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This study correlated mild traumatic brain injury (mTBI) cognitive changes with ASL-MRI glymphatic clearance rates (GCRs) and recovery with GCR improvement. mTBI disrupts the blood brain barrier (BBB), reducing capillary mean transit time and GCRs. mTBI is clinically diagnosed utilizing history/examination findings with no physiologic biomarkers. 3D TGSE (turbo-gradient spin-echo) pulsed arterial spin-labeling 3T MRI with 7 long inversion times (TIs) assessed the signal clearance of labeled protons 2800-4000 ms postlabeling in bifrontal, bitemporal, and biparietal regions within 7 days of mTBI and once clinically cleared to resume activities. The Sport Concussion Assessment Tool Version 5 (SKAT5) and Brief Oculomotor/Vestibular Assessment evaluated injured athletes' cognitive function prior to MRIs. The pilot study demonstrated significant GCRs improvement (95% CI - 0.06 to - 0.03 acute phase; to CI-recovery CI 0.0772 to - 0.0497; P < 0.001 in frontal lobes; and parietal lobes (95% CI - 0.0584 to - 0.0251 acute; CI - 0.0727 to - 0.0392 recovery; P = 0.024) in 9 mTBI athletes (8 female, 1 male). Six age/activity-matched controls (4 females, 2 males) were also compared. mTBI disrupts the BBB, reducing GCR measured using the 3D ASL MRI technique. ASL MRI is a potential noninvasive biomarker of mTBI and subsequent recovery., (© 2024. The Author(s).)

The extraordinary capabilities of the canine nose are increasingly being used by law enforcement agencies in many countries to solve and reconstruct crimes. As a result, this type of forensic evidence can be and is still being challenged in the courts. So far, only a few publications have addressed the jurisprudence concerning mantrailing. We provide an overview of the jurisprudence in Germany and the USA, as well as insights from France. Relevant databases were searched, and 201 verdicts from Germany and 801 verdicts from the USA were analyzed. As a result, 16 published verdicts on the topic of mantrailing were found for Germany, and 44 verdicts since 2010 were found for the USA. The use of mantrailers and human scent discrimination dogs is employed in the investigative process in all three countries. The results derived from these methods are admissible as evidence in court, albeit not as sole evidence., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: Vestibular dysfunction is common following sports-related concussions (SRC). Within the current practice, it is theorized that patients with vestibular dysfunction as sequelae of sports-related concussion have a prolonged recovery time compared to those without vestibular dysfunction., Study Method:  A retrospective, cohort investigation of 282 subjects with sports-related concussions with vestibular dysfunction was conducted at The Sports Medicine Concussion Clinic, Duke University. The primary endpoint was the return-to-play (RTP) date., Results: For every one-day increase in time from injury to initial vestibular therapy, the geometric mean time from injury to RTP increases by 1.02 days (exp{β}=1.02 days; 95% CI: 1.01, 1.02 days; p<0.001)., Conclusion:  Our data suggest an association between the timing of vestibular therapy in SRC and a direct relationship to earlier recovery and return to sport., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Ferry et al.)

Background: Stroke is the leading cause of acquired disability in France. While 90% of patients recover the ability to walk, it is often limited with a steady speed of approximately 0.7 m/s. This limitation of walking activity is partly related to a decrease in strength associated with more or less significant spasticity. In particular, it seems that the strength of the dorsiflexor muscles is directly related to walking speed. We hypothesise that a protocol based on gestural repetition targeted at the ankle during the subacute phase potentiates the recovery of motor control, improving walking activity, and participates in recovering better social participation., Methods: An estimated total of 60 patients with subacute stroke will be recruited to participate in this multicentre, interventional, prospective, randomised controlled trial. All participants will benefit from conventional rehabilitation. In addition, the experimental group will take part in an ankle isokinetic rehabilitation programme for 6 weeks (at least 25 sessions). The control group will receive the same duration of conventional rehabilitation. The primary outcome measure will be a 10-m walking speed at post-intervention. Secondary outcomes will include social participation, walking spatio-temporal parameters, and dorsiflexor strength. Outcome measurements will be taken at baseline, immediately after treatment (6 weeks), then at 6 months and 1 year of follow-up., Discussion: This study aims to provide scientific evidence that a protocol based on an early over-solicitation of the ankle dorsiflexor muscles to promote their "awakening" can serve to achieve a more effective walking activity, which in turn encourages social participation following discharge from the hospital. This protocol should also help optimise physical medicine and rehabilitation practices: the more systematic use of the isokinetic dynamometer as a technique associated with, and integrated into the conventional rehabilitation protocol would allow an objective evaluation of the rehabilitation benefits and should increase the rehabilitation gain in central nervous system disorders., Trial Registration: Limoges University Hospital is the sponsor of this research (Unique Protocol ID: 87RI18&#95;0010) This research is supported by the French Ministry of Health (PHRC 2020-A03328-31) and is conducted with the support of DGOS (PHRC interregional - GIRCI SOHO). The study protocol was approved by the French Human Subjects Protection Review Board (Comité de Protection des Personnes Nord-Ouest III) on February 23, 2021. The trial was registered in the ClinicalTrials.gov registry ( NCT04800601 ) on March 16, 2021., (© 2022. The Author(s).)

Physical activity has many health benefits in people with type 1 and type 2 diabetes. Clinicians must be comfortable counseling patients with both types of diabetes on how to participate safely in various types of physical activity. According to the American Diabetes Association (ADA), most people with diabetes do not need further testing before initiation of low- to moderate-intensity exercise. Recommended physical activity for adults includes at least 150 min/week of moderate-intensity aerobic activity plus resistance training 2 to 3 times/week; for children and adolescents the recommendation is 60 min/day. Important steps to ensure safe participation in physical activity include modifying the insulin regimen and carbohydrate intake, as well as more frequent monitoring of blood glucose in the time periods surrounding exercise. For patients using multiple daily insulin injections, the preprandial bolus insulin dose typically should be decreased relative to the expected intensity and duration of aerobic exercise. For those using continuous subcutaneous insulin infusion pumps, the basal insulin rate should be reduced by 50% to 80% approximately 90 min before aerobic exercise. Continuous glucose monitoring provides an opportunity for more frequent glucose monitoring and tighter glycemic control during exercise participation.

There is limited evidence regarding the proportion of dead equids in France that were euthanized and the factors influencing the decision-making of euthanasia. The better understanding of which could facilitate research on improvement of welfare, especially on end of life issues. The aim of this study was to estimate the proportion of euthanasia and identify associated factors in equids in France. A web-based survey was created and distributed by the French horse and riding institute to owners who reported an equine death between April 2017 and April 2018 (n = 5 158). Factors associated with euthanasia were identified using a multivariable logistic regression model. The percentage of responses was 10.6% (n = 548/5 158; 95% CI 9.8% to 11.5%). The proportion of euthanasia was 71.0% (n = 389/548; 95% CI 67.2% to 74.8%). The factors "age category", "cause of natural death or reason for euthanasia" and "the length of time during which the animal was reported to be ill by the owner" were significantly associated with euthanasia (P <0.001). The results highlighted that a large majority of owners faced euthanasia decisions and our findings could support veterinarians and owners to better prepare for such an eventuality., (Copyright © 2021. Published by Elsevier Inc.)

