Salmonella investigations in ruminants.
Trigger factors for Salmonella infections Salmonella Typhimurium DT104 updateControl measures for Salmonella in livestockPublic health considerations These issues are considered in this month's surveillance focus article, which has been prepared by Gareth Hateley, veterinary lead of the Cattle Expert Group, and Amanda Carson, veterinary lead of the Small Ruminant Expert Group, of the APHA Surveillance Intelligence Unit.


Cross-specialty developments: a summary of the mutually relevant recent literature from the journal of plastic, reconstructive and aesthetic surgery.
Keeping abreast of current developments is increasingly challenging when the volume of specialty articles being published is rising exponentially, and it is most acute when surgical specialties overlap, as in the case of head, neck, and facial reconstructive surgery. Here, the potential for missing key developments presents a compelling case for a summary article that highlights articles likely to be of mutual relevance. We evaluated 129 original studies and 6 reviews published in the Journal of Plastic, Reconstructive, and Aesthetic Surgery between September 2012 and August 2014, and summarised the main papers of interest and merit under the subheadings of head and neck reconstruction, cleft lip and palate, craniomaxillofacial surgery, facial palsy, facial trauma, and aesthetic surgery. Most of the evidence presented (86%) is level 4.


Laboratory evaluation of the Anyplex™ II MTB/MDR and MTB/XDR tests based on multiplex real-time PCR and melting-temperature analysis to identify Mycobacterium tuberculosis and drug resistance.
We evaluated the performance of two multiplex, real-time PCR tests (Anyplex II MTB/MDR and MTB/XDR; Seegene, Seoul, Korea), designed to detect the Mycobacterium tuberculosis complex (MTC) and drug-resistance mutations associated with isoniazid, rifampicin, fluoroquinolones, and second-line injectable drugs. We analyzed 122 clinical isolates with the Anyplex II MTB/MDR test, 68 of which were also tested with the Anyplex II MTB/XDR test. The Anyplex II MTB/MDR and MTB/XDR tests showed the following respective sensitivities and specificities: 68.8% and 100% for detecting isoniazid resistance, 93.8% and 100% for rifampicin, 82.8% and 100% for levofloxacin, 75.0% and 100% for kanamycin, and 92.6% and 100% for MTC identification. These kits correctly identified 61.8% of multi-drug resistant M. tuberculosis isolates and 64.7% of extensively drug-resistant M. tuberculosis isolates, and enabled semi-automatic detection of drug-resistant MTC in 3 hours. The Anyplex II kits could be useful as rule-in tests for detecting MTC and drug resistance.


Allergen immunotherapy practice in the United States: guidelines, measures, and outcomes.
To discuss recent issues pertinent to allergen immunotherapy practice in the United States. Allergen extract preparation guidelines, updated allergen immunotherapy practice parameter (AIPP) guidelines, and evolving trends in how immunotherapy outcomes will be measured and assessed. Allergen extract preparation guidelines have been established by 2 entities: the US Pharmacopeia and an American Academy of Allergy, Asthma, and Immunology/American College of Allergy, Asthma, and Immunology/Joint Council of Allergy, Asthma, and Immunology Joint Task Force. Minor differences exist between these guidelines, but both focus on aseptic techniques and require that compounding personnel pass a written examination and annual media fill test. The AIPP third update provides new dosing recommendations for Bermuda grass, imported fire ant, and nonstandardized extracts distinguishing between pollen (0.5 mL of a 1:100 or 1:200 vol/vol) and mold/fungi or cockroach (highest tolerated dose) extracts. Because of limited and sometimes conflicting data on high and low proteolytic-containing extract compatibility, the AIPP continues to recommend against mixing these together. Although the AIPP does not specifically recommend a specific diluent, recent evidence suggests normal saline may not be as effective a stabilizer for extract dilutions as glycerin or human serum albumin. Currently, immunotherapy efficacy is determined with subjective assessments that rely on patient reporting, but this may change as health care reform evolves. It will likely become more important for US allergy/immunology practices to demonstrate immunotherapy comparative-effectiveness and report quality measures. Recent comparative-effectiveness studies have demonstrated the cost-effectiveness of immunotherapy compared with symptomatic drug treatment.


Liposomes in ultrasonic drug and gene delivery.
Liposome-based drug and gene delivery systems have potential for significant roles in a variety of therapeutic applications. Recently, liposomes have been used to entrap gas and drugs for ultrasound-controlled drug release and ultrasound-enhanced drug delivery. Echogenic liposomes have been produced by different preparation methods, including lyophilization, pressurization, and biotin-avidin binding. Presently, significant in vivo applications of liposomal ultrasound-based drug and gene delivery are being made in cardiac disease, stroke and tumor therapy. Translation of these vehicles into the clinic will require a better understanding of improved physical properties to avoid rapid clearance, as well as of possible side effects, including those of the ultrasound. The aim of this review is to provide orientation for new researchers in the area of ultrasound-enhanced liposome drug and gene delivery.


