A LAMP point-of-care test to guide antimicrobial choice for treatment of Staphylococcus pseudintermedius pyoderma in dogs.

Staphylococcus pseudintermedius is the most common cause of pyoderma in dogs. We validated a point-of-care (PoC) test based on colorimetric loop-mediated isothermal amplification (LAMP) for rapid S. pseudintermedius identification and susceptibility testing for first line antimicrobials for systemic treatment of canine pyoderma, i.e., lincosamides, first generation cephalosporins and amoxicillin clavulanate. Newly designed LAMP primers targeting clinically relevant resistance genes were combined with a previously validated set of primers targeting spsL for species identification. After laboratory validation on 110 clinical isolates, we assessed the performance of the test on 101 clinical specimens using routine culture and susceptibility testing as a reference standard. The average hands-on and turnaround times for the PoC test were 30 and 90 min, respectively. The assay showed sensitivity and specificity near 100% for both species identification and susceptibility testing when performed on bacterial cultures or clinical specimens in the laboratory. However, the PoC test yielded less accurate results when performed on-site by clinical staff (92% sensitivity and 64% specificity for species identification, 67% sensitivity and 96% specificity for ß-lactam susceptibility, and 83% sensitivity and 71% specificity for lincosamide susceptibility). These results indicate that the PoC test should be adapted to a user-friendly technology to facilitate performance and interpretation of results by clinical staff. If properly developed, the test would allow veterinarians to gain rapid information on antimicrobial choice, limiting the risk of treatment failure and facilitating adherence to antimicrobial use guidelines in small animal veterinary dermatology.

Working memory and processing speed abilities are related to habituation and change detection in school-aged children: An ERP study.

High cognitive performance is related to efficient brain processing while accomplishing complex cognitive tasks. This efficiency is observed through a rapid engagement of the brain regions and the cognitive processes required for task accomplishment. However, it is unclear if this efficiency is also present in basic sensory processes such as habituation and change detection. We recorded EEG with 85 healthy children (51 males) aged between 4 and 13 years old, while they listened to an auditory oddball paradigm. Cognitive functioning was evaluated using the Weschler Intelligence Scales for Children Fifth Edition and the Weschler Preschool & Primary School for Intelligence Fourth Edition. Auditory evoked potentials (AEPs) analyses and repeated measure analysis of covariance as well as regression models were performed. The analysis revealed that P1 and N1 repetition effects were observed across levels of cognitive functioning. Further, working memory abilities were related to repetition suppression on the auditory P2 component amplitude, while faster processing speed was related to repetition enhancement on the N2 component amplitude. Also, Late Discriminative Negativity (LDN) amplitude, a neural correlate of change detection, increased with working memory abilities. Our results confirm that efficient repetition suppression (i.e. greater reduction in amplitudes with greater levels of cognitive functioning) and more sensitive change detection (greater amplitude changes of the LDN) are related to the level of cognitive functioning in healthy children. More specifically, working memory and processing speed abilities are the cognitive domains related to efficient sensory habituation and change detection.

Spondylodiscitis via enterospinal fistula after promontofixation.

Spondylodiscitis on enterospinal fistula after promontofixation. A case report and other spondylodiscitis etiologies.

Pollutant Pb burden in Mediterranean Centroscymnus coelolepis deep-sea sharks.

We report lead (Pb) analyses in juvenile (n = 37; mean length = 24.7 ±â€¯2.3 cm) and adult (n = 16; mean length = 52.3 ±â€¯9.3 cm) Centroscymnus coelolepis Mediterranean deep-sea sharks that are compared to Pb content in bathy-demersal, pelagic and shallow coastal sharks. Median Pb concentrations of C. coelolepis muscle (0.009-0.056 wet ppm) and liver (0.023-0.061 wet ppm) are among the lowest encountered in shark records. Stable Pb isotope imprints in adult C. coelolepis muscles highlight that most of Pb in C. coelolepis is from human origin. Lead isotopes reveal the persistence of gasoline Pb emitted in the 1970s in low-turnover adult shark's muscle while associated liver imprints are in equilibrium with recent pollutant Pb signatures suggesting an efficient pollutant Pb turnover metabolism. The comparison of Pb distribution between adult and juvenile cohorts suggests the role of dietary exposure and possible maternal offloading of Pb during gestation, likely associated to vitellogenesis in this aplacental viviparous deep-sea shark.