Techniques of stereotaxic surgery are commonly used in research laboratories by a range of students, technicians, and researchers. To meet the evolving requirements imposed by international legislation, and to promote the implementation of 3R rules (replacement, reduction, and refinement) by reducing experimental error, animal morbidity, and mortality, it is essential that standard operating procedures and proper conduct following such complex surgeries be precisely described and respected. The present report shows how refinements of our own neurosurgical techniques over decades, have significantly reduced the number of animals (rats) used in experiments and improved the animals' well-being during the post-surgical recovery period. The current pre-, per-, and post-surgical procedures used in our laboratory are detailed. We describe the practical aspects of stereotaxic neurosurgery that have been refined in our laboratory since 1992 and that cover various areas including appropriate anesthesia and pain management during and after surgery, methods to determine the stereotaxic coordinates, and the best approach to the target brain structure. The application of these optimal surgical methods that combine reliable and reproducible results with an acute awareness of ethics and animal welfare leads to a significant reduction in the number of animals included in experimental research in accordance with ethical and regulatory rules as required by the European Directive on laboratory animal welfare.

WHO defines physical activity (PA) as any bodily movement produced by skeletal muscles that requires energy expenditure (EE). The purpose of this study was to compare the EE estimations by ActiGraph GT3X+ with a gold standard measurement, the portable gas analyser in a set of 3 different PAs. This cross-sectional study involved 56 participants, age range (years, [min, max]: young people [20, 33], older adults [65, 83]). Participants completed a single session of three experimental PAs including biking, treadmill walking, and treadmill running. Each participant wore five GT3X+ triaxial accelerometers and a portable gas analyser used as the gold standard measurement. The GT3X+ were placed on the wrists, the waist (centred at the pelvis), and the ankles. ActiGraph GT3X+ and MetaMax3B records were investigated through intraclass correlation coefficient. Magnitude of measurement error was estimated using Effect Size. The GT3X+ wrist and GT3X+ waist underestimated EE regardless of the PA type. The GT3X+ ankles strongly overestimated EE during biking (mean bias = 489 ± 392%) and walking (mean bias = 106 ± 58%), while it underestimated EE during running (mean bias = -47 ± 27%). The ActiGraph GT3X+ does not provide accurate EE estimates across a range of placement locations during moderate and high-intensity PA.

Epileptic seizures constitute a significant comorbidity of Alzheimer's disease (AD), which are recapitulated in transgenic mouse models of amyloidogenesis. Here, we sought to evaluate the potential role of tau pathology regarding seizure occurrence. To this end, we performed intra-hippocampal electroencephalogram (EEG) recordings and PTZ (pentylenetetrazol) seizure threshold tests in THY-Tau22 transgenic mice of AD-like tau pathology. We demonstrate that despite a lack of spontaneous epileptiform activity in Tau22 mice, the animals display increased PTZ-induced seizure susceptibility and mortality. The increased propensity for induced seizures in THY-Tau22 mutants correlates with astrogliosis and increased expression of adenosine kinase, consistent with increased network excitability. These data support an impact of tau pathology toward AD-associated seizures and suggest that tau pathology may contribute to seizure generation in AD independent of Aβ pathology., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Trees are characterized by the large number of seeds they produce. Although most of those seeds will never germinate, plenty will. Of those which germinate, many die young, and eventually, only a minute fraction will grow to adult stage and reproduce. Is this just a random process? Do variations in germination and survival at very young stages rely on variations in adaptations to microgeographic heterogeneity? and do these processes matter at all in determining tree species distribution and abundance? We have studied these questions with the Neotropical Symphonia tree species. In the Guiana shield, Symphonia are represented by at least two sympatric taxa or ecotypes, Symphonia globulifera found almost exclusively in bottomlands, and a yet undescribed more generalist taxon/ecotype, Symphonia sp1 . A reciprocal transplantation experiment (510 seeds, 16 conditions) was set up and followed over the course of 6 years to evaluate the survival and performance of individuals from different ecotypes and provenances. Germination, survival, growth, and herbivory showed signs of local adaptation, with some combinations of ecotypes and provenances growing faster and surviving better in their own habitat or provenance region. S. globulifera was strongly penalized when planted outside its home habitat but showed the fastest growth rates when planted in its home habitat, suggesting it is a specialist of a high-risk high-gain strategy. Conversely, S. sp1 behaved as a generalist, performing well in a variety of environments. The differential performance of seeds and seedlings in the different habitats matches the known distribution of both ecotypes, indicating that environmental filtering at the very early stages can be a key determinant of tree species distributions, even at the microgeographic level and among very closely related taxa. Furthermore, such differential performance also contributes to explain, in part, the maintenance of the different Symphonia ecotypes living in intimate sympatry despite occasional gene flow., Competing Interests: The authors declare no conflicts of interest., (© 2020 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Purpose : This study determined the impact of menstrual status on bone tissue in elite post-pubertal female soccer players over an entire season. Methods : Fifty-one elite female soccer players participated. At baseline, forty-one were assigned to the low hormonal androgenic profile (low-HAPL) and 10 to the high hormonal androgenic profile (high-HAPL). Results : An 8-month training program led to increased bone mineral density content (p<0.05). The low-HAPL athletes improved the Narrow neck average cortical thickness (ACT) by 1.4% and reduced the corresponding Buckling ratio (BR) by 2.6%, thus decreasing the fracture risk (p<0.05). The high-HAPL athletes decreased the Narrow neck ACT by 5.4% and increased the BR by 2.6%, increasing fracture risk (p<0.05). Differences were assigned as being "very likely beneficial" for the low-HAPL athletes, supported by very large (d=3.41) and large (d=1.58) effect sizes for the Narrow neck ACT and BR, respectively. Conclusion : A season of soccer training has induced bone geometry improvements in adolescent females. Bone health parameters improved in the two clusters. However, high-HAPL athletes decreased its resistance to loading compare to low-HAPL athletes. Even if female players do not present clinical symptoms related to their hormonal status, sport medicine physicians should pay attention to their structural bone fragility.

