Measles in vulnerable populations: An outbreak in Roma settlements of Loire-Atlantique, France, 2019.

In May 2019, a measles outbreak occurred in the French subregion of Loire-Atlantique, particularly affecting Roma settlements. Various obstacles hindered the implementation of postexposure measures among Roma population, resulting in the spread of the cases to other settlements. Suspected cases of measles were immediately investigated and concerned settlements were visited for measles-mumps-rubella (MMR) vaccination. From July 1 to September 3, 2019, a first and then a second Health Reserve team helped for vaccination on the affected and then also the measles-free settlements. Vaccination uptake was monitored with the use of the department's vaccination center immunization registry. Genotyping of selected samples was performed for comparison with viruses circulating at the same time in France and Romania. As of September 16 2019, 109 cases of measles were confirmed among Roma population, including 99 (91%) children under 15 years. Of the 85 people eligible for vaccination, 60 (71%) had not been vaccinated and 23 (27%) had an unknown vaccination status. Sequence comparison revealed that 28/29 sequenced D8 strains were 100% identical to the strain responsible for a large number of cases throughout France in 2019, and to two sequences reported in Romania among sporadic cases. The vaccination campaign resulted in 1136 people on 35 settlements receiving at least one dose of MMR vaccine and in the increase of one-dose MMR vaccine coverage at 24 months from 43% (23/53) to 91% (48/53). With measles transmission continuing in Europe, efforts must be made to meet immunization coverage targets, particularly in hard-to-reach communities where outbreaks may be difficult to control.

Cryptosporidium-Biofilm Interactions: a Review.

Biofilms are increasingly implicated as playing a major role in waterborne cryptosporidiosis. This review aims to synthesize all currently available data on interactions between Cryptosporidium oocysts and biofilms. Initially described following a waterborne outbreak, the integration of Cryptosporidium oocysts in biofilm has been well demonstrated. Biofilms appear important in the dissemination/protection of oocysts in the environment. Consequently, it has been suggested that substrate-associated biofilms should be systematically considered in oocyst water quality assessment. The influence of physicochemical parameters has been studied on oocyst biofilm retention. Biofilm surface roughness, ionic concentration (especially Ca2+), laminar/turbulent flow, shear stress, and electrostatic repulsion forces appear important to consider regarding oocyst release from biofilm. However, data analysis carried out during this review also revealed important gaps in biological interactions within biofilms, offering many perspectives for future work.

Quantitative assessment of sciatic nerve changes in Charcot-Marie-Tooth type 1A patients using magnetic resonance neurography.

BACKGROUND AND PURPOSE: Nerve tissue alterations have rarely been quantified in Charcot-Marie-Tooth type 1A (CMT1A) patients. The aim of the present study was to quantitatively assess the magnetic resonance imaging (MRI) anomalies of the sciatic and tibial nerves in CMT1A disease using quantitative neurography MRI. It was also intended to seek for correlations with clinical variables. METHODS: Quantitative neurography MRI was used in order to assess differences in nerve volume, proton density and magnetization transfer ratio in the lower limbs of CMT1A patients and healthy controls. Disease severity was evaluated using the Charcot-Marie-Tooth Neuropathy Score version 2, Charcot-Marie-Tooth examination scores and Overall Neuropathy Limitations Scale scores. Electrophysiological measurements were performed in order to assess the compound motor action potential and the Motor Unit Number Index. Clinical impairment was evaluated using muscle strength measurements and Charcot-Marie-Tooth examination scores. RESULTS: A total of 32 CMT1A patients were enrolled and compared to 13 healthy subjects. The 3D nerve volume, magnetization transfer ratio and proton density were significantly different in CMT1A patients for the whole sciatic and tibial nerve volume. The sciatic nerve volume was significantly correlated with the whole set of clinical scores whereas no correlation was found between the tibial nerve volume and the clinical scores. CONCLUSION: Nerve injury could be quantified in vivo using quantitative neurography MRI and the corresponding biomarkers were correlated with clinical disability in CMT1A patients. The sensitivity of the selected metrics will have to be assessed through repeated measurements over time during longitudinal studies to evaluate structural nerve changes under treatment.

Complete genome sequence of a novel grapevine-infecting member of the genus Polerovirus, grapevine polerovirus 1.

