Comparative effectiveness and cost-effectiveness of natalizumab and fingolimod in rapidly evolving severe relapsing-remitting multiple sclerosis in the United Kingdom.

AIM: To evaluate the real-world comparative effectiveness and the cost-effectiveness, from a UK National Health Service perspective, of natalizumab versus fingolimod in patients with rapidly evolving severe relapsing-remitting multiple sclerosis (RES-RRMS). METHODS: Real-world data from the MSBase Registry were obtained for patients with RES-RRMS who were previously either naive to disease-modifying therapies or had been treated with interferon-based therapies, glatiramer acetate, dimethyl fumarate, or teriflunomide (collectively known as BRACETD). Matched cohorts were selected by 3-way multinomial propensity score matching, and the annualized relapse rate (ARR) and 6-month-confirmed disability worsening (CDW6M) and improvement (CDI6M) were compared between treatment groups. Comparative effectiveness results were used in a cost-effectiveness model comparing natalizumab and fingolimod, using an established Markov structure over a lifetime horizon with health states based on the Expanded Disability Status Scale. Additional model data sources included the UK MS Survey 2015, published literature, and publicly available sources. RESULTS: In the comparative effectiveness analysis, we found a significantly lower ARR for patients starting natalizumab compared with fingolimod (rate ratio [RR] = 0.65; 95% confidence interval [CI], 0.57-0.73) or BRACETD (RR = 0.46; 95% CI, 0.42-0.53). Similarly, CDI6M was higher for patients starting natalizumab compared with fingolimod (hazard ratio [HR] = 1.25; 95% CI, 1.01-1.55) and BRACETD (HR = 1.46; 95% CI, 1.16-1.85). In patients starting fingolimod, we found a lower ARR (RR = 0.72; 95% CI, 0.65-0.80) compared with starting BRACETD, but no difference in CDI6M (HR = 1.17; 95% CI, 0.91-1.50). Differences in CDW6M were not found between the treatment groups. In the base-case cost-effectiveness analysis, natalizumab dominated fingolimod (0.302 higher quality-adjusted life-years [QALYs] and £17,141 lower predicted lifetime costs). Similar cost-effectiveness results were observed across sensitivity analyses. CONCLUSIONS: This MSBase Registry analysis suggests that natalizumab improves clinical outcomes when compared with fingolimod, which translates to higher QALYs and lower costs in UK patients with RES-RRMS.

There are several medications used to treat people with relapsing remitting multiple sclerosis, such as interferon-based therapies (Betaferon/Betaseron (US), Rebif, Avonex, Extavia), glatiramer acetate (Copaxone), teriflunomide (Aubagio), and dimethyl fumarate (Tecfidera), collectively named BRACETD. Other treatments for multiple sclerosis (MS) have a narrower use, such as natalizumab (Tysabri) or fingolimod (Gilenya), among others.This study objective was to assess how well natalizumab and fingolimod helped treating MS (clinical effectiveness) and subsequently estimate what the cost of these treatments is in comparison to the benefit they bring to people with rapidly evolving severe MS that use them in the United Kingdom (UK) (cost-effectiveness).We used an international disease registry (MSBase), which collects clinical data from people with MS in various centers around the world to compare the effectiveness of natalizumab, fingolimod and BRACETD treatments. We used a technique called propensity score matching to obtain results from comparable patient groups. People treated with natalizumab had better disease control, namely with fewer relapses and higher improvement on their disability level, than patients on fingolimod or BRACETD. Conversely, there were no differences between each group of people on a measure called disability worsening.Based on these clinical results, we built an economic model that simulates the lifetime costs and consequences of treating people with MS with natalizumab in comparison with fingolimod. We found that using natalizumab was less costly and was more effective compared to using fingolimod in UK patients.

Assessing the Relative Importance of Satellite-Detected Methane Superemitters in Quantifying Total Emissions for Oil and Gas Production Areas in Algeria.