Recovery of recurrent health service costs through provincial health funds in Cameroon.
This article describes the Provincial Health Funds pioneered in two Provinces of Cameroon. These funds are non-profit associations and financed by the community through drug fees and--to a lesser extent--through fees for services. The financial objective of the Funds is the full coverage of both the costs of the drug supply and the recurrent non-salary costs of the entire public health services in the province. In addition the funds are channels for community participation in the management and improvement of health services. Following a discussion of the institutional and legal framework, the paper examines the cost recovery targets and the mark-up necessary to achieve them. Comparison is made with mark-up and prices of private for-profit pharmacies. In its third year of operation, the Fund currently covers 62% of recurrent health service costs, up from 22% in the first year. With increasing number of health centers joining the fund full coverage of recurrent costs is projected to occur at the earliest in year four of operations. The authors argue that the appropriate role of donor assistance is not only to finance investment but also to subsidize recurrent costs, until the fund has reached its optimal anticipated size, thus realizing economies of scale. While the final word on sustainability can only be said years after the funds have reached their final size, the consistent trend towards full cost recovery is encouraging.


Observations on the mode of action of an intratubal device, the P-block.
A hydrogelic intratubal device, called P-block, Mark 9, was inserted hysteroscopically with local anesthesia in the intramural part of the fallopian tube of 25 women referred for the procedure as an alternative to abdominal sterilization. Hysterosalpingography revealing bilateral oviductal patency was followed by hysteroscopic checkup verifying bilateral presence of P-blocks, except in three patients who had expulsion of the P-blocks on one side. All of the 22 patients had retention of the P-blocks 6 to 7 months after insertion. None became pregnant. Thus it is suggested that an intratubal device in the isthmic part of the human fallopian tube acts as an intrauterine contraceptive device, preventing intratubal and intrauterine pregnancies. Endeavors to explain the contraceptive effect of a nonocclusive intratubal device are discussed on the basis of our present knowledge of tubal physiology. Distension of part of the human isthmus is likely to disturb normal gamete transport through the isthmus.


Single Cell Technologies Define New Therapeutic Avenues for Huntington's Disease.
Using two independent single-cell transcriptomics technologies, Lee et al. have cataloged transcriptional changes in the subset of striatal neurons hit hardest in Huntington's disease. One downregulated pathway, oxidative phosphorylation, may also explain their observed release of mitochondrial-encoded RNAs.


Parental self-efficacy and asthma self-management skills.
To determine whether a formal asthma self-management program and social support using lay health advisors increases parent self-efficacy in the management of their child's asthma, and whether parent self-efficacy predicts asthma self-management skills. Quasi-experimental with four time points measured over 2 years. Low-income, primarily Hispanic parents (N = 303) of children with moderately severe to severe asthma. A Southwestern university medical setting in a rural state. Parent self-efficacy and parent asthma self-management skill score scales. Parent self-efficacy increased significantly from baseline, but there were no significant differences between the control and treatment groups. The increase in self-efficacy was apparent at 6 months, then leveled off. Parent self-efficacy at either baseline or 12 months did not predict parents' asthma self-management skill score. Individual education was just as effective as group education in increasing parental self-efficacy. Parents felt more comfortable treating asthma episodes than preventing them, thus clinicians need to spend time teaching preventive strategies.


ATPase site architecture and helicase mechanism of an archaeal MCM.
The subunits of the presumptive replicative helicase of archaea and eukaryotes, the MCM complex, are members of the AAA+ (ATPase-associated with various cellular activities) family of ATPases. Proteins within this family harness the chemical energy of ATP hydrolysis to perform a broad range of cellular processes. Here, we investigate the function of the AAA+ site in the mini-chromosome maintenance (MCM) complex of the archaeon Sulfolobus solfataricus (SsoMCM). We find that SsoMCM has an unusual active-site architecture, with a unique blend of features previously found only in distinct families of AAA+ proteins. We additionally describe a series of mutant doping experiments to investigate the mechanistic basis of intersubunit coordination in the generation of helicase activity. Our results indicate that MCM can tolerate catalytically inactive subunits and still function as a helicase, leading us to propose a semisequential model for helicase activity of this complex.


Consistency of Artificial Intelligence (AI)-based Diagnostic Support Software in Short-term Digital Mammography Reimaging After Core Needle Biopsy.
To evaluate the consistency in the performance of Artificial Intelligence (AI)-based diagnostic support software in short-term digital mammography reimaging after core needle biopsy. Of 276 women who underwent short-term (<3 mo) serial digital mammograms followed by breast cancer surgery from Jan. to Dec. 2017, 550 breasts were included. All core needle biopsies for breast lesions were performed between serial exams. All mammography images were analyzed using a commercially available AI-based software providing an abnormality score (0-100). Demographic data for age, interval between serial exams, biopsy, and final diagnosis were compiled. Mammograms were reviewed for mammographic density and finding. Statistical analysis was performed to evaluate the distribution of variables according to biopsy and to test the interaction effects of variables with the difference in AI-based score according to biopsy. AI-based score of 550 exams (benign or normal in 263 and malignant in 287) showed significant difference between malignant and benign/normal exams (0.48 vs. 91.97 in first exam and 0.62 vs. 87.13 in second exam, P<0.0001). In comparison of serial exams, no significant difference was found in AI-based score. AI-based score difference between serial exams was significantly different according to biopsy performed or not (-0.25 vs. 0.07, P = 0.035). In linear regression analysis, there was no significant interaction effect of all clinical and mammographic characteristics with mammographic examinations performed after biopsy or not. The results from AI-based diagnostic support software for digital mammography was relatively consistent in short-term reimaging even after core needle biopsy.


