Efficacy and risks of moricizine in inducible sustained ventricular tachycardia.
To assess the efficacy and toxicity of moricizine in treating patients with serious ventricular arrhythmias and inducible sustained ventricular tachycardia. Uncontrolled clinical trial. The intensive care and telemetry units of Northwestern Memorial Hospital, St. Francis Hospital and Medical Center, and Lenox Hill Hospital. Twenty-six patients with sustained ventricular arrhythmias or hemodynamically significant nonsustained ventricular tachycardia, most of whom failed therapy with at least one class I antiarrhythmic agent. Patients were treated with moricizine, 400 to 1000 mg/d. Efficacy was assessed by the results of programmed ventricular stimulation done during moricizine therapy. Seven of the 26 patients (27%) developed life-threatening ventricular proarrhythmia during moricizine loading. Three patients had incessant sustained ventricular tachycardia, two had incessant nonsustained ventricular tachycardia, one had new sustained ventricular tachycardia, and one had new cardiac arrest. One of these patients died of intractable ventricular fibrillation. No clinical or electrophysiologic variables clearly identified those at risk for proarrhythmia. Only 3 of 26 patients (12%) became noninducible on moricizine. Moricizine has a low rate of efficacy and carries a considerable risk for life-threatening proarrhythmia in patients with serious ventricular arrhythmias and inducible ventricular tachycardia who have failed therapy with other class I antiarrhythmic agents.


Tau reduction prevents neuronal loss and reverses pathological tau deposition and seeding in mice with tauopathy.
Accumulation of hyperphosphorylated tau directly correlates with cognitive decline in Alzheimer's disease and other primary tauopathies. One therapeutic strategy may be to reduce total tau expression. We identified antisense oligonucleotides (ASOs) that selectively decreased human tau mRNA and protein in mice expressing mutant P301S human tau. After reduction of human tau in this mouse model of tauopathy, fewer tau inclusions developed, and preexisting phosphorylated tau and Thioflavin S pathology were reversed. The resolution of tau pathology was accompanied by the prevention of hippocampal volume loss, neuronal death, and nesting deficits. In addition, mouse survival was extended, and pathological tau seeding was reversed. In nonhuman primates, tau ASOs distributed throughout the brain and spinal cord and reduced tau mRNA and protein in the brain, spinal cord, and cerebrospinal fluid. These data support investigation of a tau-lowering therapy in human patients who have tau-positive inclusions even after pathological tau deposition has begun.


The RM test for determining methicillin-resistant Staphylococcus aureus lineages.
Staphylococcus aureus lineages evolve independently and differ in hundreds of genes. Identification of lineages can be useful for epidemiological typing and infection control at the local or global level, and can also be useful when investigating differences in pathogenesis between strains. MLST (multilocus sequence typing) and spa typing (polymorphisms in the protein A gene) are useful methods for identifying lineages but can be time-consuming and expensive. Here, we describe a method for identifying lineages using PCR, which is very easy to perform and can generate results within hours. It can also be adapted to commercial or real-time platforms. The RM (restriction modification) test is based on unique sequences found in each lineage that determine the specificity of an RM system, which detects and digests foreign DNA, thereby controlling the independent evolution of the lineages; thus, it is the ideal single gene to target for a rapid lineage test.


Cost savings threshold analysis of a capacity-building program for HIV prevention organizations.
Although the incidence of HIV each year remains steady, prevention funding is increasingly competitive. Programs need to justify costs in terms of evaluation outcomes, including economic ones. Threshold analyses set performance standards to determine program effectiveness relative to that threshold. This method was used to evaluate the potential cost savings of a national capacity-building program for HIV prevention organizations. Program costs were compared with the lifetime treatment costs of HIV, yielding an estimate of the HIV infections that would have to be prevented for the program to be cost saving. The 136 persons who completed the capacity-building program between 2000 and 2003 would have to avert 41 cases of HIV for the program to be considered cost saving. These figures represent less than one tenth of 1% of the 40,000 new HIV infections that occur in the United States annually and suggest a reasonable performance standard. These data underscore the resources needed to prevent HIV.


Transduction of leucine auxotrophs of Proteus mirabilis to prototrophy or antibiotic resistance by P. mirabilis high frequency transducing bacteriophages.
High frequency transducing (HFT) phages 5006MHFTk and 5006MHFTak for kanamycin or ampicillin plus kanamycin resistance, derived from Proteus mirabilis strains PM5006(R394) and PM5006(R394) respectively, transduced (at low multiplicities of infection, m.o.i.) antibiotic resistance and prototrophy to PM5006 leu-I at high frequency. Simultaneous transduction of these markers occurred at very much lower frequencies. The latter result was correlated with the proportion of multiply-infected bacteria which, due to the great transducing potential of the phage, could register as transductants. Each HFT lysate was thus heterogenous with regard to high frequency transducing phage. Apart from the additional antibiotic resistance marker carried by one phage, no other difference between the two lysates was detected. High segregation frequencies of antibiotic-resistant or prototrophic transductants indicated transduction by lysogenization. Although antibiotic-sensitive segregants of antibiotic-resistant prototrophic transductants occurred at high frequency, no auxotrophic segregants of these transductants were found. This suggests transduction by a double cross-over event in the leucine region. Most transductants, even at low m.o.i., were lysogenically converted to homologous phage non-adsorption as a result of interaction between the transducing phage genome and the resident cryptic prophage. They could, however, be retransduced by appropriate phage lysates; thus, lysogenic conversion to non-adsorption was not absolute. Some prototrophic transductants were non-lysogenic although their segregants liberated low-titre phage. The latter anomaly, and the fact that the leucine marker and antibiotic resistance were not cotransduced, are explained by the mode of integration of the phage into the host chromosome in relation to the resident cryptic prophage and the leucine region.


Experience of primary care by racial and ethnic groups in the United States.
The purpose of this study was to examine the experience of primary care by racial and ethnic groups and identify aspects of primary care where significant disparities in experience exist across racial and ethnic groups. Data for this study came from the Household Component of the 1997-1998 Medical Expenditure Panel Survey (MEPS), a nationally representative survey of the civilian noninstitutionalized population of the United States. Measures were identified within MEPS that denote race, ethnicity, experience of primary care, and socioeconomic covariates associated with access to care. Racial and ethnic minorities experienced worse primary care, particularly in the first-contact aspect, than did white Americans. Their usual sources of care were more likely to be hospital settings than private clinics. They faced greater barriers accessing their usual source of care (USC), finding it more difficult to get an appointment and waiting longer during an appointment. Many of the significant differences persist after adjustment for sociodemographic and health-status characteristics. Racial and ethnic disparity in primary care experience is not simply a reflection of sociodemographic and health-status differences across racial/ethnic groups. Efforts must be made to reduce nonfinancial as well as financial barriers to care and ensure that quality primary care is provided in all settings, public as well as private, and to individuals of all colors.


A 5' duplication of the alpha-cardiac actin gene in BALB/c mice is associated with abnormal levels of alpha-cardiac and alpha-skeletal actin mRNAs in adult cardiac tissue.
We describe the structure and transcriptional activity of the 5' portion of the alpha-cardiac actin gene of BALB/c mice. Southern blotting and DNA sequencing reveal that the promoter and first three exons of the gene are present as perfect repeats in a direct duplication of 9.5 kbp situated immediately upstream of the gene. Both promoters are active in adult cardiac tissue. Transcripts from the partial gene duplication give rise to novel RNAs that are spliced correctly in the actin region and polyadenylated. The level of mature alpha-cardiac actin mRNA is only 16.5% that found in mice that do not possess the duplication. This is due, at least in part, to interference at the transcriptional level. Transcripts from the alpha-skeletal actin gene accumulate to abnormally high levels in the hearts of such mutant mice. This result suggests tight regulatory coupling for this actin gene pair.


A comparison of patient compliance in treated vs untreated ocular hypertension.
Eighty-nine patients with newly diagnosed asymptomatic elevations of intraocular pressure were followed up over a 12- to 20-month interval. During this period 33 (37%) of the patients were lost to ophthalmic follow-up evaluation. The majority of these patients dropped out within one month following the initial diagnosis. While institution of medical therapy for the elevated ocular pressure improved patient compliance when compared to the nontreated group, the rates of noncompliance in both groups were unacceptably high in view of the disease risk. Management of the noncompliant patient requires good physician-patient communication, emphasis on patient education activities, and the use of selective reminder and recall systems within the ophthalmologist's office.


Developmental exposure to low concentrations of two brominated flame retardants, BDE-47 and BDE-99, causes life-long behavioral alterations in zebrafish.
Polybrominated diphenyl ethers (PBDEs) were widely used as flame retardants until the early 2000s, mainly in home furnishings and electronics. The persistence of PBDEs in the environment leads to continued ubiquitous exposure to low levels, with infants and children experiencing higher exposures than adults. Accumulating evidence suggest that low-level exposures during early life stages can affect brain development and lead to long-term behavioral impairments. We investigated the effects of zebrafish exposure to low doses of the two prominent PBDEs; 2,2',4,4',5,-Pentabromodiphenyl ether (BDE-99) and 2,2',4,4',-Tetrabromodiphenyl ether (BDE-47), during embryo-development on short- and long-term behavioral endpoints. We included the organophosphate pesticide chlorpyrifos (CPF) due to its well documented neurotoxicity across species from zebrafish to humans. Zebrafish embryos were exposed to the following individual treatments; 0.1% DMSO (vehicle control); 0.3μM CPF; 0.01, 0.03, 0.1, 0.3μM BDE-47; 0.003, 0.03, 0.3, 1, 3, 10, 20μM BDE-99 from 5 until 120h post fertilization (hpf). Low exposure levels were determined as those not causing immediate overt toxicity, and behavior assays were conducted in the low-level range. At 144 hpf the larvae were tested for locomotor activity. At approximately 6 months of age adult zebrafish were tested in a behavioral battery including assays for anxiety-related behavior, sensorimotor response and habituation, social interaction, and predator avoidance. In the short-term, larval locomotor activity was reduced in larvae treated with 0.3μM CPF and 0.1μM BDE-47. BDE-99 treatment caused non-monotonic dose effects, with 0.3μM causing hyperactivity and 1μM or higher causing hypoactivity. In the long-term, adult anxiety-related behavior was reduced in all treatments as measured in both the novel tank dive test and tap test. We show that exposure of zebrafish embryos to low concentrations of the brominated flame retardants BDE-47 and BDE-99, and the organophosphate pesticide CPF, caused both short- and long-term behavioral impairments. Interestingly, we also found that at very low exposure concentrations, where there were no visible effects on larval activity, adult behavior was still strongly affected.