Athletes of various skill levels commonly use many different types of medications, often at rates higher than the general population. Common medication classes used in athletes include analgesics such as nonsteroidal anti-inflammatory drugs and acetaminophen, inhalers for asthma and exercise-induced bronchoconstriction, antihypertensives, antibiotics, and insulin. Prescribers must be aware of the unique considerations for each of these medications when using them in patients participating in physical activity. The safety, efficacy, impact on athletic performance, and regulatory restrictions of the most common medications used in athletes are discussed in this article., Competing Interests: Disclosure The authors of this article have no financial relationships or affiliations to disclose., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Advancements in reconstructive microsurgery have evolved into supermicrosurgery; connecting vessels with diameter between 0.3 and 0.8 mm for reconstruction of lymphatic flow and vascularized tissue transplantation. Supermicrosurgery is limited by the precision and dexterity of the surgeon's hands. Robot assistance can help overcome these human limitations, thereby enabling a breakthrough in supermicrosurgery. We report the first-in-human study of robot-assisted supermicrosurgery using a dedicated microsurgical robotic platform. A prospective randomized pilot study is conducted comparing robot-assisted and manual supermicrosurgical lymphatico-venous anastomosis (LVA) in treating breast cancer-related lymphedema. We evaluate patient outcome at 1 and 3 months post surgery, duration of the surgery, and quality of the anastomosis. At 3 months, patient outcome improves. Furthermore, a steep decline in duration of time required to complete the anastomosis is observed in the robot-assisted group (33-16 min). Here, we report the feasibility of robot-assisted supermicrosurgical anastomosis in LVA, indicating promising results for the future of reconstructive supermicrosurgery.

We observed strong positive relationships between soil properties and forest dynamics of growth and mortality across twelve primary lowland tropical forests in a phosphorus-poor region of the Guiana Shield. Average tree growth (diameter at breast height) increased from 0.81 to 2.1 mm yr -1 along a soil texture gradient from 0 to 67% clay, and increasing metal-oxide content. Soil organic carbon stocks in the top 30 cm ranged from 30 to 118 tons C ha -1 , phosphorus content ranged from 7 to 600 mg kg -1 soil, and the relative abundance of arbuscular mycorrhizal fungi ranged from 0 to 50%, all positively correlating with soil clay, and iron and aluminum oxide and hydroxide content. In contrast, already low extractable phosphorus (Bray P) content decreased from 4.4 to <0.02 mg kg -1 in soil with increasing clay content. A greater prevalence of arbuscular mycorrhizal fungi in more clayey forests that had higher tree growth and mortality, but not biomass, indicates that despite the greater investment in nutrient uptake required, soils with higher clay content may actually serve to sustain high tree growth in tropical forests by avoiding phosphorus losses from the ecosystem. Our study demonstrates how variation in soil properties that retain carbon and nutrients can help to explain variation in tropical forest growth and mortality, but not biomass, by requiring niche specialization and contributing to biogeochemical diversification across this region.

The core of the French equine traceability system is the census database (SIRE) managed by the French horse and riding institute (IFCE). Following the death of an equine, owners are legally obliged to take charge of cadaver removal by contacting a rendering company directly or after registration on the national ATM-équidés ANGEE association (ATM) website, which proposes negotiated prices for removal and recording of the death in the SIRE database. Despite these offers, ATM notes few users. Owners are also legally obliged to return the equine's passport to the IFCE, but only 30-40 % of owners comply with the regulation. Rendering companies register data on equine mortality in the fallen stock data interchange database (FSDI), but it is difficult to cross-reference these data with SIRE data. Consequently, the death of equines is not well registered in the SIRE database. The objective of the present study was to identify levers that could be used to improve dead equine traceability by i) investigating the level of satisfaction of equine owners with ATM and rendering company services; and ii) investigating the drawbacks of owners having to return the passport to the IFCE. An online survey was designed and distributed by email to the 5 158 owners who used ATM services between April 2017 and April 2018. The response rate was 16.4 %. Most owners were satisfied by ATM and rendering company services. The lack of simple and quick removal procedures and the lack of any connection between ATM and the rendering companies were among the main drawbacks identified. Regarding the return of the passport to the IFCE, most responding owners returned it through the rendering company (65 %) or directly (2 %). The passport was returned significantly more frequently when requested by the renderers. The main reason for not providing the passport was the owner wanted to keep it as a souvenir. These results suggest that ATM and the rendering companies are key players in dead equine traceability. ATM services should be developed through the establishment of a direct connection with rendering companies to accelerate the cadaver removal request and to allow the cross-referencing of data between the ATM, FSDI and SIRE databases for a better dead equine traceability. Rendering companies need regulatory support to help them ask owners for the equine's passport, formalizing their contribution to equine traceability. Finally, effective communication has to be established to inform owners about the removal procedures and the regulations., (Copyright © 2019 Elsevier B.V. All rights reserved.)

To decipher the long-term influences of pre-Columbian land occupations on contemporary forest structure, diversity, and functioning in Amazonia, most of the previous research focused on the alluvial plains of the major rivers of the Amazon basin. Terra firme, that is, nonflooded forests, particularly from the Guiana Shield, are yet to be explored. In this study, we aim to give new insights into the subtle traces of pre-Columbian influences on present-day forests given the archaeological context of terra firme forests of the Guiana Shield. Following archaeological prospects on 13 sites in French Guiana, we carried out forest inventories inside and outside archaeological sites and assessed the potential pre-Columbian use of the sampled tree species using an original ethnobotanical database of the Guiana Shield region. Aboveground biomass (320 and 380 T/ha, respectively), basal area (25-30 and 30-35 m 2 /ha, respectively), and tree density (550 and 700 stem/ha, respectively) were all significantly lower on anthropized plots (As) than on nonanthropized plots (NAs). Ancient human presence shaped the species composition of the sampled forests with Arecaceae, Burseraceae, and Lauraceae significantly more frequent in As and Annonaceae and Lecythidaceae more frequent in NAs. Although alpha diversity was not different between As and NAs, the presence of pre-Columbian sites enhances significantly the forest beta diversity at the landscape level. Finally, trees with edible fruits are positively associated with pre-Columbian sites, whereas trees used for construction or for their bark are negatively associated with pre-Columbian sites. Half a millennium after their abandonment, former occupied places from the inner Guiana Shield still bear noticeable differences with nonanthropized places. Considering the lack of data concerning archaeology of terra firme Amazonian forests, our results suggest that pre-Columbian influences on the structure (lower current biomass), diversity (higher beta diversity), and composition (linked to the past human tree uses) of current Amazonian forests might be more important than previously thought., (© 2019 by the Ecological Society of America.)