Double-stranded RNAs and total RNAs purified from grapevine (Vitis vinifera) phloem scrapings of two varieties held in the INRAE (France) grapevine germplasm collection were analyzed by high-throughput sequencing. BLAST annotation revealed contigs with homology to Polerovirus genus members. The full genome sequence of one isolate (KT) was determined (5651 nucleotides [nt]), and a partial sequence representing about half of the genome was assembled for a second isolate (KS) that was found to share 95% nt sequence identity with the KT isolate. The genome has a typical polerovirus organization, containing six open reading frames (ORFs) as well as a putative additional ORF3a. Based on genome organization and phylogenetic relationships, the new virus belongs to the genus Polerovirus but, similar to the recently described persimmon polerovirus 1, is characterized by a highly divergent coat-protein/readthrough domain. Considering the species demarcation criteria for the family Luteoviridae, these two isolates, together with a closely related sequence recently deposited in the GenBank database (LC507098), represent a new Polerovirus species for which the name "Grapevine polerovirus 1" is proposed.

Clinical guidelines for the management of treatment-resistant depression: French recommendations from experts, the French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental.

BACKGROUND: Clear guidance for successive antidepressant pharmacological treatments for non-responders in major depression is not well established. METHOD: Based on the RAND/UCLA Appropriateness Method, the French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental developed expert consensus guidelines for the management of treatment-resistant depression. The expert guidelines combine scientific evidence and expert clinicians' opinions to produce recommendations for treatment-resistant depression. A written survey comprising 118 questions related to highly-detailed clinical presentations was completed on a risk-benefit scale ranging from 0 to 9 by 36 psychiatrist experts in the field of major depression and its treatments. Key-recommendations are provided by the scientific committee after data analysis and interpretation of the results of the survey. RESULTS: The scope of these guidelines encompasses the assessment of pharmacological resistance and situations at risk of resistance, as well as the pharmacological and psychological strategies in major depression. CONCLUSION: The expert consensus guidelines will contribute to facilitate treatment decisions for clinicians involved in the daily assessment and management of treatment-resistant depression across a number of common and complex clinical situations.

Clinical guidelines for the management of depression with specific comorbid psychiatric conditions French recommendations from experts (the French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental).

BACKGROUND: Recommendations for pharmacological treatments of major depression with specific comorbid psychiatric conditions are lacking. METHOD: The French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental developed expert consensus guidelines for the management of depression based on the RAND/UCLA Appropriatneness Method. Recommendations for lines of treatment are provided by the scientific committee after data analysis and interpretation of the results of a survey of 36 psychiatrist experts in the field of major depression and its treatments. RESULTS: The expert guidelines combine scientific evidence and expert clinician's opinion to produce recommendations for major depression with comorbid anxiety disorders, personality disorders or substance use disorders and in geriatric depression. CONCLUSION: These guidelines provide direction addressing common clinical dilemmas that arise in the pharmacologic treatment of major depression with comorbid psychiatric conditions.

Autosomal recessive variations of TBX6, from congenital scoliosis to spondylocostal dysostosis.

Proximal 16p11.2 microdeletions are recurrent microdeletions with an overall prevalence of 0.03%. In patients with segmentation defects of the vertebra (SDV), a burden of this microdeletion was observed with TBX6 as a candidate gene for SDV. In a published cohort of patients with congenital scoliosis (CS), TBX6 haploinsufficiency was compound heterozygous with a common haplotype. Besides, a single three-generation family with spondylocostal dysostosis (SCD) was reported with a heterozygous stop-loss of TBX6. These observations questioned both on the inheritance mode and on the variable expressivity associated with TBX6-associated SDV. Based on a national recruitment of 56 patients with SDV, we describe four patients with variable SDV ranging from CS to SCD associated with biallelic variations of TBX6. Two patients with CS were carrying a proximal 16p11.2 microdeletion associated with the previously reported haplotype. One patient with extensive SDV was carrying a proximal 16p11.2 microdeletion associated with a TBX6 rare missense change. One patient with a clinical diagnosis of SCD was compound heterozygous for two TBX6 rare missense changes. The three rare variants were affecting the chromatin-binding domain. Our data illustrate the variable expressivity of recessive TBX6 ranging from CS to SCD.

The Attentional Fields of Visual Search in Simultanagnosia and Healthy Individuals: How Object and Space Attention Interact.

Simultanagnosia is a deficit in which patients are unable to perceive multiple objects simultaneously. To date, it remains disputed whether this deficit results from disrupted object or space perception. We asked both healthy participants as well as a patient with simultanagnosia to perform different visual search tasks of variable difficulty. We also modulated the number of objects (target and distracters) presented. For healthy participants, we found that each visual search task was performed with a specific "attentional field" depending on the difficulty of visual object processing but not on the number of objects falling within this "working space." This was demonstrated by measuring the cost in reaction times using different gaze-contingent visible window sizes. We found that bilateral damage to the superior parietal lobule impairs the spatial integration of separable features (within-object processing), shrinking the attentional field in which a target can be detected, but causing no deficit in processing multiple objects per se.