Comparing a novel hand held device (Peritron+) to standard urodynamics in measuring intravesical pressure.
Peritron+ is a new handheld device, which can be attached to a urethral catheter to measure intravesical pressures (Pves). The goal of this study was to assess if Pves recorded by standard urodynamics (UDs) are comparable to those recorded by the Peritron+. Patients with voiding dysfunction and an indication for UD underwent measurement of Pves with nonvideo UD and Peritron+. Pves were recorded at volumes of 50, 100, and 200 mL for the supine and sitting positions. A failure of the Peritron+ was considered to be a discrepancy of Pves values >3 cmH2 O between Peritron+ and UD recordings. Two-way ANOVA was used to assess for statistical significance. P-values < 0.05 were considered significant. Ten female patients, mean age 51 years old, were enrolled in the study. The difference in Pves measurements between Peritron+ and UD were ≤3 cmH2 O at all bladder volumes measured in a supine and sitting positions. There were no adverse events and there were no malfunctions of the Peritron+ device during the study. Peritron+ handheld device accurately assessed Pves at different intravesical volumes when compared to UD measurements. The Peritron+ is a simple and safe device, which can be used in the office by a clinician and at home by a patient to monitor Pves and help to select patients who may require standard UD re-evaluation. This will be a valuable tool in managing patients with neurogenic and nonneurogenic bladders who are at a risk of upper urinary tract deterioration.


Uncertainty and sensitivity analysis of spatial predictions of heavy metals in wheat.
Heavy metals seriously threaten the health of human beings when they enter the food chain. Therefore, policymakers require precise predictions of heavy metal concentrations in agricultural crops. In this paper we quantify the uncertainty of regression predictions of Cd and Pb in wheat (Triticum aestivum L.) and the contributions to the uncertainties in these predictions associated with inputs to the regression model. For each node of the 500- x 500-m grid covering the arable soils in The Netherlands, a latin hypercube sample size of 1000 is constructed from the uncertainty distributions of the explanatory variables (pH, soil organic matter [SOM], and heavy metal concentration in soil), the regression coefficients, and the random term of the regression model. This sample is used as input for the regression model to obtain 1000 values from the uncertainty distributions of the log(Cd) and log(Pb) concentration in wheat. There were no nodes where the recent EU quality standards for Cd and Pb (0.2 mg kg(-1) fresh wt.) in wheat were almost certain to be exceeded. For most nodes with clay soils, the quality standard for Cd in wheat almost certainly will not be exceeded; for Pb this is much less certain. The uncertainty in the Cd concentration in soil contributes most to the uncertainty in the predicted Cd concentrations in wheat (36% on the average), followed by the random term of the regression model (23%). For Pb the contribution of the random term is by far the largest (52%).


The therapeutic dilemma in pre-transplant asymptomatic aspergilloma: A case report and review of literature.
Aspergillus species are ubiquitous, and inhalation of infectious conidia is not so uncommon. With immunosuppression, it can invade adjacent structures and lead to widespread invasive disease. There is no randomized, prospective trial for optimized treatment including the antifungal and surgical approach for aspergilloma. The available literature related to the management of asymptomatic aspergilloma in pre-renal transplant setting is scarce and debatable. Opinion favoring surgery is that it is necessary to eliminate the fungus reservoir before transplantation because of the inadequacy of pharmacological fungus control measures in immunocompromised patients. We present a case of end-stage renal disease that was planned for renal transplantation and during the workup, was detected to have asymptomatic right upper lobe aspergilloma. He underwent surgical resection of the aspergilloma before undergoing successful renal transplantation. In this case report, we will discuss this case and controversies related to its management before undergoing successful renal transplantation.


Hyperactivation of the folded gastrulation pathway induces specific cell shape changes.
During Drosophila gastrulation, mesodermal precursors are brought into the interior of the embryo by formation of the ventral furrow. The first steps of ventral furrow formation involve a flattening of the apical surface of the presumptive mesodermal cells and a constriction of their apical diameters. In embryos mutant for folded gastrulation (fog), these cell shape changes occur but the timing and synchrony of the constrictions are abnormal. A similar phenotype is seen in a maternal effect mutant, concertina (cta). fog encodes a putative secreted protein whereas cta encodes an (alpha)-subunit of a heterotrimeric G protein. We have proposed that localized expression of the fog signaling protein induces apical constriction by interacting with a receptor whose downstream cellular effects are mediated by the cta G(alpha)protein. <P> In order to test this model, we have ectopically expressed fog at the blastoderm stage using an inducible promoter. In addition, we have examined the constitutive activation of cta protein by blocking GTP hydrolysis using both in vitro synthesized mutant alleles and cholera toxin treatment. Activation of the fog/cta pathway by any of these procedures results in ectopic cell shape changes in the gastrula. Uniform fog expression rescues the gastrulation defects of fog null embryos but not cta mutant embryos, arguing that cta functions downstream of fog expression. The normal location of the ventral furrow in embryos with uniformly expressed fog suggests the existence of a fog-independent pathway determining mesoderm-specific cell behaviors and invagination. Epistasis experiments indicate that this pathway requires snail but not twist expression.


[Anterior radial nerve transposition in humerus midshaft fractures: anatomic and clinical study].
Plate fixation of midshaft humerus fractures raises the risk of radial nerve injury. Anterior transposition of the radial nerve has been proposed as a possible solution but few reports have been published. The purpose of the present study was to validate the effect of transposition on the transposed radial nerve and its branches. We conducted an anatomic study on 10 cadavers. The length of the radial nerve between 2 anatomic landmarks was determined before and after transposition and plate fixation. A clinical evaluation was performed four years after surgery in 6 patients with midshaft humerus fractures treated with plate fixation after radial nerve transposition. The anatomic study demonstrated a mean gain of 11 mm in the length of the radial nerve with no problem for the transposed nerve or its branches. Clinically, osteosynthesis was facilitated and tension on the nerve was reduced. These 2 complementary studies demonstrated the releasing effect of transposition on the radial nerve and the facilitated osteosynthesis reported by others. The benefit of transposition is particularly important when bone fixation is particularly difficult to achieve without risk of injuring the radial nerve. Transposition does however require an extensive dissection, and the patient must be informed. The ideal indication for anterior transposition of the radial nerve is an oblique fracture of the mid-third to lower-third of the humeral shaft with radial palsy at onset. A certain degree of comminution facilitates the technique. Indications for this technique could however be widened to include cases of difficult osteosynthesis where the option to transpose the radial nerve is always a peroperative decision.


Comparing substance use and mental health among sexual and gender minority and heterosexual cisgender youth experiencing homelessness.
Youth homelessness has been demonstrated to disproportionately affect sexual and gender minority (SGM) youth compared to heterosexual cisgender peers. In this context, we aimed to compare health risks between service-seeking SGM and heterosexual cisgender youth experiencing homelessness, including harmful risks stemming from substance use and severity of symptoms of mental health disorders. We recruited 100 racially diverse, unstably housed participants aged 18-24 who access services at an urban non-profit organization in San Francisco, CA. Data analysis included 56 SGM participants who identified as gay, lesbian, bisexual, pansexual, unsure, transgender, and nongender, and 44 heterosexual cisgender participants. In contrast to previous studies reporting significantly higher frequency of substance use and more severe symptoms of depression, generalized anxiety, and post-traumatic stress disorder among SGM youth compared to heterosexual cisgender peers, many of these health disparities were not observed in our diverse study population of service-seeking youth. Furthermore, with the exception of methamphetamine, SGM participants did not exhibit greater harmful risks resulting from substance use, such as health, social, financial, and legal complications. We discuss the reduced burden of health disparities between SGM and heterosexual cisgender youth in our service-seeking study population within the context of gender- and sexuality-affirming programming offered at the partnering community organization. We conclude that longitudinal data on these tailored community-level interventions are needed to further explore the reduced burden of health disparities observed among service-seeking SGM youth experiencing homelessness in San Francisco in order to continue supporting pathways out of homelessness for youth of all sexual and gender identities nationwide.


Self-orienting in human and machine learning.
A current proposal for a computational notion of self is a representation of one's body in a specific time and place, which includes the recognition of that representation as the agent. This turns self-representation into a process of self-orientation, a challenging computational problem for any human-like agent. Here, to examine this process, we created several 'self-finding' tasks based on simple video games, in which players (N = 124) had to identify themselves out of a set of candidates in order to play effectively. Quantitative and qualitative testing showed that human players are nearly optimal at self-orienting. In contrast, well-known deep reinforcement learning algorithms, which excel at learning much more complex video games, are far from optimal. We suggest that self-orienting allows humans to flexibly navigate new settings.


Adaptive multilayer perceptrons with long- and short-term memories.
Multilayer perceptrons (MLPs) with long- and short-term memories (LASTMs) are proposed for adaptive processing. The activation functions of the output neurons of such a network are linear, and thus the weights in the last layer affect the outputs of the network linearly and are called linear weights. These linear weights constitute the short-term memory and other weights the long-term memory. It is proven that virtually any function f(x, theta) with an environmental parameter theta can be approximated to any accuracy by an MLP with LASTMs whose long-term memory is independent of theta. This independency of theta allows the long-term memory to be determined in an a priori training and allows the online adjustment of only the short-term memory for adapting to the environmental parameter theta. The benefits of using an MLP with LASTMs include less online computation, no poor local extrema to fall into, and much more timely and better adaptation. Numerical examples illustrate that these benefits are realized satisfactorily.