Searching for unity in diversity of animal magnetoreception: From biology to quantum mechanics and back.
How animals sense the geomagnetic field remains a mystery today. A remarkable diversity has been revealed in animal magnetoreception and several sophisticated models have been put forward in the past few decades, but none have been commonly accepted yet. Cryptochrome (Cry) has been proposed in both the radical pair model and the MagR/Cry-based biocompass model. How exactly it participates in magnetic sensing is an ongoing discussion. Here we wish to suggest an intermolecular electron transport (ET) pathway conserved in evolution in the MagR/Cry complex, in which electrons travel stepwise along a flavin-tryptophan chain as described in the classic radical pair model, and further extends to iron-sulfur clusters in MagR via a series of stepping-stone amino acids as an ET bridge. The hypothesis we presented here may provide a solution to unite different models, and a feasible explanation for the intrinsic magnetic features of MagR, as well as a mechanism for signaling in animal magnetoreception, which are of considerable interest in both biology and physics.


Early course of Wallerian degeneration in myelinated fibres of the rat phrenic nerve.
A quantitative study of Wallerian degeneration was carried out on teased fibres. The breakdown into ovoids was used as the criterion of degeneration. The fragmentation of fibres begins near the point of nerve interrruption and spreads along the unbranched parts of axons at velocities correlated with fibre diameter and internodal length. The latent period, preceding the onset of fragmentation, lasts from 25.6 h in thin fibres to 45.0 h in the thickest fibres. The speed of the subsequent advance along the nerve varies correspondingly from 250 to 46 mm/day. In each internode the first ovoids appear in the middle, the ends of the internodal segment being initially spared. The spatiotemporal pattern of degeneration is consistent with the hypothesis that a neuronal trophic substance, normally ensuring the integrity of the axon, exerts transcellularly an inhibitory influence on the Schwann cell. This influence disappears when the amount or concentration of migrating trophic substances falls below a critical level in a stretch of axon. The overlying Schwann cells become mobile and exhibit intense metabolic activity, leading eventually to axonal disruption.


Predictors of treatment outcome in the behavioural treatment of obsessive-compulsive disorder.
An investigation to determine which prognostic variables are associated with behavioural treatment failure in obsessive-compulsive disorder (OCD). Empirically established prognostic variables measured at the start of treatment may lead to adjusted treatment programmes for these patients. Forty patients, diagnosed with OCD, received a standardised treatment consisting of 18 sessions in vivo exposure and response prevention. Compulsive behaviour (MOCI) and obsessive fear (ADS) were the outcome measures. Prognostic variables included were initial severity of OC complaints, initial level of depression, problem duration, patients' motivation for treatment, quality of the therapeutic relationship, and marital dissatisfaction. Greater initial severity of complaints (P < 0.01), and depression (P = 0.03) predicted poorer outcome for compulsive behaviour. Greater initial severity of complaints (P < 0.01), and the conjoint variables higher level of depression, longer problem duration, poorer motivation for treatment, and dissatisfaction with the therapeutic relationship predicted poorer outcome for obsessive fear (P < 0.01). The complaint-related variables of initial severity, initial depression, and problem duration, and the non-specific treatment variables of patients' motivation and quality of the therapeutic relationship, affect behavioural treatment outcome in OCD.


Misleading testicular masses.
Benign intrascrotal neoplasms of the testicle account for less than 10 per cent of all intrascrotal masses in postpubertal males. Radical inguinal orchiectomy is standard treatment for a firm, intratesticular mass. Of those patients so treated, 93 per cent of patients with this finding will have had the appropriate operation. There are misleading conditions, however, that can cause firm lesions in the testicle. There is a controversy over whether or not our current technology preoperatively can detect these benign lesions accurately. We encountered five different benign testicular masses within a twelve-month period. We present our findings and comments on some of the difficulties in dealing with these.


Catalytic and regulatory roles of divalent metal cations on the phosphoryl-transfer mechanism of ADP-dependent sugar kinases from hyperthermophilic archaea.
In some archaea, glucose degradation proceeds through a modified version of the Embden-Meyerhof pathway where glucose and fructose-6-P phosphorylation is carried out by kinases that use ADP as the phosphoryl donor. Unlike their ATP-dependent counterparts these enzymes have been reported as non-regulated. Based on the three dimensional structure determination of several ADP-dependent kinases they can be classified as members of the ribokinase superfamily. In this work, we have studied the role of divalent metal cations on the catalysis and regulation of ADP-dependent glucokinases and phosphofructokinase from hyperthermophilic archaea by means of initial velocity assays as well as molecular dynamics simulations. The results show that a divalent cation is strictly necessary for the activity of these enzymes and they strongly suggest that the true substrate is the metal-nucleotide complex. Also, these enzymes are promiscuous in relation to their metal usage where the only considerations for metal assisted catalysis seem to be related to the ionic radii and coordination geometry of the cations. Molecular dynamics simulations strongly suggest that this metal is bound to the highly conserved NXXE motif, which constitutes one of the signatures of the ribokinase superfamily. Although free ADP cannot act as a phosphoryl donor it still can bind to these enzymes with a reduced affinity, stressing the importance of the metal in the proper binding of the nucleotide at the active site. Also, data show that the binding of a second metal to these enzymes produces a complex with a reduced catalytic constant. On the basis of these findings and considering evolutionary information for the ribokinase superfamily, we propose that the regulatory metal acts by modulating the energy difference between the protein-substrates complex and the reaction transition state, which could constitute a general mechanism for the metal regulation of the enzymes that belong this superfamily.