[French Society for Biological Psychiatry and Neuropsychopharmacology and Fondation FondaMental task force: Formal Consensus for the management of treatment-resistant depression]. / Prise en charge des troubles dépressifs résistants : recommandations françaises formalisées par des experts de l'AFPBN et de la fondation FondaMental.

Major depression represents among the most frequent psychiatric disorders in the general population with an estimated lifetime prevalence of 16-17%. It is characterized by high levels of comorbidities with other psychiatric conditions or somatic diseases as well as a recurrent or chronic course in 50 to 80% of the cases leading to negative repercussions on the daily functioning, with an impaired quality of life, and to severe direct/indirect costs. Large cohort studies have supported that failure of a first-line antidepressant treatment is observed in more than 60% of patients. In this case, several treatment strategies have been proposed by classical evidence-based guidelines from internationally recognized scientific societies, referring primarily on: I) the switch to another antidepressant of the same or different class; II) the combination with another antidepressant of complementary pharmacological profile; III) the addition of a wide range of pharmacological agents intending to potentiate the therapeutic effects of the ongoing antidepressant medication; IV) the association with appropriate psychological therapies; and, V) the use of non-invasive brain stimulation techniques. However, although based on the most recently available data and rigorous methodology, standard guidelines have the significant disadvantage of not covering a large variety of clinical conditions, while currently observed in everyday clinical practice. From these considerations, formalized recommendations by a large panel of French experts in the management of depressed patients have been developed under the shared sponsorship of the French Association of Biological Psychiatry and Neuropsychopharmacology (AFPBN) and the Fondation FondaMental. These French recommendations are presented in this special issue in order to provide relevant information about the treatment choices to make, depending particularly on the clinical response to previous treatment lines or the complexity of clinical situations (clinical features, specific populations, psychiatric comorbidities, etc.). Thus, the present approach will be especially helpful for the clinicians enabling to substantially facilitate and guide their clinical decision when confronted to difficult-to-treat forms of major depression in the daily clinical practice. This will be expected to significantly improve the poor prognosis of the treatment-resistant depression thereby lowering the clinical, functional and costly impact owing directly to the disease.

[Unusual association between auto-immune hepatitis and pyoderma gangrenosum. A case report]. / Association inhabituelle entre une hépatite auto-immune et un pyoderma gangrenosum. A propos d'un cas.

Pyoderma gangrenosum is an uncommon neutrophilic dermatosis that presents as an inflammatory and ulcerative disorder of the skin. This entity is associated with systemic diseases and autoimmune diseases but exceptionally with autoimmune hepatitis. We report the case of a 40 year-old woman diagnosed with type 1 autoimmune hepatitis 12 years earlier and admitted for the appearance of an ulcerative lesion in the left leg. Histology confirmed pyoderma gangrenosum.

Le Pyoderma gangrenosum (PG) est une affection rare appartenant au groupe des dermatoses neutrophiliques. Cette entité est associée à l'existence de maladies systémiques et autoimmunes, mais exceptionnellement à une hépatite auto-immune. Nous rapportons l'observation d'une patiente âgée de 40 ans atteinte d'une hépatite auto-immune (HAI) de type 1 depuis 12 ans admise pour une lésion ulcéreuse du membre inférieur gauche. L'histologie confirmera l'existence d'un pyoderma gangrenosum.

Diagnostic odyssey in severe neurodevelopmental disorders: toward clinical whole-exome sequencing as a first-line diagnostic test.

The current standard of care for diagnosis of severe intellectual disability (ID) and epileptic encephalopathy (EE) results in a diagnostic yield of ∼50%. Affected individuals nonetheless undergo multiple clinical evaluations and low-yield laboratory tests often referred to as a 'diagnostic odyssey'. This study was aimed at assessing the utility of clinical whole-exome sequencing (WES) in individuals with undiagnosed and severe forms of ID and EE, and the feasibility of its implementation in routine practice by a small regional genetic center. We performed WES in a cohort of 43 unrelated individuals with undiagnosed ID and/or EE. All individuals had undergone multiple clinical evaluations and diagnostic tests over the years, with no definitive diagnosis. Sequencing data analysis and interpretation were carried out at the local molecular genetics laboratory. The diagnostic rate of WES reached 32.5% (14 out of 43 individuals). Genetic diagnosis had a direct impact on clinical management in four families, including a prenatal diagnostic test in one family. Our data emphasize the clinical utility and feasibility of WES in individuals with undiagnosed forms of ID and EE and highlight the necessity of close collaborations between ordering physicians, molecular geneticists, bioinformaticians and researchers for accurate data interpretation.