Early small bowel obstruction in laparoscopic Roux-en-Y gastric bypass.

Alimentary limb kinking after laparoscopic Roux-en-Y gastric bypass suggested by CT-scan and diagnosed at laparoscopic surgery. Surgical treatment principles.

Validation of the Seegene RV15 multiplex PCR for the detection of influenza A subtypes and influenza B lineages during national influenza surveillance in hospitalized adults.

Background. The Serious Outcomes Surveillance Network of the Canadian Immunization Research Network (CIRN SOS) has been performing active influenza surveillance since 2009 (ClinicalTrials.gov identifier: NCT01517191). Influenza A and B viruses are identified and characterized using real-time reverse-transcriptase polymerase chain reaction (RT-PCR), and multiplex testing has been performed on a subset of patients to identify other respiratory virus aetiologies. Since both methods can identify influenza A and B, a direct comparison was performed.Methods. Validated real-time RT-PCRs from the World Health Organization (WHO) to identify influenza A and B viruses, characterize influenza A viruses into the H1N1 or H3N2 subtypes and describe influenza B viruses belonging to the Yamagata or Victoria lineages. In a subset of patients, the Seeplex RV15 One-Step ACE Detection assay (RV15) kit was also used for the detection of other respiratory viruses.Results. In total, 1111 nasopharyngeal swabs were tested by RV15 and real-time RT-PCRs for influenza A and B identification and characterization. For influenza A, RV15 showed 98.0 % sensitivity, 100 % specificity and 99.7 % accuracy. The performance characteristics of RV15 were similar for influenza A subtypes H1N1 and H3N2. For influenza B, RV15 had 99.2 % sensitivity, 100 % specificity and 99.8 % accuracy, with similar assay performance being shown for both the Yamagata and Victoria lineages.Conclusions. Overall, the detection of circulating subtypes of influenza A and lineages of influenza B by RV15 was similar to detection by real-time RT-PCR. Multiplex testing with RV15 allows for a more comprehensive respiratory virus surveillance in hospitalized adults, without significantly compromising the reliability of influenza A or B virus detection.

[Urinary catheters prevalence study in a university hospital]. / Enquête de prévalence sur le sondage vésical dans un centre hospitalo-universitaire.

INTRODUCTION: Urinary tract infection is the most common healthcare-association infection, especially because of urinary catheter. We evaluated our practices concerning catheter insertion and management in our institution. MATERIALS AND METHODS: We conducted a single-centre descriptive cross-sectional study during 1 week in September 2014 in all adult departments. We noted prevalence, indications, length, management of urinary catheter (UC) and symptomatic catheter-associated urinary tract infections (SCAUTI). RESULTS: Amongst 1046 patients audited, 125 (12%) had UC. The mean age was 72 years (64.8-79.2). UC prevalence was higher in surgical (88%) and medical (87%) intensive care, urology (50%), geriatrics (18%) and long-term care (18%) departments. The average catheterisation length was 7.8 days (3.8-11.8); it was shorter in surgery than in medicine departments (3.6 vs 9.7 days, P<0.001). Catheters were present for more than 4 days in 60% of the cases. Acute urinary retention was the most frequent indication (59%), significantly more in medical than surgical departments (75% vs 26%). Others indications were perioperative (17%), diuresis monitoring (12%), strict immobilization (4%) and unnecessary indications or staff comfort (4%). A SCAUTI was present in 10% of cases, mostly in medicine department (30% vs 8%). CONCLUSION: The prevalence of our institution is higher than the national prevalence (8.1%), but still below the European average (17.2%). Control of the risk of CAUTI requires compliance with UC appropriate indications, UC management, and prompt removal of unnecessary UC. LEVEL OF EVIDENCE: 4.

Intraspinal microstimulation and diaphragm activation after cervical spinal cord injury.

