes us a step closer to the ultimate goal of predicting mutual recognition sites in protein and DNA sequences.


Relative efficacy of buprenorphine, nalbuphine and morphine in opioid-treated rhesus monkeys discriminating naltrexone.
Efficacy is one determinant of whether a drug is an agonist or an antagonist under a particular set of conditions. Relative efficacy among the micro opioid receptor (MOR) ligands buprenorphine, nalbuphine, and morphine was examined in monkeys dependent on morphine (3.2 mg/kg/day) or l-alpha-acetylmethadol (LAAM) (1.0 mg/kg twice daily) and that discriminated naltrexone (0.0178 mg/kg) from saline. In morphine-treated monkeys, buprenorphine and not nalbuphine substituted for naltrexone. When administered before naltrexone in morphine-treated monkeys, morphine and nalbuphine shifted the naltrexone dose-effect curve to the right, while buprenorphine shifted the naltrexone dose-effect curve to the left. Under conditions of acute morphine deprivation, naltrexone-lever responding was slightly attenuated by buprenorphine and markedly attenuated by nalbuphine and morphine. In LAAM-treated monkeys, buprenorphine substituted completely for naltrexone in only one monkey, while nalbuphine and morphine failed to substitute in any monkey. When administered before naltrexone in LAAM-treated monkeys, buprenorphine, nalbuphine, and morphine dose dependently shifted the naltrexone dose-effect curve to the right, with the exception of one monkey in which buprenorphine shifted the naltrexone dose-effect curve to the left. These results demonstrate that a low efficacy MOR ligand can exert agonist or antagonist actions in the same animal depending on immediate pharmacologic history. The qualitatively different effects of buprenorphine in morphine- and LAAM-treated monkeys might be related to magnitude of dependence insofar as dependence can determine the efficacy required for agonist activity. Thus, buprenorphine has markedly different effects across different levels of opioid dependence.


Emergent magnetic monopole dynamics in macroscopically degenerate artificial spin ice.
Magnetic monopoles, proposed as elementary particles that act as isolated magnetic south and north poles, have long attracted research interest as magnetic analogs to electric charge. In solid-state physics, a classical analog to these elusive particles has emerged as topological excitations within pyrochlore spin ice systems. We present the first real-time imaging of emergent magnetic monopole motion in a macroscopically degenerate artificial spin ice system consisting of thermally activated Ising-type nanomagnets lithographically arranged onto a pre-etched silicon substrate. A real-space characterization of emergent magnetic monopoles within the framework of Debye-Hückel theory is performed, providing visual evidence that these topological defects act like a plasma of Coulomb-type magnetic charges. In contrast to vertex defects in a purely two-dimensional artificial square ice, magnetic monopoles are free to evolve within a divergence-free vacuum, a magnetic Coulomb phase, for which features in the form of pinch-point singularities in magnetic structure factors are observed.


Effect of systemic antibiotics and topical chlorhexidine on meticillin-resistant Staphylococcus aureus carriage in intensive care unit patients.
Antibiotics and antiseptics have the potential to influence carriage and transmission of meticillin-resistant Staphylococcus aureus (MRSA), although effects are likely to be complex, particularly in a setting where multiple agents are used. Here admission and weekly MRSA screens and daily antibiotic and antiseptic prescribing data from 544 MRSA carriers on an intensive care unit (ICU) are used to determine the effect of these agents on short-term within-host MRSA carriage dynamics. Longitudinal data were analysed using Markov models allowing patients to move between two states: MRSA positive (detectable MRSA carriage) and MRSA negative (no detectable carriage). The effect of concurrent systemic antibiotic and topical chlorhexidine (CHX) on movement between these states was assessed. CHX targeted to MRSA screen carriage sites increased transition from culture positive to negative and there was also weaker evidence that it decreased subsequent transition from negative back to positive. In contrast, there was only weak and inconsistent evidence that any antibiotic influenced transition in either direction. For example, whereas univariate analysis found quinolones to be strongly associated with both increased risk of losing and then reacquiring MRSA carriage over time intervals of one day, no effect was seen with weekly models. Similar studies are required to determine the generalisability of these findings.


The Impact of Cosmetic Surgery on Women's Marital Satisfaction and Self-Concept.
Today, cosmetic surgery is one of the most common procedures worldwide, and its use is increasing. This study aimed to identify the impact of cosmetic surgery on married women's marital satisfaction and self-concept. From January 1st, 2015 to June 6th, 2015, 44 married women operated in a plastic surgery clinic or seeking for a cosmetic surgery and 55 non-applicants as general population were enrolled. ENRICH marital satisfaction questionnaire and Rogers' Self-concept Inventory were used to compare groups. Operated applicants revealed a significant higher level of satisfaction in comparison with other groups regarding personality, conflict and leisure. Compared to control group, the surgical group had significantly higher satisfaction in marital and familial relationship, friendship, and financial management. It can be drawn that expectation for postoperative positive outcome probably is an important factor affecting high level of marital satisfaction in cosmetic surgery applicants. Furthermore, the self-concept is significant predictor of applying for cosmetic surgery.


Cariology Education in Canadian Dental Schools: Where Are We? Where Do We Need to Go?
The aim of this study was to document cariology education across Canadian dental schools. Ten faculty members who supervise cariology education at each of the ten Canadian dental schools were invited to participate in the study in 2016. An adapted version of the European Organization for Caries Research-Association for Dental Education in Europe cariology curriculum group questionnaire was used. Representatives of all ten dental schools completed the questionnaire, for a 100% response rate. In four schools, cariology and restorative dentistry were taught by the same department. Five schools had didactic/laboratory courses focusing primarily on cariology as well as a specific written curriculum. Six schools provided cariology-related hands-on workshops/laboratories before students started working with patients. In teaching cariology, seven institutions included dental hard tissues defects. The following caries detection methods were addressed didactically in cariology education: visual (10/10 total schools), tactile (9/10), International Caries Detection and Assessment System criteria (6/10), caries activity assessment (9/10), radiographic (10/10), and other detection tools (8/10). Seven schools charted activity of carious lesions in clinic. Only one school used the concept of caries risk assessment regularly in clinic. Clinical cariology teaching was carried out mostly by private dentists hired as clinical instructors (7/10) and faculty members involved in didactic cariology education (9/10). Calibration of faculty members for caries detection criteria was reported by only one school. The main concern reported by all institutions was the difficulty of implementing didactic instruction on cariology into clinical training. This study found that contemporary cariology concepts are in the process of being implemented in didactic education across Canadian dental schools, but all schools lacked appropriate integration of cariology education into clinical training. These findings suggest a need for harmonization of evidence-based cariology education in Canada.


A 5-cm colonic J pouch colo-anal reconstruction following anterior resection for low rectal cancer results in acceptable evacuation and continence in the long term.
Optimal treatment for low rectal cancer is total mesorectal excision, with most patients suitable for low colo-rectal or colo-anal anastomosis. A colon pouch has early functional benefits, although long-term function, especially evacuation, might mitigate against its routine use. The aim of this study was to assess evacuation and continence in patients with a colon pouch, and to examine the impact of possible risk factors. In 1998, all 102 surviving patients with a colon pouch, whose stoma had been closed for more than one year, were sent a postal questionnaire. A composite incontinence score was calculated from questions on urgency, use of a pad, incontinence of gas, liquid or faeces; and a composite evacuation score from questions on medication taken to evacuate, straining, the need and number of times returned to evacuate. The response rate was 90% (50 M, 42 F), with a median age of 68 years (IQR 60-78) and median follow-up of 2.6 years (IQR 1.7-3.9). The anastomosis was 3 cm or less from the anus in 45/92 (49%), and incontinence scores were worse in this group (P = 0.001). There were significantly higher incontinence scores in females (P = 0.014). Age, preoperative radiotherapy, part of colon used for anastomosis, postoperative leak and length of follow-up had no demonstrable effect on either score. Gender and anastomotic height were the only variables which influenced incontinence. Ninety percent of patients reported that their bowel function did not affect their overall wellbeing, and none would have preferred to have a stoma.