Phosphodiesterase-5 expression and function in the lower urinary tract: a critical review.
Both clinical and preclinical studies have mostly shown beneficial effects for Phosphodiesterase-5 (PDE-5) inhibitors in the treatment of lower urinary tract symptoms. Molecular studies have consistently shown abundant PDE-5 expression in bladder smooth muscle. Data concerning urethral PDE-5 expression have been surprising because striated muscle was not only positively identified, but also found to express more PDE-5 than the smooth muscle. In the prostate, highly variable results have been obtained. For PDE-5 expression, the data have ranged from extremely low to highly abundant. PDE-5 has been found in the glandular epithelium, vascular smooth muscle, endothelium, and fibromuscular stroma.


Constraints on Sterile Neutrino Models from Strong Gravitational Lensing, Milky Way Satellites, and the Lyman-α Forest.
The nature of dark matter is one of the most important unsolved questions in science. Some darkf matter candidates do not have sufficient nongravitational interactions to be probed in laboratory or accelerator experiments. It is thus important to develop astrophysical probes which can constrain or lead to a discovery of such candidates. We illustrate this using state-of-the-art measurements of strong gravitationally lensed quasars to constrain four of the most popular sterile neutrino models, and also report the constraints for other independent methods that are comparable in procedure. First, we derive effective relations to describe the correspondence between the mass of a thermal relic warm dark matter particle and the mass of sterile neutrinos produced via Higgs decay and grand unified theory (GUT)-scale scenarios, in terms of large-scale structure and galaxy formation astrophysical effects. Second, we show that sterile neutrinos produced through the Higgs decay mechanism are allowed only for mass >26 keV, and GUT-scale scenario >5.3 keV. Third, we show that the single sterile neutrino model produced through active neutrino oscillations is allowed for mass >92 keV, and the three sterile neutrino minimal standard model (νMSM) for mass >16 keV. These are the most stringent experimental limits on these models.


Tissue culture on a chip: Developmental biology applications of self-organized capillary networks in microfluidic devices.
Organ culture systems are used to elucidate the mechanisms of pattern formation in developmental biology. Various organ culture techniques have been used, but the lack of microcirculation in such cultures impedes the long-term maintenance of larger tissues. Recent advances in microfluidic devices now enable us to utilize self-organized perfusable capillary networks in organ cultures. In this review, we will overview past approaches to organ culture and current technical advances in microfluidic devices, and discuss possible applications of microfluidics towards the study of developmental biology.


Comparison of in vitro susceptibilities of Bacteroides and Fusobacterium species in inland southern California to published patterns as a guide to empiric therapy.
Anaerobic bacteria, particularly the Bacteroides group, are becoming increasingly resistant to antimicrobials. Anaerobic susceptibility testing is often not done routinely in clinical laboratories, causing clinicians to depend on national survey results or susceptibility patterns published by different centers. In this study, we have determined anaerobic susceptibility patterns of 200 clinical isolates of anaerobic gram-negative bacilli from four hospitals in the inland countries of southern California (Inland Empire). Of 11 antibiotics tested, metronidazole and chloramphenicol were the most active, with no resistance noted, followed by imipenem, ticarcillin/clavulanate, and ampicillin/sulbactam. Among cephalosporins, cefoxitin was the most active and cefotetan the least. Significant differences in the susceptibility pattern to cefoxitin were observed in one hospital. Differences between our inland patterns and those for Los Angeles Wadsworth VA Hospital were seen for cefoxitin in the B fragilis group and piperacillin for B fragilis. We confirmed the National Committee for Clinical Laboratory Standards (NCCLS) recommendation for periodic determination of anaerobic susceptibility patterns. We also suggest that clinical laboratories routinely identify anaerobes to the species level to facilitate clinical application of in vitro results.


Tolerability and well-being with indapamide in the treatment of mild-moderate hypertension. An Italian multicenter study.
Since hypertension is an important risk factor of cardiovascular morbidity and mortality that can be at least in part decreased by pharmacologic reduction in elevated blood pressure, it is necessary that an antihypertensive agent be effective, but at the same time well tolerated and, according to some recent hypotheses, have no deleterious effect on serum electrolyte levels, as well as lipoprotein and glucose tolerance. However, due to different cultural and social backgrounds, lifestyles, and so on, the tolerability may differ from one population to another and the conclusions drawn from a population cannot be extrapolated to people of other countries. For these reasons, the well-being of patients, as well as the tolerability of indapamide, a non-thiazide diuretic, have been investigated in patients with hypertension of mild and moderate degree from different parts of Italy with a satisfactory blood-pressure response to this drug (-22.8 +/- 0.6/-17.1 +/- 0.5 mm Hg). Simultaneous to the significant blood-pressure reduction, the only significant change among the metabolic effects was a slight reduction in plasma potassium levels (-0.37 +/- 0.03 meq/liter). The tolerability was, on the whole, very good with a tendency toward an improvement of well-being in patients, the majority of whom were already asymptomatic before starting the treatment.


