[What is the impact of changes in the drug circuit on dispensing activity during pharmaceutical duty?] / Quel impact des évolutions du circuit du médicament sur l'activité de dispensation durant la permanence pharmaceutique ?

INTRODUCTION: Pharmaceutical permanence (PP), outside the working hours of an in-house pharmacy (PUI), allows to guarantee the continuity of care in health-care institutions. A retrospective review of urgent drug dispensing was carried out in the light of changes in the drug circuit. MATERIALS AND METHOD: The analysis of drug dispensations was performed over a period from 2011 to 2019. The average number of drugs dispensed per shift, annual dispensations, and their variation by day of the week were studied. The increase is statistically significant and is found on both weekdays and weekends. Each drug was identified according to its Anatomical Therapeutic Chemical (ATC) classification. Data on the activities of our institution (number of hospitalizations, average length of stay) were also collected. RESULTS: In 2011, an average of 36 medications were dispensed per on-call period, compared with 77 in 2019 (a doubling of activity). The increase is statistically significant and is found on both weekdays and weekends. Neurological drugs and anti-infectives represent on average 43 % of the drugs dispensed. At the same time, there was a decrease in average length of stay and an increase in hospitalizations (-10 % and +16 % respectively). DISCUSSION: The increase in the average number of medications dispensed per shift is notable. It reflects a strong and gradual increase in activity, which was increased when the full vacuum cabinets (FVCs) were introduced, which improved the quality and safety of the pharmaceutical circuit. The revision of the allocations and the information of prescribers on the drug circuit will optimize the activity and refocus it on the pharmaceutical analysis of urgent needs.

Incidence of Melanoma in the Basque Province of Álava, Spain, From 2015 to 2018: A Descriptive Study. / Estudio descriptivo de los pacientes diagnosticados de melanoma en la provincia de Álava (País Vasco) entre los años 2015 y 2018.

INTRODUCTION: The incidence of cutaneous melanoma is rising fast, and its prevalence has doubled in the past 3 decades. Detailed local epidemiological information is essential for informing community-based prevention strategies and optimizing hospital resources. MATERIAL AND METHODS: We included all patients diagnosed with cutaneous melanoma at Hospital Universitario Araba in the Basque province of Álava, Spain, between January 2015 and December 2018. We described clinical and pathologic characteristics and calculated annual incidence rates adjusted to the European standard population. RESULTS: A total of 242 new cases of melanoma were diagnosed between 2015 and 2018. The age-standardized annual incidence rose from 12.92 cases per 100 000 population in 2015 to 18.30 cases per 100 000 population in 2018. CONCLUSIONS: The incidence of melanoma in our area is higher than that reported for Spanish series in 2017 and 2018. Lentigo maligna accounted for a high proportion of cases and was the second largest histologic subgroup.

Wolbachia-mediated protection against viruses in the invasive pest Drosophila suzukii.

The maternally inherited bacterium Wolbachia is well known for spreading in natural populations by manipulating the reproduction of its arthropod hosts, but can also have mutualist effects that increase host fitness. In mosquitoes and Drosophila some Wolbachia strains can lead to an increase in survival of virus-infected insects, and in most cases this is associated with reduced accumulation of the virus in host tissues. We investigated if the Wolbachia strain wSuz, which naturally infects Drosophila suzukii, is able to confer protection against Drosophila C virus and Flock House virus in different host genetic backgrounds. We found that this strain can increase host survival upon infection with these two viruses. In some cases this effect was associated with lower viral titres, suggesting that it confers resistance to the viruses rather than allowing the flies to tolerate infection. Our results indicate that, in D. suzukii, the antiviral protection provided by Wolbachia is not correlated to its density as found in other Drosophila species. This study demonstrates a phenotypic effect induced by wSuz on its native host which could explain its maintenance in natural populations of D. suzukii.

Lyme snap: A feasibility study of on-line declarations of erythema migrans in a rural area of France.