Optimization of CH fluorescence diagnostics in flames: range of applicability and improvements with hydrogen addition.
This study quantifies the range of premixed flame conditions for which CH fluorescece diagnostics are applicable, and it shows that the CH fluorescence signal can be increased if some of the hydrocarbon fuel is replaced with hydrogen. The CH fluorescence signal is found to be adequate for fuel-air equivalence ratios (phi) as small as 0.85 for both methane-air and propane-air flames. The CH signal increases until a maximum at phi = 1.25 and phi = 1.35 for methane-air and propane-air flames, respectively, and then decreases for richer conditions. A strategy to increase the CH fluorescence signal and decrease interference from soot precursors is proposed by addition of the proper amount of hydrogen to the hydrocarbon fuel. Hydrogen addition reduces the background signal from soot precursors by as much as afactor of 10 and increases the CH fluorescence signal by as much as 80%. The normalized CH fluorescence measurements are compared with computations that utilize GRI-MECH 3.0 chemistry. Sources experimental uncertainties are discussed.


Gene trapping identifies transiently induced survival genes during programmed cell death.
The existence of a constitutively expressed machinery for death in individual cells has led to the notion that survival factors repress this machinery and, if such factors are unavailable, cells die by default. In many cells, however, mRNA and protein synthesis inhibitors induce apoptosis, suggesting that in some cases transcriptional activity might actually impede cell death. To identify transcriptional mechanisms that interfere with cell death and survival, we combined gene trap mutagenesis with site-specific recombination (Cre/loxP system) to isolate genes from cells undergoing apoptosis by growth factor deprivation. From an integration library consisting of approximately 2 x 106 unique proviral integrations obtained by infecting the interleukin-3 (IL-3)-dependent hematopoietic cell line - FLOXIL3 - with U3Cre gene trap virus, we have isolated 125 individual clones that converted to factor independence upon IL-3 withdrawal. Of 102 cellular sequences adjacent to U3Cre integration sites, 17% belonged to known genes, 11% matched single expressed sequence tags (ESTs) or full cDNAs with unknown function and 72% had no match within the public databases. Most of the known genes recovered in this analysis encoded proteins with survival functions. We have shown that hematopoietic cells undergoing apoptosis after withdrawal of IL-3 activate survival genes that impede cell death. This results in reduced apoptosis and improved survival of cells treated with a transient apoptotic stimulus. Thus, apoptosis in hematopoietic cells is the end result of a conflict between death and survival signals, rather than a simple death by default.


Maternal circulating levels of activin A, inhibin A, sFlt-1 and endoglin at parturition in normal pregnancy and pre-eclampsia.
Maternal circulating levels of anti-angiogenic factors such as soluble fms-like tyrosine kinase-1 (sFlt-1), endoglin (sEng) and placental proteins like activin A and inhibin A are increased before the onset of pre-eclampsia. There is evidence for oxidative stress in pre eclampsia. Recently it was shown that placental oxygen concentration is related to sFlt-1 and inhibin A. In addition it is reported that oxidative stress markers are increased in placental tissue delivered after labour. Therefore, the objective of this study is to investigate if these proteins are altered in maternal circulation of labouring pre-eclampsia and normal pregnancies. To assess the effects of labour, samples were taken from 10 normal pregnant (NP) and 10 pre-eclamptic (PE) women pre-labour, full dilation, placental delivery and 24 h. To assess the effects of placental delivery, plasma samples were taken from 10NP and 10PE women undergoing elective Caesarean section, pre-delivery, placental delivery and 10 min, 60 min and 24 h post delivery. SFlt-1 and sEng and activin A and inhibin A were measured using commercial and in house ELISA's respectively. The levels of sFlt-1 and sEng were significantly higher in PE compared to NP women in both groups. In labour, sFlt-1 levels increased significantly at full dilatation in PE women, before declining by 24 hr. However there was no significant rise in sEng levels in labour. Activin A and inhibin A levels declined rapidly with placental delivery in NP and PE pregnancies. There was a significant rise in activin A levels during labour in PE compared to pre labour, but inhibin levels did not increase. Labour in pre-eclamptic women increases the levels of sFlt-1 and activin A. This pilot data suggests that increase in the maternal levels of these factors in labour could predict and/or contribute to the maternal syndrome postpartum.


Explosive strength: effect of knee-joint angle on functional, neural, and intrinsic contractile properties.
The present study compared knee extension explosive isometric torque, neuromuscular activation, and intrinsic contractile properties at five different knee-joint angles (35°, 50°, 65°, 80°, and 95°; 0° = full knee extension). Twenty-eight young healthy males performed two experimental sessions each involving: 2 maximum, and 6-8 explosive voluntary contractions at each angle; to measure maximum voluntary torque (MVT), explosive voluntary torque (EVT; 50-150 ms after contraction onset) and quadriceps surface EMG (QEMG, 0-50, 0-100, and 0-150 ms after EMG onset during the explosive contractions). Maximum twitch and M-wave (MMAX) responses as well as octet contractions were evoked with femoral nerve stimulation at each angle. Absolute MVT and EVT showed an inverted 'U' relationship with higher torque at intermediate angles. There were no differences between knee-joint angles for relative EVT (%MVT) during the early phase (≤ 75 ms) of contraction and only subtle differences during the late phase (≥ 75 ms) of contraction (≤ 11%). Neuromuscular activation during explosive contractions was greater at more flexed than extended positions, and this was also the case during MVT. Whilst relative twitch torque (%MVT) was higher at knee flexed positions (P ≤ 0.001), relative octet torque (%MVT) was higher at knee extended positions (P ≤ 0.001). Relative EVT was broadly similar between joint angles, likely because neuromuscular activation during both explosive and plateau (maximum) phases of contraction changed proportionally, and due to the opposing changes in twitch and octet evoked responses with joint angle.


Monochloramine and chlorine dioxide for controlling Legionella pneumophila contamination: biocide levels and disinfection by-product formation in hospital water networks.
Legionella colonization in hospital hot water distribution networks was evaluated following 36 months of continuous treatment with monochloramine and compared with chlorine dioxide. Nitrite, nitrate, chlorite, chlorate, bromide, trihalomethanes and haloacetic acids as well as the biocide concentration at sampled points were measured. Only 8/84 samples treated with monochloramine were found contaminated and after the first 8 months of treatment no Legionella was isolated. Chlorine dioxide was associated with a strong reduction in Legionella contamination compared to pre-treatment, but differences according to the device were observed. Monochloramine between 2 and 3 mg l(-1) and chlorine dioxide between 0.50 and 0.70 mg l(-1) were needed to control Legionella colonization. Comparing no- and post-flush samples, a higher frequency of no-flush positive samples was noted using chlorine dioxide, suggesting an increased risk for patients when they open the tap. No increase in chlorite levels and no water nitrification occurred by using monochloramine. Chlorite at levels exceeding the limit requested for drinking water was measured when chlorine dioxide was applied. In conclusion, we highlight that continuous injection of monochloramine should be considered as an effective alternative to chlorine dioxide in controlling legionellae contamination inside hospital water distribution systems.