Stopping long-acting beta2-agonists (LABA) for adults with asthma well controlled by LABA and inhaled corticosteroids.
Poorly controlled asthma often leads to preventable exacerbations that require additional medications, as well as unscheduled hospital and clinic visits.Long-acting beta2-agonists (LABA) are commonly given to adults with asthma whose symptoms are not well controlled by inhaled corticosteroids (ICS). US and UK regulators have issued warnings for LABA in asthma, and now recommend they be used "for the shortest duration of time required to achieve control of asthma symptoms and discontinued, if possible, once asthma control is achieved". To compare cessation of long-acting beta2-agonists (LABA) versus continued use of LABA/inhaled corticosteroids (LABA/ICS) for adults whose asthma is well controlled, and to determine whether stopping LABA:1. results in loss of asthma control or deterioration in quality of life;2. increases the likelihood of asthma attacks or 'exacerbations'; or3. increases or decreases the likelihood of serious adverse events of any cause. We searched the Cochrane Airways Group Specialised Register (CAGR), www.ClinicalTrials.gov, www.who.int/ictrp/en/, reference lists of primary studies and existing reviews and manufacturers' trial registries (GlaxoSmithKline (GSK) and AstraZeneca). We searched all databases from their inception to April 2015, and we imposed no restriction on language of publication. We looked for parallel randomised controlled trials (RCTs) of at least eight weeks' duration, in which adults whose asthma was well controlled by any dose of ICS+LABA combination therapy were randomly assigned to (1) step-down therapy to ICS alone versus (2) continuation of ICS and LABA. Two review authors independently screened all records identified by the search strategy. We used an Excel extraction tool to manage searches, document reasons for inclusion and exclusion and extract descriptive and numerical data from trials meeting inclusion criteria.Prespecified primary outcomes were (1) exacerbations requiring oral steroids, (2) asthma control and (3) all-cause serious adverse events. Six randomised, double-blind studies between 12 and 24 weeks' long met the inclusion criteria. Five studies contributed data to the meta-analysis, assigning 2781 people with stable asthma to the comparison of interest. The definition of stable asthma and inclusion criteria varied across studies, and Global Initiative for Asthma (GINA) criteria were not used. Risk of bias across studies was generally low, and most evidence was rated as moderate quality.Stopping LABA might increase the number of people having exacerbations and requiring oral corticosteroids (odds ratio (OR) 1.74, 95% confidence interval (CI) 0.83 to 3.65; participants = 1257; studies = 4), although the confidence intervals did not exclude the possibility that stopping LABA was beneficial; over 17 weeks, 19 people per 1000 who continued their LABA had an exacerbation, compared with 32 per 1000 when LABA were stopped (13 more per 1000, 95% CI 3 fewer to 46 more).People who stopped LABA had worse scores on the Asthma Control Questionnaire (mean difference (MD) 0.24, 95% CI 0.13 to 0.35; participants = 645; studies = 3) and on measures of asthma-related quality of life (standardised mean difference (SMD) 0.36, 95% CI 0.15 to 0.57; participants = 359; studies = 2) than those who continued LABA, but the effects were not clinically relevant.Too few events occurred for investigators to tell whether stopping LABA has a greater effect on serious adverse events compared with continuing LABA+ICS (OR 0.82, 95% CI 0.28 to 2.42; participants = 1342; studies = 5), and no study reported exacerbations requiring an emergency department visit or hospitalisation as a separate outcome. Stopping LABA may result in fewer adverse events of any kind compared with continuing, although the effect was not statistically significant (OR 0.83, 95% CI 0.66 to 1.05; participants = 1339; studies = 5), and stopping LABA made people more likely to withdraw from participation in research studies (OR 1.95, 95% CI 1.47 to 2.58; participants = 1352; studies = 5). This review suggests that stopping LABA in adults who have stable asthma while they are taking a combination of LABA and ICS inhalers may increase the likelihood of asthma exacerbations that require treatment with oral corticosteroids, but this is not certain. Stopping LABA may slightly reduce asthma control and quality of life, but evidence was insufficient to show whether this had an effect on important outcomes such as serious adverse events and exacerbations requiring hospital admission, and longer trials are warranted. Trialists should include patient-important outcomes such as asthma control and quality of life and should use validated measurement tools. Definitions of exacerbations should be provided.


[Analysis of X-ray signs of cervical spondylosis between vertebral artery type and radiculopathy].
To improve the X-ray diagnosis of cervical spondylosis of vertebral artery type (VCS). A blinded design research. The X-ray signs both 60 patients with VCS and 60 patients with cervical spondylotic radiculopathy were collected from January 2011 to November 2012. There were 36 males and 84 females, aged from 25 to 65 years old with an average of (48.4 ± 12.3) years old. Cervical curvature, atlanto-occipital joint angle, atlanto-axial joint angle, C2/C3 joint angle and lower cervical instability condition and segmental distribution were measured and recorded by X-rays. These data were analyzed and compared between the two groups after unblended. Combined with clinical manifestations,the X-ray imaging features of VCS were further analyzed. There was significant difference in cervical curvature between two groups in anteflexion X-ray films (P < 0.05). There was significant difference in extension degree of atlanto-occipital joint angle between two groups (P < 0.01). There was significant difference in atlanto-axial joint angle between two groups in lateral X-ray films (P< 0.05). There was significant.difference in anteflexion degree of atlanto-axial joint angle between two groups (P < 0.05). There was no significant difference in C2/C3 joint angle between two groups. There was no significant difference in the lower cervical instability condition and segmental distribution between two groups. In VCS group, the mild and moderate dizziness was main symptom, flexion and extension activities of neck was most common cause in the dizziness; and always accompanied with headache; tenderness mostly concentrated in the upper cervical area. Both X-ray signs and clinical manifestations can prompt the abnormalities of the upper cervical structure or function in patients with VCS. Anteflexion activities of neck observed by functional position of X-ray films should be emphasized in diagnosis of VCS.


Resistant cutaneous infection caused by Mycobacterium chelonei.
Induration of the lower parts of the legs with abscess and ulcer formation occurred in a 60-year-old woman. Mycobacterium chelonei, a ubiquitous, saprophytic pathogen that uncommonly causes human disease, was cultured from biopsy material. Although spontaneous healing usually occurs in a few months with such infections, our patient's disease persisted for more than two years until control was achieved with minocycline hydrochloride.


Purification and properties of 5-aminolaevulinate dehydratase from human erythrocytes.
A new procedure for the isolation of homogeneous human 5-aminolaevulinate dehydratase (porphobilinogen synthase, EC 184.108.40.206) is described in which the enzyme is purified 35000-fold and in 65-74% yield. The specific activity of the purified enzyme, 24 units/mg, is the highest yet reported. An efficient stage for the removal of haemoglobin is incorporated in the method, which has general application to the purification of other erythrocyte enzymes. The erythrocyte dehydratase (Mr 285 000) is made up of eight apparently identical subunits of Mr 35 000. The enzyme is sensitive to oxygen, and its activity is maintained by the presence of thiols such as dithioerythritol. Zn2+ is obligatory for enzyme activity, the apoenzyme being essentially inactive (approximately equal to 12% of control) when assayed in buffers devoid of Zn2+. Addition of Zn2+ to the apoenzyme restores activity as long as the sensitive thiol groups are fully reduced; optimal stimulation occurs between 100 and 300 microM-Zn2+. The human enzyme is inhibited by Pb2+ in a non-competitive fashion [KiI (dissociation constant for E X S X Pb2+ complex) = 25.3 +/- 3.0 microM; KiS (dissociation constant for E X Pb2+ complex) = 9.0 +/- 2.0 microM]. Modification of thiol groups, inactivation by oxidation, alkylation or reaction with thiophilic reagents demonstrates the importance of sensitive thiol groups for full enzymic activity.


[Recent progress and future direction of neurodegenerative disease research].
Although the pathogenetic mechanisms underlying neurodegenerative diseases have been long elusive, recent progress in molecular neurogenetics and neurobiology has suggested that accumulation of misfolded protein leads to dysfunction and degeneration of neurons. Misfolded proteins have propensities to form fibrils termed amyloid fibrils. In the process of amyloid fibrils, intermediate forms such as oligomers and protofibrils are produced and thought to have cytotoxic effects to neurons. Neurotoxicity mediated by misfolded proteins are also caused by stress response such as unfolded protein response. Moreover, recent findings indicate that nonneuronal cells surrounding neurons or extracellular misfolded proteins promote neurodegeneration. To eliminate toxic proteins would constitute promising future therapy for neurodegenerative disorders.


Effects of reduced-oil corn distillers dried grains with solubles composition on digestible and metabolizable energy value and prediction in growing pigs.
Two experiments were conducted to determine the DE and ME content of corn distillers dried grains with solubles (corn-DDGS) containing variable ether extract (EE) concentrations and to develop DE and ME prediction equations based on chemical composition. Ether extract content of corn-DDGS ranged from 4.88 to 10.88% (DM basis) among 4 corn-DDGS samples in Exp. 1 and from 8.56 to 13.23% (DM basis) among 11 corn-DDGS samples in Exp. 2. The difference in concentration of total dietary fiber (TDF) and NDF among the 4 corn-DDGS sources was 2.25 and 3.40 percentage units, respectively, in Exp. 1 but was greater among the 11 corn-DDGS sources evaluated in Exp. 2, where they differed by 6.46 and 15.18 percentage units, respectively. The range in CP and ash were from 28.97 to 31.19% and 5.37 to 6.14%, respectively, in Exp. 1 and from 27.69 to 32.93% and 4.32 to 5.31%, respectively, in Exp. 2. Gross energy content among corn-DDGS samples varied from 4,780 to 5,113 kcal/kg DM in Exp. 1 and from 4,897 to 5,167 kcal/kg DM in Exp. 2. In Exp. 1, the range in DE content was from 3,500 to 3,870 kcal/kg DM and ME content varied from 3,266 to 3,696 kcal/kg DM. There were no differences in ME:DE content among the 4 corn-DDGS sources in Exp. 1, but ME:GE content differed (P = 0.04) among sources (66.82 to 74.56%). In Exp. 2, the range in DE content among the 11 corn-DDGS sources was from 3,474 to 3,807 kcal/kg DM and ME content varied from 3,277 to 3,603 kcal/kg DM. However, there were no differences in DE:GE, ME:DE, or ME:GE among sources in Exp. 2. In Exp. 1, no ingredient physical or chemical measurement [bulk density (BD), particle size, GE, CP, starch, TDF, NDF, ADF, hemicellulose, EE, or ash)] was statistically significant at P ≤ 0.15 to predict DE or ME content in corn-DDGS. In Exp. 2, the best fit DE equation was DE (kcal/kg DM) = 1,601 - (54.48 × % TDF) + (0.69 × % GE) + (731.5 × BD) [R(2) = 0.91, SE = 41.25]. The best fit ME equation was ME (kcal/kg DM) = 4,558 + (52.26 × % EE) - (50.08 × % TDF) [R(2) = 0.85, SE = 48.74]. Apparent total tract digestibility of several nutritional components such as ADF, EE, and N were quite variable among corn-DDGS sources in both experiments. These results indicate that although EE may be a good predictor of GE content in corn-DDGS, it is not a primary factor for predicting DE or ME content. Measures of dietary fiber, such as ADF or TDF, are more important than EE in determining the DE or ME content of corn-DDGS for growing pigs.