A scent lineup is generally a procedure whereby a dog's alerting behavior is used to establish that the dog detects two scents, one from a crime scene and one from a suspect, as deriving from the same person. The aim of this article is to compare methodologies of using dogs in scent lineups as a means of identifying perpetrators of crimes. It is hoped that this comparative approach, looking at countries where the method is currently or has in the past been used, will help determine what issues should be addressed in order to assure that the scent lineup will have a future as a forensic technique. Participants from eleven countries-Belgium, The Czech Republic, Finland, France, Germany, Hungary, Lithuania, The Netherlands, Poland, Russia, and the U.S.-completed a survey questionnaire regarding key aspects of the scent lineup procedures used by the police in their countries. Although there was broad overlap on certain matters, such as the use of control and zero trials, collection of decoy scents from individuals of similar gender and race as the suspect, materials for holding scent, frequency of cleaning and changing stations, and use and timing of rewards, there were significant differences in the degree of blindness required, who calls an alert (handler or experimenter), and whether handlers can work with more than one dog. The gap between recommendations and results available from the scientific literature and procedures used in police practice was greater for some countries than others, even taking into account that some scientific methodologies might be expensive or impractical given agency resources. The authors make recommendations about how to go forward if scent lineups are to remain a valid forensic technique., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Previous work has shown that β-adrenergic and GABAergic systems in the basolateral amygdala (BLA) are involved in the acquisition of conditioned odor aversion (COA) learning. The involvement of α 2 -adrenoreceptors, however, is poorly documented. In a first experiment, male Long-Evans rats received infusions of 0.1 μg of the selective α 2 -antagonist dexefaroxan (Dex) in the BLA before being exposed to COA learning. In a second experiment, levels of norepinephrine (NE) were analyzed following Dex retrodialysis into the BLA. While microdialysis data showed a significant enhancement of NE release in the BLA with Dex, behavioral results showed that pre-CS infusion of Dex impaired, rather than facilitated, the acquisition of COA. Our results show that the NE system in the BLA is involved in the acquisition of COA, including a strong α 2 -receptor modulation until now unsuspected. Supported by the recent literature, the present data suggest moreover that the processes underlying this learning are probably mediated by the balanced effects of NE excitatory/inhibitory signaling in the BLA, in which interneurons are highly involved.

Background: Robotic assistance in microsurgery could enhance human precision and dexterity to improve clinical outcomes. Because no robotic device has been designed primarily for microsurgery, the authors developed a dedicated microsurgical robotic system. This preclinical study investigates whether microsurgical anastomosis can be successfully completed on silicone vessels using a prototype of this new robotic system, and compares outcomes of robot-assisted versus conventional microsurgery., Methods: Three participants at different levels of microsurgical training completed 10 anastomoses by hand and 10 anastomoses with robotic assistance. Four blinded, experienced microsurgeons evaluated the quality of the microsurgical skills using a modified version of the Structured Assessment of Microsurgical Skills. Time to perform the anastomosis and adverse events were recorded., Results: The total time to perform the anastomoses with and without robotic assistance decreased to 35.1 minutes and 12.5 minutes, respectively, during the study. The overall performance and indicative skill of the Structured Assessment of Microsurgical Skills improved with the conventional method (from 2.8 to 3.6 and from 2.6 to 3.7, respectively) and the robot-assisted method (from 2.3 to 3.0 and from 2.3 to 3.1, respectively)., Conclusions: It is feasible to complete anastomotic microsurgery on silicone vessels using the MicroSure robotic system. In comparison with the conventional method, time to perform the anastomosis was longer and quality of microsurgical skills was lower in the robot-assisted group. However, the robot-assisted performance showed steeper learning curves for both surgical time and domains of microsurgical skills. The encouraging results indicate further development of the system and (pre)clinical trials.

Vaccine-specific antibody responses are essential in the diagnosis of antibody deficiencies. Responses to Pneumovax II are used to assess the response to polysaccharide antigens, but interpretation may be complicated. Typhim Vi ® , a polysaccharide vaccine for Salmonella typhoid fever, may be an additional option for assessing humoral responses in patients suspected of having an immunodeficiency. Here we report a UK multi-centre study describing the analytical and clinical performance of a Typhi Vi immunoglobulin (Ig)G enzyme-linked immunosorbent assay (ELISA) calibrated to an affinity-purified Typhi Vi IgG preparation. Intra- and interassay imprecision was low and the assay was linear, between 7·4 and 574 U/ml (slope = 0·99-1·00; R 2  > 0·99); 71% of blood donors had undetectable Typhi Vi IgG antibody concentrations. Of those with antibody concentrations  > 7·4 U/ml, the concentration range was 7·7-167 U/ml. In antibody-deficient patients receiving antibody replacement therapy the median Typhi Vi IgG antibody concentrations were  < 25 U/ml. In vaccinated normal healthy volunteers, the median concentration post-vaccination was 107 U/ml (range 31-542 U/ml). Eight of eight patients (100%) had post-vaccination concentration increases of at least threefold and six of eight (75%) of at least 10-fold. In an antibody-deficient population (n = 23), only 30% had post-vaccination concentration increases of at least threefold and 10% of at least 10-fold. The antibody responses to Pneumovax II and Typhim Vi ® correlated. We conclude that IgG responses to Typhim Vi ® vaccination can be measured using the VaccZyme Salmonella typhi Vi IgG ELISA, and that measurement of these antibodies maybe a useful additional test to accompany Pneumovax II responses for the assessment of antibody deficiencies., (© 2018 The Authors. Clinical & Experimental Immunology published by John Wiley & Sons Ltd on behalf of British Society for Immunology.)

The present study is aimed at describing some aspects of the neural dynamics supporting discrimination of olfactory-tactile paired-associated stimuli during acquisition of new pairs and during recombination of previously learned pairs in the rat. To solve the task, animals have to identify one odor-texture (OT) combination associated with a food reward among three cups with overlapping elements. Previous experiments demonstrated that the lateral entorhinal cortex (LEC) is involved in the processes underlying OT acquisition, whereas the dorsal hippocampus (DH) is selectively involved in the recombination processes. In the present study, local field potentials were recorded form the anterior piriform cortex (aPC), LEC, and DH in freely moving rats performing these tasks. Signal analysis focused on theta (5-12 Hz)- and beta-band (15-40 Hz) oscillatory activities in terms of both amplitude and synchrony. The results show that cue sampling was associated with a significant increase in the beta-band activity during the choice period in both the aPC and the LEC, and is modulated by level of expertise and the animal's decision. In addition, this increase was significantly higher during the recombination compared with the acquisition of the OT task, specifically when animals had to neglect the odor previously associated with the reward. Finally, a significant decrease in coherence in the theta band between LEC and DH was observed in the recombination but not in the acquisition task. These data point to specific neural signatures of simple and complex cross-modal sensory processing in the LEC-DH complex. NEW & NOTEWORTHY This study is the first to describe electrophysiological correlates of cross-modal olfactory-tactile integration in rats. Recordings were sought from the lateral entorhinal cortex and the dorsal hippocampus because previous studies have shown their role in the formation and in the recombination of previously learned associations. We identified specific oscillatory-evoked neural responses in these structures in the theta and beta bands, which characterize acquisition and recombination of cross-modal olfactory-tactile pairs.