Visual computed tomographic scoring of emphysema and its correlation with its diagnostic electrocardiographic sign: the frontal P vector.
Verticalization of the frontal P vector in patients older than 45 years is virtually diagnostic of pulmonary emphysema (sensitivity, 96%; specificity, 87%). We investigated the correlation of P vector and the computed tomographic visual score of emphysema (VSE) in patients with established diagnosis of chronic obstructive pulmonary disease/emphysema. High-resolution computed tomographic scans of 26 patients with emphysema (age, >45 years) were reviewed to assess the type and extent of emphysema using the subjective visual scoring. Electrocardiograms were independently reviewed to determine the frontal P vector. The P vector and VSE were compared for statistical correlation. Both P vector and VSE were also directly compared with the forced expiratory volume at 1 second. The VSE and the orientation of the P vector (ÂP) had an overall significant positive correlation (r = +0.68; P = .0001) in all patients, but the correlation was very strong in patients with predominant lower-lobe emphysema (r = +0.88; P = .0004). Forced expiratory volume at 1 second and ÂP had almost a linear inverse correlation in predominant lower-lobe emphysema (r = -0.92; P < .0001). Orientation of the P vector positively correlates with visually scored emphysema. Both ÂP and VSE are strong reflectors of qualitative lung function in patients with predominant lower-lobe emphysema. A combination of more vertical ÂP and predominant lower-lobe emphysema reflects severe obstructive lung dysfunction.


Overexpression of the CDC25 gene, an upstream element of the RAS/adenylyl cyclase pathway in Saccharomyces cerevisiae, allows immunological identification and characterization of its gene product.
The product of the START gene CDC25, an upstream element of the RAS/adenylyl cyclase pathway in Saccharomyces cerevisiae, was identified using specific antibodies raised against a chimeric beta-galactosidase/CDC25 protein. The CDC25 protein is poorly expressed and can be detected only when the CDC25 gene is overexpressed under the control of the galactose-inducible GAL1-10 strong promoter elements. It has a molecular weight of 180,000, is not glycosylated and is strongly associated with the particulate fraction. After deletion of residues 1255-1550 the protein is found in the soluble fraction.


Inhibition of the 5-lipoxygenase pathway with piriprost (U-60,257) protects normal primates from ozone-induced methacholine hyperresponsive small airways.
Weekly exposure to ozone in seven normal Rhesus monkeys led to induction of methacholine hypersensitive airways (RL increases 242 +/- 60% and Cdyn decreases 68 +/- 13% of baseline methacholine responses). It took 19 weeks to establish this hyperresponse that persisted for greater than 15 weeks once ozone was stopped. A second exposure led to similar response peaks in 6 weeks. At the peak of the second response, weekly 1% piriprost exposure before ozone led to a return to baseline that was not different between placebo and piriprost treated animals (9.4 +/- 1.0 and 4.3 +/- 2.9 weeks, placebo and treated, respectively P = 0.09 NS). A statistical difference in the mecholyl response in placebo and piriprost treated groups while on ozone was shown only in the Cdyn measurement (Cdyn% change 68 +/- 13 vs 24 +/- 14, placebo and piriprost, respectively P = 0.03). Off ozone (or return to baseline), a statistical difference could be detected both in RL and Cdyn (RL% changed 151 +/- 41 vs 31.1 +/- 49, P = 0.03, and for Cdyn 62.7 +/- 8 vs 9 +/- 10, P = 0.0006, placebo and piriprost, respectively). We conclude tha the primate provides a chronic model of airways reactivity in which the role of lipoxygenase is implicated because of the beneficial role of piriprost, and further that the ozone lesion is primarily in the smaller airways (possibly and alveolitis).


Long-term survival of patients with stage II and III gastric cancer who underwent gastrectomy with inadequate nodal assessment.
Gastric cancer is an aggressive disease with frequent lymph node (LN) involvement. The NCCN recommends a D2 lymphadenectomy and the harvesting of at least 16 LNs. This threshold has been the subject of great debate, not only for the extent of surgery but also for more appropriate staging. The reclassification of stage IIB through IIIC based on N3b nodal staging in the eighth edition of the American Joint Committee on Cancer (AJCC) staging system highlights the efforts to more accurately discriminate survival expectancy based on nodal number. Furthermore, studies have suggested that pathologic assessment of 30 or more LNs improve prognostic accuracy and is required for proper staging of gastric cancer. To evaluate the long-term survival of advanced gastric cancer patients who deviated from expected survival curves because of inadequate nodal evaluation. Eligible patients were identified from the Surveillance, Epidemiology, and End Results database. Those with stage II-III gastric cancer were considered for inclusion. Three groups were compared based on the number of analyzed LNs. They were inadequate LN assessment (ILA, < 16 LNs), adequate LN assessment (ALA, 16-29 LNs), and optimal LN assessment (OLA, ≥ 30 LNs). The main outcomes were overall survival (OS) and cancer-specific survival. Data were analyzed by the Kaplan-Meier product-limit method, log-rank test, hazard risk, and Cox proportional univariate and multivariate models. Propensity score matching (PSM) was used to compare the ALA and OLA groups. The analysis included 11607 patients. Most had advanced T stages (T3 = 48%; T4 = 42%). The pathological AJCC stage distribution was IIA = 22%, IIB = 18%, IIIA = 26%, IIIB = 22%, and IIIC = 12%. The overall sample divided by the study objective included ILA (50%), ALA (35%), and OLA (15%). Median OS was 24 mo for the ILA group, 29 mo for the ALA group, and 34 mo for the OLA group (P < 0.001). Univariate analysis showed that the ALA and OLA groups had better OS than the ILA group [ALA hazard ratio (HR) = 0.84, 95% confidence interval (CI): 0.79-0.88, P < 0.001 and OLA HR = 0.73, 95%CI: 0.68-0.79, P < 0.001]. The OS outcome was confirmed by multivariate analysis (ALA HR = 0.68, 95%CI: 0.64-0.71, P < 0.001 and OLA: HR = 0.48, 95%CI: 0.44-0.52, P < 0.001). A 1:1 PSM analysis in 3428 patients found that the OLA group had better survival than the ALA group (OS: OLA median = 34 mo vs ALA median = 26 mo, P < 0.001, which was confirmed by univariate analysis (HR = 0.81, 95%CI: 0.75-0.89, P < 0.001) and multivariate analysis: (HR = 0.71, 95%CI: 0.65-0.78, P < 0.001). Proper nodal staging is a critical issue in gastric cancer. Assessment of an inadequate number of LNs places patients at high risk of adverse long-term survival outcomes.