Triage nurse initiation of corticosteroids in pediatric asthma is associated with improved emergency department efficiency.
To assess the effectiveness of nurse-initiated administration of oral corticosteroids before physician assessment in moderate to severe acute asthma exacerbations in the pediatric ED. A time-series controlled trial evaluated nurse initiation of treatment with steroids before physician assessment in children with Pediatric Respiratory Assessment Measure score ≥4. One-to-one periods (physician-initiated and nurse-initiated) were analyzed from September 2009 through May 2010. In both phases, triage nurses initiated bronchodilator therapy before physician assessment, per Pediatric Respiratory Assessment Measure score. We reviewed charts of 644 consecutive children aged 2 to 17 years for the following outcomes: admission rate; times to clinical improvement, steroid receipt, mild status, and discharge; and rate of return ED visit and subsequent admission. Nurse-initiated phase children improved earlier compared to physician-initiated phase (median difference: 24 minutes; 95% confidence interval [CI]: 1-50; P = .04). Admission was less likely if children received steroids at triage (odds ratio = 0.56; 95% CI: 0.36-0.87). Efficiency gains were made in time to steroid receipt (median difference: 44 minutes; 95% CI: 39-50; P < .001), time to mild status (median difference: 51 minutes; 95% CI: 17-84; P = .04), and time to discharge (median difference: 44 minutes; 95% CI: 17-68; P = .02). No differences were found in return visit rate or subsequent admission. Triage nurse initiation of oral corticosteroid before physician assessment was associated with reduced times to clinical improvement and discharge, and reduced admission rates in children presenting with moderate to severe acute asthma exacerbations.


Using self-organizing maps to learn geometric hash functions for model-based object recognition.
A major problem associated with geometric hashing and methods which have emerged from it is the nonuniform distribution of invariants over the hash space. This has two serious effects on the performance of the method. First, it can result in an inefficient storage of data which can increase recognition time. Second, given that geometric hashing is highly amenable to parallel implementation, a nonuniform distribution of data poses difficulties in tackling the load-balancing problem. Finding a "good" geometric hash function which redistributes the invariants uniformly over the hash space is not easy. Current approaches make assumptions about the statistical characteristics of the data and then use techniques from probability theory to calculate a transformation that maps the nonuniform distribution of invariants to a uniform one. In this paper, a new approach is proposed based on an elastic hash table. In contrast to existing approaches which try to redistribute the invariants over the hash bins, we proceed oppositely by distributing the hash bins over the invariants. The key idea is to associate the hash bins with the output nodes of a self-organizing feature map (SOFM) neural network which is trained using the invariants as training examples. In this way, the location of a hash bin in the space of invariants is determined by the weight vector of the node associated with the hash bin. During training, the SOFM spreads the hash bins proportionally to the distribution of invariants (i.e., more hash bins are assigned to higher density areas while less hash bins are assigned to lower density areas) and adjusts their size so that they eventually hold almost the same number of invariants. The advantage of the proposed approach is that it is a process that adapts to the invariants through learning. Hence, it makes absolutely no assumptions about the statistical characteristics of the invariants and the geometric hash function is actually computed through learning. Furthermore, SOFM's "topology preserving" property ensures that the computed geometric hash function should be well behaved. The proposed approach, was shown to perform well on both artificial and real data.


Contactless magnetocardiographic study of ventricular repolarization in intact Wistar rats: evidence of gender-related differences.
Magnetocardiographic (MCG) mapping is increasingly used for the non-invasive study of coronary artery disease (CAD), cardiomyopathy (CMP) and arrhythmias. MCG study of small animals with ischemia or CMP would provide useful experimental models for the interpretation of abnormal human patterns. The aim of this study was to assess the range of normality of MCG ventricular repolarization parameters, in intact adult rats. 10 adult Wistar rats (weight 250 - 350 grams) were investigated with a 36-channel MCG mapping instrumentation (sensitivity is 20 fT/ radical Hz, at 1 Hz), designed for clinical recordings in unshielded hospital laboratories. To assess ventricular repolarization, MCG Q-T(peak), Q-T(end), J-T(peak), J-T(end), T(peak)-T(end) intervals were measured. MCG imaging was obtained by automatic calculation of isofield contour maps, and with inverse source localization based on the Equivalent Current Dipole and Effective Magnetic Dipole models, in a semi-infinite space with homogeneous conductance. Magnetic field (MF) orientation, dynamics and stability during the J-T(end) segment were also calculated. After averaging 300 s of continuous MCG recording, the S/N ratio was good enough for reproducible reconstruction of both atrial and ventricular magnetic maps and for three-dimensional localization of the underlying cardiac generators. Clear gender-related differences in ventricular repolarization duration were found, evidenced by significantly longer Q-T(end), J-T(end) and T(peak)-T(end) intervals in females. The differences in MF orientation, and stability during the J-T(end) segment were not significant. For J-T(peak) MF dynamics, only the ratio between the strengths of the positive and negative poles was significantly lower in the female group ( p < 0.05). Contactless MCG recording is a novel approach, which simplifies non-invasive mapping in small animals. In normal rats, gender-related differences of ventricular repolarization parameters equivalent to those reported in previous ECG studies were demonstrated.


Population Health Intervention Research Initiative for Canada: progress and prospects.
Actions in Canada are being designed to transform the way research evidence is generated and used to improve population health. Capacity is being built in population health intervention research. The primary target is more understanding and examination of policies and programs that could redress inequities in health. The Population Health Intervention Research Initiative for Canada is a loosely-networked collaboration designed to advance the science of the field as well as the quantity, quality and use of population health intervention research to improve the health of Canadians. In the first few years there have been new training investments, new funding programs, new working guidelines for peer review, symposia and new international collaborations. This has been brought about by the strategic alignment of communication, planning and existing investments and the leveraging of new resources.


How to reduce the complication rate of multiple burr holes surgery in moyamoya angiopathy.
This study is aimed at analyzing clinical outcome, absence of stroke recurrence, revascularization, and complications and long-term follow-up in the surgical treatment of moyamoya angiopathy (MMA) using the multiple burr holes (MBH) technique with dura opening and arachnoid preservation as a single procedure. To the best of our knowledge, this is the first to describe an MBH technique with arachnoid preservation. We retrospectively reviewed all patients operated from June 2001 to March 2021, for a symptomatic and progressive MMA operated with opening of the dura but arachnoid preservation. Clinical examinations were obtained in all patients, and radiological monitoring was performed by cerebral 3D-magnetic resonance angiography (MRA) with perfusion or single-photon emission computed tomography (SPECT) with acetazolamide. In total, 21 consecutive patients (6 children and 15 adults) were included with a mean age of 7.4 years in the pediatric group and 36.9 years in the adult group. Initial presentation was permanent ischemic stroke in 15 cases, transient ischemic attack (TIA) in 5 cases, and cerebral hemorrhage in one case. The MBH with dura opening and arachnoid preservation was performed bilaterally in 9 cases (43%) and unilaterally in 12 cases (57%). One patient died due to intraoperative bilateral ischemic stroke. Of the 20 other patients, 30% demonstrated clinical stability and 70% showed partial or complete recovery. Although one patient experienced a perioperative stroke, we did not observe any pseudomeningocele or postoperative ischemic stroke (IS) recurrence in all surviving cases during the average follow-up period of 55.5 months (range: 1-195). These outcomes emphasize the importance of preoperative monitoring to ensure the effectiveness and safety of the intervention. Postoperative angiography studies showed revascularization in 96.3% of treated hemispheres (100% in the adult group vs 80% in the pediatric group). Our results on this small cohort suggest that the MBH technique with opening of the dura and arachnoids preservation can prevent recurrent strokes and reduce the risk of pseudomeningocele.


Sequence and conformational specificity in substrate recognition: several human Kunitz protease inhibitor domains are specific substrates of mesotrypsin.
Mesotrypsin is an isoform of trypsin that is uniquely resistant to polypeptide trypsin inhibitors and can cleave some inhibitors rapidly. Previous studies have shown that the amyloid precursor protein Kunitz protease inhibitor domain (APPI) is a specific substrate of mesotrypsin and that stabilization of the APPI cleavage site in a canonical conformation contributes to recognition by mesotrypsin. We hypothesized that other proteins possessing potential cleavage sites stabilized in a similar conformation might also be mesotrypsin substrates. Here we evaluated a series of candidate substrates, including human Kunitz protease inhibitor domains from amyloid precursor-like protein 2 (APLP2), bikunin, hepatocyte growth factor activator inhibitor type 2 (HAI2), tissue factor pathway inhibitor-1 (TFPI1), and tissue factor pathway inhibitor-2 (TFPI2), as well as E-selectin, an unrelated protein possessing a potential cleavage site displaying canonical conformation. We find that Kunitz domains within APLP2, bikunin, and HAI2 are cleaved by mesotrypsin with kinetic profiles of specific substrates. TFPI1 and TFPI2 Kunitz domains are cleaved less efficiently by mesotrypsin, and E-selectin is not cleaved at the anticipated site. Cocrystal structures of mesotrypsin with HAI2 and bikunin Kunitz domains reveal the mode of mesotrypsin interaction with its canonical substrates. Our data suggest that major determinants of mesotrypsin substrate specificity include sequence preferences at the P1 and P'2 positions along with conformational stabilization of the cleavage site in the canonical conformation. Mesotrypsin up-regulation has been implicated previously in cancer progression, and proteolytic clearance of Kunitz protease inhibitors offers potential mechanisms by which mesotrypsin may mediate pathological effects in cancer.