Modulating prime molecular expressions and in vitro wound healing rate in keratinocyte (HaCaT) population under characteristic honey dilutions.
In traditional medicines honey is known for healing efficacy and vividly used as "Anupan" in Ayurvedic medicines appreciating roles in dilutions. Validating efficacy of physico-chemically characterized honey in dilutions, studies on in vitro wound healing and attainment of cellular confluence epithelial cells including expressions of cardinal genes is crucial. To evaluate effects of characterized honey in varied dilutions on cellular viability, in vitro wound healing and modulation of prime epithelial gene expressions. Six Indian honey-samples from different sources were physico-chemically characterized and optimal one was explored in dilutions (v/v%) through in vitro studies on human epithelial (HaCaT) cells for viability, wound healing and expressions of genes p63, E-cadherin, β-catenin, GnT-III and GnT-V. Studied honey samples (i.e. A-F) depicted range of pH (2-4), water (12.48-23.95), electrical conductivity (2.57-14.34), carbohydrate (68.73-98.65), protein (.316-5.36) and antioxidant potential. Though sample A and F showed physico-chemical proximity, but overall bio-impact of the earlier was better, thus studied in 8-.1% (v/v) dilution range. Four dilutions (.01, .04, .1, .25 v/v%) augmented cellular viability but in vitro wound healing was fastest (p<.05) under .1%. Such efficacy was further documented for p63 up-regulation by immunocytochemistry and mRNA studies. The E-cadherin and β-catenin mRNA-expressions were also up-regulated and their proteins were predominantly cytoplasmic. E-cadherin up-regulation was corroborative with down-regulation and up-regulation of GnT-III and GnT-V respectively. Present study illustrated efficacy of particular honey dilution (.1%) with characteristic free radical scavenging activity in facilitating cell proliferation and attainment of confluence towards faster wound healing and modulation of cardinal epithelial genes (viz. p63, E-cadherin, β-catenin, Gnt-III and V).


Regional distribution of monoamines in the nucleus accumbens of the rat.
Monoamine concentrations were low in the rostral area of the nucleus accumbens. Their distributions were not identical. Differences were observed in the medial area. DA concentrations were high in both medial and caudal areas. Noradrenaline (NA) and serotonin (5-HT) concentrations were considerably lower than the dopamine (DA) concentration. The NA concentration was highest in the caudal area of the nucleus accumbens and the (5-HT) concentration was highest in the ventrocaudal area. There was a rostrocaudal decrease in the 3,4-dihydroxyphenylacetic acid (DOPAC)/DA and 5-hydroxyindole-3-acetic acid (5-HIAA)/5-HT ratios. Uptake of [3H]DA and [14C]choline was lowest in the rostral area. The K+-stimulated release of [14C]acetylcholine (ACh) was also lowest rostrally, but there was no rostrocaudal difference in the K+-stimulated release of [3H]DA. These results provide further evidence of the heterogeneity of the nucleus accumbens.


Feasibility of a Mobile Phone-Based Surveillance for Surgical Site Infections in Rural India.
To assess the feasibility of using mobile communication technology in completing a 30-day follow-up of surgical site infection (SSI). SSIs are infections occurring up to 30 days after an operative procedure. This prospective exploratory study was conducted in a cohort of patients who were admitted and operated on in the general surgery wards of a rural hospital in India from October 2010 to June 2011. At the time of discharge, all patients were requested to follow-up in the surgical outpatient clinic at 30 days after surgery. If this was not done, a mobile phone-based surveillance was done to complete the follow-up. The mean age of the 536 operated-on patients was 40 years (95% confidence interval [CI], 38-41 years). The mean duration of hospital stay was 10.7 days (95% CI, 9.9-11.6 days). Most (81%) operated-on patients were from rural areas, and 397 (75%) were male. Among the operated-on patients the ownership of mobile phones was 75% (95% CI, 73-78%). The remaining 25% of patients (n=133) used a shared mobile phone. For 380 patients (74.5%) the follow-up was completed by mobile phones. The SSI rate at follow-up was 6.3% (n=34). In 10 patients, an SSI was detected over the mobile phone. Mobile communication technology is feasible to be used in rural settings to complete case follow-up for SSIs.


ReaxFF study of the oxidation of lignin model compounds for the most common linkages in softwood in view of carbon fiber production.
Lignin is an underused but major component of biomass. One possible area of utilization is the production of carbon fiber. A necessary processing step is the stabilization of lignin fiber (typically in an oxygen environment) before high temperature treatment. We investigate oxidative, thermal conversion of lignin using computational methods. Dilignol model compounds for the most common (seven) linkages in softwood are chosen to represent the diverse structure of lignin. We perform molecular dynamics simulation where the potential energy surface is described by a reactive force field (ReaxFF). We calculate overall activation energies for model conversion and reveal initial mechanisms of formaldehyde formation. We record fragmentation patterns and average carbon oxidation numbers at various temperatures. Most importantly, we identify mechanisms for stabilizing reactions that result in cyclic and rigid connections in softwood lignin fibers that are necessary for further processing into carbon fibers.


Cycling cadence affects heart rate variability.
The purpose of this study was to examine the effect different cycling cadences have on heart rate variability (HRV) when exercising at constant power outputs. Sixteen males had ECG and respiratory measurements recorded at rest and during 8, 10 min periods of cycling at four different cadences (40, 60, 80 and 100 revs min(-1)) and two power outputs (0 W (unloaded) and 100 W (loaded)). The cycling periods were performed following a Latin square design. Spectral analyses of R-R intervals by fast Fourier transforms were used to quantify absolute frequency domain HRV indices (ms(2)) during the final 5 min of each bout, which were then log transformed using the natural logarithm (Ln). HRV indices of high frequency (HF) power were reduced when cadence was increased (during unloaded cycling (0 W) log transformed HF power decreased from a mean [SD] of 6.3 [1.4] Ln ms(2) at 40 revs min(-1) to 3.9 [1.3] Ln ms(2) at 100 revs min(-1)). During loaded cycling (at 100 W), the low to high frequency (LF:HF) ratio formed a 'J' shaped curve as cadence increased from 40 revs min(-1) (1.4 [0.4]) to 100 revs min(-1) (1.9 [0.7]), but dipped below the 40 revs min(-1) values during the 60 revs min(-1) 1.1 (0.3) and 80 revs min(-1) 1.2 (0.6) cadence conditions. Cardiac frequency (f(C)) and ventilatory variables were strongly correlated with frequency domain HRV indices (r = -0.80 to -0.95). It is concluded that HRV indices are influenced by both cycling cadence and power output; this is mediated by the f(C) and ventilatory changes that occur as cadence or exercise intensity is increased. Consequently, if HRV is assessed during exercise, both power output/exercise intensity and cadence should be standardized.


Structural and functional analysis of the tandem β-zipper interaction of a Streptococcal protein with human fibronectin.
Bacterial fibronectin-binding proteins (FnBPs) contain a large intrinsically disordered region (IDR) that mediates adhesion of bacteria to host tissues, and invasion of host cells, through binding to fibronectin (Fn). These FnBP IDRs consist of Fn-binding repeats (FnBRs) that form a highly extended tandem β-zipper interaction on binding to the N-terminal domain of Fn. Several FnBR residues are highly conserved across bacterial species, and here we investigate their contribution to the interaction. Mutation of these residues to alanine in SfbI-5 (a disordered FnBR from the human pathogen Streptococcus pyogenes) reduced binding, but for each residue the change in free energy of binding was <2 kcal/mol. The structure of an SfbI-5 peptide in complex with the second and third F1 modules from Fn confirms that the conserved FnBR residues play equivalent functional roles across bacterial species. Thus, in SfbI-5, the binding energy for the tandem β-zipper interaction with Fn is distributed across the interface rather than concentrated in a small number of "hot spot" residues that are frequently observed in the interactions of folded proteins. We propose that this might be a common feature of the interactions of IDRs and is likely to pose a challenge for the development of small molecule inhibitors of FnBP-mediated adhesion to and invasion of host cells.


Measuring the evolution of contemporary western popular music.
Popular music is a key cultural expression that has captured listeners' attention for ages. Many of the structural regularities underlying musical discourse are yet to be discovered and, accordingly, their historical evolution remains formally unknown. Here we unveil a number of patterns and metrics characterizing the generic usage of primary musical facets such as pitch, timbre, and loudness in contemporary western popular music. Many of these patterns and metrics have been consistently stable for a period of more than fifty years. However, we prove important changes or trends related to the restriction of pitch transitions, the homogenization of the timbral palette, and the growing loudness levels. This suggests that our perception of the new would be rooted on these changing characteristics. Hence, an old tune could perfectly sound novel and fashionable, provided that it consisted of common harmonic progressions, changed the instrumentation, and increased the average loudness.


