Cluster of serogroup W invasive meningococcal disease in a university campus.

INTRODUCTION: In France, the expansion of an hypervirulent strain causing serogroup W invasive meningococcal disease (MenW) has been observed since 2015/16. We describe a cluster of three MenW cases, causing two deaths, at the end of 2016 in a university campus, and the vaccination campaign which was consequently organized. METHODS: Epidemiological and microbiological analyses led a multidisciplinary expertise group to recommend the organization of a mass vaccination campaign using ACWY vaccine targeting more than 30,000 students and staff in the university campus. Individual data on vaccination was collected using the lists of students and staff registered at the university to estimate vaccine coverage. RESULTS: Three MenW cases occurred within a 2-month period among students in different academic courses. All three isolates were identical and belonged to the "UK-2013 strain" phylogenetic branch. The attack rate was 10.8/100,000 students. The vaccination campaign was organized only 15 days after the third case occurred. In total, 13,198 persons were vaccinated. Vaccine coverage was estimated at 41% for students of the university and 35% for university staff. CONCLUSION: Timely notification of cases to health authorities was essential for the detection of the cluster and the rapid implementation of the vaccination campaign. No further cases occurred in the campus in the year following the vaccination campaign. This episode is the second cluster of MenW caused by the "UK-2013 strain" in a university since 2016.

Contribution of myofibrillar and connective tissue components to the Warner-Bratzler shear force of cooked beef.

Myofibrillar (MF-SF) and connective tissue (CT-SF) peak shear forces were interpolated from Warner-Bratzler shear force (SF) deformation curves of cooked bovine M. gluteus medius (GM) and M. semitendinosus (ST) from 112 crossbred steers in a 2×2×2 factorial experiment examining the interactions between slaughter age, growth promotants and breed cross (British versus Continental). Mixed model analyses, Pearson correlations and stepwise multiple regression identified relationships between shear forces, meat quality measurements and production treatments. Connective tissue contribution to SF increased with slaughter age and implantation in the ST and with slaughter age only in the GM. Myofibrillar contribution to SF increased with slaughter age for the ST and with Continental genetics for the GM. Variation in ST SF and MF-SF was best described by muscle weight, which increased with animal age, while GM SF and MF-SF variation was best described by cooking loss, indicating that ST and GM SF were most affected by connective and myofibrillar proteins, respectively.

[Risk factors for developing pneumothorax in full-term neonates with respiratory distress]. / Détresse respiratoire du nouveau-né à terme : quels facteurs de risque de développer un pneumothorax ?

OBJECTIVES: To describe respiratory distress (RD) in full-term neonates hospitalized in the NICU and to determine risk factors in this population for pneumothorax. STUDY DESIGN: Retrospective inclusion for 4 years of full-term neonates hospitalized for RD before the 2nd day of life. Neonates were separated into Group I (RD with no pneumothorax) and Group II (RD with pneumothorax). Data collected from maternal and newborn medical records were obstetrical, perinatal, and postnatal. P<0.05 was set as the significance level. RESULTS: Ninety-six neonates were included. In this population, 64 (66.7%) were male, 45 (46.9%) were born by cesarean section, and 30 (31.3%) by elective cesarean section. Neonatal outcome was 4.6 days of hospital stay, 47.4% odds of mechanical ventilation, and 17.7% of persistent pulmonary hypertension of the neonate (PPHN). A central catheter was needed in 25% of the patients and amine treatment in 3.1%. The number of neonates born by cesarean section was lower as term increased. Those born by cesarean section were more likely to develop PPHN (26.7 vs 9.8%; P=0.03), and those born without labor were more likely to require oxygen (83.3 vs 63.6%; P=0.05). When comparing Group I and Group II (32 neonates), absence of labor (RR 1.5) and birth outside of a level III maternity unit (RR 1.6) were risk factors for pneumothorax. These results were confirmed in multivariate analysis. In Group II, birth before 39 weeks was a risk factor for bilateral pneumothorax (P=0.01). The median length of hospitalization was significantly longer in Group II than in Group I (5.8 days vs 4 days, P=0.03). CONCLUSIONS: RD at term exposes the infant to high morbidity and pneumothorax, especially if born outside of a level III maternity unit and absence of labor.