Stimulation of [1-14C]oleate oxidation to 14CO2 in isolated rat hepatocytes by the catecholamines, vasopressin and angiotensin. A possible mechanism of action.
Adrenaline, noradrenaline, vasopressin and angiotensin increased 14CO2 production from [1-14C]oleate by hepatocytes from fed rats but not by hepatocytes from starved rats. The hormones did not increase 14CO2 production when hepatocytes from fed rats were depleted of glycogen in vitro. Increased 14CO2 production from ]1-14C]oleate in response to the hormones was observed when hepatocytes from starved rats were incubated with 3-mercaptopicolinate, an inhibitor of phosphoenolpyruvate carboxykinase. 3-Mercaptopicolinate inhibited uptake and esterification of [1-14C]oleate, slightly increased 14CO2 production from [1-14C]oleate and greatly increased the [3-hydroxybutyrate]/[acetoacetate] ratio. In the presence of 3-mercaptopicolinate 14CO2 production in response to the catecholamines was blocked by the alpha-antagonist phentolamine and required extracellular Ca2+. The effects of vasopressin and angiotensin were also Ca2+-dependent. The actions of the hormones of 14CO2 production from [I-14C]oleate by hepatocytes from starved rats in the presence of 3-mercaptopicolinate thus have the characteristics of the response to the hormones found with hepatocytes from fed rats incubated without 3-mercaptopicolinate. The stimulatory effects of the hormones on 14CO2 production from [1-14C]oleate were not the result of decreased esterification (as the hormones increased esterification) or increased beta-oxidation. It is suggested that the effect of the hormones to increase 14CO2 production from [1-14C]oleate are mediated by CA2+-activation of NAD+-linked isocitrate dehydrogenase, the 2-oxoglutarate dehydrogenase complex, and/or electron transport. The results also demonstrate that when the supply of oxaloacetate is limited it is utilized for gluconeogenesis rather than to maintain tricarboxylic acid-cycle flux.


Contribution of mitochondrial proton leak to respiration rate in working skeletal muscle and liver and to SMR.
Proton pumping across the mitochondrial inner membrane and proton leak back through the natural proton conductance pathway make up a futile cycle that dissipates redox energy. We measured respiration and average mitochondrial membrane potential in perfused rat hindquarter with maximal tetanic contraction of the left gastrocnemius-soleus-plantaris muscle group, and we estimate that the mitochondrial proton cycle accounted for 34% of the respiration rate of the preparation. Similar measurements in rat hepatocytes given substrates to cause a high rate of gluconeogenesis and ureagenesis showed that the proton cycle accounted for 22% of the respiration rate of these cells. Combining these in vitro values with literature values for the contribution of skeletal muscle and liver to standard metabolic rate (SMR), we calculate that the proton cycle in working muscle and liver may account for 15% of SMR in vivo. Although this value is less than the 20% of SMR we calculated previously using data from resting skeletal muscle and hepatocytes, it is still large, and we conclude that the futile proton cycle is a major contributor to SMR.


Red blood cell microrheology (clinical and pharmacological applications).
In order to understand blood circulation, knowledge of the rheological properties of blood is required. However, the characteristic parameters which must be considered differ according to the circulatory region investigated. A distinction must therefore be made between the macrorheological parameters (viscosity, viscoelasticity) and the microrheological parameters (aggregation, cell deformability). As far as the microrheological parameters are concerned, red blood cell deformability is quite definitely the most important parameter in any physiopathological study of capillary circulation and the resulting exchanges. The main intrinsic parameters of red blood cell deformability are: inner viscosity of the cell, surface/volume ratio and membrane properties related to the lipid bilayer or to the cytoskeleton. Abnormal erythrocyte microrheology may result form alterations any one of these three parameters and would affect the ability of the cell to transit in the capillaries. Disturbances of red blood cell deformability are encountered in many clinical cases, mainly during anomalies relating to hemoglobin structure or its oxygen affinity, in constitutional deficiency of the membrane and during degenerative cardiovascular diseases or diseases which are considered to be atherosclerosis risk factors.


The effect of particle shape on discharge and clogging.
Granular flow is common across different fields from energy resource recovery and mineral processing to grain transport and traffic flow. Migrating particles may jam and form arches that span constrictions and hinder particle flow. Most studies have investigated the migration and clogging of spherical particles, however, natural particles are rarely spherical, but exhibit eccentricity, angularity and roughness. New experiments explore the discharge of cubes, 2D crosses, 3D crosses and spheres under dry conditions and during particle-laden fluid flow. Variables include orifice-to-particle size ratio and solidity. Cubes and 3D crosses are the most prone to clogging because of their ability to interlock or the development of face-to-face contacts that can resist torque and enhance bridging. Spheres arriving to the orifice must be correctly positioned to create stable bridges, while flat 2D crosses orient their longest axes in the direction of flowlines across the orifice and favor flow. Intermittent clogging causes kinetic retardation in particle-laden flow even in the absence of inertial effects; the gradual increase in the local particle solidity above the constriction enhances particle interactions and the probability of clogging. The discharge volume before clogging is a Poisson process for small orifice-to-particle size ratio; however, the clogging probability becomes history-dependent for non-spherical particles at large orifice-to-particle size ratio and high solidities, i.e., when particle-particle interactions and interlocking gain significance.


Cooling of alpaca spermatozoa using an extender with the addition of different percentages of seminal plasma.
The objective of this study was to evaluate the effect of the addition of different percentages of seminal plasma (SP) during the cooling at 5 °C of alpaca spermatozoa from vas deferens. Fifteen pools of sperm from vas deferens were evaluated and then divided into four aliquots that were diluted to a final concentration of 30 × 106 sperm/ml with either: (1) Tris with 20% egg yolk (T-EY) (control, 0% SP), (2) T-EY with 10% SP, (3) T-EY with 25% SP, and (4) T-EY with 50% SP. Samples were cooled at 5 °C and the following sperm parameters were evaluated after 24 and 48 h of storage: motility, viability, membrane function, acrosome integrity, morphology, and chromatin condensation. Motility was also evaluated after 72 h of storage. A significant decrease in progressive and total sperm motility was observed in samples cooled with 50% SP with respect to all diluted samples, while these parameters were preserved in samples cooled with 0%, 10%, and 25% SP. The percentages of sperm viability, normal morphology, and highly condensed chromatin did not change after the cooling process and were similar between cooled samples. Although a significant decrease was observed in the percentage of spermatozoa with functional membranes and with an intact acrosome in all refrigerated samples compared to raw sperm, the greatest decrease was observed in samples cooled with 50% SP. No advantage was observed from the addition of SP to alpaca spermatozoa obtained from vas deferens and being cooled. In addition, to preserve the sperm motility of cooled samples for up to 72 h, it should be recommended to include a 10% SP in the extender.


Turkish League Against Rheumatism (TLAR) Recommendations for the Pharmacological Management of Rheumatoid Arthritis: 2018 Update Under Guidance of Current Recommendations.
This study aims to report the assessment of the Turkish League Against Rheumatism (TLAR) expert panel on the compliance and adaptation of the European League Against Rheumatism (EULAR) 2016 recommendations for the management of rheumatoid arthritis (RA) in Turkey. The EULAR 2016 recommendations for the treatment of RA were voted by 27 specialists experienced in this field with regard to participation rate for each recommendation and significance of items. Afterwards, each recommendation was brought forward for discussion and any alteration gaining ≥70% approval was accepted. Also, Turkish version of each item was rearranged. Last version of the recommendations was then revoted to determine the level of agreement. Levels of agreement of the two voting rounds were compared with Wilcoxon signed-rank test. In case of significant difference, the item with higher level of agreement was accepted. In case of no difference, the changed item was selected. Four overarching principles and 12 recommendations were assessed among which three overarching principles and one recommendation were changed. The changed overarching principles emphasized the importance of physical medicine and rehabilitation specialists as well as rheumatologists for the care of RA patients in Turkey. An alteration was made in the eighth recommendation on treatment of active RA patients with unfavorable prognostic indicators after failure of three conventional disease modifying anti-rheumatic drugs. Remaining principles were accepted as the same although some alterations were suggested but could not find adequate support to reach significance. Expert opinion of the TLAR for the treatment of RA was composed for practices in Turkish rheumatology and/or physical medicine and rehabilitation clinics.


Clinical symptoms and IgE responses to common food proteins in atopic and healthy children.
The appearance of symptoms suggestive of allergy through the first 4 years of life was studied prospectively in eighty-six healthy newborn babies. Blood samples were obtained at birth, at 3, 8, 25 and 48 months of age and analyzed for levels of total serum IgE and for IgE antibodies to some common foods. The occurrence of IgE antibodies was related to atopic manifestations and to a detailed history of infant feeding and family history of allergy. All infants with elevated cord blood IgE (more than 1.3 kU/l) developed manifestations of atopy. Specific IgE antibodies against egg, cow's milk and soy were demonstrated at 3, 8, 25 and 48 months in nine, twenty-three, six and two children respectively. Egg was a more potent sensitizing agent than cow's milk, IgE antibodies to egg being present in thirty-one samples, to cow's milk in eleven and to soy in five samples. Nine infants developed IgE antibodies to eggs or cow's milk before the introduction of these nutrients into the food. The IgE antibody levels were generally low in healthy non-atopic children and did, with one exception, not reach RAST class 1. In contrast, the levels of IgE antibodies to egg or cow's milk were higher in eleven blood samples from atopic children. We conclude that transient low IgE antibody responses to food proteins appear relatively often even in healthy infants. High concentrations of IgE antibodies however are almost exclusively seen in infants with atopic disease. Sensitization may appear early in infancy sometimes even before the offending food has been introduced into the diet.


Transcriptomic responses in the fish intestine.
The intestine, being a multifunctional organ central to both nutrient uptake, pathogen recognition and regulating the intestinal microbiome, has been subjected to intense research. This review will focus on the recent studies carried out using high-throughput gene expression approaches, such as microarray and RNA sequencing (RNA-seq). These techniques have advanced greatly in recent years, mainly as a result of the massive changes in sequencing methodologies. At the time of writing, there is a transition between relatively well characterised microarray platforms and the developing RNA-seq, with the prediction that within a few years as costs decrease and computation power increase, RNA-seq related approaches will supersede the microarrays. Comparisons between the approaches are made and specific examples of how the techniques have been used to examine intestinal responses to pathogens, dietary manipulations and osmoregulatory challenges are given.


A taxonomic note on the authorship and date of valid publication of Rhodococcus sputi.
Authorship of the name Rhodococcus sputi is variously attributed to Tsukamura 1978 or Tsukamura and Yano 1985. DNA-DNA binding data indicate that this species and Rhodococcus obuensis Tsukamura 1983 and Rhodococcus chubuensis Tsukamura 1983 are subjective (heterotypic) synonyms. Although these organisms have been placed in the genus Gordonia as Gordonia sputi, the correct name of the taxon created by unification of these three species is directly affected by the date of valid publication of these species as members of the genus Rhodococcus. Thus, the name R. sputi only has priority if the authorship is attributed to Tsukamura 1978. The question of authorship and priority is clarified in the present work.