Acute hemodynamic effects of inhaled nitroglycerine, intravenous nitroglycerine, and their combination with intravenous dobutamine in patients with secondary pulmonary hypertension.
The presence of pulmonary artery hypertension (PAH) affects the prognosis of patients; therefore, it is important to treat it. The aim of this study is to compare the acute hemodynamic effects of inhaled nitroglycerine (iNTG), intravenous nitroglycerine (IV NTG) alone and their combination with intravenous dobutamine (IV DOB) during the early postoperative period, in patients with PAH undergoing mitral valve or double valve replacement surgery. In the study, 40 patients with secondary PAH were administered iNTG 2.5 microg/kg/min, IV NTG 2.5 microg/kg/min, a combination of iNTG 2.5 microg/kg/min + IV DOB 10 microg/kg/min, and IV NTG 2.5 microg/kg/min + IV DOB 10 microg/kg/min for 10 minutes each following valve replacement surgery, in random order. The hemodynamic parameters were recorded before (T0) and immediately after the intervention. (T1). iNTG effectively decreased mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance index (PVRI), and the PVR / SVR ratio, without affecting arterial pressures, systemic vascular resistance or mixed venous oxygen saturation (SvO2). IV NTG produced both systemic and pulmonary vasodilation along with a significant fall in SvO2. The combination of iNTG and IV DOB caused a significant decrease in mPAP and PVRI, with no significant change in SVRI, PVR / SVR ratio, and SvO2. A combination of IV NTG + IV DOB caused both pulmonary and systemic vasodilatation with a significant decrease in SvO2. None of the drugs caused any significant change in the cardiac index. All drugs were of similar efficacy in reducing the pulmonary vascular resistance index. Only iNTG produced selective pulmonary vasodilatation, while IV NTG and its combination with IV dobutamine had a significant concomitant systemic vasodilatory effect.


Brain Connectivity Networks and the Aesthetic Experience of Music.
Listening to music is above all a human experience, which becomes an aesthetic experience when an individual immerses himself/herself in the music, dedicating attention to perceptual-cognitive-affective interpretation and evaluation. The study of these processes where the individual perceives, understands, enjoys and evaluates a set of auditory stimuli has mainly been focused on the effect of music on specific brain structures, as measured with neurophysiology and neuroimaging techniques. The very recent application of network science algorithms to brain research allows an insight into the functional connectivity between brain regions. These studies in network neuroscience have identified distinct circuits that function during goal-directed tasks and resting states. We review recent neuroimaging findings which indicate that music listening is traceable in terms of network connectivity and activations of target regions in the brain, in particular between the auditory cortex, the reward brain system and brain regions active during mind wandering.


"Inflammatory response to colloids compared to crystalloid priming in cardiac surgery patients with cardiopulmonary bypass".
"Cardiac surgery with cardiopulmonary bypass (CPB) induces a systemic inflammatory response syndrome that may contribute to postoperative morbidity and mortality. We investigated the in-flammatory responses to colloids compared to crystalloid priming in cardiac surgery patients with cardiopulmonary bypass. Thirty patients undergoing coronary artery bypass grafting (CABG) preparing for CPB were randomized into Ringer's solution (RS), 10% hydroxyethyl starch (HES) or 25% human albumin (HA) group. Serum concentrations of tumor necrosis factor-α (TNF-α), interleukin-1 β (IL-1β ), interleukin-6 (IL-6) and interleukin-10 (IL-10) were measured before CPB, at the end of CPB and 1, 6 and 12 h after CPB. Serum C-reactive protein (CRP) was determined pre-operatively and then daily for 2 days. Body-weight gain was significantly decreased on the day after surgery in the HES group than in the RS group. Volume priming in CPB for CABG patients using HA or HES preparation had less tendency for intense inflammatory response with lower levels of TNF-α, IL-1 β , IL-6 and higher levels of IL-10 compared to patients treated with RS. HES prime had lower levels of circulating CRP than in patients treated with HA or Ringer prime on the second post-operative day. Our data indicate that volume priming using colloid during CPB in CABG patients might exert beneficial effects on inflammatory responses."


Cognitive intervention programmes on patients affected by Mild Cognitive Impairment: a promising intervention tool for MCI?
This paper examines and reviews studies on the efficacy of computer-based cognitive intervention programmes in the elderly affected by Mild Cognitive Impairment (MCI). MCI patients are at higher risk to progress to dementia. Recent effort has been made to slow the cognitive decline and delay the onset of dementia in this population. MEDLINE sources were searched with the following subject headings: computer-based cognitive intervention, cognitive stimulation, cognitive training, aging, elderly, cognitive impairment. Selected studies were quality assessed and data extracted by two reviewers. Several studies reported encouraging results on cognitive interventions programmes as a means to improve cognitive abilities and emotional states and to decrease subjective memory complaints in MCI patients. Though both traditional and computer-based cognitive intervention programmes seem to be effective, the computer-based ones present more advantages: 1) they could individualize the programme tailored to the patient's neuropsychological pattern and needs. 2) they permit the user to make an immediate objective comparison with data collected earlier and thus help in setting up a systematic training plan by providing instant value-free feedback. 3) they offer a possibility of a widescale dissemination.


Tantalum inhalation and airway responses.
We studied the effects of tantalum inhalation bronchography on pulmonary function in 14 normal volunteers. Based on the radiographic type of deposition, the subjects were divided into three groups: (1) subjects who deposited tantalum mainly in the trachea, (2) subjects who deposited tantalum in segmental bronchi without radiographic evidence of bronchospasm, and (3) subjects who deposited tantalum in segmental bronchi with radiographic evidence of bronchospasm. Unlike the first two groups, the third group developed a significant but small decrease in the FEV. Airway reactivity as assessed by methacholine challenge did not explain the difference in response to tantalum in the third group. There were no consistent changes in total lung capacity, residual volume, or closing volume in any of the groups. Even though there were falls in FEV and specific conductance in individuals in groups 2 and 3, these changes did not pose any significant clinical risk.


Hypercarnivory and the brain: protein requirements of cats reconsidered.
The domestic hypercarnivores cat and mink have a higher protein requirement than other domestic mammals. This has been attributed to adaptation to a hypercarnivorous diet and subsequent loss of the ability to downregulate amino acid catabolism. A quantitative analysis of brain glucose requirements reveals that in cats on their natural diet, a significant proportion of protein must be diverted into gluconeogenesis to supply the brain. According to the model presented here, the high protein requirement of the domestic cat is the result of routing of amino acids into gluconeogenesis to supply the needs of the brain and other glucose-requiring tissues, resulting in oxidation of amino acid in excess of the rate predicted for a non-hypercarnivorous mammal of the same size. Thus, cats and other small hypercarnivores do not have a high protein requirement per se, but a high endogenous glucose demand that is met by obligatory amino acid-based gluconeogenesis. It is predicted that for hypercarnivorous mammals with the same degree of encephalisation, endogenous nitrogen losses increase with decreasing metabolic mass as a result of the allometric relationships of brain mass and brain metabolic rate with body mass, possibly imposing a lower limit for body mass in hypercarnivorous mammals.