The incidence of Lyme borreliosis remains a matter of debate, but it can be estimated using the incidence of erythema migrans (EM), which is pathognomonic of the first phase. The aim of this prospective pilot study was to assess the feasibility of the on-line declaration of EM in rural areas where the incidence of Lyme borreliosis was previously estimated at 85 per 100,000 inhabitants per year. The study was limited to a rural area (Les Combrailles, Auvergne) of approximately 52,800 inhabitants and was preceded by an information campaign for the inhabitants and the healthcare professionals. Patients who sent a photo of the suspected EM by email or MMS message between April 2017 and April 2018 and who accepted to answer a questionnaire were included in the study. Two physicians then evaluated the quality of the photographs and the probability of EM. In parallel, the number of EM seen by physicians and pharmacists in the area over the given period was recorded. Out of the 113 emails and MMS messages received, 73 people were outside of the trial area or period and 9 did not complete the questionnaire. The photos of the remaining 31 people were analysed. The median age was 51.5 years old ([38-58] IQR) and 18 (58%) were women. Seven people (25%) stated that they did not have a smartphone and in 9 cases (29%) the photo was sent by a third party. The quality of the photos was considered very good in 22 (71%) cases, good in 7 (23%) cases, and average in 2 (6%) cases. The probability of EM was determined to be strong or possible in 12 (38%) cases, i.e. an estimated incidence of 22.7 per 100,000 inhabitants. Over the study period, 40 physicians and 20 pharmacists were contacted on a monthly basis. A median of 5 physicians [3;7] and 4 pharmacists [3 ;7] answered each month for a total of 18 and 36 declared EM respectively. The EM (strong probability/possible) collected by on-line declaration and those declared by healthcare professionals were all sent between April and October 2017. The total time spent on the information campaign and collection has been estimated at 265 h (divided between 10 people) for an overall cost of 10,669 Euros. The incidence of EM recorded by on-line self-declaration in our study seems to be lower than in previous studies, the under-reporting was probably linked to the low use of new technologies in the rural areas. Increasing the human resources and finances appears difficult to achieve in practice over a longer time period but the development of an application for the automatic recognition of EM could be one method for a more exhaustive collection in the long term and at lower cost.

Phenotypic plasticity of abdomen pigmentation in two geographic populations of Drosophila melanogaster: male-female comparison and sexual dimorphism.

In Drosophila melanogaster male, the last abdominal tergites (A5-A6) are completely dark due to a strong internal constraint while, in female, all abdominal tergites (A2-A7) are phenotypically variable and highly plastic. Male A2-A4 are quite similar to those of female, but their plasticity was never investigated. In this paper, we compared the phenotypic plasticity of A2-A4 in both sexes in order to know if the major dimorphism (SD) expressed in male A5-A6 also extended toward the more anterior segments. We also compared two geographic populations living under very different climates in order to know if adaptive differences, previously observed in females also existed in males. With an isofemale line design, pigmentation variation according to growth temperature was investigated in the two populations from France and India. Male and female data were compared and sexual dimorphism (SD) analyzed in various ways. Reaction norms were quite similar in both sexes for A2 and A3, but clearly different for A4. Considering the total pigmentation (A2 + A3 + A4) males were darker than females at low temperatures and either identical to them (France) or lighter (India) above 25 degrees C. SD (male-female difference) was genetically variable among lines and significantly different among segments. Reaction norms of SD exhibited an overall decrease with temperature and also a significant difference among populations, suggesting a local adaptation of SD to thermal conditions. The three plastic segments in male (A2-A4) seem to react adaptively to the thermal environment more efficiently than the same segments in female, in agreement with the thermal budget hypothesis. To our knowledge, it is the first time that a SD trait exhibits an adaptive difference between geographic populations.

Data from a targeted proteomics approach to discover biomarkers in saliva for the clinical diagnosis of periodontitis.

This study focused on the search for new biomarkers based on liquid chromatography-multiple reaction monitoring (LC-MRM) proteomics profiling of whole saliva from patients with periodontitis compared to healthy subjects. The LC-MRM profiling approach is a new and innovative method that has already been validated for the absolute and multiplexed quantification of biomarkers in several diseases. The dataset for this study was produced using LC-MRM to monitor protein levels in a multiplex assay, it provides clinical information on salivary biomarkers of periodontitis. The data presented here is an extension of our recently published research article (Mertens et al., 2017) [1].

Invasive Drosophila suzukii facilitates Drosophila melanogaster infestation and sour rot outbreaks in the vineyards.

How do invasive pests affect interactions between members of pre-existing agrosystems? The invasive pest Drosophila suzukii is suspected to be involved in the aetiology of sour rot, a grapevine disease that otherwise develops following Drosophila melanogaster infestation of wounded berries. We combined field observations with laboratory assays to disentangle the relative roles of both Drosophila in disease development. We observed the emergence of numerous D. suzukii, but no D. melanogaster flies, from bunches that started showing mild sour rot symptoms days after field collection. However, bunches that already showed severe rot symptoms in the field mostly contained D. melanogaster. In the laboratory, oviposition by D. suzukii triggered sour rot development. An independent assay showed the disease increased grape attractiveness to ovipositing D. melanogaster females. Our results suggest that in invaded vineyards, D. suzukii facilitates D. melanogaster infestation and, consequently, favours sour rot outbreaks. Rather than competing with close species, the invader subsequently permits their reproduction in otherwise non-accessible resources and may cause more frequent, or more extensive, disease outbreaks.