Intraspinal microstimulation (ISMS) using implanted electrodes can evoke locomotor movements after spinal cord injury (SCI) but has not been explored in the context of respiratory motor output. An advantage over epidural and direct muscle stimulation is the potential of ISMS to selectively stimulate components of the spinal respiratory network. The present study tested the hypothesis that medullary respiratory activity could be used to trigger midcervical ISMS and diaphragm motor unit activation in rats with cervical SCI. Studies were conducted after acute (hours) and subacute (5-21 days) C2 hemisection (C2Hx) injury in adult rats. Inspiratory bursting in the genioglossus (tongue) muscle was used to trigger a 250-ms train stimulus (100 Hz, 100-200 µA) to the ventral C4 spinal cord, targeting the phrenic motor nucleus. After both acute and subacute injury, genioglossus EMG activity effectively triggered ISMS and activated diaphragm motor units during the inspiratory phase. The ISMS paradigm also evoked short-term potentiation of spontaneous inspiratory activity in the previously paralyzed hemidiaphragm (i.e., bursting persisting beyond the stimulus period) in ∼70% of the C2Hx animals. We conclude that medullary inspiratory output can be used to trigger cervical ISMS and diaphragm activity after SCI. Further refinement of this method may enable "closed-loop-like" ISMS approaches to sustain ventilation after severe SCI.NEW & NOTEWORTHY We examined the feasibility of using intraspinal microstimulation (ISMS) of the cervical spinal cord to evoke diaphragm activity ipsilateral to acute and subacute hemisection of the upper cervical spinal cord of the rat. This proof-of-concept study demonstrated the efficacy of diaphragm activation, using an upper airway respiratory EMG signal to trigger ISMS at the level of the ipsilesional phrenic nucleus during acute and advanced postinjury intervals.

The Impact of Breakthrough Therapy Designation on Development Strategies and Timelines for Nononcology Drugs and Vaccines.

The US Food and Drug Administration (FDA) Safety and Innovation Act (FDASIA, 2012) introduced the Breakthrough Therapy Designation (BTD), a new tool to expedite development of medicines to treat serious or life-threatening diseases. The majority of BTDs have gone to oncology drugs, and a recent publication by Shea et al.1 reviewed the impact of BTD on oncology drug development. This article reviews the impact of BTD on development strategies and timelines for nononcology drugs.

An event-based hydrologic simulation model for bioretention systems.

Bioretention systems are designed to treat stormwater and provide attenuated drainage between storms. Bioretention has shown great potential at reducing the volume and improving the quality of stormwater. This study introduces the bioretention hydrologic model (BHM), a one-dimensional model that simulates the hydrologic response of a bioretention system over the duration of a storm event. BHM is based on the RECARGA model, but has been adapted for improved accuracy and integration of pollutant transport models. BHM contains four completely-mixed layers and accounts for evapotranspiration, overflow, exfiltration to native soils and underdrain discharge. Model results were evaluated against field data collected over 10 storm events. Simulated flows were particularly sensitive to antecedent water content and drainage parameters of bioretention soils, which were calibrated through an optimisation algorithm. Temporal disparity was observed between simulated and measured flows, which was attributed to preferential flow paths formed within the soil matrix of the field system. Modelling results suggest that soil water storage is the most important short-term hydrologic process in bioretention, with exfiltration having the potential to be significant in native soils with sufficient permeability.

Closing the drug lag for new drug submission and review in Japan: An industry perspective.

Previous publications have focused on drug lag in Japan and the government's initiatives to address the situation.(1) Japan is the third largest pharmaceutical market, and yet has experienced significant drug lag for many years. This article reviews the progress resulting from industry adaptation of new regulatory paradigms that include Japan in global drug development programs.

Partial depletion of the proinflammatory monocyte population is neuroprotective in the myenteric plexus but not in the basal ganglia in a MPTP mouse model of Parkinson's disease.

Parkinson's disease (PD) patients often suffer from gastrointestinal (GI) impairments that are associated with the alteration of dopaminergic (DAergic) neurons in the myenteric nervous system. Growing evidence suggests that inflammation originating from the gut may have a major impact in both the initiation and progression of PD. Here, we investigated the role of the innate immune response in neurodegeneration occurring in central nervous system (CNS) and enteric nervous system (ENS) in response to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a neurotoxin that produces Parkinsonism in both humans and animal models. We found a strong immune response in the gut of mice treated with MPTP, as demonstrated by the prominent presence of macrophages derived from CD115(+) CD11b(+) Ly6C(Hi) monocytes, known as M1 monocytes, and increased production of IL-1ß and IL-6. Partial depletion of proinflammatory M1 monocytes through intravenous injections of clodronate-encapsulated liposome protects against MPTP-induced reduction of tyrosine hydroxylase (TH) expression in the ENS. In contrast, loss of striatal TH expression in the CNS after MPTP intoxication occurs regardless of partial monocyte depletion. Examination of brain tissue revealed that microglial activation, comprising the majority of the immune response in the CNS after MPTP injections is unaffected by M1 depletion. In vitro experiments revealed that MPTP and MPP(+) act directly on monocytes to elicit a proinflammatory response that is, in part, dependent on the MyD88/NF-κB signaling pathway resulting in nitrite and proinflammatory cytokine production. Taken together, our results demonstrate a critical role for proinflammatory M1 monocytes/macrophages in DAergic alterations occurring in the GI, but not in the brain, in the MPTP model of PD.