Methane emissions from oil and gas production provide an important contribution to global warming. We investigate 2020 emissions from the largest gas field in Algeria, Hassi R'Mel, and the oil-production-dominated area Hassi Messaoud. We use methane data from the high-resolution (20 m) Sentinel-2 instruments to identify and estimate emission time series for 11 superemitters (including 10 unlit flares). We integrate this information in a transport model inversion that uses methane data from the coarser (7 km × 5.5 km) but higher-precision TROPOMI instrument to estimate emissions from both the 11 superemitters (>1 t/h individually) and the remaining diffuse area source (not detected as point sources with Sentinel-2). Compared to a bottom-up inventory for 2019 that is aligned with UNFCCC-reported emissions, we find that 2020 emissions in Hassi R'Mel (0.16 [0.11-0.22] Tg/yr) are lower by 53 [24-73]%, and emissions in Hassi Messaoud (0.22 [0.13-0.28] Tg/yr) are higher by 79 [4-188]%. Our analysis indicates that a larger fraction of Algeria's methane emissions (∼75%) come from oil production than national reporting suggests (5%). Although in both regions the diffuse area source constitutes the majority of emissions, relatively few satellite-detected superemitters provide a significant contribution (24 [12-40]% in Hassi R'Mel; 49 [27-71]% in Hassi Messaoud), indicating that mitigation efforts should address both. Our synergistic use of Sentinel-2 and TROPOMI can produce a unique and detailed emission characterization of oil and gas production areas.

A metagenomics method for the quantitative detection of bacterial pathogens causing hospital-associated and ventilator-associated pneumonia.

IMPORTANCE: The management of ventilator-associated pneumonia and hospital-acquired pneumonia requires rapid and accurate quantitative detection of the infecting pathogen. To this end, we propose a metagenomic sequencing assay that includes the use of an internal sample processing control for the quantitative detection of 20 relevant bacterial species from bronchoalveolar lavage samples.

Phylogenetics of Archerfishes (Toxotidae) and Evolution of the Toxotid Shooting Apparatus.

Synopsis: Archerfishes (Toxotidae) are variously found in the fresh- and brackish-water environments of Asia Pacific and are well known for their ability to shoot water at terrestrial prey. These shots of water are intended to strike their prey and cause it to fall into the water for capture and consumption. While this behavior is well known, there are competing hypotheses (blowpipe vs. pressure tank hypothesis) of how archerfishes shoot and which oral structures are involved. Current understanding of archerfish shooting structures is largely based on two species, Toxotes chatareus and T. jaculatrix. We do not know if all archerfishes possess the same oral structures to shoot water, if anatomical variation is present within these oral structures, or how these features have evolved. Additionally, there is little information on the evolution of the Toxotidae as a whole, with all previous systematic works focusing on the interrelationships of the family. We first investigate the limits of archerfish species using new and previously published genetic data. Our analyses highlight that the current taxonomy of archerfishes does not conform to the relationships we recover. Toxotes mekongensis and T. siamensis are placed in the synonymy of T. chatareus, Toxotes carpentariensis is recognized as a species and removed from the synonymy of T. chatareus, and the genus Protoxotes is recognized for T. lorentzi based on the results of our analyses. We then take an integrative approach, using a combined analysis of discrete hard- and soft-tissue morphological characters with genetic data, to construct a phylogeny of the Toxotidae. Using the resulting phylogenetic hypothesis, we then characterize the evolutionary history and anatomical variation within the archerfishes. We discuss variation in the oral structures and the evolution of the mechanism with respect to the interrelationships of archerfishes, and find that the oral structures of archerfishes support the blowpipe hypothesis but soft-tissue oral structures may also play a role in shooting. Finally, by comparing the morphology of archerfishes to their sister group, we find that the Leptobramidae has relevant shooting features in the oral cavity, suggesting that some components of the archerfish shooting mechanism are examples of co-opted or exapted traits. Sinopsis Malay: Pelbagai jenis Ikan Sumpit (Toxotidae) dapat dijumpai di persekitaran air tawar dan payau di Asia Pasifik dan mereka terkenal dengan kebolehan mereka menembak air ke arah mangsa di darat. Tembakan air ini bertujuan untuk menyerang mangsa mereka dan menyebabkan mereka jatuh ke dalam air untuk ditangkap dan dimakan. Walaupun tingkah laku ini diketahui umum, terdapat hipotesis yang bersaing (hipotesis sumpitan vs. tangki tekanan) tentang cara ikan sumpit menembak dan struktur mulut yang terlibat. Pemahaman semasa tentang struktur menembak ikan sumpit adalah sebahagian besarnya berdasarkan dua spesies, Toxotes chatareus dan T. jaculatrix. Kami tidak pasti sama ada semua ikan sumpit mempunyai struktur mulut yang sama untuk menembak air, jika variasi anatomi terdapat dalam struktur mulut ini, atau bagaimana ciri-ciri ini telah berkembang. Tambahan pula, terdapat sedikit maklumat tentang evolusi Toxotidae secara keseluruhan, dengan semua penyelidikan sistematik sebelum ini memfokuskan pada hubungan saling keluarga. Kami pada mulanya mengkaji had spesies ikan sumpit ini menggunakan data genetik baharu dan yang diterbitkan sebelum ini. Analisis kami menunjukkan bahawa taksonomi semasa ikan sumpit tidak mematuhi hubungan yang kami perolehi. Toxotes mekongensis dan T. siamensis diletakkan bersama kesinoniman T. chatareus, Toxotes carpentariensis yang diiktiraf sebagai satu spesies dan dikeluarkan daripada kesinoniman T. chatareus, dan genus Protoxotes yang diiktiraf untuk T. lorentzi adalah berdasarkan hasil analisis kami. Kemudian kami mengambil pendekatan integratif, menggunakan analisis gabungan karakter morfologi tisu keras dan lembut diskret dengan data genetik, untuk membina filogeni Toxotidae. Menggunakan hipotesis filogenetik yang terhasil, kami kemudian mencirikan sejarah evolusi dan variasi anatomi dalam ikan sumpit. Kami membincangkan variasi dalam struktur mulut dan evolusi mekanisme berkenaan yang berkaitan dengan ikan sumpit, dan mendapati bahawa struktur mulut ikan sumpit menyokong hipotesis sumpitan tetapi struktur mulut tisu lembut juga mungkin memainkan peranan dalam cara menembak. Akhir sekali, dengan membandingkan morfologi ikan sumpit kepada kumpulan saudara mereka, kami mendapati bahawa Leptobramidae mempunyai ciri penangkapan yang relevan dalam rongga mulut mereka, menunjukkan bahawa beberapa komponen mekanisme penangkapan ikan sumpit merupakan contoh ciri-ciri yang diikut-sertakan atau diguna semula.