Post-traumatic stress disorder (PTSD) is a common consequence of exposure to a life-threatening event. Currently, pharmacological treatments are limited by high rates of relapse, and novel treatment approaches are needed. We have recently demonstrated that propranolol, a β-adrenergic antagonist, inhibited aversive memory reconsolidation in animals. Following this, in an open-label study 70% of patients with PTSD treated with propranolol during reactivation of traumatic memory exhibited full remission. However, the reason why 30% of these patients did not respond positively to propranolol treatment is still unclear. One of the major candidates as factor of treatment resistance is the patient's early-life traumatic history. To test the role of this factor, mice with pre- or postnatal stress are being tested in fear conditioning and in a new behavioral task, the "city-like", specifically designed as a mouse model of PTSD. After reactivation of the traumatic event, mice received propranolol injection to block the noradrenergic system during memory reconsolidation. Results show that, in the "city-like" test, control mice strongly avoided the shock compartment but also the compartments containing cues associated with the electric shocks. Injection of propranolol after reactivation greatly reduced the memory of the traumatic event, but this effect was not present when mice had received pre- or postnatal stress. Moreover, propranolol produced only a very weak effect in the fear conditioning test, and never changed the corticosterone level whatever the behavioral experiment. Taken together our results suggest that our new behavioural paradigm is well adapted to PTSD study in mice, and that early stress exposure may have an impact on propranolol PTSD treatment outcome. These data are critical to understanding the effect of propranolol treatment, in order to improve the therapeutic protocol currently used in humans.

Background In the subacute stroke phase, the monitoring of ambulatory activity and activities of daily life with wearable sensors may have relevant clinical applications. Do current commercially available wearable activity trackers allow us to objectively assess the energy expenditure of these activities? The objective of the present study was to compare the energy expenditure evaluated by indirect calorimetry during the course of a scenario consisting of everyday activities while estimating the energy expenditure using several commercialised wearable sensors in post-stroke patients (less than six months since stroke). Method Twenty-four patients (age 68.2 ± 13.9; post-stroke delay 34 ± 25 days) voluntarily participated in this study. Each patient underwent a scenario of various everyday tasks (transfer, walking, etc.). During the implementation, patients wore 14 wearable sensors (Armband, Actigraph GT3X, Actical, pedometer) to obtain an estimate of the energy expenditure. The actual energy expenditure was concurrently determined by indirect calorimetry. Results Except for the Armband worn on the non-plegic side, the results of our study show a significant difference between the energy expenditure values estimated by the various sensors and the actual energy expenditure when the scenario is considered as a whole. Conclusion The present results suggest that, for a series of everyday tasks, the wearable sensors underestimate the actual energy expenditure values in post-stroke patients in the subacute phase and are therefore not accurate. Several factors are likely to confound the results: types of activity, prediction equations, the position of the sensor and the hemiplegia side.

Background: Quantitative information about equine mortality is relatively scarce, yet it could be of great value for epidemiological purposes. In France, data from rendering plants are centralised in the Fallen Stock Data Interchange database (FSDI), managed by the French Ministry of Agriculture, while individual equine data are centralised in the French equine census database, SIRE, managed by the French horse and riding institute (IFCE)., Objectives: To evaluate whether the combined use of the FSDI and SIRE databases can provide representative and accurate quantitative information on mortality for the French equine population and to propose enhancements of these databases to improve the quality of the resulting demographic information., Study Design: Descriptive study., Methods: Mortality ratios for the French equine population were calculated per year between 2011 and 2014 and temporal variations in equine mortality modelled during the same period. Survival analyses were performed on a sample of equines traceable in both the FSDI and SIRE databases., Results: Estimates of the annual mortality ratios varied from 3.02 to 3.40% depending on the years. Survival rates of equines 2-years-old and over differed according to breed categories with the highest median age at death for the ponies. The weekly description of mortality highlighted marked seasonality of deaths whatever the category of equines. Modelling temporal variations in equine mortality also brought to light excess mortality., Main Limitations: Insufficient traceability of equines between the two databases., Conclusion: The FSDI database provided an initial approach to equine death ratios on a national scale and an original description of temporal variations in mortality. Improvement in the traceability of equines between the FSDI and SIRE databases is needed to enable their combined use, providing a representative description of equine longevity and a more detailed description of temporal variations in mortality., (© 2017 The Authors. Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.)

Background & Aims: IgG subclass 4-related disease (IgG4-RD) is characterized by increased serum levels of IgG4 and infiltration of biliary, pancreatic, and other tissues by IgG4-positive plasma cells. We assessed the prevalence of allergy and/or atopy, serum, and tissue IgE antibodies, and blood and tissue eosinophils in patients with IgG4-RD. We investigated the association between serum IgE and diagnosis and relapse of this disease., Methods: We performed a prospective study of 48 patients with IgG4-RD, 42 patients with an increased serum level of IgG4 with other inflammatory and autoimmune conditions (disease control subjects), and 51 healthy individuals (healthy control subjects) recruited from Oxford, United Kingdom from March 2010 through March 2014, and followed for a median of 41 months (range, 3-73 months). Serum levels of immunoglobulin were measured at diagnosis, during steroid treatment, and at disease relapse for patients with IgG4-RD; levels at diagnosis were compared with baseline levels of control subjects. Allergen-specific IgEs were measured using the IgE ImmunoCAP. Levels and distribution of IgG4 and IgE antibodies in lymphoid, biliary, and pancreatic tissues from patients with IgG4-RD and disease control subjects were measured by immunohistochemistry. We analyzed data using the Spearman rank correlation and receiver operating characteristic curves., Results: Serum levels of IgG4 increased to 1.4 g/L or more, and IgE increased to 125 kIU/L or more, in 81% and 54% of patients with IgG4-RD, respectively, compared with 6% and 16% of healthy control subjects (P < .0001). Peripheral blood eosinophilia was detected in 38% of patients with IgG4-RD versus 9% of healthy control subjects (P = .004). Of patients with IgG4-RD, 63% had a history of allergy and 40% had a history of atopy with an IgE-specific response; these values were 60% and 53% in patients with increased serum levels of IgE (P < .05). Level of IgE at diagnosis >480 kIU/L distinguished patients with IgG4-RD from disease control subjects with 86% specificity, 36% sensitivity, and a likelihood ratio of 3.2. Level of IgE at diagnosis >380 kIU/L identified patients with disease relapse with 88% specificity, 64% sensitivity, and a likelihood ratio of 5.4. IgE-positive mast cells and eosinophilia were observed in lymphoid, biliary, and pancreatic tissue samples from 50% and 86% of patients with IgG4-RD, respectively., Conclusions: In a prospective study, we associated IgG4-RD with allergy, atopy, eosinophilia, increased serum levels of IgE, and IgE-positive mast cells in lymphoid, biliary, and pancreatic tissue. An IgE-mediated allergic response therefore seems to develop in most patients with IgG4-RD; levels of IgE might be used in diagnosis and predicting relapse., (Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Helicobacter pylori (H.pylori) plasminogen binding protein (PBP) has been proposed as an antigen triggering autoimmune pancreatitis (AIP), the pancreatic manifestation of IgG4-related disease (IgG4-RD). We investigated exposure to H. pylori infection, cytokine response and immunological memory to H. pylori PBP in a prospective IgG4-RD cohort in the UK., Methods: Clinical and endoscopic evidence of peptic ulceration, serological H. pylori exposure and serum IgG4 levels were obtained in 55 IgG4-RD patients and 52 disease controls (DC) with autoimmune or inflammatory conditions with an elevated serum IgG4. Gastric and duodenal tissues were assessed for H. pylori and immunostained for IgG4. B and T cell ELISpot and cytokine luminex assays were used to detect immune responses to H. pylori PBP., Results: 85% of IgG4-RD patients had pancreatic and/or biliary disease, 89% had extra-pancreatic manifestations, and 84% had an increased serum IgG4. Clinical dyspepsia (35.2%), gastritis (58%), peptic ulceration (7.4%) and H. pylori colonisation (24%) in IgG4-RD was similar to DC. In IgG4-RD, gastric tissue contained a chronic inflammatory infiltrate with a low IgG4+ plasma-cell count (<10/HPF; range 1-4/HPF), and duodenal specimens had an increased IgG4 count (>10/HPF; range 7-54) compared with DC (p < 0.01). Th1 and Th2 cytokine response and immunological B-cell memory to H. pylori PBP did not differ between IgG4-RD and DC., Conclusions: In a prospective UK cohort, the prevalence of gastric ulceration, exposure to H. pylori, cytokine response and immunological memory to H. pylori PBP did not differ in IgG4-RD patients compared with DC. This study does not support a role for H. pylori PBP as a microbial antigen in IgG4-RD., Keywords for Abstract: Peptic ulceration, Antigens, B cells, T cells, Interleukins, Helicobacter pylori., (Copyright © 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Tropical forests store large amounts of biomass despite they generally grow in nutrient-poor soils, suggesting that the role of soil characteristics in the structure and dynamics of tropical forests is complex. We used data for >34 000 trees from several permanent plots in French Guiana to investigate if soil characteristics could predict the structure (tree diameter, density and aboveground biomass), and dynamics (growth, mortality, aboveground wood productivity) of nutrient-poor tropical forests. Most variables did not covary with site-level changes in soil nutrient content, indicating that nutrient-cycling mechanisms other than the direct absorption from soil (e.g. the nutrient uptake from litter, the resorption, or the storage of nutrients in the biomass), may strongly control forest structure and dynamics. Ecosystem-level adaptations to low soil nutrient availability and long-term low levels of disturbance may help to account for the lower productivity and higher accumulation of biomass in nutrient-poor forests compared to nutrient-richer forests.