ITC recommendations for transporter kinetic parameter estimation and translational modeling of transport-mediated PK and DDIs in humans.

This white paper provides a critical analysis of methods for estimating transporter kinetics and recommendations on proper parameter calculation in various experimental systems. Rational interpretation of transporter-knockout animal findings and application of static and dynamic physiologically based modeling approaches for prediction of human transporter-mediated pharmacokinetics and drug-drug interactions (DDIs) are presented. The objective is to provide appropriate guidance for the use of in vitro, in vivo, and modeling tools in translational transporter science.

Transporter studies in drug development: experience to date and follow-up on decision trees from the International Transporter Consortium.

The International Transporter Consortium (ITC) organized a second workshop in March 2012 to expand on the themes developed during the inaugural ITC workshop held in 2008. The final session of the workshop provided perspectives from regulatory and industry-based scientists, with input from academic scientists, and focused primarily on the decision trees published from the first workshop. These decision trees have become a central part of subsequent regulatory drug-drug interaction (DDI) guidances issued over the past few years.

[Adjuvant treatment of keloid scars: electrons or brachytherapy?]. / Traitement postopératoire des cicatrices chéloïdes : électrons ou irradiation interstitielle ?

PURPOSE: Evaluation of perioperative treatment of keloid scars with electron beam therapy or iridium 192 low dose rate brachytherapy. PATIENTS AND METHODS: From 1994 to 2010, 95 patients with 142 keloid scars have been treated by immediate perioperative irradiation and retrospectively reviewed in our institute: 116 scars were treated by electrontherapy and 26 by brachytherapy. RESULTS: In the electrontherapy group treated locations were: earlobe (n=88, 76%), thorax (n=14, 12%), neck (n=9, 8%), limbs (n=5, 4%). The median size of lesions was 3cm (range [R]: 0.5-18cm). In 95.6% of cases, a dose of 15Gy was delivered in five fractions of 3Gy. The median follow-up was 70 months (R: 7-161 months). The 2-year and 5-year local control were respectively 69% (95% confidence interval [95% CI]: 59-76%) and 55% (95% CI: 45-64%). In the brachytherapy group treated locations were: neck (n=3, 11%), earlobe (n=8, 32%), abdomen (n=3, 11%), thorax (n=2, 8%), limbs (n=10, 38%). The median size of lesions was 6.6cm (R: 1.7-28cm). The median dose delivered at 5mm from the source was 20Gy (R: 15-20.69). The median follow-up was 113 months (R: 21-219 months). The 2-year and 5-year local control were respectively 84.6% (95% CI: 64-94%) and 73.5% (95% CI: 49-87%). So far, no radiation-induced cancer has occurred. A trend to a better local control with brachytherapy was noted (compared to electrontherapy, 2-year relapse is halved with brachytherapy) though this difference did not reach the significance (P=0.0991), probably due to the reduced number of patients in the brachytherapy group. CONCLUSION: Brachytherapy seems to provide better local control compared to electrontherapy, and should be proposed as first line treatment. However, electrontherapy is an interesting alternative in case of difficulty to realize brachytherapy. There is probably a dose effect: according to published data, 25 to 30Gy should at least be proposed.

[Esophageal cancer: outcome according to therapeutic strategy]. / Évolution des cancers de l'œsophage : impact de la stratégie thérapeutique.