Higher Body Mass Index in Adolescence Predicts Cardiomyopathy Risk in Midlife.
Modifiable lifestyle factors in relation to risk for cardiomyopathy, a common and increasing cause of heart failure in the young, have not been widely studied. We sought to investigate a potential link between obesity, a recognized predictor of early heart failure, in adolescence and being diagnosed with cardiomyopathy in adulthood. This was a nationwide register-based prospective cohort study of 1 668 893 adolescent men (mean age, 18.3 years; SD, 0.7 years) who enlisted for compulsory military service from 1969 to 2005. At baseline, body mass index (BMI), blood pressure, and medical disorders were registered, along with test results for fitness and muscle strength. Cardiomyopathy diagnoses were identified from the National Hospital Register and Cause of Death Register during an up to 46-year follow-up and divided into categories: dilated, hypertrophic, alcohol/drug-induced, and other. Hazard ratios were calculated with Cox proportional hazards models. During follow-up (median, 27 years; Q1-Q3, 19-35 years), 4477 cases of cardiomyopathy were identified, of which 2631 (59%) were dilated, 673 (15%) were hypertrophic, and 480 (11%) were alcohol/drug-induced. Increasing BMI was strongly associated with elevated risk of cardiomyopathy, especially dilated, starting at levels considered normal (BMI, 22.5-<25 kg/m2; hazard ratio, 1.38 [95% CI, 1.22-1.57]), adjusted for age, year, center, and baseline comorbidities, and with a >8-fold increased risk at BMI ≥35 kg/m2 compared with BMI of 18.5 to <20 kg/m2. For each 1-unit increase in BMI, similarly adjusted hazard ratios were 1.15 (95% CI, 1.14-1.17) for dilated cardiomyopathy, 1.09 (95% CI, 1.06-1.12) for hypertrophic cardiomyopathy, and 1.10 (1.06-1.13) for alcohol/drug-induced cardiomyopathy. Even mildly elevated body weight in late adolescence may contribute to being diagnosed with cardiomyopathy in adulthood. The already marked importance of weight control in youth is further strengthened by these findings, as well as greater evidence for obesity as a potential important cause of adverse cardiac remodeling that is independent of clinically evident ischemic heart disease.


Impaired auxin biosynthesis in the defective endosperm18 mutant is due to mutational loss of expression in the ZmYuc1 gene encoding endosperm-specific YUCCA1 protein in maize.
The phytohormone auxin (indole-3-acetic acid [IAA]) plays a fundamental role in vegetative and reproductive plant development. Here, we characterized a seed-specific viable maize (Zea mays) mutant, defective endosperm18 (de18) that is impaired in IAA biosynthesis. de18 endosperm showed large reductions of free IAA levels and is known to have approximately 40% less dry mass, compared with De18. Cellular analyses showed lower total cell number, smaller cell volume, and reduced level of endoreduplication in the mutant endosperm. Gene expression analyses of seed-specific tryptophan-dependent IAA pathway genes, maize Yucca1 (ZmYuc1), and two tryptophan-aminotransferase co-orthologs were performed to understand the molecular basis of the IAA deficiency in the mutant. Temporally, all three genes showed high expression coincident with high IAA levels; however, only ZmYuc1 correlated with the reduced IAA levels in the mutant throughout endosperm development. Furthermore, sequence analyses of ZmYuc1 complementary DNA and genomic clones revealed many changes specific to the mutant, including a 2-bp insertion that generated a premature stop codon and a truncated YUC1 protein of 212 amino acids, compared with the 400 amino acids in the De18. The putative, approximately 1.5-kb, Yuc1 promoter region also showed many rearrangements, including a 151-bp deletion in the mutant. Our concurrent high-density mapping and annotation studies of chromosome 10, contig 395, showed that the De18 locus was tightly linked to the gene ZmYuc1. Collectively, the data suggest that the molecular changes in the ZmYuc1 gene encoding the YUC1 protein are the causal basis of impairment in a critical step in IAA biosynthesis, essential for normal endosperm development in maize.


Endoscopic dacryocystorhinostomy appears to impair nasal mucociliary clearance.
We conducted a prospective study of 50 adults to investigate changes in nasal mucociliary clearance following endoscopic intranasal dacryocystorhinostomy (DCR). Each operation was performed with the use of a drill to perforate the lateral nasal wall in order to reach the lacrimal sac. Each patient's mucociliary clearance time (MCT) was determined by the saccharin test on both the operated and nonoperated sides; the preoperative times were compared with postoperative measurements made 1 and 3 months following DCR. Preoperatively, the mean MCTs were 14.48 minutes on the operated side and 14.50 minutes on the nonoperated side-not a statistically significant difference (p > 0.05). Postoperatively, the corresponding MCTs were 25.22 and 14.98 minutes at 1 month and 18.44 and 15.62 minutes at 3 months. On the operated side, both postoperative MCTs were significantly longer than the preoperative value (p < 0.001), while on the nonoperated side, neither postoperative MCT was significantly different from the preoperative value (p > 0.05). Also, the postoperative MCTs were significantly longer on the operated side than on the nonoperated side at both 1 month (p < 0.001) and 3 months (p < 0.05). Only 1 of the 50 operations was considered to be unsuccessful; the reason for this surgical failure was the patient's ongoing complaints of chronic postoperative dacryocystitis. We conclude that endoscopic DCR disturbs mucociliary clearance. Changes in MCTs may be attributable to injury to the nasal mucosa or to the continuous flow of tears through the nasal mucosa.


New Insights Into the Circadian Rhythm and Its Related Diseases.
Circadian rhythms (CR) are a series of endogenous autonomous oscillators generated by the molecular circadian clock which acting on coordinating internal time with the external environment in a 24-h daily cycle. The circadian clock system is a major regulatory factor for nearly all physiological activities and its disorder has severe consequences on human health. CR disruption is a common issue in modern society, and researches about people with jet lag or shift works have revealed that CR disruption can cause cognitive impairment, psychiatric illness, metabolic syndrome, dysplasia, and cancer. In this review, we summarized the synchronizers and the synchronization methods used in experimental research, and introduced CR monitoring and detection methods. Moreover, we evaluated conventional CR databases, and analyzed experiments that characterized the underlying causes of CR disorder. Finally, we further discussed the latest developments in understanding of CR disruption, and how it may be relevant to health and disease. Briefly, this review aimed to synthesize previous studies to aid in future studies of CR and CR-related diseases.


Automatic preparation, calibration, and simulation of deformable objects.
Many simulation environments - particularly those intended for medical simulation - require solid objects to deform at interactive rates, with deformation properties that correspond to real materials. Furthermore, new objects may be created frequently (for example, each time a new patient's data is processed), prohibiting manual intervention in the model preparation process. This paper provides a pipeline for rapid preparation of deformable objects with no manual intervention, specifically focusing on mesh generation (preparing solid meshes from surface models), automated calibration of models to finite element reference analyses (including a novel approach to reducing the complexity of calibrating nonhomogeneous objects), and automated skinning of meshes for interactive simulation.


Outcomes of reduced-intensity transplantation for chronic myeloid leukemia: an analysis of prognostic factors from the Chronic Leukemia Working Party of the EBMT.
This study reports outcomes of allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning (RIC) in 186 patients with chronic myeloid leukemia (CML) from the European Group for Blood and Marrow Transplantation (EBMT). The median age was 50 years, and 64% were in first chronic phase (CP1), CP2 13%, accelerated phase 17%, and blast crises 6%. The median EBMT transplant score was 3. The day 100 transplantation-related mortality (TRM) was 6.1% (confidence interval [CI], 3.4%-11%) but rose to 23.3% (CI, 14%-27%) at 2 years. Fludarabine, busulfan, and antithymocyte globulin (Fd/Bu/ATG) was associated with the lowest TRM of 11.6% (CI, 4.7%-11%) at 1 year. Acute graft-versus-host disease (GvHD) grade II to IV occurred in 32% and chronic GvHD in 43% (extensive in 24%). ATG was associated with a lower incidence of chronic GvHD (cGvHD). The overall survival (OS) and progression-free survival (PFS) at 3 years were 58% (CI, 50%-66%) and 37% (CI, 30%-45%), respectively. Adverse OS was associated with advanced disease (relative risk [RR], 3.4). PFS was inferior in advanced disease (RR, 2.7) and a trend to improved outcomes with Fd/Bu/ATG (RR, 0.58). RIC allografts are feasible in CML in first or second CP. Since no other RIC regimen demonstrated superiority, Fd/Bu/ATG should be considered as baseline in future prospective trials.