The invasive pest Drosophila suzukii uses trans-generational medication to resist parasitoid attack.

Animal medication is a behavioral strategy to resist enemies based on the use of substances from the environment. While it has been observed in several animals, whether invasive species can use medication to resist new enemies during its expansion is unknown. Here, we show that the worldwide invasive pest Drosophila suzukii performs trans-generational prophylactic medication by adapting its oviposition behavior in the presence of enemies. We find that flies preferentially lay their eggs on media containing atropine - an entomotoxic alkaloid - in the presence of parasitoids. We further show that flies developing on atropine more efficiently resist parasitization by parasitoids. Finally, we find that developing in hosts reared on atropine strongly impacts the life-history traits of parasitoids. This protective behavior is reported for the first time in a pest and invasive species, and suggests that animal medication may be an important driver of population dynamics during invasions.

Exposure of Wildlife to the Schmallenberg Virus in France (2011-2014): Higher, Faster, Stronger (than Bluetongue)!

The Schmallenberg virus (SBV) has recently emerged in Europe, causing losses to the domestic livestock. A retrospective analysis of serodata was conducted in France for estimating seroprevalence of SBV among six wildlife species from 2011-2012 to 2013-2014, that is during the three vector seasons after the emergence of the SBV in France. Our objective was to quantify the exposure of wildlife to SBV and the potential protective effect of elevation such as previously observed for bluetongue. We also compared the spatiotemporal trends between domestic and wild animals at the level of the departments. We tested 2050 sera using competitive ELISA tests. Individual and population risk factors were further tested using general linear models among 1934 individuals. All populations but one exhibited positive results, seroprevalence up to 30% being observed for all species. The average seroprevalence did not differ between species but ranged from 0 to 90% according to the area and period, due to the dynamic pattern of infection. Seroprevalence was on average higher in the lowlands compared to areas located up to 800 m. Nevertheless, seroprevalence above 50% occurred in areas located up to 1500 m. Thus, contrary to what had been observed for bluetongue during the late 2000s in the same areas, SBV could spread to high altitudes and infect all the studied species. The spatial spread of SBV in wildlife did not fully match with SBV outbreaks reported in the domestic livestock. The mismatch was most obvious in mountainous areas where outbreaks in wildlife occurred on average one year after the peak of congenital cases in livestock. These results suggest a much larger spread and vector capacity for SBV than for bluetongue virus in natural areas. Potential consequences for wildlife dynamics are discussed.

Estudio descriptivo de los pacientes diagnosticados de melanoma en la provincia de Álava (País Vasco) entre los años 2015 y 2018 / Incidence of Melanoma in the Basque Province of Álava, Spain, From 2015 to 2018: A Descriptive Study

Introducción: La incidencia del melanoma cutáneo está aumentando rápidamente y ha duplicado su prevalencia durante las últimas tres décadas. Tener un conocimiento detallado de la epidemiología local es fundamental para el desarrollo de estrategias de prevención comunitaria y optimizar los recursos hospitalarios. Material y métodos: Se incluyeron todos los pacientes diagnosticados de melanoma cutáneo en el Hospital Universitario Araba, en la provincia de Álava del País Vasco, entre enero de 2015 y diciembre de 2018. Se realizó un análisis descriptivo de las variables clínico-patológicas y un análisis de la incidencia ajustado a la población europea. Resultados: Se incluyeron un total de 242 nuevos casos de melanoma entre 2015 y 2018. La incidencia estandarizada por edad ha aumentado de 12,92 en 2015 a 18,30 casos por 100.000 habitantes y año en 2018. Conclusiones: Hemos observado una incidencia de melanoma más elevada que en la publicada en series nacionales en los años 2017 y 2018. Además, existe una gran proporción del subtipo histológico de tipo lentigo maligno, ocupando el segundo subtipo histológico en frecuencia (AU)

Introduction: The incidence of cutaneous melanoma is rising fast, and its prevalence has doubled in the past 3 decades. Detailed local epidemiological information is essential for informing community-based prevention strategies and optimizing hospital resources. Material and methods: We included all patients diagnosed with cutaneous melanoma at Hospital Universitario Araba in the Basque province of Álava, Spain, between January 2015 and December 2018. We described clinical and pathologic characteristics and calculated annual incidence rates adjusted to the European standard population. Results: A total of 242 new cases of melanoma were diagnosed between 2015 and 2018. The age-standardized annual incidence rose from 12.92 cases per 100 000 population in 2015 to 18.30 cases per 100 000 population in 2018. Conclusions: The incidence of melanoma in our area is higher than that reported for Spanish series in 2017 and 2018. Lentigo maligna accounted for a high proportion of cases and was the second largest histologic subgrou (AU)