[Neonatal intoxication with pyrimethamine: risk due to the absence of pediatric formulation?]. / Intoxication néonatale à la pyriméthamine : un risque lié à l'absence de forme galénique pédiatrique ?

Curative treatment of congenital toxoplasmosis is based on the association of pyrimethamine and sulfonamide. There is currently no pediatric galenic formulation. We report the case of a newborn child affected by asymptomatic congenital toxoplasmosis who received an overdose of pyrimethamine. The patient received a dose of pyrimethamine 4 times, equal to 100 times the recommended dose, due to an error in the prescription. He had partial seizures 48 h after the last medicinal absorption. We noted a lack of appetite and vomiting, with a favorable progression in 5 days. Blood analysis showed isolated, spontaneously regressive moderate cholestasis. We propose a pharmacological clarification on the treatment of congenital toxoplasmosis.

[Neonatal seizures, buprenorphine abstinence syndrome, and substitutive treatment with morphine]. / Convulsions néonatales, syndrome de sevrage à la buprénorphine et traitement morphinique substitutif.

We report the case of a hypotrophic twin who presented neonatal abstinence syndrome to buprenorphine and developed neonatal seizures when the substitutive treatment by morphine was stopped. The other eutrophic twin did not develop withdrawal symptoms. This case demonstrates the unpredictable nature of transplacental transfer of buprenorphine. It also shows that neonatal abstinence syndrome can be potentially severe and that morphine treatment is not without risk.

Effects of feeding dry propylene glycol to early postpartum Holstein dairy cows on production and blood parameters.

In all, 18 multiparous and 19 primiparous Holstein dairy cows were used in a completely randomized design with restrictions to evaluate the effects of feeding propylene glycol (PG) as a dry product, via two delivery methods, on production and blood parameters. PG treatments were administered from parturition through 21 days postpartum. Treatments were: (i) control, no PG; (ii) top dress, 162.5 g PG/day by top dressing onto the total mixed ration (TMR) and; (iii) mixing, 162.5 g PG/day as a part of the TMR by incorporating it into the TMR. PG used was a dry product which contained 65% pure PG and 35% silicon dioxide as the dry carrier. Coccygeal blood was sampled on 4, 7, 14 and 21 days in milk (±1.50 pooled s.d.). Supplementation of dry PG by top dressing onto, or incorporating into, the TMR had no effects on average dry matter intake, milk yield and composition, serum insulin, serum and plasma metabolites and milk ketones. Concentrations of urine ketones tended (P = 0.10) to be reduced by PG supplementation from 41.5 to 15.2 mg/dl. Supplementation of PG tended (P = 0.07) to decrease the incidence for subclinical ketosis from 39% to 24% and 13% for cows fed a TMR supplemented with no dry PG, with dry PG as a top dress and dry PG as a part of the TMR, respectively. It is concluded that supplementing PG as a dry product via incorporating into the TMR is as effective as when used as a top dress, based on the efficacies of both delivery methods to numerically reduce urine ketones concentrations and, therefore, the incidence for subclinical ketosis during the first 21 days of lactation. However, it should be noted that the number of cows used in the current study was minimal, and more cows are needed to confirm the efficacy of supplementing PG as a dry product on reducing the prevalence of subclinical ketosis in dairy cows during the first month of lactation.

Effect of a preparation of Saccharomyces cerevisiae on microbial profiles and fermentation patterns in the large intestine of horses fed a high fiber or a high starch diet.