Paraventricular nucleus projections mediating pineal melatonin and gonadal responses to photoperiod in the hamster.
Knife cuts were placed around the paraventricular nucleus of the hypothalamus (PVN) in order to identify the pathways mediating photoperiodism and pineal melatonin production in male golden hamsters. Cuts in the coronal plane caudal to the PVN, have no effect on photoperiodic control of the testes unless they actually damage the PVN. Bilateral parasagittal cuts at the medial border of the lateral hypothalamus block short photoperiod-induced gonadal regression. Nighttime levels of pineal melatonin are reduced by these cuts, but unaffected by caudal cuts. Projections from the lateral PVN region descending towards the spinal cord appear to be critical for the control of pineal melatonin production and the control of the testicular function by short photoperiod.


Extranodal non-Hodgkin's lymphoma of the head and neck.
Forty-six patients referred to our department between 1970 and 1982 with biopsy proven extranodal non-Hodgkin's lymphoma (NHL) of the head and neck were analysed. The median follow-up was 78 months. As a result of histological revision, six cases were excluded. By retrospective staging, 10 patients were found to have advanced disease (stage IV) at the moment of presentation, and three showed infradiaphragmatical nodes (stage III). All stage I-II patients except one were treated with radiotherapy. The 5-year actuarial relapse-free survival was 50% for the whole group, and 77% for the 26 patients who achieved complete remission after initial treatment. All stage IV patients died from lymphoma. Initial response and localised disease were the most significant prognostic features.


[Scanning electron microscopy of microbes and their mechanism of attachment to human small intestinal mucosa].
In connection with the electron-microscopy of bioptic material from the upper small intestine of children with intestinal diseases and diarrhea (10 months to 8 years) we found some cases of fungus infection (26%) besides many cases of bacterial attachment to the intestinal epithelium (72%). On the intestinal wall normal yeasts, pseudomycelium and common mycelium are visible. Partly the epithelium was entirely covered with mycelium. In some cases the hyphae invaded in the intestinal wall. The epithelium and the villi are not or only slightly altered. This gives the reason to believe that the fungi participate in inducing diarrhea. After medicamentous treatment with nystatine-preparations in some cases the health state of these children was improved.


Effect of benzo[a]pyrene on the expression of miR-126, miR-190a and their target genes EGFL7, TP53INP1 and PHLPP1 in primary endometrial cells.
The main topic of this study was to investigate the effect of benzo[a]pyrene (BP) on microRNAs and their target genes expression levels in primary cell cultures from normal and malignant endometrial tissue. MicroRNA-126 (miR-126) and miR-190a were most sensitive to BP treatment. The treatment of both cultures with BP was accompanied by a decrease of miR-126 level and an increase of EGFL7 gene expression level. BP-induced upregulation of miR-190a was detected only in normal cells and it was accompanied with decrease of mRNA levels of TP53INP1 and PHLPP1 genes. Taking into account that BP promoted the proliferation of normal cells and amplified apoptosis of cancer cells, it is possible that miR-190a is involved in general cellular response to BP. The findings of this study indicate that miR-190a and its target genes may be involved in the regulation of cell fate under BP treatment.


Rapid quantification of the aminoglycoside arbekacin in serum using high performance liquid chromatography-tandem mass spectrometry.
This project entails the development and validation of a method for quantification of the aminoglycoside antibiotic arbekacin in serum using liquid chromatography tandem mass spectrometry (LC-MS/MS) for therapeutic drug monitoring in future clinical trials. Following a protein precipitation with 0.3 mol/l perchloric acid containing internal standard dibekacin at a concentration of 0.6 μg/ml, human serum samples containing arbekacin were analyzed using a Hypersil Gold PFP column and a liquid chromatography system. Elution occurred with a gradient of water and acetonitrile, each containing 0.05% (v/v) trifluoroacetic acid and 0.1% (v/v) formic acid. Analytes were detected over a 3.25 minute run time using a tandem mass spectrometer with a heated electrospray-ionization (HESI) source in positive ionization mode with selected reaction monitoring (SRM). Matrix effects, carryover, linearity, recovery, precision, and limit of quantification were carefully evaluated. The limit of quantification for arbekacin was 0.1 μg/ml. All simple and total precision CV's were less than 6.2%. The method was linear from 0.1 μg/ml to 45.9 μg/ml (slope of 0.973). The mean recovery ranged from 94.7 to 103.8%. No matrix effects were detected. This developed and validated LC-MS/MS method allows for the quantification of arbekacin in serum following protein precipitation.