Background: Psychosis is a common presenting feature in antibody-mediated encephalitis, for which prompt recognition and treatment usually leads to remission. We aimed to investigate whether people with circumscribed schizophrenia-like illnesses have such antibodies-especially antibodies against the N-methyl-D-aspartate receptor (NMDAR)-more commonly than do healthy controls., Methods: We recruited patients aged 14-35 years presenting to any of 35 mental health services sites across England with first-episode psychosis, less than 6 weeks of treatment with antipsychotic medication, and a score of 4 or more on at least one selected Positive and Negative Syndrome Scale (PANSS) item. Patients and controls provided venous blood samples. We completed standardised symptom rating scales (PANSS, ACE-III, GAF) at baseline, and tested serum samples for antibodies against NMDAR, LGI1, CASPR2, the GABA A receptor, and the AMPA receptor using live cell-based assays. Treating clinicians assessed outcomes of ICD diagnosis and functioning (GAF) at 6 months. We included healthy controls from the general population, recruited as part of another study in Cambridge, UK., Findings: Between Feb 1, 2013, and Aug 31, 2014, we enrolled 228 patients with first-episode psychosis and 105 healthy controls. 20 (9%) of 228 patients had serum antibodies against one or more of the neuronal cell surface antibodies compared with four (4%) of 105 controls (unadjusted odds ratio 2·4, 95% CI 0·8-7·3). These associations remained non-significant when adjusted for current cigarette smoking, alcohol consumption, and illicit drug use. Seven (3%) patients had NMDAR antibodies compared with no controls (p=0·0204). The other antibodies did not differ between groups. Antibody-positive patients had lower PANSS positive, PANSS total, and catatonia scores than did antibody-negative patients. Patients had comparable scores on other PANSS items, ACE-III, and GAF at baseline, with no difference in outcomes at 6 months., Interpretation: Some patients with first-episode psychosis had antibodies against NMDAR that might be relevant to their illness, but did not differ from patients without NMDAR antibodies in clinical characteristics. Our study suggests that the only way to detect patients with these potentially pathogenic antibodies is to screen all patients with first-episode psychosis at first presentation., Funding: Medical Research Council., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The hippocampal formation has been extensively described as a key component for object recognition in conjunction with place and context. The present study aimed at describing neural mechanisms in the hippocampal formation that support olfactory-tactile (OT) object discrimination in a task where space and context were not taken into account. The task consisted in discriminating one baited cup among three, each of them presenting overlapping olfactory or tactile elements. The experiment tested the involvement of the entorhinal cortex (EC) and the dorsal hippocampus (DH) in the acquisition of this cross-modal task, either with new items or with familiar but recombined items. The main results showed that DH inactivation or cholinergic muscarinic blockade in the DH selectively and drastically disrupted performance in the recombination task. EC inactivation impaired OT acquisition of any OT combinations while cholinergic blockade only delayed it. Control experiments showed that neither DH nor EC inactivation impaired unimodal olfactory or tactile tasks. As a whole, these data suggest that DH-EC interactions are of importance for flexibility of cross-modal representations with overlapping elements., (© 2016 Boisselier et al.; Published by Cold Spring Harbor Laboratory Press.)