Eight horses were allotted into pairs consisting of one cecum- and right ventral colon-fistulated animal and one cecum-fistulated animal. They were fed daily at the same level of intake either a high-fiber (HF) or a high-starch (HS) diet without or with 10 g of a Saccharomyces cerevisiae preparation, in a 4 x 4 Latin square design. The HS diet provided a starch overload (i.e., 3.4 g starch x kg(-1) BW x meal(-1)) while maintaining a high amount of fiber intake (i.e., dietary NDF/starch ratio was 1.0). A 21-d period of adaptation to the treatments occurred before cecal and colonic contents were withdrawn 4 h after the morning meal to count total anaerobic, cellulolytic, and lactic acid-utilizing bacteria, lactobacilli, and streptococci. Lactic acid, volatile fatty acids, ammonia concentrations, and pH were measured on cecal and colonic fluid samples collected hourly during the first 12-h postfeeding. When the HS diet was fed, the concentration of total anaerobic and lactic acid-utilizing bacteria increased (P < 0.001), whereas that of cellulolytic bacteria decreased (P < 0.05) in the cecum. The concentration of lactobacilli and streptococci increased (P < 0.001) in the cecal and colonic contents. These alterations of the microbial profiles were associated with decreases (P < 0.001) of pH, (acetate + butyrate)/propionate ratio and with an increase (P < 0.001) of lactic acid concentration. Supplementing the S. cerevisiae preparation increased (P < 0.01) the concentration of viable yeast cells, averaging 4.3 x 10(6) and 4.5 x 10(4) cfu/mL in the cecal and colonic contents, respectively. Yeast supplementation had almost no effect on microbial counts in the cecum and colon. The supplementation of S. cerevisiae appeared to modify (P < 0.05) pH, concentrations of lactic acid and ammonia, molar percentages of acetate and butyrate with the HS diet and [(acetate + butyrate)/propionate] ratio when the HF diet was fed. The effects of the S. cerevisiae preparation were greater in the cecum than in the colon, which coincided with the abundance of yeast cells. When the digestion of starch in the small intestine was saturated, the effect of the addition of a S. cerevisiae preparation appeared to limit the extent of undesirable changes in the intestinal ecosystem of the horse.

Plasma corticosterone response to acute and chronic voluntary exercise in female house mice.

Plasma levels of corticosterone (B) respond acutely to exercise in all mammals that have been studied, but the literature contains conflicting reports regarding how chronic activity alters this response. We measured acute and chronic effects of voluntary activity on B in a novel animal model, mice selectively bred for high voluntary wheel running. Female mice were housed with or without wheels for 8 wk beginning at 26 days of age. Wheel-access selection mice had significantly higher B at night 8, day 15, and night 29, compared with wheel-access controls. Elevation of B was an acute effect of voluntary exercise. When adjusted for running in the previous 20 min, no difference between wheel-access selection and control animals remained. No training effect on B response was observed. These results are among the strongest evidence that, in some animals, the acute B response is unaffected by chronic voluntary exercise. In mice without wheels, selection mice had significantly higher B than controls at day 15, night 29, and night 50, suggesting that selection resulted in a modulation of the hypothalamic-pituitary-adrenal axis. Growth over the first 4 wk of treatment was significantly and inversely related to average night B levels within each of the four treatment groups.

Maternal-care behavior and life-history traits in house mice (Mus domesticus) artificially selected for high voluntary wheel-running activity.

To test the hypothesis that selective breeding for high voluntary wheel running negatively affects maternal performance in house mice, we observed maternal behavior and compared litter size and mass, in replicate lines of selected (N=4) and control (N=4) mice from generations 20 and 21 of an artificial selection experiment. At generation 21, selected-line females ran 2.8-times more revolutions per day than females from random-bred control lines, when tested at approximately 6 weeks of age as part of the normal selection protocol. After giving birth, dams from selected and control lines exhibited similar frequencies of maternal behaviors and also spent similar amounts of time in general locomotor activity at litter ages of both 9 and 16 days. Dams from selected lines also performed equally well as controls in repeated pup-retrieval trials. At first parturition, selected-line dams averaged 2.4 g smaller in body mass as compared with dams from the control lines; however, neither litter size nor litter mass at birth (generation 20) or at weaning (generation 21) differed significantly between selected and control lines. We conclude that, at least under the husbandry conditions employed, maternal behavior and reproductive output at first parturition are genetically independent of wheel-running behavior.