Psychomotor semiology in depression: a standardized clinical psychomotor approach.

BACKGROUND: Although psychomotor symptoms are associated with the clinical symptomatology of depression, they are rarely assessed and standardized clinical evaluation tools are lacking. Psychomotor retardation is sometimes assessed through direct patient observations by clinicians or through a clinical observation grid, in the absence of a standardized psychomotor assessment. In this pilot study, we evaluated the feasibility of standardized psychomotor examination of patients with major depressive disorder (MDD) and detailed a psychomotor semiology in these patients. METHODS: We used a standardized psychomotor assessment to examine 25 patients with MDD and 25 age- and sex-matched healthy controls (HC) and compared their psychomotor profiles. Using standardized tests, we assessed muscle tone and posture, gross motor skills, perceptual-motor skills, and body image/organization. Clinical assessments of depressive symptoms (levels of psychomotor retardation, anxiety, and self-esteem) comprised this detailed psychomotor examination. RESULTS: All participants were examined using the standardized psychomotor assessment. The main results of the psychomotor examination highlighted low body image of MDD participants (p < 0.001). Significant differences between groups were found in passive muscle tone, posture, emotional control, jumping, manual dexterity, walking, and praxis. Among these psychomotor variables, body image, passivity, jumping and rhythm scores predicted an MDD diagnosis. CONCLUSIONS: Beyond the psychomotor retardation known to be present in MDD patients, this examination revealed an entire psychomotor symptomatology characterized by elevated muscle tone, poor body image associated with poor self-esteem, slowness in global motor skills and manual praxis, and poor rhythmic adaptation. In light of these results, we encourage clinicians to consider using a standardized tool to conduct detailed psychomotor examination of patients with depressive disorders. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04031937 , 24/07/2019.

Does vitamin C supplementation improve rotator cuff healing? A preliminary study.