Equine viral arteritis (EVA) may have serious economic impact on the equine industry. For this reason, it is monitored in many countries, especially in breeding stock, to avoid its spread during breeding activities. In France, surveillance is mainly based on serological tests, since mares are not vaccinated, but difficulties in interpreting certain series of results may impair the estimation of the number of outbreaks. In this study, we propose specific rules for identifying seroconversion in order to estimate the number of outbreaks that were detected by the breeding stock surveillance component (BSSC) in France between 2006 and 2013. A consensus among multidisciplinary experts was reached to consider seroconversion as a change in antibody titer from negative to at least 32, or as an eight-fold or greater increase in antibody level. Using these rules, 239 cases and 177 outbreaks were identified. Subsequently, we calculated the BSSC's sensitivity as the ratio of the number of detected outbreaks to the total number of outbreaks that occurred in breeding stock (including unreported outbreaks) estimated using a capture-recapture model. The total number of outbreaks was estimated at 215 (95% credible interval 195-249) and the surveillance sensitivity at 82% (CrI95% 71-91). Our results confirm EVA circulation in French breeding stock, show that neutralizing antibodies can persist up to eight years in naturally infected mares and suggest that certain mares have been reinfected. This study shows that the sensitivity of the BSSC is relatively high and supports its relevance to prevent the disease spreading through mating., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objectives: Elevated serum immunoglobulin G4 (IgG4) levels have been associated with autoimmune pancreatitis and IgG4-related disease (IgG4-RD) for over a decade. However, an elevated serum IgG4 is not specific for the disease. There have been inconsistent reports of its use in diagnosis, as a marker of disease relapse, and its relationship to organ involvement in retrospective cohorts. The aims of this study were to ascertain conditions that are associated with an elevated serum IgG4 and to investigate the role of IgG4 in diagnosis, relapse, and organ involvement in a prospective cohort of patients with IgG4-RD., Methods: We evaluated serum IgG4 measurements in the Oxford Immunology Laboratory over 6 years. Patients in whom serum IgG4 was requested to differentiate IgG4-RD from other diseases were recruited into a longitudinal follow-up study to determine final diagnosis. In a prospective cohort of IgG4-RD patients, organ involvement, response to therapy, and disease relapse were determined., Results: Two thousand and sixty-seven samples from 1,510 patients had serum IgG4 measured. Of these, IgG4 was elevated (≥1.4 g l(-1)) in 243 (16.1%) patients. The main indication (85.6%) was to distinguish between IgG4-RD and non-IgG4-RD conditions. Only 5.1% of patients who had serum IgG4 measured for this purpose had a final diagnosis of IgG4-RD. Of those with an elevated serum IgG4, 22.4% met IgG4-RD diagnostic criteria. Serum IgG4 was elevated in 48 (82.8%) of IgG4-RD patients. An IgG4 cutoff of 1.4 g l(-1) gave a sensitivity of 82.8% and specificity of 84.7% to diagnose IgG4-RD. Increasing this to 2.8 g l(-1) increased specificity to 96.2% and negative predictive value to 97.7%, with a lower sensitivity of 56.9% and positive predictive value of 44.5%. Serum IgG4 levels fell with corticosteroid therapy, but this was not disease-specific. A serum IgG4 of ≥2.8 g l(-1) at diagnosis was associated with multi-organ involvement and risk of relapse., Conclusions: Serum IgG4 levels are elevated in multiple non-IgG4-RD inflammatory and malignant conditions, with less than one-quarter of those with an elevated IgG4 meeting IgG4-RD diagnostic criteria. A serum IgG4 of ≥2.8 g l(-1) is useful in distinguishing between IgG4-RD and non-IgG4-RD diagnoses, predicting multiple-organ involvement and risk of relapse in IgG4-RD.

Chronic mucocutaneous candidiasis (CMC) is characterized by recurrent and persistent superficial infections, with Candida albicans affecting the mucous membranes, skin and nails. It can be acquired or caused by primary immune deficiencies, particularly those that impair interleukin (IL)-17 and IL-22 immunity. We describe a single kindred with CMC and the identification of a STAT1 GOF mutation by whole exome sequencing (WES). We show how detailed clinical and immunological phenotyping of this family in the context of WES has enabled revision of disease status and clinical management. Together with analysis of other CMC cases within our cohort of patients, we used knowledge arising from the characterization of this family to develop a rapid ex-vivo screening assay for the detection of T helper type 17 (Th17) deficiency better suited to the routine diagnostic setting than established in-vitro techniques, such as intracellular cytokine staining and enzyme-linked immunosorbent assay (ELISA) using cell culture supernatants. We demonstrate that cell surface staining of unstimulated whole blood for CCR6⁺ CXCR3⁻ CCR4⁺ CD161⁺ T helper cells generates results that correlate with intracellular cytokine staining for IL-17A, and is able to discriminate between patients with molecularly defined CMC and healthy controls with 100% sensitivity and specificity within the cohort tested. Furthermore, removal of CCR4 and CD161 from the antibody staining panel did not affect assay performance, suggesting that the enumeration of CCR6⁺ CXCR3⁻ CD4⁺ T cells is sufficient for screening for Th17 deficiency in patients with CMC and could be used to guide further investigation aimed at identifying the underlying molecular cause., (© 2016 The Authors. Clinical & Experimental Immunology published by John Wiley & Sons Ltd on behalf of British Society for Immunology.)

Human scent identification is based on a matching-to-sample task in which trained dogs are required to compare a scent sample collected from an object found at a crime scene to that of a suspect. Based on dogs' greater olfactory ability to detect and process odours, this method has been used in forensic investigations to identify the odour of a suspect at a crime scene. The excellent reliability and reproducibility of the method largely depend on rigor in dog training. The present study describes the various steps of training that lead to high sensitivity scores, with dogs matching samples with 90% efficiency when the complexity of the scents presented during the task in the sample is similar to that presented in the in lineups, and specificity reaching a ceiling, with no false alarms in human scent matching-to-sample tasks. This high level of accuracy ensures reliable results in judicial human scent identification tests. Also, our data should convince law enforcement authorities to use these results as official forensic evidence when dogs are trained appropriately.

Loss-of-function mutations in DOCK8 are linked to hyper-IgE syndrome. Patients typically present with recurrent sinopulmonary infections, severe cutaneous viral infections, food allergies and elevated serum IgE. Although patients may present with a spectrum of disease-related symptoms, molecular mechanisms explaining phenotypic variability in patients are poorly defined. Here we characterized a novel compound heterozygous mutation in DOCK8 in a patient diagnosed with primary combined immunodeficiency which was not typical of classical DOCK8 deficiency. In contrast to previously identified mutations in DOCK8 which result in complete loss of function, the newly identified single nucleotide insertion results in expression of a truncated DOCK8 protein. Functional evaluation of the truncated DOCK8 protein revealed its hypomorphic function. In addition we found somatic reversion of DOCK8 predominantly in T cells. The combination of somatic reversion and hypomorphic DOCK8 function explains the milder and atypical phenotype of the patient and further broadens the spectrum of DOCK8-associated disease., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Quantitative information about equine mortality is relatively scarce, yet it could be of great value for epidemiology purposes. Several European projects based on the exploitation of data from rendering plants have been developed to improve livestock surveillance. Similar data are available for equines in France but have never been studied to date. The objective of this research was to evaluate the potential of the French Ministry of Agriculture's Fallen Stock Data Interchange (FSDI) database to provide quantitative mortality information on the French equine population. The quality of FSDI equine data from 2011 to 2014 was assessed using complementary data registered in the French equine census database, SIRE. Despite a perfectible quality, the FSDI database proved to be a valuable source for studying the basal patterns of mortality over time in the French equine population as illustrated by the spatial representation of the number of deaths. However, improvements in the FSDI database are needed, in particular regarding the registration of animal identification numbers, in order to detail equine mortality for epidemiology purposes., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Consumption of caffeine, a non-selective adenosine A2A receptor (A2AR) antagonist, reduces the risk of developing Alzheimer's disease (AD) in humans and mitigates both amyloid and Tau burden in transgenic mouse models. However, the impact of selective A2AR blockade on the progressive development of AD-related lesions and associated memory impairments has not been investigated. In the present study, we removed the gene encoding A2AR from THY-Tau22 mice and analysed the subsequent effects on both pathological (Tau phosphorylation and aggregation, neuro-inflammation) and functional impairments (spatial learning and memory, hippocampal plasticity, neurotransmitter profile). We found that deleting A2ARs protect from Tau pathology-induced deficits in terms of spatial memory and hippocampal long-term depression. These effects were concomitant with a normalization of the hippocampal glutamate/gamma-amino butyric acid ratio, together with a global reduction in neuro-inflammatory markers and a decrease in Tau hyperphosphorylation. Additionally, oral therapy using a specific A2AR antagonist (MSX-3) significantly improved memory and reduced Tau hyperphosphorylation in THY-Tau22 mice. By showing that A2AR genetic or pharmacological blockade improves the pathological phenotype in a Tau transgenic mouse model, the present data highlight A2A receptors as important molecular targets to consider against AD and Tauopathies.