Differential sensitivity to acute administration of cocaine, GBR 12909, and fluoxetine in mice selectively bred for hyperactive wheel-running behavior.

RATIONALE: To study the neural basis of genetic hyperactivity, we measured acute drug responses of mice (Mus domesticus) from four replicate lines that had been selectively bred (23-24 generations) for increased running-wheel activity. OBJECTIVES: We tested the hypothesis that the high-running lines would respond differently to cocaine, GBR 12909, and fluoxetine (Prozac) compared with four replicate, random-bred, control lines. We also tested the hypothesis that the high-running lines would display hyperactivity in cages without wheels. METHODS: Drug trials were conducted at night, during peak activity, after animals were habituated (3 weeks) to their cages with attached wheels. Revolutions on wheels 10-40 min post-injection were used to quantify drug responses. In a separate study, total photobeam breaks (produced on the first and second 24-h period of exposure) were used to quantify basal activity in animals deprived of wheels. RESULTS: Cocaine and GBR 12909 decreased wheel running in selected lines by reducing the average speed but not the duration of running, but these drugs had little effect in control lines. Fluoxetine reduced running speed and duration in both selected and control animals, and the magnitude of the reduction was proportional to baseline activity. Basal activity in animals deprived of wheels (quantified using photobeam breaks) was significantly higher in selected than control lines on the second day of testing. CONCLUSIONS: These results suggest an association between genetically determined hyperactive wheel-running behavior and dysfunction in the dopaminergic neuromodulatory system. Our selected lines may prove to be a useful genetic model for attention deficit hyperactivity disorder.

Open-field behavior of house mice selectively bred for high voluntary wheel-running.

Open-field behavioral assays are commonly used to test both locomotor activity and emotionality in rodents. We performed open-field tests on house mice (Mus domesticus) from four replicate lines genetically selected for high voluntary wheel-running for 22 generations and from four replicate random-bred control lines. Individual mice were recorded by video camera for 3 min in a 1-m2 open-field arena on 2 consecutive days. Mice from selected lines showed no statistical differences from control mice with respect to distance traveled, defecation, time spent in the interior, or average distance from the center of the arena during the trial. Thus, we found little evidence that open-field behavior, as traditionally defined, is genetically correlated with wheel-running behavior. This result is a useful converse test of classical studies that report no increased wheel-running in mice selected for increased open-field activity. However, mice from selected lines turned less in their travel paths than did control-line mice, and females from selected lines had slower travel times (longer latencies) to reach the wall. We discuss these results in the context of the historical open-field test and newly defined measures of open-field activity.

Field cost of activity in the kit fox, Vulpes macrotis.

Field metabolic rates and daily movement distances were measured in 26 individual kit foxes (Vulpes macrotis) over a 29-mo period in the southern Mojave Desert of California. Kit foxes traveled long distances (up to 32 km d(-1)), with males usually traveling farther than females. Daily movement distances were affected by season, since males traveled the greatest distances in spring and females traveled farthest in summer. Individual foxes tracked multiple times demonstrated repeatability of daily movement distance between nights, between summer and winter, and between consecutive winters. The field cost of activity per unit distance was estimated as 15.6 kJ km(-1) from the partial regression coefficient of a multiple linear regression model, a value not significantly different from the incremental cost of locomotion derived from laboratory measurements. The field cost of activity was not affected by season, despite the expectation of higher costs of activity in the winter with increased thermoregulatory expenditure. The large daily movement distances resulted in significant activity energy expenditure (11%-33% of field metabolic rate), with a mean of 21% of field metabolic rate expended in activity during nonreproductive seasons.

Selection for high voluntary wheel-running increases speed and intermittency in house mice (Mus domesticus).