[Translated article] Incidence of Melanoma in the Basque Province of Álava, Spain, From 2015 to 2018: A Descriptive Study / Estudio descriptivo de los pacientes diagnosticados de melanoma en la provincia de Álava (País Vasco) entre los años 2015 y 2018

Introduction: The incidence of cutaneous melanoma is rising fast, and its prevalence has doubled in the past 3 decades. Detailed local epidemiological information is essential for informing community-based prevention strategies and optimizing hospital resources. Material and methods: We included all patients diagnosed with cutaneous melanoma at Hospital Universitario Araba in the Basque province of Álava, Spain, between January 2015 and December 2018. We described clinical and pathologic characteristics and calculated annual incidence rates adjusted to the European standard population. Results: A total of 242 new cases of melanoma were diagnosed between 2015 and 2018. The age-standardized annual incidence rose from 12.92 cases per 100 000 population in 2015 to 18.30 cases per 100 000 population in 2018. Conclusions: The incidence of melanoma in our area is higher than that reported for Spanish series in 2017 and 2018. Lentigo maligna accounted for a high proportion of cases and was the second largest histologic subgrou (AU)

Introducción: La incidencia del melanoma cutáneo está aumentando rápidamente y ha duplicado su prevalencia durante las últimas tres décadas. Tener un conocimiento detallado de la epidemiología local es fundamental para el desarrollo de estrategias de prevención comunitaria y optimizar los recursos hospitalarios. Material y métodos: Se incluyeron todos los pacientes diagnosticados de melanoma cutáneo en el Hospital Universitario Araba, en la provincia de Álava del País Vasco, entre enero de 2015 y diciembre de 2018. Se realizó un análisis descriptivo de las variables clínico-patológicas y un análisis de la incidencia ajustado a la población europea. Resultados: Se incluyeron un total de 242 nuevos casos de melanoma entre 2015 y 2018. La incidencia estandarizada por edad ha aumentado de 12,92 en 2015 a 18,30 casos por 100.000 habitantes y año en 2018. Conclusiones: Hemos observado una incidencia de melanoma más elevada que en la publicada en series nacionales en los años 2017 y 2018. Además, existe una gran proporción del subtipo histológico de tipo lentigo maligno, ocupando el segundo subtipo histológico en frecuencia (AU)

Locomotor performance of Drosophila melanogaster: interactions among developmental and adult temperatures, age, and geography.

We explored the extent to which a phenotypic trait (walking speed) of Drosophila melanogaster is influenced by population, developmental temperature, adult temperature, and age. Our goals were to estimate the importance of these factors and to test the beneficial acclimation hypothesis. We measured speed of flies from two populations (the Congo and France) that developed at different temperatures (18, 25, and 29 degrees C) and were tested at different temperatures (18, 25, and 29 degrees C) and ages (2, 7, 13 days). Not surprisingly, speed increased strongly with test temperature. Speed was generally greatest for flies reared at an intermediate developmental temperature, contrary to the beneficial acclimation hypothesis, which predicts that speed would be greatest when influenced by interactions involving population. For example, speed was greatest for flies from France that developed at a low temperature, but for flies from the Congo that developed at a high temperature. The impact of developmental temperature declined with age. Surprisingly, speed actually increased with age for flies raised and maintained at a low temperature, but decreased with age for flies raised and maintained at an intermediate or at a high temperature. Thus, walking performance is highly dynamic phenotypically, complicating potential attempts to predict responses to selection on performance.

Chill-coma tolerance, a major climatic adaptation among Drosophila species.

Most drosophilid species can be classified either as temperate or tropical. Adults of species were submitted to a cold treatment (0 degrees C) and then brought back to ambient temperature. They generally exhibited a chill coma and the time needed to recover was measured. We found in a set of 26 temperate species that recovery was rapid (average 1.8 min, range 0.15-4.9). In contrast, a long recovery time (average 56 min, range 24-120) was observed for 48 tropical species. A few species, like Drosophila melanogaster, are cosmopolitan and can proliferate under temperate and tropical climates. In 9 of 10 such species, slight genetic differences were found: a shorter recovery in temperate than in tropical populations. Comparing physiological data to phylogeny suggests that chill-coma tolerance has been a recurrent adaptation that is selected for in cold climates but tends to disappear under a permanently warm environment. This major climatic adaptation, evidenced in drosophilids, seems to occur in other insect groups also.