Genetic counselling difficulties and ethical implications of incidental findings from array-CGH: a 7-year national survey.

Microarray-based comparative genomic hybridization (aCGH) is commonly used in diagnosing patients with intellectual disability (ID) with or without congenital malformation. Because aCGH interrogates with the whole genome, there is a risk of being confronted with incidental findings (IF). In order to anticipate the ethical issues of IF with the generalization of new genome-wide analysis technologies, we questioned French clinicians and cytogeneticists about the situations they have faced regarding IF from aCGH. Sixty-five IF were reported. Forty corresponded to autosomal dominant diseases with incomplete penetrance, 7 to autosomal dominant diseases with complete penetrance, 14 to X-linked diseases, and 4 were heterozygotes for autosomal recessive diseases with a high prevalence of heterozygotes in the population. Therapeutic/preventive measures or genetic counselling could be argued for all cases except four. These four IF were intentionally not returned to the patients. Clinicians reported difficulties in returning the results in 29% of the cases, mainly when the question of IF had not been anticipated. Indeed, at the time of the investigation, only 48% of the clinicians used consents mentioning the risk of IF. With the emergence of new technologies, there is a need to report such national experiences; they show the importance of pre-test information on IF.

Consequences of urban pollution upon skin status. A controlled study in Shanghai area.

OBJECTIVE: After preliminary studies aimed at measuring pertinent biochemical parameters, potentially modified in subjects exposed to bad environmental conditions, a dedicated study was performed in Shanghai city to evaluate the effect of Urban pollution upon human skin and to collect feedback from the volunteers under study. METHODS: This study was performed during summer 2008 in two different districts of Shanghai, on 159 local residents: 79 subjects from Xu Jia Hui (a centre Shanghainese area), more exposed to pollution, and 80 subjects from Chong Ming, an agricultural region closely located north of Shanghai (<100 kms) and less exposed to pollution, according to official data. Biochemical parameters were measured on skin, and feedback from volunteers was collected through a graduated 'Likert scale' questionnaire under a point scale (strongly agree, agree, disagree, strongly disagree and none). RESULTS: The study demonstrated significant differences in several biochemical parameters measured in Chong Ming area, as compared to Urban area, with an increased ratio of squalene/lipids, a lower level of lactic acid and a better cohesion of stratum corneum. Both sebum excretion rate and sebum casual levels did not differ between the two districts. The volunteer's feedback evidenced a perceived link between pollution and their skin problems. CONCLUSION: This study demonstrated a significant impact of the pollution upon the skin status, as illustrated by changes in superficial biochemical parameters and volunteers' perception.

Evaluation of the impact of urban pollution on the quality of skin: a multicentre study in Mexico.

OBJECTIVE: After pilot and preliminary studies aimed at identifying pertinent biochemical parameters, a multicenter clinical study was performed to evaluate the effect of pollution on human skin. METHODS: The clinical study was performed in collaboration with the 'Centre Régional de lutte contre le cancer de Montpellier' and the 'National Institute of Public Health of Mexico' on 96 subjects in Mexico City (exposed to pollution) and 93 subjects in Cuernavaca (less exposed to pollution). Both biochemical and clinical skin parameters were studied. RESULTS: The study demonstrated significant quantitative and qualitative modifications of parameters related to sebum excretion in Mexico City compared to Cuernavaca one: An increased level of sebum excretion rate, a lower level of vitamin E and squalene in sebum, an increase of lactic acid and a higher erythematous index on the face of the subjects. In the stratum corneum, a significant higher level of carbonylated proteins and a lower level of IL 1α were noticed, as well as a decrease of ATP concentration with a decrease of chymotrysin like activity, without modifications of corneodesmosin content and trypsin like activity. From a clinical point of view, a higher frequency of atopic and urticarial skins, a higher frequency of red dermographism, an important seborrheic status at the forehead level and a lower level of dandruffs were noted in Mexico City population. The analysis taking into account the sex does not modify the observed results. CONCLUSION: The study demonstrated an important impact of polluted environmental conditions on skin quality, evidencing important modifications of superficial biochemical parameters. The cause/effects relationships of these modifications remain, however, to be further assessed by a complementary in vitro/in vivo approaches.

Multicenter study of environmental contamination with antineoplastic drugs in 36 Canadian hospitals: a 2013 follow-up study.