In nature, many animals use intermittent rather than continuous locomotion. In laboratory studies, intermittent exercise regimens have been shown to increase endurance compared with continuous exercise. We hypothesized that increased intermittency has evolved in lines of house mice (Mus domesticus) that have been selectively bred for high voluntary wheel-running (wheel diameter 1.12 m) activity. After 23 generations, female mice from four replicate selection lines ran 2.7 times more revolutions per day than individuals from four random-bred control lines. To measure instantaneous running speeds and to quantify intermittency, we videotaped mice (N=41) during a 5-min period of peak activity on night 6 of a 6-day exposure to wheels. Compared with controls (20 revs min(-1) while actually running), selection-line females (41 revs min(-1)) ran significantly faster. These instantaneous speeds closely matched the computer-recorded speeds over the same 5-min period. Selection-line females also ran more intermittently, with shorter (10.0 s bout(-1)) and more frequent (7.8 bouts min(-1)) bouts than controls (16.8 s bout(-1), 3.4 bouts min(-1)). Inter-bout pauses were also significantly shorter in selection-line (2.7 s) than in control-line (7.4 s) females. We hypothesize that intermittency of locomotion is a key feature allowing the increased wheel-running performance at high running speeds in selection-line mice.

Energetics of free-ranging mammals, reptiles, and birds.

We summarize the recent information on field metabolic rates (FMR) of wild terrestrial vertebrates as determined by the doubly labeled water technique. Allometric (scaling) relationships are calculated for mammals (79 species), reptiles (55 species), and birds (95 species) and for various taxonomic, dietary, and habitat groups within these categories. Exponential equations based on body mass are offered for predicting rates of daily energy expenditure and daily food requirements of free-ranging mammals, reptiles, and birds. Significant scaling differences between various taxa, dietary, and habitat groups (detected by analysis of covariance with P < or = 0.05) include the following: (a) The allometric slope for reptiles (0.889) is greater than that for mammals (0.734), which is greater than that for birds (0.681); (b) the slope for eutherian mammals (0.772) is greater than that for marsupial mammals (0.590); (c) among families of birds, slopes do not differ but elevations (intercepts) do, with passerine and procellariid birds having relatively high FMRs and gallinaceous birds having low FMRs; (d) Scleroglossan lizards have a higher slope (0.949) than do Iguanian lizards (0.793); (e) desert mammals have a higher slope (0.785) than do nondesert mammals; (f) marine birds have relatively high FMRs and desert birds have low FMRs; and (g) carnivorous mammals have a relatively high slope and carnivorous, insectivorous, and nectarivorous birds have relatively higher FMRs than do omnivores and granivores. The difference detected between passerine and nonpasserine birds reported in earlier reviews is not evident in the larger data set analyzed here. When the results are adjusted for phylogenetic effects using independent contrasts analysis, the difference between allometric slopes for marsupials and eutherians is no longer significant and the slope difference between Scleroglossan and Iguanian lizards disappears as well, but other taxonomic differences remain significant. Possible causes of the unexplained variations in FMR that could improve our currently inaccurate FMR prediction capabilities should be evaluated, including many important groups of terrestrial vertebrates that remain under- or unstudied and such factors as reproductive, thermoregulatory, social, and predator-avoidance behavior.

Heterogeneous effect of quinidine on the ventricular depolarization process assessed by the spatial velocity electrocardiogram of the QRS complex. Preliminary report of a new investigative method.

The negative conduction effect of quinidine on each of the successive phases of the ventricular depolarization was investigated using an original noninvasive method: the spatial velocity electrocardiogram of the QRS complex (SVECG-QRS). We performed a randomized placebo-controlled trial in 10 healthy subjects with a single oral dose of quinidine (330 mg) or placebo. Electrocardiographic acquisition and processing (220 recordings for the complete trial) were performed using the Lyon vectorcardiographic program. For each SVECG-QRS curve, the position of seven specific points from A (onset of QRS) to G (end of QRS) were determined precisely. The six successive time intervals between these points (AB-FG) and five velocity values (B-F) were then calculated. The QRS complex was longer under quinidine than placebo (102.4 +/- 1.6 vs. 100.3 +/- 1.5 ms). The difference was at the periphery of statistical significance (p = 0.05), and this lack of statistical difference may be mainly due to the low serum levels of quinidine obtained at the peak of the concentration (1.46 +/- 0.4 mg/1). All six QRS time intervals were longer under quinidine, but only the BC interval was significantly different (9.3 +/- 1.1 vs. 18.8 +/- 1.1 ms; p < 0.05) suggesting a more pronounced negative conduction effect at the onset of ventricular depolarization. No significant modifications were observed for the velocity values. We conclude that (1) the negative conduction effect of quinidine is heterogeneous, but a further study with a higher dose of quinidine (concentration-dependent effect) is required to confirm this hypothesis and (2) the spatial velocity electrocardiogram of the QRS complex allows a detailed analysis of the ventricular conduction phases. The results of the measurement were found to be reproducible. This noninvasive tool could be used in clinical practice to assess effects of antiarrhythmic drugs on successive ventricular depolarization phases.