Interest in cell-derived microvesicles (or microparticles) within cardiovascular diagnostics and therapeutics is rapidly growing. Microvesicles are often measured in the circulation at a single time point. However, it is becoming clear that microvesicle levels both increase and decrease rapidly in response to certain stimuli such as hypoxia, acute cardiac stress, shear stress, hypertriglyceridaemia and inflammation. Consequently, the levels of circulating microvesicles will reflect the balance between dynamic mechanisms for release and clearance. The present review describes the range of triggers currently known to lead to microvesicle release from different cellular origins into the circulation. Specifically, the published data are used to summarize the dynamic impact of these triggers on the degree and rate of microvesicle release. Secondly, a summary of the current understanding of microvesicle clearance via different cellular systems, including the endothelial cell and macrophage, is presented, based on reported studies of clearance in experimental models and clinical scenarios, such as transfusion or cardiac stress. Together, this information can be used to provide insights into potential underlying biological mechanisms that might explain the increases or decreases in circulating microvesicle levels that have been reported and help to design future clinical studies., (© 2015 Authors; published by Portland Press Limited.)

Background: Urinary tract infections (UTIs) are common bacterial infections dominated by lower UTI in women (LUTIW). Symptoms only are insufficient for diagnosis and accordingly, near patient diagnostic tests confidently confirming significant bacteriuria are desirable. The nitrite test (NIT) has low sensitivity, while bacterial and leukocyte counts disjunctively paired in urine sediment microscopy (SED) have high sensitivity. Similar symptomatic cure rates are found post antibiotic vs. placebo therapy in patients with negative cultures. Consequently, prescription on symptoms only implies unnecessary antibiotic therapy., Aims: to evaluate the diagnostic outcomes of NIT, SED and NIT disjunctively paired with SED (NIT+SED) vs. urine culture, with special focus on bladder incubation time (BIT), and to assess if NIT+SED can reduce unnecessary antibiotic therapy., Methods: A diagnostic, primary care, multicentre study including 1070 women with symptoms suggestive of lower UTI., Results: Significant bacteriuria was found in 77%. The BIT highly influenced the diagnostic outcomes and the optimal duration was ≥4h with sensitivity of 66, 90 and 95% for NIT, SED and NIT+SED, respectively. SED performed only in NIT negative specimens could reduce unnecessary antibiotics by 10% vs. prescription on symptoms only. The number needed to test with SED to reduce one unnecessary antibiotic course was five patients at BIT ≥4h and six patients at ≤3h or overall., Conclusion: The BIT highly influences the diagnostic outcomes with the highest accuracy of NIT+SED. Diagnosis of LUTIW with NIT+SED can reduce unnecessary antibiotic therapy and subsequently decrease antimicrobial resistance., Trial Registration: The Swedish Medical Product Agency 1995 03 01:151:01783/94.

In a natural environment, avoidance of a particular food source is mostly determined by a previous intake experience during which sensory stimuli such as food odor, become aversive through a simple associative conditioned learning. Conditioned odor aversion learning (COA) is a food conditioning paradigm that results from the association between a tasteless scented solution (conditioned stimulus, CS) and a gastric malaise (unconditioned stimulus, US) that followed its ingestion. In the present experimental conditions, acquisition of COA also led to acquisition of aversion toward the context in which the CS was presented (conditioned context aversion, CCA). Previous data have shown that the entorhinal cortex (EC) is involved in the memory processes underlying COA acquisition and context fear conditioning, but whether EC lesion modulates CCA acquisition has never be investigated. To this aim, male Long-Evans rats with bilateral EC lesion received CS-US pairings in a particular context with different interstimulus intervals (ISI). The results showed that the establishment of COA with long ISI obtained in EC-lesioned rats is associated with altered CCA learning. Since ISI has been suggested to be the determining factor in the odor- and context-US association, our results show that the EC is involved in the processes that control both associations relative to ISI duration.

Background: Weight loss is a public health concern in obesity-related diseases such as metabolic syndrome (MetS). However, restrictive diets might induce bone loss. The nature of exercise and whether exercise with weight loss programs can protect against potential bone mass deficits remains unclear. Moreover, compliance is essential in intervention programs. Thus, we aimed to investigate the effects that modality and exercise compliance have on bone mineral content (BMC) and density (BMD)., Methods: We investigated 90 individuals with MetS who were recruited for the 1-year RESOLVE trial. Community-dwelling seniors with MetS were randomly assigned into three different modalities of exercise (intensive resistance, intensive endurance, moderate mixed) combined with a restrictive diet. They were compared to 44 healthy controls who did not undergo the intervention., Results: This intensive lifestyle intervention (15-20 hours of training/week + restrictive diet) resulted in weight loss, body composition changes and health improvements. Baseline BMC and BMD for total body, lumbar spine and femoral neck did not differ between MetS groups and between MetS and controls. Despite changes over time, BMC or BMD did not differ between the three modalities of exercise and when compared with the controls. However, independent of exercise modality, compliant participants increased their BMC and BMD compared with their less compliant peers. Decreases in total body lean mass and negative energy balance significantly and independently contributed to decreases in lumbar spine BMC., Conclusion: After the one year intervention, differences relating to exercise modalities were not evident. However, compliance with an intensive exercise program resulted in a significantly higher bone mass during energy restriction than non-compliance. Exercise is therefore beneficial to bone in the context of a weight loss program., Trial Registration: ClinicalTrials.gov NCT00917917.

XMEN disease (X-linked immunodeficiency with Magnesium defect, Epstein-Barr virus infection and Neoplasia) is a novel primary immune deficiency caused by mutations in MAGT1 and characterised by chronic infection with Epstein-Barr virus (EBV), EBV-driven lymphoma, CD4 T-cell lymphopenia, and dysgammaglobulinemia [1]. Functional studies have demonstrated roles for magnesium as a second messenger in T-cell receptor signalling [1], and for NKG2D expression and consequently NK- and CD8 T-cell cytotoxicity [2]. 7 patients have been described in the literature; the oldest died at 45 years and was diagnosed posthumously [1-3]. We present the case of a 58-year-old Caucasian gentleman with a novel mutation in MAGT1 with the aim of adding to the phenotype of this newly described disease by detailing his clinical course over more than 20 years.