PURPOSE: One of the complications after rotator cuff repair is a tendon non-healing. It has already been posited in the literature that vitamin C (VC) promotes tendon healing through its antioxidant properties and its role as a cofactor in collagen synthesis. The aim of this study was to evaluate the effect of postoperative VC supplementation on the tendon healing following repair. METHODS: This randomized monocentric prospective study included 98 patients who underwent arthroscopic rotator cuff repair in 1-year period and follow-up ultrasound 6 months postoperatively. The cohort was divided into two groups: the VC+ group (500 mg/day PO for 45 days postoperatively) and the VC- group (no supplementation). The evaluation criterion was tendon healing at 6 months postoperatively according to the Sugaya ultrasound classification. Preoperative and postoperative clinical evaluations were based on active mobilities, the Constant score and the subjective shoulder value. RESULTS: There was no difference in term of postoperative outcomes between the two groups. At an average follow-up of 6.3 months, the non-healing rate in the overall population was 17%. This rate was higher in VC- compared to VC+, respectively, 23% vs. 11%), p = 0.2. CONCLUSION: This study showed a trend to improve tendon healing after rotator cuff repair with VC supplementation. However, a prospective study with a larger patient population should be conducted to confirm this finding.

Ethical considerations of the dynamics of clinical trials in an epidemic context: Studies on COVID-19.

The COVID-19 epidemic has led to the intense mobilization of all health professionals, including those involved in research. From the very beginning, research ethics committees (RECs) have been called upon and mobilized to carry out the scientific and ethical evaluations of research projects to achieve a sound analysis of their risk/benefit balance. The aim of this article is to present an ethical reflection on the challenges and consequences of the fast-track procedure for the evaluation of COVID-19 research projects in the context of a public health emergency. Indeed, a large number of protocols of reduced rigor were hastily prepared without collaboration between researchers and in the absence of national regulation. As a result, a number of ethical dilemmas have emerged concerning the opposing needs of pragmatism imposed by the emergency context and the ethical principles that should govern the conduct of research. Moreover, the dispersion of these individual projects, aggravated by excessive media coverage of specific treatments, has resulted in a weakened impact of the research in the epidemic context. This article provides suggestions for the ethical management of ongoing and upcoming research, giving RECs the opportunity to adapt their evaluations to avoid allowing the pragmatism of the emergency context to subvert the inviolability of the epistemological and ethical principles of research on humans. This reflection may strengthen the ethical basis for the formulation of their decisions.

Pain Intensity and Functional Outcomes for Activities of Daily Living, Gait and Balance in Older Adults Accessing Outpatient Rehabilitation Services: A Retrospective Study.

PURPOSE: Older adults are referred for outpatient physical therapy to improve their functional capacities. The goal of the present study was to determine if pain had an influence on functional outcomes in older adults who took part in an outpatient physical rehabilitation program. PATIENTS AND METHODS: A retrospective study was performed on the medical records of patients aged 65 and over referred for outpatient physical therapy to improve physical functioning (n=178). Pain intensity (11-point numeric pain scale) and results from functional outcome measures (Timed Up and Go [TUG], Berg Balance Scale [BBS], 10-meter walk test, 6-minute walk test and Functional Autonomy Measuring System [SMAF]) were extracted at initial (T1) and final (T2) consultations. Paired t-tests were performed to determine if there were differences in functional outcome measures between T1 and T2 in all the patients. Patients were stratified to those with pain (PAIN, n=136) and those without pain (NO PAIN, n=42). Differences in functional outcome measures between T1 and T2 (delta scores) were compared between groups with independent t-tests with Welch corrections for unequal variances. Pearson correlation coefficients between initial pain intensity and changes in functional outcome measures (T2-T1) were also performed. Correcting for multiple comparisons, a p-value of p≤0.01 was considered as statistically significant. RESULTS: The TUG, BBS, 10-meter walk test, 6-minute walk test all demonstrated improvement between T1 and T2 (all p<0.01). There was no difference between groups for delta scores for TUG (p=0.14), BBS (p=0.03), 10-meter walk test (p=0.54), 6-minute walk test (p=0.94) and SMAF (p=0.23). Pearson correlation coefficients were weak between initial pain intensity and changes in functional outcome scores between T1 and T2 (r= -0.16 to 0.15, all p-values >0.10). CONCLUSION: These results suggest that pain is not an impediment to functional improvements in older individuals who participated in an outpatient physical rehabilitation program.