Protein binding of methohexital. Study of parameters and modulating factors using the equilibrium dialysis technique.

This paper describes the parameters that characterize methohexital-albumin binding and the influence of physiological or analytical factors on this binding. Two useful and reproducible methods for measuring the free concentration-equilibrium dialysis (ED) and ultrafiltration (UF)-are described and their performances are compared. Methohexital binds exclusively to albumin according to a two-class binding model. The first is a saturable class site of high affinity constant (KA = 11 200 M-1) and a number of sites per albumin molecule of 1. The second is a non-saturable site of poorer affinity (nKA = 810 M-1). The bound fraction of methohexital in the therapeutic range and at physiological albumin concentration is 86.7 +/- 0.9% in isolated albumin solution. In serum, it ranges from 80 to 84.5%, according to subjects (n = 6). Binding is inhibited by the presence of endogenous compounds of serum (for a given albumin concentration the bound fraction decreases from 90.3% in isolated albumin solution to 82.6% in serum), probably by free fatty acids. An increase in the bound fraction is observed when the pH is increased from 7 to 9. This phenomenon may be explained by a higher affinity of the drug towards the basic (B-form) conformation of the albumin molecule, in analogy with the close barbiturate thiopental. A decrease in the bound fraction against temperature is shown, as though binding forces diminished with increase in temperature. Indeed, the binding modification is less pronounced in the presence of serum endogenous compounds. As expected, there is no evidence of any effect of heparin anticoagulant on the bound fraction. Methohexital binding is strongly modified by the albumin concentration; the bound fractions change from 67 to 91% in the albumin range 150-900 microM.

Electrophysiologic effects of a potassium channel activator (pinacidil) on repolarization parameters in healthy volunteers: a surface ECG study.

About a quarter to a third of patients receiving pinacidil, a new cyanoguanidine vasodilator, show ECG changes, in particular T-wave modifications that sometimes mimic myocardial ischemia. To investigate these changes, we performed a randomized placebo-controlled trial in 10 carefully selected, healthy subjects who received single oral doses of either pinacidil (25 mg), quinidine (330 mg), and placebo. Quinidine, which induces specific modifications to the surface ECG signal, was used as an internal control. The complete experimental design involved five consecutive administrations of the drugs in random order: pinacidil (twice), quinidine (twice), and placebo (once), separated by a week-long washout period. Electrophysiologic data acquisition and signal analysis were performed with the Lyon vectocardiographic processing system. Pinacidil decreased T-wave amplitude (-0.26 +/- 0.1 mV) significantly as compared with placebo (-0.14 +/- 0.06 mV), but did not change the duration of the T-wave. Although the cardiac rate increased with pinacidil, the QTc interval remained constant. Conversely, quinidine did not modify the RR interval but significantly increased duration of the T-wave (+67 +/- 20 ms) and QTc interval (+53 +/- 13 ms) as compared with placebo (+17 +/- 13 and +18 +/- 11 ms). In addition, no specific ischemic changes to the T-loop were observed with pinacidil. The modifications to the surface ECG signal caused by pinacidil appear to be drug-specific and related to its electrophysiologic properties rather than involving any ischemic mechanism. Such an approach may be useful for describing morphologic ECG changes caused by new drugs and identifying possible underlying electrophysiologic mechanism(s), which should then be confirmed in further studies.