[Clinical evaluation of the influence of certain initial status parameters on the development of type 2 diabetes mellitus in patients with metabolic syndrome].
Type 2 diabetes mellitus (DM2) is one of the clinical outcomes of metabolic syndrome (MS). We observed 201 patients with MS during 10 years. At the study end-point 144 (71.9%) of them developed DM2. The study aimed at evaluating effect of initial parameter of MS on the rate of DM2 development. Results of correlation analysis show that the rate of DM2 development depends in the first place on the patients' age, severity of abdominal obesity, vicious habits and their combination with disturbed lipid metabolism, sympatho-adrenal disbalance , and arterial hypertension rather than on disordered carbohydrate metabolism at the onset of the disease.


The role of Ca2+ in triggering inositol 1,4,5-trisphosphate receptor ubiquitination.
The IP3R (inositol 1,4,5-trisphosphate receptor) forms tetrameric Ca2+ channels in ER (endoplasmic reticulum) membranes, where channel activity is largely under the control of the co-agonists IP3 and Ca2+. In cells stimulated using extracellular ligands that persistently elevate phosphoinositidase C activity, IP3Rs are rapidly ubiquitinated and then degraded by the proteasome through as yet undefined mechanisms. Whereas binding of IP3 has been suggested to be a key event in the triggering of IP3R ubiquitination the role of Ca2+ in this process remains unknown. In the present study we use alphaT3-1 mouse pituitary cells expressing exogenous wild-type or mutant-type-I IP3Rs (IP3R1) to provide several lines of evidence that Ca2+ is also a trigger. Firstly, depletion of ER Ca2+ stores with thapsigargin blocked wild-type IP3R1 ubiquitination. Secondly, ubiquitination was blocked by mutating Glu2100 to Asp, which is known to markedly suppress Ca2+-binding to IP3R1 and the potency of Ca2+ as a stimulus for channel opening. Thirdly, mutating Asp2550 to Ala, which inhibits Ca2+ flux through the channel pore, partially inhibited ubiquitination indicating that Ca2+ released via wild-type IP3R1 contributes to triggering ubiquitination. Fourthly, and consistent with this conclusion, although suppression of increases in cytoplasmic Ca2+ concentration did not inhibit the ubiquitination of wild-type IP3R1, it strongly inhibited the ubiquitination of the Asp2550 to Ala mutant. Overall, these results show that Ca2+ plays an important role in triggering IP3R ubiquitination. Additional experiments with IP3R1 containing an Arg265 to Gln mutation, which decreases IP3-binding affinity, confirmed that IP3-binding also plays a role. Finally, the mutations at Glu2100, Asp2550 and Arg265 inhibited IP3R1 degradation to an extent that paralleled their inhibitory effects on ubiquitination. We conclude that IP3R ubiquitination and degradation are triggered by the concerted action of IP3- and Ca2+-binding.


Circumstances and outcomes of sudden unexpected death in patients with high-risk myocardial infarction: implications for prevention.
Sudden death (SD) is a frequent catastrophic complication in patients after myocardial infarction. Circumstances of SD may affect strategies for prevention. We reviewed source documentation for 1067 patients who had SD in the Valsartan in Acute Myocardial Infarction Trial (VALIANT) trial. We determined the circumstances of these events and assessed long-term mortality in patients who were resuscitated. Location of the SD event was available in 978 of 1067 patients, with 226 events occurring within the first 40 days. Although SD was more likely to occur at home (645 of 978, 66%) than in hospital (204 of 978, 21%), the proportion of in-hospital events was higher early on (99 of 226, 44%). Home events were less likely to be witnessed regardless of time frame. Preceding activity was known for 42% of patients with home arrest; of these, 52% were determined to be asleep at time of event, and these deaths were more likely to be unwitnessed. A majority of patients for whom initial ECG rhythm was reported had ventricular tachycardia/ventricular fibrillation (189 of 283, 67%). Of the 155 patients successfully resuscitated, 24% subsequently received an implantable cardioverter-defibrillator. Nineteen percent of those who received an implantable cardioverter-defibrillator subsequently died compared with 49% of patients who did not receive an implantable cardioverter-defibrillator (hazard ratio, 0.36; 95% confidence interval, 0.14 to 0.93; P=0.04). A high proportion of SD events after high-risk myocardial infarction occurred at home, but in-hospital events were more common early on. Patients who were asleep were more likely to have unwitnessed arrests. Alternative strategies for the prevention of SD in patients who are not candidates for implantable cardioverter-defibrillator will need to take into account the circumstances of SD events.


Perioperative Coagulation Management of a Hemophilia A Patient During Cardiac Surgery.
Perioperative management of cardiovascular surgical procedures requiring cardiopulmonary bypass (CPB) in patients with hemophilia A poses a clinical challenge in coagulation management. Use of CPB requires the administration of an anticoagulant, usually unfractionated heparin, and also causes dilutional coagulopathy, platelet dysfunction or platelet consumption coagulopathy. Hypothermia and activation of the inflammatory cascade also affect coagulation. The effects of CPB on circulating levels of factor VIII have not been clearly defined. In this review, the effects of CPB and hemodilution on FVIII are shown in a case presentation, and perioperative laboratory testing in patients with hemophilia A having cardiac surgery is discussed along with perioperative and postoperative coagulation management.


The effect of pentosan polysulphate (SP54) on the human fibrinolytic system.
In human volunteers the oral and subcutaneous (s.c.) administration of SP54 enhanced the fibrinolytic potential of plasma. When the effect was compared between exercise and s.c. administration of SP54 the latter was found to "peak" at about 3 hours and to have a more sustained effect than the exercise. Oral versus s.c. administration suggests that only about 10% of the SP54 reaches the circulation by the oral route. However, repeat SP54 oral dosage did not elicit any resistance to the daily response over a period of five days and suggests that the volunteers used in this study tolerated repeated use of the drug with no ill-effects. The source of the fibrinolytic enhancement is as yet not fully explained and a hypothesis is presented which suggests that very small elevations of t-PA in plasma can affect the fibrinolytic potential in the presence of forming fibrin but may remain undetected by conventional immunometric assays.


Folic acid and vitamin B-12 supplementation and common infections in 6-30-mo-old children in India: a randomized placebo-controlled trial.
Young children in low- and middle-income countries frequently have inadequate vitamin B-12 (cobalamin) status. Poor folate status is also common and is associated with increased diarrheal and respiratory morbidity. The objective was to measure the effect of folic acid and/or vitamin B-12 administration on the incidence of diarrhea and acute lower respiratory tract infections. One thousand North Indian children (6-30 mo of age) were enrolled in a randomized, double-blind, placebo-controlled trial to receive 2 times the Recommended Dietary Allowance of folic acid and/or vitamin B-12 or placebo daily for 6 mo. Children were individually randomly assigned in a 1:1:1:1 ratio in blocks of 16. Primary outcomes were the number of episodes of acute lower respiratory infections, diarrhea, and prolonged diarrhea. Folic acid and vitamin B-12 supplementation significantly improved vitamin B-12 and folate status, respectively. Neither folic acid nor vitamin B-12 administration reduced the incidence of diarrhea or lower respiratory infections. In comparison with placebo, children treated with folic acid alone or in combination with vitamin B-12 had a significantly higher risk of persistent diarrhea (OR: 2.1; 95% CI: 1.1, 3.8). Folic acid or vitamin B-12 supplementation did not reduce the burden of common childhood infections. In view of the increased risk of diarrhea, the safety of folic acid supplements in young children should be further assessed. This trial was registered at www.clinicaltrials.gov as NCT00717730 and at www.ctri.nic.in as CTRI/2010/091/001090.


Epigenetic alterations fuel brain metastasis via regulating inflammatory cascade.
Brain metastasis (BrM) is a major threat to the survival of melanoma, breast, and lung cancer patients. Circulating tumor cells (CTCs) cross the blood-brain barrier (BBB) and sustain in the brain microenvironment. Genetic mutations and epigenetic modifications have been found to be critical in controlling key aspects of cancer metastasis. Metastasizing cells confront inflammation and gradually adapt in the unique brain microenvironment. Currently, it is one of the major areas that has gained momentum. Researchers are interested in the factors that modulate neuroinflammation during BrM. We review here various epigenetic factors and mechanisms modulating neuroinflammation and how this helps CTCs to adapt and survive in the brain microenvironment. Since epigenetic changes could be modulated by targeting enzymes such as histone/DNA methyltransferase, deacetylases, acetyltransferases, and demethylases, we also summarize our current understanding of potential drugs targeting various aspects of epigenetic regulation in BrM.


Helicobacter pylori and associated duodenal ulcer.
Twenty three children with coexistent duodenal ulcer and Helicobacter pylori infection were treated with either two weeks of amoxycillin (25 mg/kg/day) in addition to six weeks of cimetidine, or cimetidine alone. Endoscopy with antral and duodenal biopsies for urease test, microaerophilic culture, and histological studies were performed at entry, six weeks, 12 weeks, and at six months. Children with persistent H pylori infection at six weeks were given a further two weeks' course of amoxycillin. H pylori persisted in all children not receiving amoxycillin treatment but cleared in six of the 13 children (46%) treated with amoxycillin. With failure of H pylori clearance at six months, only two out of six (33%) ulcers had healed and 50% of patients had experienced ulcer recurrence. In contrast, when H pylori remained cleared all ulcers healed and no ulcer recurred. Persistent H pylori infection was associated with persistent gastritis and duodenitis despite endoscopic evidence of ulcer healing. Detection and eradication of H pylori deserves particular attention in the routine management of duodenal ulceration in children.