Chestnut extract but not sodium salicylate decreases the severity of diarrhea and enterotoxigenic Escherichia coli F4 shedding in artificially infected piglets.

The development of alternatives to antibiotics is crucial to limiting the incidence of antimicrobial resistance, especially in prophylactic and metaphylactic use to control post-weaning diarrhea (PWD). Feed additives, including bioactive compounds, could be a promising alternative. This study aimed to test two bioactive compounds, sodium salicylate (SA) and a chestnut extract (CE) containing hydrolysable tannins, on the occurrence of PWD. At weaning, 72 piglets were assigned to four treatments that combined two factors: CE supplementation (with 2% of CE (CE+) or without (CE-)) and SA supplementation (with 35 mg/kg BW of SA (SA+) or without (SA-)). Then, 4 days after weaning, all piglets were infected with a suspension at 108 CFU/ml of enterotoxigenic Escherichia coli (ETEC F4ac). Each piglet had free access to an electrolyte solution containing, or not, SA. This SA supplementation was administered for 5 days (i.e., from the day of infection (day 0) to 4 days post-infection (day 4). During the 2 weeks post-infection, supplementation with SA had no effect (P > 0.05) on growth performances nor on fecal scores. A significant SA × time interaction (P < 0.01) for fecal scores and the percentage of diarrhea indicated that piglets with SA did not recover faster and did have a second episode of diarrhea. In contrast to SA treatment, inclusion of CE increased (P < 0.05) growth performances and feed intake. In the first week post-infection, CE decreased (P < 0.001) the overall fecal scores, the percentage of piglets with diarrhea, the days in diarrhea, and ETEC shedding in the feces. There was a SA×CE interaction (P < 0.05) for ETEC shedding, suggesting a negative effect of combining SA with CE. This study highlighted that, in contrast to SA, CE could represent a promising alternative to antibiotics immediately after weaning for improving growth performance and reducing PWD.

Invited review: Tannins as a potential alternative to antibiotics to prevent coliform diarrhea in weaned pigs.

In addition to a multifactorial etiology of nutritional, social and environmental stressors, post-weaning diarrhea (PWD) in pigs is often related to infection with specific pathogens such as enterotoxigenic Escherichia coli (ETEC). In swine farming operations, the incidence of PWD is a global concern and is associated with an unbalanced gut status, resulting in poor performance and high antimicrobial consumption via prophylaxis and metaphylaxis. Increases in antimicrobial resistance are reinforcing an already-urgent need for sustainable, alternative solutions for maintaining optimal gut health in livestock. Tannin-rich plants and extracts contain bioactive compounds that could be of great interest in this respect. This review describes how the use of tannins around weaning could be beneficial for pigs, with special emphasis on the reduction of ETEC-related PWD. An overview of the broad chemical diversity of tannins is presented together with their physicochemical and biological properties, as well as how they may be metabolized in the digestive tract. The pharmacological effects exerted by tannins are summarized; more precisely, the possible mechanisms by which tannins can disrupt the different steps of the pathogenesis of ETEC-related PWD are highlighted. The factors affecting the bioactivity of tannins are also discussed, shedding light on the importance of chemical structure among different tannins.

Efficacy of the NICHD vaginal birth after cesarean delivery calculator: a single center experience.

Objective: As the cesarean delivery rate has risen future pregnancy outcomes are impacted including the decision to undergo a repeat cesarean or a vaginal birth after cesarean (VBAC) in the subsequent pregnancy. A calculator was developed by the maternal fetal medicine units (MFMUs) network in 2007 to estimate the chance of successful VBAC and is used widely. The purpose of this study was to investigate the calculator's validity on our obstetric patient population.Study design: This was a retrospective study of patients attempting a VBAC delivery at a single center from January 2012 to June 2014. Chances for success were estimated using the MFMU network VBAC calculator in 201 evaluable patients. We then compared the calculator's results with the outcomes observed. In order to determine if the MFMU VBAC calculator was accurately predicting successful vaginal deliveries, we discretized our dataset by binning into MFMU score deciles. Each decile was then tested for significant deviations from the predicted success rate using an exact binomial test. Significance was determined at 0.05 levels.Results: Two hundred and one patients were included. Our results demonstrated higher actual VBAC success than anticipated by using the MFMU network calculator for patients with scores in the 40-80% decile range. When stratified by race, we found the calculator to be a better predictor of success in African-American patients, as the calculator appears to underestimate success in white and Hispanic patients.Conclusion: Calculators are helpful to facilitate patient counseling and shared decision-making regarding the patient's choice for VBAC. When providing such counseling, the potential for reduced predicted VBAC success in the mid-decile range with the MFMU calculator should be recognized.