Cry1Ac, a bacillus thuringiensis toxin, triggers extracellular Ca2+ influx and Ca2+ release from intracellular stores in Cf1 cells
Intracellular Ca2+ concentration was measured in single Cf1 cells (Choristoneura fumiferana, spruce budworm) loaded with Fura-2, a Ca2+-sensitive fluorescent probe. Cf1 cells displayed Ca2+ surges in response to Cry1Ac and Cry1C proteins, two Cf1-toxic Bacillus thuringiensis products, but not to Cry1Aa and Cry3A, which are not toxic to Cf1 cells. In the presence of extracellular Ca2+, the toxin-induced Ca2+ response was insensitive to methoxyverapamil, a voltage-dependent Ca2+ channel blocker, but was abolished by lanthanum, a general inhibitor of Ca2+ transport. In the absence of external Ca2+, Cry1Ac induced a small intracellular Ca2+ transient which was inhibited by TMB-8, a blocker of Ca2+ release from inositol-1,4,5-trisphosphate-sensitive pools. Under these conditions, thapsigargin, which inhibits intracellular Ca2+-ATPases, elicited a Ca2+ surge when applied alone. However, subsequent addition of Cry1Ac failed to induce a Ca2+ signal, indicating a depletion of intracellular Ca2+ pools. In Cf1 cells, therefore, bioactive B. thuringiensis toxins triggered intracellular Ca2+ surges which were mainly due to the influx of extracellular Ca2+ through toxin-made pores, as confirmed by planar lipid bilayer experiments. Furthermore, TMB-8- and thapsigargin-sensitive Ca2+ stores contributed to the Cry1Ac-induced Ca2+ signal.


Comparison of 1 month with 3 months of anticoagulation for a first episode of venous thromboembolism associated with a transient risk factor.
The risk of recurrence is lower after treatment of an episode of venous thromboembolism associated with a transient risk factor, such as recent surgery, than after an episode associated with a permanent, or no, risk factor. Retrospective analyses suggest that 1 month of anticoagulation is adequate for patients whose venous thromboembolic event was provoked by a transient risk factor. In this double-blind study, patients who had completed 1 month of anticoagulant therapy for a first episode of venous thromboembolism provoked by a transient risk factor were randomly assigned to continue warfarin or to placebo for an additional 2 months. Our goal was to determine if the duration of treatment could be reduced without increasing the rate of recurrent venous thromboembolism during 11 months of follow-up. Of 84 patients assigned to placebo, five (6.0%) had recurrent venous thromboembolism, compared with three of 81 (3.7%) assigned to warfarin, resulting in an absolute risk difference of 2.3%[95% confidence interval (CI) - 5.2, 10.0]. The incidence of recurrent venous thromboembolism after discontinuation of warfarin was 6.8% per patient-year in those who received warfarin for 1 month and 3.2% per patient-year in those who received warfarin for 3 months (rate difference of 3.6% per patient-year; 95% CI - 3.8, 11.0). There were no major bleeds in either group. Duration of anticoagulant therapy for venous thromboembolism provoked by a transient risk factor should not be reduced from 3 months to 1 month as this is likely to increase recurrent venous thromboembolism without achieving a clinically important decrease in bleeding.


Study on the influence of pregnancy-induced hypertension on neonatal birth weight.
To explore the effect of pregnancy-induced hypertension (PIH) on neonatal birth weight and provide the necessary reference value for the maternal and children health service. A cross-sectional study was carried out in Shaanxi Province of China in 2013. And a total of 28 045 singleton live infants and their mothers were recruited using a stratified, multistage, probability-proportional-to-size sampling method. Among the 28 045 women of childbearing age surveyed, multiple linear regression and quantile regression analysis all showed that the birth weight of newborns whose mothers had suffered from PIH during pregnancy was significantly lower than those whose mothers had not suffered from PIH during pregnancy from very low to higher birth weight percentiles (q=0-0.85), an average decrease of 137.45 g (β=-137.45, t=-5.77 and p<0.001). When birth weight was at q=0.90-1.00 percentiles, there was no birth weight difference between two groups. The present cross-sectional study indicated that PIH had an effect of on neonatal birth weight. When pregnant women with PIH are identified then the healthcare professional initiates a closer supervision of their pregnancy in order to ameliorate the status of BP and provide a good intrauterine environment for the fetus. In addition, the gynecologists should admonish the pregnant women that their health is related to the health of their fetus, then gravidas may be more engaged to alert their physician and accept early or preventative interventions. And the healthcare professional should ask and be alert to the issues of hypertension during pregnancy.


[Study on medical economic evaluation methods for metastatic brain tumors therapy].
Treatment design for metastatic brain tumors is required to firstly care about the life and function for which the patient hopes because it is terminal care. Therefore, to discuss the value of the therapy, a viewpoint of the QOL and the socioeconomic factors other than the survival rate is important. However, examination that applies these factors to the therapy needs to be carried out more thoroughly. With this in mind, we discuss cost effectiveness of therapy for metastatic brain tumor, through a pilot study on gamma knife therapy. We studied 18 patients (mean age 61.6 years old) undergoing therapy for metastatic brain tumors. The health rate QOL was assessed by the profile-type measure SF-36 (Short-Form 36-Item Ver1.2) and the preference-based measure EQ-5D (EuroQoL-5D), before and six months after gamma knife therapy. Cost-utility-analysis (yen/Qaly) was carried out from quality adjusted life years (Qalys) and medical fee claims. In addition, we made a correlation analysis of the irradiation procedure and the gains attained. The observation by SF-36 for six months was useful for metastatic brain tumor. As a result, the QOL indicators showed increased mental health (MH: p=0.040) and role emotional (RE: p=0.029) with significant difference. In the measurement of EQ-5D, it was added only for one month based on the significant difference (p=0.022) from the pre-therapy QOL. The utilities that were analyzed became 0.052+/-0.175SD (score), and Qalys were 0.135. Because the cost was 721.4+/-5.2SD (thousand yen), the performance of cost-utility-analysis was estimated as 5, 330, 000 (yen/Qaly). In addition, positive correlation (r=0.845/p=0.034) was found between the EQ-5D utility score and the tumor irradiation energy (mJ), etc. We established a new value over and above mere survival rate concerning metastatic brain tumor therapy. The socioeconomics and efficacy of therapy are more difficult to discuss in this disease than in other diseases. We did this by clarifying the measurement and analysis of QOL as compared with the cost factor. We found that quantitatively, the mental health rate involved in the QOL, had improved. We established that it is appropriate to cover this disease by public insurance, because cost-utility-analysis showed that it was under the threshold line. Our study also suggested that, when guessing the QOL of the prognosis, there should be grades of sensitivity according to the irradiation element involved in the therapy.


Lifetime body size and reproductive factors: comparisons of data recorded prospectively with self reports in middle age.
Data on lifetime exposures are often self-reported in epidemiologic studies, sometimes many years after the relevant age. Validity of self-reported data is usually inferred from their agreement with measured values, but few studies directly quantify the likely effects of reporting errors in body size and reproductive history variables on estimates of disease-exposure associations. The MRC National Survey of Health and Development (NSHD) and the Million Women Study (MWS) are UK population-based prospective cohorts. The NSHD recruited participants at birth in 1946 and has followed them at regular intervals since then, whereas the MWS recruited women in middle age. For 541 women who were participants in both studies, we used statistical measures of association and agreement to compare self-reported MWS data on body size throughout life and reproductive history, obtained in middle age, to NSHD data measured or reported close to the relevant ages. Likely attenuation of estimates of linear disease-exposure associations due to the combined effects of random and systematic errors was quantified using regression dilution ratios (RDRs). Data from the two studies were very strongly correlated for current height, weight and body mass index, and age at menopause (Pearson r = 0.91-0.95), strongly correlated for birth weight, parental heights, current waist and hip circumferences and waist-to-height ratio (r = 0.67-0.80), and moderately correlated for age at menarche and waist-to-hip ratio (r = 0.52-0.57). Self-reported categorical body size and clothes size data for various ages were moderately to strongly associated with anthropometry collected at the relevant times (Spearman correlations 0.51-0.79). Overall agreement between the studies was also good for most quantitative variables, although all exhibited both random and systematic reporting error. RDRs ranged from 0.66 to 0.86 for most variables (slight to moderate attenuation), except weight and body mass index (1.02 and 1.04, respectively; little or no attenuation), and age at menarche, birth weight and waist-to-hip ratio (0.44, 0.59 and 0.50, respectively; substantial attenuation). This study provides some evidence that self-reported data on certain anthropometric and reproductive factors may be adequate for describing disease-exposure associations in large epidemiological studies, provided that the effects of reporting errors are quantified and the results are interpreted with caution.