PURPOSE: To assess the outcome of esophageal cancer according to therapeutic strategy. PATIENTS AND METHODS: One-hundred and twenty patients with esophageal cancer treated by an association of radiotherapy and chemotherapy and possibly surgery, between 2004 and 2010, were retrospectively studied. The first site of relapse was classified as follows: local (tumour), locoregional (tumour and/or nodal: celiac, mediastinal, sus-clavicular) or metastatic. RESULTS: With a 15.7-months (1.4-62) median follow-up, there were 89 deaths and 79 recurrences. Three types of treatments were performed: 50Gy exclusive chemoradiotherapy (47 patients) or 50 to 65Gy exclusive chemoradiotherapy (44 patients) or chemoradiotherapy followed by surgery (27 patients). The local first relapse was as much frequent as distant relapse (50 patients). With a-5cm margin up and down to the tumour, there was only one nodal relapse. Two-year survival was 39.5% (95% confidence interval [IC]: 30.5-40.8) and relapse-free survival was 26.5% (CI: 18.6-35). Multivariate analysis revealed that treatment type and disease stage had a significant impact on survival, relapse-free survival and locoregional control. Compared to exclusive chemoradiotherapy, surgery improved locoregional control (40.2 versus 8.7 months, P=0.0004) but in a younger population. Despite postoperative mortality, the gain was maintained for distance relapse-free survival (40.2 versus 10 months, P=0.0147) and overall survival (29.3 versus 14.2 months, P=0.0088). Compared to 50Gy chemoradiotherapy, local control was improved if high dose chemoradiotherapy was performed (13.8 versus 7.5 months, P=0.05) but not overall survival (14.0 versus 15.4 months, P=0.24). CONCLUSION: More than one-third relapse is local. Locoregional control is better with high dose chemoradiotherapy. In this study, surgery performed in selected patients only, improved locoregional control, relapse-free disease and overall survival.

[Oncology blood transfusion and quality of life: review]. / Qualité de vie et transfusion en cancérologie: revue de la littérature.

Blood transfusion's repercussions on quality of life are less well studied in cancer research, and rarer in palliative situation. It is necessary to look for studies dealing with anaemia to estimate its effects. In curative palliative situation, the situation is similar to that of curative stage patients. It is necessary landing quickly for anaemia to assure the patient's quality of life. Blood transfusion and more recently erythropoïesis-stimulating agents are effective treatments. In advanced palliative stage, transfusion improves symptoms (weakness and dyspnoea bound anaemia) and the patients' well being. The treatment choice must be individual and has to follow an ethical behaviour in respect with the legislation.

A multicentre, open-label, randomized comparative study of tigecycline versus ceftriaxone sodium plus metronidazole for the treatment of hospitalized subjects with complicated intra-abdominal infections.

Tigecycline (TGC) has demonstrated clinical efficacy and safety, in comparison with imipenem/cilastatin in phase 3 clinical trials, for complicated intra-abdominal infection (cIAI). The present study comprised a multicentre, open-label, randomized study of TGC vs. ceftriaxone plus metronidazole (CTX/MET) for the treatment of patients with cIAI. Eligible subjects were randomized (1:1) to receive either an initial dose of TGC (100 mg) followed by 50 mg every 12 h or CTX (2 g once daily) plus MET (1-2 g daily), for 4-14 days. The primary endpoint was the clinical response in the clinically evaluable (CE) population at the test of cure (TOC) assessment. Of 473 randomized subjects, 376 were CE. Among these, clinical cure rates were 70.4% (133/189) with TGC vs. 74.3% (139/187) with CTX/MET (95% CI -13.1 to 5.1; p 0.009 for non-inferiority). Clinical cure rates for subjects with Acute Physiological and Chronic Health Evaluation II scores > or =10 were 56.8% (21/37) with TGC vs. 58.3% (21/36) with CTX/MET. The microbiologic response was similar between the two treatment arms, with microbiological eradication at TOC achieved in 68.1% (94/138) of TGC-treated subjects and 71.5% (98/137) of CTX/MET-treated subjects. (The most frequently reported adverse events (AEs) for both treatment arms were nausea (TGC, 38.6% vs CTX/MET, 27.7%) and vomiting (TGC, 23.3% vs CTX/MET, 17.7%). Overall discontinuation rates as a result of an AE were 8.9% and 4.8% in TGC- and comparator-treated subjects, respectively. The results obtained in the present study demonstrate that TGC monotherapy is non-inferior to a combination regimen of CTX/MET with respect to treating subjects with cIAI.