From genotype to antibiotic susceptibility phenotype in the order Enterobacterales: a clinical perspective.

OBJECTIVES: Predicting the antibiotic susceptibility phenotype from genomic data is challenging, especially for some specific antibiotics in the order Enterobacterales. Here we aimed to assess the performance of whole genomic sequencing (WGS) for predicting the antibiotic susceptibility in various Enterobacterales species using the detection of antibiotic resistance genes (ARGs), specific mutations and a knowledge-based decision algorithm. METHODS: We sequenced (Illumina MiSeq, 2×250 bp) 187 clinical isolates from species possessing (n = 98) or not (n = 89) an intrinsic AmpC-type cephalosporinase. Phenotypic antibiotic susceptibility was performed by the disc diffusion method. Reads were assembled by A5-miseq and ARGs were identified from the ResFinder database using Diamond. Mutations on GyrA and ParC topoisomerases were studied. Piperacillin, piperacillin-tazobactam, ceftazidime, cefepime, meropenem, amikacin, gentamicin and ciprofloxacin were considered for prediction. RESULTS: A total of 1496 isolate/antibiotic combinations (187 isolates × 8 antibiotics) were considered. In 230 cases (15.4%), no attempt of prediction was made because it could not be supported by current knowledge. Among the 1266 attempts, 1220 (96.4%) were correct (963 for predicting susceptibility and 257 for predicting resistance), 24 (1.9%) were major errors (MEs) and 22 (1.7%) were very major errors (VMEs). Concordance were similar between non-AmpC and AmpC-producing Enterobacterales (754/784 (96.2%) vs 466/482 (96.7%), chi-square test p 0.15), but more VMEs were observed in non-AmpC producing strains than in those producing an AmpC (19/784 (2.4%) vs 3/466 (0.6%), chi-square test p 0.02). The majority of VMEs were putatively due to the overexpression of chromosomal genes. CONCLUSIONS: In conclusion, the inference of antibiotic susceptibility from genomic data showed good performances for non-AmpC and AmpC-producing Enterobacterales species. However, more knowledge about the mechanisms underlying the derepression of AmpC are needed.

Anti-inflammatory disease-modifying treatment and disability progression in primary progressive multiple sclerosis: a cohort study.

BACKGROUND AND PURPOSE: Treatment options in primary progressive multiple sclerosis (PPMS) are scarce and, with the exception of ocrelizumab, anti-inflammatory agents have failed to show efficacy in ameliorating disability progression. The aim of this study was to investigate a potential effect of anti-inflammatory disease-modifying treatment on disability outcomes in PPMS. METHODS: Using MSBase, a large, international, observational database, we identified patients with PPMS who were either never treated or treated with a disease-modifying agent. Propensity score matching was used to select subpopulations with similar baseline characteristics. Expanded Disability Status Scale (EDSS) outcomes were compared with an intention-to-treat and an as-treated approach in paired, pairwise-censored analyses. RESULTS: Of the 1284 included patients, 533 were matched (treated, n = 195; untreated n = 338). Median on-study pairwise-censored follow-up was 3.4 years (quartiles 1.2-5.5). No difference in the hazard of experiencing 3-month confirmed EDSS progression events was observed between the groups [hazard ratio (HR), 1.0; 95% confidence interval (CI), 0.6-1.7, P = 0.87]. We did not find significant differences in the hazards of confirmed EDSS improvement (HR, 1.0; 95% CI, 0.6-1.6, P = 0.91) or reaching a confirmed EDSS step ≥7 (HR, 1.1; 95% CI, 0.7-1.6, P = 0.69). CONCLUSION: Our pooled analysis of disease-modifying agents suggests that these therapies have no substantial effect on short- to medium-term disability outcomes in PPMS.

Chemical stabilization of polymers: Implications for dermal exposure to additives.