Cardiac Effects of Novel Histamine H2 Receptor Agonists.
In an integrative approach, we studied cardiac effects of recently published novel H2 receptor agonists in the heart of mice that overexpress the human H2 receptor (H2-TG mice) and littermate wild type (WT) control mice and in isolated electrically driven muscle preparations from patients undergoing cardiac surgery. Under our experimental conditions, the H2 receptor agonists UR-Po563, UR-MB-158, and UR-MB-159 increased force of contraction in left atrium from H2-TG mice with pEC50 values of 8.27, 9.38, and 8.28, respectively, but not in WT mice. Likewise, UR-Po563, UR-MB-158, and UR-MB-159 increased the beating rate in right atrium from H2-TG mice with pEC50 values of 9.01, 9.24, and 7.91, respectively, but not from WT mice. These effects could be antagonized by famotidine, a H2 receptor antagonist. UR-Po563 (1 µM) increased force of contraction in Langendorff-perfused hearts from H2-TG but not WT mice. Similarly, UR-Po563, UR-MB-158, or UR-MB-159 increased the left ventricular ejection fraction in echocardiography of H2-TG mice. Finally, UR-Po563 increased force of contraction in isolated human right atrial muscle strips. The contractile effects of UR-Po563 in H2-TG mice were accompanied by an increase in the phosphorylation state of phospholamban. In summary, we report here three recently developed agonists functionally stimulating human cardiac H2 receptors in vitro and in vivo. We speculate that these compounds might be of some merit to treat neurologic disorders if their cardiac effects are blocked by concomitantly applied receptor antagonists that cannot pass through the blood-brain barrier or might be useful to treat congestive heart failure in patients. SIGNIFICANCE STATEMENT: Recently, a new generation of histamine H2 receptor (H2R) agonists has been developed as possible treatment option for Alzheimer's disease. Here, possible cardiac (side) effects of these novel H2R agonists have been evaluated.


A national survey of antibacterial consumption in Sri Lanka.
Optimizing the use of antibacterial medicines is an accepted strategy to combat the antibacterial resistance. Availability of reliable antibacterial consumption (ABC) data is a prerequisite to implement this strategy. To quantify and describe the national ABC in Sri Lanka and to examine any differences in the consumption between public and private sector. The methodology for this survey was adapted from World Health Organization (WHO) methodology for a global programme on surveillance of antimicrobial consumption. Aggregate data on national consumption of systemic antibacterials (J01- Anatomical Therapeutic Chemical Classification (ATC) for 2017 were retrospectively extracted from all available data sources and classified using ATC classification. Quantity of consumption was converted to Defined Daily Doses (DDDs). Data are presented as total consumption and comparison between the public and private sector. Selected key quality indicators of ABC were compared between these two sectors. From the available data sources, the total ABC in 2017 was 343.46 million DDDs. Private sector consumption accounted for 246.76 million DDDs compared to 97.96 million DDDs distributed to entire public sector by the Ministry of Health. Beta-lactam-penicillins antibacterial group accounted for 58.79% in public sector compared to 27.48% in private sector while macrolides, quinolones and other beta-lactam antibacterials accounted for 60.51% in the private compared to 28.41% in public sector. Consumption of Reserve group antibacterials was negligible, and limited to private sector. Watch category antibacterials accounted for 46%, 24% and 54% of the total, public and private sector consumption, respectively. A disproportionately higher use of broad spectrum and Watch category antibacterials was observed in the private sector which needs further study. This national consumption survey highlights the need and provides the opening for establishment of ABC surveillance in Sri Lanka.


Transforming growth interacting factor expression in leiomyoma compared with myometrium.
To investigate the expression of transforming growth interacting factor (TGIF), a Smad transcriptional corepressor, in leiomyoma and matched myometrial tissue samples and the effect of TGIF overexpression in myometrial cells. Experimental study. Tertiary university hospital. Uterine leiomyoma and myometrial tissues from 16 patients. None. The distribution of TGIF in leiomyoma and myometrial tissues by immunohistochemistry stain, mRNA, and protein expression levels by real-time quantitative polymerase chain-reaction (QPCR) and Western blot. Transcriptional regulation of TGIF in myometrial cells with overexpressed TGIF. Although TGIF is present in the smooth muscle cells of the leiomyoma and the myometrium, it is not found in the extracellular matrix. The TGIF mRNA and protein expressions were statistically significantly higher in the leiomyoma compared with the matched, unaffected myometrial tissues in both phases of the menstrual cycle. There were no differences in mRNA or protein expression throughout the menstrual cycle. Overexpression of TGIF protein in myometrial cells statistically significantly suppressed up-regulation of plasminogen activator inhibitor (PAI-1) induced by TGF-beta1 treatment. Expression of TGIF is increased in leiomyoma compared with myometrium. This increase in TGIF expression is not affected by endogenous ovarian hormones. Thus, TGIF is a potential repressor of TGF-beta pathways in myometrial cells.


Endothelial protection and viscoelastic retention during phacoemulsification and intraocular lens implantation.
Endothelial protection (measured by vital-dye staining and computerized planimetry) and viscoelastic retention during phacoemulsification with and without traumatic lens implantation were assessed in a rabbit model comparing four viscoelastics (Healon, Amvisc Plus, Occucoat, and Viscoat). No significant differences in cell damage were noted between unoperated on controls and groups that underwent atraumatic phacoemulsification with viscoelastic. Cell damage after traumatic lens insertion was reduced significantly by all four viscoelastics. Cell damage with and without traumatic lens implantation was significantly lower when viscoelastics were retained. Viscoat and Occucoat were significantly more likely to be retained than Healon.


Effect of cigarette smoking on muscle strength of flexibility of athletes.
Kraus-Webber test which indicates muscle strength and flexibility of certain group of muscles showed significant decrease in cigarette smoking athletes in the age group of 19-30 years compared to nonsmoking athletes. The results indicate tobacco smoke inhalation affects muscle flexibility and strength required for athletes.


Orchestration of angiogenesis by immune cells.
It is widely accepted that the tumor microenvironment (TUMIC) plays a major role in cancer and is indispensable for tumor progression. The TUMIC involves many "players" going well beyond the malignant-transformed cells, including stromal, immune, and endothelial cells (ECs). The non-malignant cells can acquire tumor-promoting functions during carcinogenesis. In particular, these cells can "orchestrate" the "symphony" of the angiogenic switch, permitting the creation of new blood vessels that allows rapid expansion and progression toward malignancy. Considerable attention within the context of tumor angiogenesis should focus not only on the ECs, representing a fundamental unit, but also on immune cells and on the inflammatory tumor infiltrate. Immune cells infiltrating tumors typically show a tumor-induced polarization associated with attenuation of anti-tumor functions and generation of pro-tumor activities, among these angiogenesis. Here, we propose a scenario suggesting that the angiogenic switch is an immune switch arising from the pro-angiogenic polarization of immune cells. This view links immunity, inflammation, and angiogenesis to tumor progression. Here, we review the data in the literature and seek to identify the "conductors" of this "orchestra." We also suggest that interrupting the immune → inflammation → angiogenesis → tumor progression process can delay or prevent tumor insurgence and malignant disease.


Abductor laryngeal dystonia: a series treated with botulinum toxin.
Abductor laryngeal dystonia (LD) is characterized by a hoarse voice quality which is broken up by breathy or whispered portions. Botulinum toxin injection (Botox) has been a safe and effective treatment for adductor laryngeal dystonia and is currently accepted medical therapy. As an extension of the established treatment program, in 1989 treatment of abductor LD was initiated. Thirty-two patients have been treated by sequential percutaneous electromyogram-guided (EMG) injections of the posterior cricoarytenoid (PCA) muscles. Most patients required treatment of both PCA muscles and improved to an average of 70% of normal voice. Patients who had a preexisting tremor, evidence of dystonia in other muscle groups, vocal tremor, or respiratory dysrhythmia had less improvement. Ten patients also required injection of the cricothyroid muscles and/or type I laryngoplasty.


Adenovirus, MS2 and PhiX174 interactions with drinking water biofilms developed on PVC, cement and cast iron.
Biofilms colonizing pipe surfaces of drinking water distribution systems could provide habitat and shelter for pathogenic viruses present in the water phase. This study aims (i) to develop a method to detect viral particles present in a drinking water biofilm and (ii) to study viral interactions with drinking water biofilms. A pilot scale system was used to develop drinking water biofilms on 3 materials (7 cm(2) discs): PVC, cast iron and cement. Biofilms were inoculated with viral model including MS2, PhiX174 or adenovirus. Five techniques were tested to recover virus from biofilms. The most efficient uses beef extract and glycine at pH = 9. After sonication and centrifugation, the pH of the supernatant is neutralized prior to viral analysis. The calculated recovery rates varied from 29.3 to 74.6% depending on the virus (MS2 or PhiX174) and the material. Applying this protocol, the interactions of virus models (MS2 and adenovirus) with drinking water biofilms were compared. Our results show that adsorption of viruses to biofilms depends on their isoelectric points, the disc material and the hydrodynamic conditions. Applying hydrodynamic conditions similar to those existing in drinking water networks resulted in a viral adsorption corresponding to less than 1% of the initial viral load.


Policy of Labor Management and Health Education: a ProgeSUS experience.
To evaluate the stage of labor management and education policies in municipal and state health secretariats (SMS and SES, respectively), having as reference the adherence to a qualification and structuring program of work management and education in the Unified Health System. A descriptive and quantitative study, developed with 519 representatives from the Human Resources (HR) area of SMS and SES, through a survey composed of 56 questions, via a computer-assisted telephone interview in 2012. Responses were processed in a computerized database and the data treated by descriptive statistics. Changes in professional qualification, the establishment of job and salary plans and negotiation processes were identified; on the other hand, there was no progress related to the financial and budgetary autonomy of the area of work management and health education. It is observed progress in the incorporation of innovations in the management in SES and SMS from the process of training of managers and financial induction. It is necessary to monitor and periodically evaluate the operationalization of labor and education policies aimed at strengthening them, correcting directions and implementing innovative actions.


[Increased VEGFR-1 immunoreactivity in the choroid-scleral complex in hypercholesterolemia experimental model].
The aim of this study is to investigate the expression of vascular endothelial growth factor (VEGF) in the choroid and sclera using hypercholesterolemia experimental model. New Zealand rabbits were divided into two groups: 8 rabbits (8 eyes), in the normal diet group (NG), were fed by a standard diet for 4 weeks; and 13 rabbits (13 eyes), in the hypercholesterolemic group (HG), were fed by a 1% cholesterol-enriched diet for 8 weeks. Total serum cholesterol, triglyceride, HDL cholesterol and fasting blood glucose exams were performed at the initiation of the experiment and at the euthanasia time. After hypercholesterolemic group 8th week and NG 4th week, animals were euthanized and their eyes underwent immunohistochemical analysis with the RAM-11 and VEGFR-1). The diet has induced a significant increase in total cholesterol and triglyceride levels in HG when compared with NG (p<0.001). There was a significant increase in the RAM-11 and VEGFR-1 expressions in hypercholesterolemic group choroid and sclera in relation to NG (p<0,001). This study has revealed that the hypercholesterolemic diet in rabbits induces an increase in the macrophage concentration and immunoreactivity to VEGFR-1 in the choroid and sclera, resembling human age-related macular degeneration (ARMD).