The effectiveness of narrative therapy with young people with autism.
The aim of this pilot study was to be the first step toward empirically determining whether narrative therapy is effective in helping young people with autism who present with emotional and behavioral problems. Autism is increasingly being recognized in young people with average and above intelligence. Because of the nature of autism, these young people have difficulty navigating the challenges of school and adolescence. Narrative therapy can help them with their current difficulties and also help them develop skills to address future challenges. Narrative therapy involves working with a person to examine and edit the stories the person tells himself or herself about the world. It is designed to promote social adaptation while working on specific problems of living. This pilot intervention study used a convenience sample of 10 young people with autism (10-16 years) to evaluate the effectiveness of five 1 hr sessions of narrative therapy conducted over 10 weeks. The study used the parent-rated Strengths and Difficulties Questionnaire (SDQ) as the primary outcome measure. Secondary outcome measures were the Kessler-10 Scale of Psychological Distress (K-10), the Beck Hopelessness Scale, and a stress biomarker, the salivary cortisol to dehydroepiandrosterone (DHEA) ratio. Significant improvement in psychological distress identified through the K-10 was demonstrated. Significant improvement was identified on the Emotional Symptoms Scale of the SDQ. The cortisol:DHEA ratio was responsive and a power analysis indicated that further study is indicated with a larger sample. Narrative therapy has merit as an intervention with young people with autism. Further research is indicated.


Simultaneous Drug Targeting of the Promoter MYC G-Quadruplex and BCL2 i-Motif in Diffuse Large B-Cell Lymphoma Delays Tumor Growth.
Secondary DNA structures are uniquely poised as therapeutic targets due to their molecular switch function in turning gene expression on or off and scaffold-like properties for protein and small molecule interaction. Strategies to alter gene transcription through these structures thus far involve targeting single DNA conformations. Here we investigate the feasibility of simultaneously targeting different secondary DNA structures to modulate two key oncogenes, cellular-myelocytomatosis (MYC) and B-cell lymphoma gene-2 (BCL2), in diffuse large B-cell lymphoma (DLBCL). Cotreatment with previously identified ellipticine and pregnanol derivatives that recognize the MYC G-quadruplex and BCL2 i-motif promoter DNA structures lowered mRNA levels and subsequently enhanced sensitivity to a standard chemotherapy drug, cyclophosphamide, in DLBCL cell lines. In vivo repression of MYC and BCL2 in combination with cyclophosphamide also significantly slowed tumor growth in DLBCL xenograft mice. Our findings demonstrate concurrent targeting of different DNA secondary structures offers an effective, precise, medicine-based approach to directly impede transcription and overcome aberrant pathways in aggressive malignancies.


The effect of chromium on inflammatory markers, 1st and 2nd phase insulin secretion in type 2 diabetes.
Impaired insulin sensitivity (SI) and β-cell function are the two main causes of type 2 diabetes (T2D) and are related to low-grade inflammation status. Trivalent chromium has shown to improve SI in our previous study. This might be due to the ability of decreasing interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) shown in animal studies. In the current study, we measured SI, β-cell function, and plasma levels of IL-6 and TNF-α after treatment of chromium chloride (GaCr) in T2D. Sixty-six patients were randomly assigned to the 20 g of GaCr milk powder studying group or the milk powder placebo group. Oral glucose tolerance test was performed before and after the treatment. The SI and the β-cell function were measured as well. The SI was significantly improved. At the same time, the static insulin responsivity index (Φs) was significantly higher after the treatment (p = 0.003). On the other hand, the dynamic insulin responsivity index (Φd) remained unchanged. Interestingly, a significant decrease in the IL-6 level after the treatment (p = 0.015) was noted. Although there was a trend of decreasing in TNF-α, it was not statistically significant. Finally, there was no significant correlation between the δ-IL-6, SI, and Φd after GaCr treatment. In conclusion, other than the improvement of SI, GaCr could also improve the second phase of insulin responsivity (Φs) and IL-6. However, δ-IL-6 was correlated with neither δ-SI nor δ-Φs which indicated that the improvement of SI and Φs might involve mechanisms other than lower inflammatory effect.


Expression of transforming growth factor-beta (TGF-beta) in chronic idiopathic cough.
In patients with chronic idiopathic cough, there is a chronic inflammatory response together with evidence of airway wall remodelling and an increase in airway epithelial nerves expressing TRPV-1. We hypothesised that these changes could result from an increase in growth factors such as TGFbeta and neurotrophins. We recruited 13 patients with persistent non-asthmatic cough despite specific treatment of associated primary cause(s), or without associated primary cause, and 19 normal non-coughing volunteers without cough as controls, who underwent fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) and bronchial biopsies. There was a significant increase in the levels of TGFbeta in BAL fluid, but not of nerve growth factor(NGF) and brain-derived nerve growth factor(BDNF) compared to normal volunteers. Levels of TFGbeta gene and protein expression were assessed in bronchial biopsies. mRNA expression for TGFbeta was observed in laser-captured airway smooth muscle and epithelial cells, and protein expression by immunohistochemistry was increased in ASM cells in chronic cough patients, associated with an increase in nuclear expression of the transcription factor, smad 2/3. Subbasement membrane thickness was significantly higher in cough patients compared to normal subjects and there was a positive correlation between TGF-beta levels in BAL and basement membrane thickening. TGFbeta in the airways may be important in the airway remodelling changes observed in chronic idiopathic cough patients, that could in turn lead to activation of the cough reflex.


Infusion volumes of Ringer's lactate and 3% albumin solution as they relate to survival after resuscitation of a lethal intestinal ischemic shock.
Previously, we have shown improved survival rate with colloid solutions of 2-4% concentration compared to 10% solutions or a colloid-free electrolyte solution, when given in volumes required to maintain the same intravascular volume expansion. This study examines the effect of increasing infusion volumes of Ringer's lactate (RL) and 3% albumin on survival time and blood volume expansion using the lethal intestinal ischemic shock model in rats. Shock was induced by exteriorization of the small intestine with added occlusion of the superior mesenteric vessels for 75 minutes. Untreated animals developed hemoconcentration to 60% in hematocrit (Hct), representing a plasma volume (PV) decrease to 57% of the preshock level. Infusion of 3% albumin increased PV linearly up to 200% above shock levels with infusion volumes of 0-45 ml/100 g bwt. RL increased PV linearly up to 80% above shock baseline level with infusion volumes up to 50 ml/100g. No further PV increase occurred despite increasing volumes of RL. No infusion volume, therefore, of RL restored PV to preshock levels. To achieve the same volume expansion up to 80% above the shock PV levels, 4.4 times larger volume of RL was needed compared to 3% albumin solution. With the same volumes infused (up to 45 ml/100 g), 4-5 times more of the 3% albumin volume infused remained in the vascular space compared to RL. Also, the excreted volume was larger with albumin than with RL, for the same volumes infused. Accordingly, the major portion of the infused RL (60-80%) was located in the extravascular space. No control animals survived 24 hours. Survival time was prolonged with both RL and 3% albumin infusions. The effect on survival time with albumin was obtained with approximately 25% of the fluid required for RL.


Impact of Prebiotics on Poultry Production and Food Safety.
With the phasing out of routine use of antibiotics in animal agriculture, interest has grown for the need to develop feed supplements that augment commercial poultry performance and provide food safety benefits. From a food safety perspective, alternative feed supplements can be broadly categorized as either agents which reduce or eliminate already colonized foodborne pathogens or prevent colonization of incoming pathogens. Prebiotics are considered preventative agents since they select for gastrointestinal microbiota which not only benefits the host but can serve as a barrier to pathogen colonization. In poultry, prebiotics can elicit both indirect effects on the bird by shifting the composition and fermentation patterns of the gastrointestinal microbiota or directly by influencing host systems such as immune responses. Generation of short chain fatty acids is believed to be a primary inhibitory mechanism against pathogens when prebiotics are fermented by gastrointestinal bacteria, but other mechanisms such as interference with attachment can occur as well. While most of the impact of the prebiotic is believed to occur in the lower parts of the bird gastrointestinal tract, particularly the ceca, it is possible that some microbial hydrolysis could occur in upper sections such as the crop. Development of next generation sequencing has increased the resolution of identifying gastrointestinal organisms that are involved in metabolism of prebiotics either directly or indirectly. Novel sources of non-digestible oligosaccharides such as cereal grain brans are being explored for potential use in poultry to limit Salmonella establishment. This review will cover the current applications and prospects for use of prebiotics in poultry to improve performance and limit pathogens in the gastrointestinal tract.