Technical benefits of additives in polymers stand in marked contrast to their associated health risks. Here, a multi-analyte method based on gas chromatography coupled to tandem mass spectrometry (GC-MS/MS) was developed to quantify polymer additives in complex matrices such as low-density polyethylene (LDPE) and isolated human skin layers after dermal exposure ex vivo. That way both technical aspects and dermal exposure were investigated. The effects of polymer additivation on the material were studied using the example of LDPE. To this end, a tailor-made polymer was applied in aging studies that had been furnished with two different mixtures of phenol- and diarylamine-based antioxidants, plasticizers and processing aids. Upon accelerated thermo-oxidative aging of the material, the formation of LDPE degradation products was monitored with attenuated total reflectance-Fourier transformed infrared (ATR-FTIR) spectroscopy. Compared to pure LDPE, a protective effect of added antioxidants could be observed on the integrity of the polymer. Further, thermo-oxidative degradation of the additives and its kinetics were investigated using LDPE or squalane as matrix. The half-lives of additives in both matrices revealed significant differences between the tested additives as well as between LDPE and squalane. For instance, 2-tert-butyl-6-[(3-tert-butyl-2-hydroxy-5-methylphenyl)methyl]-4-methylphenol (Antioxidant 2246) showed a half-life 12 times lower when incorporated in LDPE as compared to squalane. As a model for dermal exposure of consumers, human skin was brought into contact with the tailor-made LDPE containing additives ex vivo in static Franz diffusion cells. The skin was then analyzed for additives and decomposition products. This study proved 10 polymer additives of diverse pysicochemical properties and functionalities to migrate out of the polymer and eventually overcome the intact human skin barrier during contact. Moreover, their individual distribution within distinct skin layers was demonstrated. This is exemplified by the penetration of the procarcinogenic antioxidant N-phenylnaphthalen-2-amine (Neozon D) into the viable epidermis and the permeation through the skin of the neurotoxic plasticizer N-butylbenzenesulfonamide (NBBS). In addition, the analyses of additive degradation products in the isolated skin layers revealed the presence of 2-tert-butyl-4-methylphenol in all layers after contact to a polymer with substances of origin like Antioxidant 2246. Thus, attention needs to be paid to absorption of polymer additives together with their degradation products when it comes to dermal exposure assessment.

In vivo selection of a multidrug-resistant Aeromonas salmonicida during medicinal leech therapy.

We report the selection in a 15-year-old boy of a multidrug-resistant, extended-spectrum ß-lactamase (ESBL)-producing Aeromonas salmonicida after medicinal leech therapy that required an antibiotic prophylaxis based on piperacillin/tazobactam and cotrimoxazole. Whole genome sequencing of the strain indeed revealed 13 antibiotic resistance genes, including the ESBL CTX-M-3 and the unusual ß-lactamase SCO-1.

[Trauma and pregnancy: Is the Kleihauer-Betke test really useful?] / Traumatisme et grossesse : le test de Kleihauer est-il vraiment utile ?

OBJECTIVE: To evaluate the pertinence of Kleihauer-Betke (KB) test, in case of abdominal trauma during pregnancy in forecast of fetal outcomes, according to trauma severity. METHODS: A single-center retrospective study conducted between January 2014 and April 2016 in a maternity type III and a trauma center, which included the pregnant women admitted for abdominal trauma. The trauma's severity was assessed using the guidelines of the Society of Obstetricians and Gynaecologists of Canada. The impact of a positive KB test, defined as>0.1%, was analyzed. Adverse outcome was defined as one or more of the following complications: intrauterine fetal death, placental abruption, pre-term birth<37 weeks of gestation, and fetal or neonatal anemia. RESULTS: During the study period, 265 pregnancies involved into an abdominal trauma were included: 69% with a minor trauma and 31% with a severe trauma. Of all patients, 5.6% presented a positive KB test, among then 15.4% had an adverse outcome. There was no significant difference in the rate of adverse outcomes in the positive KB group and the KB negative group either in the overall population (P=0.16), in the minor trauma population (P=1) or in the major trauma population (P=0.14). The predictive positive values were respectively in the global population, in the minor trauma group and in the severe trauma group 15.4%, 0% and 25%. CONCLUSIONS: The KB test does not seem to be useful in case of trauma during pregnancy to define adverse outcome.