Chiral-phase high-performance liquid chromatography of rotenoid racemates.
The high-performance liquid chromatographic (HPLC) behavior of parent rotenoids (type I) and the hydroxy-analogues (type II) on three different chiral stationary phases (CSPs) was studied. Separations of optical isomers were achieved in various degrees depending largely upon the rotenoidal structures and the CSP types employed. Enantiomers of all but elliptone compounds were separable on beta-cyclodextrin-bonded silica (CDS). Without exception, the 12a-hydroxyrotenoid antipodes were resolved on Pirkle's phenylglycine-bonded silica (PGS) despite unsuccessful attempts to resolve the type I rotenoidal racemates. Conversely, optical resolution of the latter rotenoids was accomplished by using a helical polytriphenylmethylacrylate-coated silica (TPS) column and the observed separation factors (alpha values) ranged from 1.14 to 1.90. The results from HPLC of type II rotenoids on TPS (alpha = 1.00-1.63) suggested that variations in E-ring structures had profound influence on the resolution outcome. Conjugated double bonds on the E-ring and the desisopropylation of the five-membered E-ring of type II rotenoids appeared to be important structural features for chiral recognition involving the TPS substrate. In both reversed-phase (CDS) and normal-phase (PGS and TPS) HPLC modes, the less polar enantiomers were the 6a beta,12a beta-rotenoids as observed in most cases, though this relationship was reversed in the cases of deguelin and hydroxyelliptone probably due to conformational effects of rotenoidal ring systems.


[Changes in synovial fluid in different knee-joint diseases].
To analyse the changes in synovial fluid (SF) in the most common knees joint diseases, and to establish a relationship according to its concentration. A total of 62 synovial fluids were analysed from knees with, meniscus disease (32), anterior cruciate ligament (ACL) (17) and isolated chondral injury (13). A quantitative and quality study was performed on each sample, which included cytokines IL-1, IL-2, IL-6, IL-10, TNF-α, and growth factors, IGF-1 and TGF-ß). The SF environment in the ACL injury was mainly anabolic and inflammatory, with increased levels of IL1, IL6, significant levels of TGF-ß (P=.02 and P=.004), IL-10 (P=.046 and P=.047) and significantly decreased levels of TNF-α (P=.02 and P=.004). There was mainly a catabolic environment in chondral and meniscal disease, with a significant increase in TNF-α and a significant decrease in TGF-ß (P=.02 and P=.004). The differences were greater in the case of isolated chondral injury. The changes observed show that, as well as the biomechanical changes, the SF has a negative effect on joint homeostasis, it composition varying depending on the type of pathology.


Speciation of Cr(III) and Cr(VI) in environmental samples determined by selective separation and preconcentration on silica gel chemically modified with niobium(V) oxide.
In this study a new method for chromium speciation in water using solid phase extraction coupled to a flow injection system and flame atomic absorption spectrometry was developed. The adsorption behavior of Cr(III) and Cr(VI) on Nb2O5-SiO2 allowed the selective separation of Cr(III) from Cr(VI) in the pH range of 6-9. Thus, a method for Cr(III) preconcentration and extraction using Nb2O5-SiO2 was developed. Total chromium was determined after the reduction of Cr(VI) to Cr(III) using sodium sulfite in acidic medium. The operational variables of the preconcentration and reduction procedures were optimized through full factorial and Doehlert designs. The limit of detection for Cr(III) was 0.34microgL(-1) and the precision was below 4.6%. Results for recovery tests using different environmental samples were between 90 and 105%. Certified reference materials (NIST 1640 and NIST 1643e) were analyzed in order to check the accuracy of the proposed method, and the results were in agreement with the certified values.


Human leukocyte antigens in cutaneous T cell lymphoma.
Mycosis fungoides (MF) and Sézary syndrome (SS) are malignant non-Hodgkin's lymphomas, characterized by the proliferation of helper type T lymphocytes with a predilection for the skin. Because of the similarities in cytologic, histologic, cytogenetic, immunologic, and functional aspects of the malignant cells, as well as overlapping clinical features, these disorders are currently classified as cutaneous T cell lymphoma (CTCL). Though the etiology of these disorders remains obscure, environmental factors as well as viral infection have been implicated. In this study, seventy-six white patients with CTCL were typed for human leukocyte antigen (HLA)-A, -B, and -C to assess genetic susceptibility as determined by the major histocompatibility complex. An increase in the frequency of B8 and Bw35 was seen in SS patients but not in MF patients.