The complete genome sequence of Clostridium difficile phage phiC2 and comparisons to phiCD119 and inducible prophages of CD630.
The complete genomic sequence of a previously characterized temperate phage of Clostridium difficile, C2, is reported. The genome is 56 538 bp and organized into 84 putative ORFs in six functional modules. The head and tail structural proteins showed similarities to that of C. difficile phage CD119 and Streptococcus pneumoniae phage EJ-1, respectively. Homologues of structural and replication proteins were found in prophages 1 and 2 of the sequenced C. difficile CD630 genome. A putative holin appears unique to the C. difficile phages and was functional when expressed in Escherichia coli. Nucleotide sequence comparisons of C2 to CD119 and the CD630 prophage sequences showed relatedness between C2 and the prophages, but less so to CD119. C2 integrated into a gene encoding a putative transcriptional regulator of the gntR family. C2, CD119 and CD630 prophage 1 genomes had a Cdu1-attP-integrase arrangement, suggesting that the pathogenicity locus (PaLoc) of C. difficile, flanked by cdu1, has phage origins. The attP sequences of C2, CD119 and CD630 prophages were dissimilar. C2-related sequences were found in 84 % of 37 clinical C. difficile isolates and typed reference strains.


BLMP-1 promotes developmental cell death in C. elegans by timely repression of ced-9 transcription.
Programmed cell death (PCD) is a common cell fate in metazoan development. PCD effectors are extensively studied, but how they are temporally regulated is less understood. Here, we report a mechanism controlling tail-spike cell death onset during Caenorhabditis elegans development. We show that the zinc-finger transcription factor BLMP-1, which controls larval development timing, also regulates embryonic tail-spike cell death initiation. BLMP-1 functions upstream of CED-9 and in parallel to DRE-1, another CED-9 and tail-spike cell death regulator. BLMP-1 expression is detected in the tail-spike cell shortly after the cell is born, and blmp-1 mutations promote ced-9-dependent tail-spike cell survival. BLMP-1 binds ced-9 gene regulatory sequences, and inhibits ced-9 transcription just before cell-death onset. BLMP-1 and DRE-1 function together to regulate developmental timing, and their mammalian homologs regulate B-lymphocyte fate. Our results, therefore, identify roles for developmental timing genes in cell-death initiation, and suggest conservation of these functions.


Stability of methods for differential expression analysis of RNA-seq data.
As RNA-seq becomes the assay of choice for measuring gene expression levels, differential expression analysis has received extensive attentions of researchers. To date, for the evaluation of DE methods, most attention has been paid on validity. Yet another important aspect of DE methods, stability, is overlooked and has not been studied to the best of our knowledge. In this study, we empirically show the need of assessing stability of DE methods and propose a stability metric, called Area Under the Correlation curve (AUCOR), that generates the perturbed datasets by a mixture distribution and combines the information of similarities between sets of selected features from these perturbed datasets and the original dataset. Empirical results support that AUCOR can effectively rank the DE methods in terms of stability for given RNA-seq datasets. In addition, we explore how biological or technical factors from experiments and data analysis affect the stability of DE methods. AUCOR is implemented in the open-source R package AUCOR, with source code freely available at https://github.com/linbingqing/stableDE .


Neurotechnology ethics and relational agency.
Novel neurotechnologies, like deep brain stimulation and brain-computer interface, offer great hope for treating, curing, and preventing disease, but raise important questions about effects these devices may have on human identity, authenticity, and autonomy. After briefly assessing recent narrative work in these areas, we show that agency is a phenomenon key to all three goods and highlight the ways in which neural devices can help to draw attention to the relational nature of our agency. Drawing on insights from disability theory, we argue that neural devices provide a kind of agential assistance, similar to that provided by caregivers, family, and others. As such, users and devices participate in a kind of co-agency. We conclude by suggesting the need for developing relational agency-competencies-skills for reflecting on the influence of devices on agency, for adapting to novel circumstances ushered in by devices, and for incorporating the feedback of loved ones and others about device effects on agency.


Esophageal carcinoma. Radiologic appearance of minimal lesions.
Twelve minimal lesions were found over a period of 18 months at the Istituto Nazionale Tumori of Milan at the end of the radiologic, endoscopic and histologic procedures. Eleven lesions were radiologically detected, and a radiologic diagnosis of malignancy was perspectively made in 10 of the identified lesions. The radiologic aspects of minimal lesions are described. Double contrast study of the esophagus allows excellent mucosal detail and good reproduction of lesions. Simplicity and minimal discomfort for the patient justify it as a first diagnostic step for detection of neoplastic pathology.


Contrasting Perspectives of Practice Leaders and Practice Facilitators May Be Common in Quality Improvement Initiatives.
Practice facilitation is an approach for advancing quality improvement (QI), but its success depends on effective relationships and communication among participants. Our goal was to identify patterns of contrasting perspectives on implementation issues between practice leaders and their practice facilitators, and factors that may contribute to them. We conducted individual interviews with practice leaders and the practice facilitators assigned to them as part of a program focused on preventive cardiology within primary care practices. We used summative content analysis to quantify the incidence of contrasting perspectives, and bivariate and qualitative analyses to explore relationships between contrasting perspectives and contextual factors. Among the 16 dyads, contrasting perspectives commonly related to the easiest or hardest QI interventions to implement (8 of 16 dyads) and the practice's success implementing interventions (5 of 16 dyads). There was a nonsignificant, inverse correlation (r = -0.19, p = .47) between the number of in-person QI visits from the facilitator and the total number of contrasting perspectives. Turnover of staff was frequently reported in dyads with contrasting perspectives. Although the impact of contrasting perspectives warrants additional study, planners of QI initiatives using practice facilitation should consider taking steps to minimize contrasting perspectives, or the potential adverse consequences of them, by addressing turnover challenges and encouraging opportunities to share perspectives.


Assessment of the elution of charcoal, cellulose acetate, and other particles from cigarettes with charcoal and activated charcoal/resin filters.
This experiment was designed to study the release of cellulose acetate fibers, charcoal, and other particles from cigarettes with charcoal and activated charcoal/resin filters. For the first time in such studies, efforts were made to identify the particles that were eluted using other analytical techniques in addition to light microscopy. Other corrective measures were also implemented. During the studies it was found that trimming of larger filters to fit smaller filter housings introduced cellulose acetate-like particles from the fibers of the filter material. Special, custom made-to-fit filters were used instead. Tools such as forceps that were used to retrieve filters from their housings were also found to introduce fragments onto the filters. It is believed that introduction of such debris may have accounted for the very large number of cellulose acetate and charcoal particles that had been reported in the literature. Use of computerized particle-counting microscopes appeared to result in excessive number of particles. This could be because the filter or smoke pads used for such work do not have the flat and level surfaces ideal for computerized particle-counting microscopes. At the high magnifications that the pads were viewed for particles, constant focusing of the microscope would be essential. It was also found that determination of total particles by using extrapolation of particle count by grid population usually gave extremely high particle counts compared to the actual number of particles present. This could be because particle distributions during smoking are not uniform. Lastly, a less complex estimation of the thickness of the particles was adopted. This and the use of a simple mathematical conversion coupled with the Cox equation were utilized to assess the aerodynamic diameters of the particles. Our findings showed that compared to numbers quoted in the literature, only a small amount of charcoal, cellulose acetate shards, and other particles are released. It was also shown that those particles would have a low likelihood of reaching the lung.


Analysis of wastewater for anionic and cationic nutrients by ion chromatography in a single run with sequential flow injection analysis.
To prevent nutrient enrichment and, hence the undesirable ecological impacts, the nutrients monitored in wastewater samples include two anionic species, i.e., nitrate and orthophosphate, and a cationic species, ammonium. Ion chromatography (IC) is one of the popularly used techniques for determinations of nitrate and phosphate in these samples, whereas determination of ammonium in wastewater samples is typically done using manual or automated wet chemistry, e.g., flow injection analysis (FIA). We have developed a sequential IC-FIA method, using Lachat's QC8000 IC system, which allows determinations of nitrate, phosphate and ammonia in a single injection. In this system, a QuickChem Small Suppressor cartridge is regenerated in between the samples. A sample is injected while leaving the suppressor off-line. Ammonium, a cation, elutes in the void volume of an anion-exchange column. The unsuppressed column effluent, exiting the conductivity flow cell, up to this point is used for FIA determination of ammonia. When ammonia exits the conductivity flow cell, a fully regenerated suppressor is brought in-line for conductometric detection of the anions. Analog data are simultaneously acquired from colorimetric and conductometric detectors, for the cationic and anionic nutrients, respectively. The method is accurate with spike recoveries in wastewater samples ranging from 91% for nitrate to 114% for chloride. It is precise with RSD values, for replicate analyses (n = 7) of a mid-range standard, ranging from 0.4% for phosphate to 1% for nitrate.


[Mitral valve insufficiency in a 2.5-year-old girl as a result of endocarditis? A case report].
We present a case of a 2.5-year-old girl with a history recurrent pneumonia, followed by decreased physical capacity. Echocardiography showed severe (grade IV) mitral regurgitation with anterior leaflet perforation. The patient was selected for cardiac surgery. The possibility of endocarditis as a cause of mitral valve insufficiency is discussed.


Convex lens-induced confinement for imaging single molecules.
Fluorescence imaging is used to study the dynamics of a wide variety of single molecules in solution or attached to a surface. Two key challenges in this pursuit are (1) to image immobilized single molecules in the presence of a high level of fluorescent background and (2) to image freely diffusing single molecules for long times. Strategies that perform well by one measure often perform poorly by the other. Here, we present a simple modification to a wide-field fluorescence microscope that addresses both challenges and dramatically improves single-molecule imaging. The technique of convex lens-induced confinement (CLIC) restricts molecules to a wedge-shaped gap of nanoscale depth, formed between a plano-convex lens and a planar coverslip. The shallow depth of the imaging volume leads to 20-fold greater rejection of background fluorescence than is achieved with total internal reflection fluorescence (TIRF) imaging. Elimination of out-of-plane diffusion leads to an approximately 10,000-fold longer diffusion-limited observation time per molecule than is achieved with confocal fluorescence correlation spectroscopy. The CLIC system also provides a new means to determine molecular size. The CLIC system does not require any nanofabrication, nor any custom optics, electronics, or computer control.