Obesity and reproduction: a study to determine how effectively medical education enhances awareness of the reproductive risks related to obesity.

OBJECTIVE: To explore awareness of the reproductive versus the medical risks of obesity in a medical and non-medical college educated population. METHODS: An exploratory prospective research design was used. A 26-question online survey was developed and offered to a sample of medical students/residents (n=325) and non-medical college students (n=102). The data were analyzed using Graph Pad software. RESULTS: 102 non-medical undergraduate students (28% male and 72% female) and 325 resident physicians and medical students (46% male, 47% female, 7% unspecified) responded. Both groups reported higher awareness of the general risks of obesity as compared to the reproductive risks. As expected, lay students reported less awareness of female reproductive issues as compared to the medical group (all p-values <0.01). Over 90% of respondents would be motivated to lose weight before pregnancy if they knew of these risks, with more than half planning to have children in the future. CONCLUSION: This exploratory study found that despite having at least a college education, the populations studied had relatively low levels of awareness of obesity-related reproductive risks. The medical population had much more knowledge about the other health risks of obesity. The survey provided initial data that might be used to consider knowledge gaps and strategies for engaging and educating medical trainees and the public about the reproductive risks of obesity.

In vitro ruminal fermentation characteristics and utilisable CP supply of sainfoin and birdsfoot trefoil silages and their mixtures with other legumes.

The extensive protein degradation occurring during ensiling decreases the nutritive value of silages, but this might be counteracted by tannins. Therefore, silages from two legume species containing condensed tannins (CT) - sainfoin (SF) and birdsfoot trefoil (two cultivars: birdsfoot trefoil, cv. Bull (BTB) and birdsfoot trefoil, cv. Polom) - were compared for their in vitro ruminal fermentation characteristics. The effect of combining them with two CT-free legume silages (lucerne (LU) and red clover (RC)) was also determined. The supply of duodenally utilisable CP (uCP) in the forages was emphasised. The legumes were each harvested from three field sites. After 24 h of wilting on the field, the legumes were ensiled in laboratory silos for 86 days. Proximate constituents, silage fermentation characteristics, CT content and CP fractions were determined. Subsequently, silage samples and 1 : 1 mixtures of the CT-containing and CT-free silages were incubated for 24 h in batch cultures using ruminal fluid and buffer (1 : 2, v/v). Each treatment was replicated six times in six runs. The effects on pH, ammonia and volatile fatty acid concentrations, protozoal counts, and total gas and methane production were determined. uCP content was calculated by considering the CP in the silage and the ammonia in the incubation fluid from treatments and blanks. Statistical evaluation compared data from single plants alone and together with that from the mixtures. Among treatments, SF silage contained the least CP and the most CT. The non-protein nitrogen content was lower, favouring neutral detergent soluble and insoluble protein fractions, in the SF and RC silages. Absolute uCP content was lowest in SF and SF mixtures, although the ratio to total CP was the highest. In comparison with LU, the ammonia concentration of the incubation fluid was lower for SF, RC and BTB and for the mixture of SF with LU. The total gas and methane production was similar among the treatments, and the total volatile fatty acid production was decreased with the CT-containing legumes. Protozoal count was increased with the mixtures containing LU and either SF or BTB compared with single LU. In conclusion, compared with the other legumes, SF and RC have similar advantages as they show limited proteolysis during ensiling. In addition, SF supplies more uCP relative to total CP. The CT-containing legumes also differed in their effect on ruminal fermentation and ammonia formation, probably because of their different CT contents. Thus, SF and its mixtures appear promising for improving the protein utilisation of ruminants.

Laterality and Lateralization in Autism Spectrum Disorder, Using a Standardized Neuro-Psychomotor Assessment.

A detailed assessment of laterality in children with Autism Spectrum Disorder (ASD) was realized, including handedness and other measures (muscle tone, manual performance, dominant eye), using a standardized battery for the developmental assessment of neuro-psychomotor functions. The results of the laterality tests relating to cerebral hemisphere organization (spontaneous gestural laterality and tonic laterality) were different in ASD children, and indicate that the cerebral organization could be disrupted. These assessments, added to the observations of usual laterality most often reported in the literature, provide better understanding of the developmental organization from the pathophysiological point of view in children with ASD.