Time to initial clinician-reported inactivation of neovascular age-related macular degeneration treated primarily with ranibizumab.
To characterize in more detail routine treatment patterns of intravitreal ranibizumab for neovascular age-related macular degeneration (nAMD), we analyzed the length of time and the number of injections required until lesions with choroidal neovascularization (CNV) were first graded inactive. Database observational study. Treatment-naïve eyes receiving predominantly ranibizumab for nAMD in routine clinical practice that were tracked in the Fight Retinal Blindness! observational registry. Eyes treated with ranibizumab were followed until CNV was first reported to be "inactive" (i.e., absence of intraretinal fluid and hemorrhages). The length of time until lesion inactivation occurred and the number of injections required. A total of 1096 eyes (65.8% from women) were included in the study. The median number of weeks until a lesion was graded as inactive after beginning treatment was 15 weeks. One to 3 injections were sufficient to inactivate the lesion in 61.1% of eyes. A mean change in visual acuity of +5.5 logarithm of the minimum angle of resolution letters (95% confidence interval, 4.8-6.3) was found from treatment initiation to the time that eyes were reported as inactive. In eyes with a mean treatment frequency less than every 5.3 weeks, a median of only 3 injections (mean=3.7) were required before lesions with CNV were graded as inactive, but if the mean treatment interval extended beyond 5.3 weeks, the median number of injections required increased sharply to 6 injections (mean, 7 injections). Occult lesions became inactive more slowly than classic lesions. Most lesions with CNV became inactive with 3 injections of ranibizumab, but a small proportion remained active for more than 12 months. Injection frequency and lesion type were the main factors that predicted the time and number of injections required to render lesions inactive.


The role of social networking web sites in influencing residency decisions.
Social networking Web sites such as Facebook have grown rapidly in popularity. It is unknown how such sites affect the ways in which medical trainees investigate and interact with graduate medical education (GME) programs. To evaluate the use of social networking Web sites as a means for osteopathic medical students, interns, residents, and fellows to interact with GME programs and report the degree to which that interaction impacts a medical trainee's choice of GME program. An anonymous, 10-item electronic survey on social networking Web sites was e-mailed to osteopathic medical student, intern, resident, and fellow members of the American College of Osteopathic Family Physicians. The weighted least squares test and the Fisher exact test were used for data analysis. A total of 9606 surveys were distributed, and 992 (10%) were completed. Nine hundred twenty-eight (93%) of the respondents used social networking Web sites, with the most popular services being Facebook (891 [90%]; P=.03), the Student Doctor Network (278 [28%]), and LinkedIn (89 [9%]; P=.03). Three hundred fifty-three respondents (36%; P=.52) were connected with a professional organization and 673 (68%; P=.73) used social networking Web sites for job searching related to GME programs or postresidency employment. Within the population of 497 third-, fourth-, and fifth-year osteopathic medical students, 136 (27%) reported gleaning information about programs through social networking Web sites (P=.01). Within the total population, 100 of 992 (10%) reported that this information influenced their decisions (P=.07). Of note, 144 (14%) of the total 992 respondents reported that the programs they applied to did not have any presence on social networking Web sites (P=.05). Our results indicate that social networking Web sites have a present and growing influence on how osteopathic medical students, interns, residents, and fellows learn about and select a GME program.


Functionally impaired plasmacytoid dendritic cells and non-haematopoietic sources of type I interferon characterize human autoimmunity.
Autoimmune connective tissue diseases arise in a stepwise fashion from asymptomatic preclinical autoimmunity. Type I interferons have a crucial role in the progression to established autoimmune diseases. The cellular source and regulation in disease initiation of these cytokines is not clear, but plasmacytoid dendritic cells have been thought to contribute to excessive type I interferon production. Here, we show that in preclinical autoimmunity and established systemic lupus erythematosus, plasmacytoid dendritic cells are not effector cells, have lost capacity for Toll-like-receptor-mediated cytokine production and do not induce T cell activation, independent of disease activity and the blood interferon signature. In addition, plasmacytoid dendritic cells have a transcriptional signature indicative of cellular stress and senescence accompanied by increased telomere erosion. In preclinical autoimmunity, we show a marked enrichment of an interferon signature in the skin without infiltrating immune cells, but with interferon-κ production by keratinocytes. In conclusion, non-hematopoietic cellular sources, rather than plasmacytoid dendritic cells, are responsible for interferon production prior to clinical autoimmunity.


Lymphatic mapping for upper gastrointestinal malignancies.
Recent studies on lymphatic mapping of upper gastrointestinal (GI) malignancies have provided new insights with regard to the sentinel node (SN) concept in solid tumors. At present, the SN concept seems to be valid not only for breast cancer, but also for esophageal and gastric cancers, which have multidirectional and complicated lymphatic flows. In addition to the staging merits, individualized surgical management has been proposed for upper GI cancer based on the SN concept. Gastric cancer is now a suitable target of SN-guided surgery after breast cancer because of its anatomical situation. Laparoscopic local resection is theoretically feasible for curative treatment of SN-negative early gastric cancer. Because SNs in esophageal cancer are multiple and widespread, complete sampling of SNs is not a minimally invasive procedure, as it is in breast cancer. However, selective and modified lymphadenectomy targeting SNs for clinically N0 esophageal cancer instead of three-field lymph node dissection should become not only feasible but also clinically important. When performing chemoradiotherapy as curative treatment for cT1N0 esophageal cancer, lymphoscintigrams revealing the distribution of SNs in each individual case are useful to tailor the field of irradiation to control occult micrometastases. Although there are several issues to be resolved, this novel procedure has the potential to improve quality control in upper GI cancer.


Design of guided-wave grating-assisted tunable filters for telecommunications systems.
In this paper, a number of critical aspects in the design and performance of guided-wave grating-assisted tunable filters for dense telecommunications systems are investigated by using a rigorous numerical approach. It is shown how highly narrow filters, with the potential to be tunable over a large number of channels (> 50), can be accurately designed by using well-selected apodization windows.


Imprimatins A and B: novel plant activators targeting salicylic acid metabolism in Arabidopsis thaliana.
Plant activators are agrochemicals that protect plants from a broad range of pathogens by activating the plant immune system. Unlike pesticides, they do not target pathogens; therefore, plant activators provide durable effects that are not overcome by pathogenic microbes. Although certain plant activators have been applied to paddy fields for more than 30 years, the molecular basis of the underlying immune induction are unclear. From the screening of 10,000 diverse chemicals by a high-throughput screening procedure to identify compounds that specifically enhance pathogen-induced cell death in Arabidopsis cultured cells, we identified 7 compounds, which we designated as immune priming chemicals (Imprimatins). These compounds increased disease resistance against pathogenic Pseudomonas bacteria in Arabidopsis plants. Pretreatments increased the accumulation of endogenous salicylic acid (SA) but reduced its metabolite, SA-O-β-D-glucoside (SAG). Imprimatins inhibited the enzymatic activities of 2 SA glucosyltransferases (SAGTs) in vitro at concentrations effective for immune priming. Single and double knockout Arabidopsis plants for both SAGTs consistently exhibited enhanced disease resistance and SA accumulation. Our results demonstrate that the control of the free SA pool through SA-inactivating enzymes can be a useful methodology to confer disease resistance in plants. SAGTs can pave the way for target-based discovery of novel crop protectants.