The genetics of phenotypic plasticity. IX. Genetic architecture, temperature, and sex differences in Drosophila melanogaster.

We examined the genetic architecture of plasticity of thorax and wing length in response to temperature in Drosophila melanogaster. Reaction norms as a function of growth temperature were analyzed in 20 isofemale lines in a natural population collected from Grande Ferrade near Bordeaux (southern France) in two different years. We found evidence for a complex genetic architecture underlying the reaction norms and differences between males and females. Reaction norms were negative quadratics. Genetic correlations were moderately high between traits within environments. Among characteristic values, the magnitudes of genetic correlations varied among traits and sexes. We hypothesized that genetic correlations among environments would decrease as temperatures became more different. This expectation was upheld for only one trait, female thorax length. For males for both traits, the correlations were large for both very similar and very different temperatures. These correlations may constrain the evolution of the shape of the reaction norms. Whether the extent of independence implies specific regulatory genes or only a specific allelic regulation of trait genes can not be decided from our results.

The strength of phenotypic selection in natural populations.

How strong is phenotypic selection on quantitative traits in the wild? We reviewed the literature from 1984 through 1997 for studies that estimated the strength of linear and quadratic selection in terms of standardized selection gradients or differentials on natural variation in quantitative traits for field populations. We tabulated 63 published studies of 62 species that reported over 2,500 estimates of linear or quadratic selection. More than 80% of the estimates were for morphological traits; there is very little data for behavioral or physiological traits. Most published selection studies were unreplicated and had sample sizes below 135 individuals, resulting in low statistical power to detect selection of the magnitude typically reported for natural populations. The absolute values of linear selection gradients |beta| were exponentially distributed with an overall median of 0.16, suggesting that strong directional selection was uncommon. The values of |beta| for selection on morphological and on life-history/phenological traits were significantly different: on average, selection on morphology was stronger than selection on phenology/life history. Similarly, the values of |beta| for selection via aspects of survival, fecundity, and mating success were significantly different: on average, selection on mating success was stronger than on survival. Comparisons of estimated linear selection gradients and differentials suggest that indirect components of phenotypic selection were usually modest relative to direct components. The absolute values of quadratic selection gradients |gamma| were exponentially distributed with an overall median of only 0.10, suggesting that quadratic selection is typically quite weak. The distribution of gamma values was symmetric about 0, providing no evidence that stabilizing selection is stronger or more common than disruptive selection in nature.

Variable modes of inheritance of morphometrical traits in hybrids between Drosophila melanogaster and Drosophila simulans.

We investigated body-size inheritance in interspecific sterile hybrids by crossing a Drosophila simulans strain with 13 strains of Drosophila melanogaster, which were of various origins and chosen for their broad range of genetic variation. A highly significant parent-offspring correlation was observed, showing that the D. melanogaster genes for size are still expressed in a hybrid background. Superimposed on to this additive inheritance, the size of hybrids was always less than the mid-parent value. This phenomenon, which at first sight might be described as dominance or overdominance, is more precisely interpreted as a consequence of a hybrid breakdown, that is, a dysfunction of the parental genes for size when put to work together. This interpretation is enforced by the fact that phenotypic variability was much more prevalent in hybrids than in parents. We also analysed body pigmentation inheritance in the same crosses and got a very different picture. There was no increase in the phenotypic variance of F(1) hybrids and only a low parent-offspring correlation. Apparent overdominance could be observed but in opposite directions, with no evidence of hybrid breakdown. Our data point to the possibility of analysing a diversity of quantitative traits in interspecific hybrids, and indicate that breakdown might be restricted to some traits only.

Serum fatty acid imbalance in bone loss: example with periodontal disease.

Among the numerous factors of bone remodelling, the local action of arachidonic acid metabolites together with cytokines, is particularly important, especially that of prostaglandin PGE2. It has been suggested that the alveolar bone destruction in periodontal disease and osteoporosis can be treated by reducing the ratio of arachidonic acid in phospholipids, which would diminish prostaglandin production. The aim of this study was to evaluate the main serum polyunsaturated fatty acids and a possible alteration in the level of arachidonic acid in patients suffering from periodontal bone loss. Of the 105 patients who participated the study, 78 were suffering from periodontal bone loss and 27 served as a control group. The fatty acids were measured in serum by gas-chromatography. The results showed that the level of fatty acids of the n-6 pathway was higher in our patients with bone loss than in the control group, whereas the reverse was observed with fatty acids of the n-3 pathway. In conclusion, our patients' bone losses are linked with an imbalance between n-6 and n-3 fatty acids, which seems to justify a diet increase in 20- and 22-carbon fatty acids.