No occupational exposure limit exists for antineoplastic drugs. The main objective of this study was to describe environmental contamination with cyclophosphamide, ifosfamide, and methotrexate in pharmacy and patient care areas of Canadian hospitals in 2013. The secondary objective was to compare the 2013 environmental monitoring results with previous studies. Six standardized sites in the pharmacy and six sites on patient care areas were sampled in each participating center. Samples were analyzed for the presence of cyclophosphamide, ifosfamide, and methotrexate by UPLC-MSMS. The limit of detection (LOD) in pg/cm(2) was 1.8 for cyclophosphamide, 2.2 for ifosfamide, and 7.5 for methotrexate. The 75th percentile of cyclophosphamide concentration was compared between the 2013, 2008-2010, and 2012 studies. Thirty-six hospitals participated in the study and 422 samples were collected. Overall, 47% (198/422) of the samples were positive for cyclophosphamide, 18% (75/422) were positive for ifosfamide, and 3% (11/422) were positive for methotrexate. In 2013, the 75th percentile value of cyclophosphamide surface concentration was reduced to 8.4pg/cm(2) (n = 36), compared with 9.4pg/cm(2) in 2012 (n = 33) and 40pg/cm(2) (n = 25) in 2008-2010. The 75th percentile for ifosfamide and methotrexate concentration remained lower than the LOD. The 2013 study shows an improvement in the surface contamination level, and a plateau effect in the proportion of positive samples.

[Incomplete form of hypertrophc osteoarthropathy in a patient with breast cancer]. / LE CAS CLINIQUE DU MOIS. Ostéoarthropathie hypertrophique de forme incomplète chez une patiente présentant un cancer du sein.

Hypertrophic osteoarthropathy is sometimes the paraneoplasic manifestation of cancer of pulmonary origin. It is rarely present in case of breast cancer, even at a metastatic stage. In its complete form, this entity includes periostitis (predominantly bilateral and affecting upper and lower limbs), digital clubbing and, rarely, arthritis. We report the case of a female patient with metastatic breast cancer and an incomplete form of hypertrophic osteoarthropathy, clearly asymetric and without digital clubbing.

Multispecies high-energy emitter for CO2, CH4, and H2O monitoring in the 2 µm range.

We demonstrate the first emitter, based on a single optical source device, capable of addressing three species of interest (CO2, CH4, and H2O) for differential absorption Lidar remote sensing of atmospheric greenhouse gases from space in the 2 µm region. It is based on an amplified nested cavity optical parametric oscillator. The single frequency source shows a total conversion efficiency of 37% and covers the 2.05-2.3 µm range.

Spatial Pattern of Strawberry Powdery Mildew (Podosphaera aphanis) and Airborne Inoculum.

The relationship between strawberry powdery mildew and airborne conidium concentration (ACC) of Podosphaera aphanis was studied using data collected from 2006 to 2009 in 15 fields, and spatial pattern was described using 2 years of airborne inoculum and disease incidence data collected in fields planted with the June-bearing strawberry (Fragaria × ananassa) cultivar Jewel. Disease incidence, expressed as the proportion of diseased leaflets, and ACC were monitored in fields divided into 3 × 8 grids containing 24 100 m2 quadrats. Variance-to-mean ratio, index of dispersion, negative binomial distribution, Poisson distribution, and binomial and beta-binomial distributions were used to characterize the level of spatial heterogeneity. The relationship between percent leaf area diseased and daily ACC was linear, while the relationship between ACC and disease incidence followed an exponential growth curve. The V/M ratios were significantly greater than 1 for 100 and 96% of the sampling dates for ACC sampled at 0.35 m from the ground (ACC0.35m) and for ACC sampled at 1.0 m from the ground (ACC1.0m), respectively. For disease incidence, the index of dispersion D was significantly greater than 1 for 79% of the sampling dates. The negative binomial distribution fitted 86% of the data sets for both ACC1.0m and ACC0.35m. For disease incidence data, the beta-binomial distribution provided a good fit of 75% of the data sets. Taylor's power law indicated that, for ACC at both sampling heights, heterogeneity increased with increasing mean ACC, whereas the binary form of the power law suggested that heterogeneity was not dependent on the mean for disease incidence. When the spatial location of each sampling location was taken into account, Spatial Analysis by Distance Indices showed low aggregation indices for both ACCs and disease incidence, and weak association between ACC and disease incidence. Based on these analyses, it was found that the distribution of strawberry powdery mildew was weakly aggregated. Although a higher level of heterogeneity was observed for airborne inoculum, the heterogeneity was low with no distinct foci, suggesting that epidemics are induced by well-distributed inoculum. This low level of heterogeneity allows mean airborne inoculum concentration to be estimated using only one sampler per field with an overall accuracy of at least 0.841. The results obtained in this study could be used to develop a sampling scheme that will improve strawberry powdery mildew risk estimation.