Anammox reactor exposure to thiocyanate: Long-term performance and microbial community dynamics.
Anaerobic ammonium oxidation (anammox) is an autotrophic denitrification process that has broad application potential for treating coking wastewaters. The present study estimated the effects of thiocyanate (SCN-), a common pollutant in coking wastewaters, on anammox processes and microbial communities in anammox reactors for over two years of continuous exposure. The addition of SCN- (from 50 to 200 mg L-1) showed negative effects on the denitrification performance of the anammox reactors. In SCN--dosed reactors, increased effluent ammonium concentrations indicated the occurrence of SCN--based biodegradation processes. Microbial analysis revealed that the anammox species almost disappeared in the reactor dosed with SCN- at over 100 mg L-1. Instead, an abundance of chemolithoautotrophic bacteria belonging to the Thiobacillus genus demonstrated a linear increase with SCN- addition. The competition between anammox species and SCN--degrading microorganisms was expected to dominate the inhibition effects of SCN- addition on the performance of anammox reactors.


Primitive reflexes in healthy, adult volunteers and neurological patients: methodological issues.
A study was made to determine whether two experienced clinicians elicited and scored primitive reflexes (PR) differently and whether reliability could be improved by standardization. Three studies were carried out, using a protocol for the examination of 14 PR. In the first study with 31 healthy young subjects, two investigators found virtually no difference in the routine neurological examination. However, the interobserver agreement was very poor, indicating the need for a further improvement of the PR protocol. In the second study, 30 neurological patients were examined with an improved, more explicit and standardized protocol, in which the amplitude and the persistence of the reflex were scored separately. Interobserver agreement improved considerably, and was high for amplitude as well as persistence. In the third study, 36 neurological patients were examined twice by one investigator within 2 weeks. Good to excellent intraobserver agreement was found. No pathognomonic or strictly localizing reflex could be distinguished.


A novel fexA variant from a canine Staphylococcus pseudintermedius isolate that does not confer florfenicol resistance.
Transposon Tn558 integrated in the chromosomal radC gene was detected for the first time in Staphylococus pseudintermedius. It carried a novel fexA variant (fexAv) that confers only chloramphenicol resistance. The exporter FexAv exhibited two amino acid substitutions, Gly33Ala and Ala37Val, both of which seem to be important for substrate recognition. Site-directed mutagenesis that reverted the mutated base pairs to those present in the original fexA gene restored the chloramphenicol-plus-florfenicol resistance phenotype.


A Kohonen neural network description of scoliosis fused regions and their corresponding Lenke classification.
Surgical instrumentation for adolescent idiopathic scoliosis (AIS) is a complex procedure where selection of the appropriate curve segment to fuse, i.e., fusion region, is a challenging decision in scoliosis surgery. Currently, the Lenke classification model is used for fusion region evaluation and surgical planning. Retrospective evaluation of Lenke classification and fusion region results was performed. Using a database of 1,776 surgically treated AIS cases, we investigated a topologically ordered self organizing Kohonen network, trained using Cobb angle measurements, to determine the relationship between the Lenke class and the fusion region selection. Specifically, the purpose was twofold (1) produce two spatially matched maps, one of Lenke classes and the other of fusion regions, and (2) associate these two maps to determine where the Lenke classes correlate with the fused spine regions. Topologically ordered maps obtained using a multi-center database of surgically treated AIS cases, show that the recommended fusion region agrees with the Lenke class except near boundaries between Lenke map classes. Overall agreement was 88%. The Lenke classification and fusion region agree in the majority of adolescent idiopathic scoliosis when reviewed retrospectively. The results indicate the need for spinal fixation instrumentation variation associated with the Lenke classification.


Characterization of Desulfomicrobium salsuginis sp. nov. and Desulfomicrobium aestuarii sp. nov., two new sulfate-reducing bacteria isolated from the Adour estuary (French Atlantic coast) with specific mercury methylation potentials.
Three strains of sulfate-reducing bacteria (ADR21, ADR26 and ADR28) were isolated from Adour estuary sediments (French South Atlantic coast). Cells of these isolates were rod-shaped, motile and stained Gram-negative. The 16S rRNA and dsrAB genes sequence analyses indicated that these three strains belonged to the genus Desulfomicrobium within the delta Proteobacteria, with Desulfomicrobium escambiense strain DSM10707T as their closest relative. According to phenotypic characteristics, strains ADR21 and ADR28 could be considered as members of the same species. The relatedness values, based on DNA-DNA hybridization studies, between strains ADR21/DSM10707T, ADR26/DSM10707T and ADR21/ADR26 ranged between 30.6-40.8%, 45.2-43.0% and 19.0-26.4%, respectively. Strains ADR21 and ADR28 grew well on lactate, fumarate, malate, formate, ethanol and H2/acetate in the presence of sulfate as an electron acceptor. Thiosulfate, nitrate, fumarate and DMSO were alternative electron acceptors. Malate was well fermented but pyruvate and fumarate only poorly. Strain ADR26 could not grow on ethanol or fumarate and was unable to use DMSO or fumarate as electron acceptors. The three new strains exhibited differences compared to the type strain of D. escambiense, such as temperature optima, substrate utilization and mercury methylation capacities. On the basis of both genetic and phenotypic evidences, strain ADR21 is proposed as the type strain of the species Desulfomicrobium salsuginis sp. nov., and strain ADR26 as the type strain of the species Desulfomicrobium aestuarii sp. nov.