Genome Sequences of Rare Human Enterovirus Genotypes Recovered from Clinical Respiratory Samples in Bern, Switzerland.

We report on genomic sequences of human enteroviruses (EVs) that were identified in respiratory samples in Bern, Switzerland, in 2018 and 2019. Besides providing sequences for coxsackievirus A2, echovirus 11, and echovirus 30, we determined the sequences of rare EV-D68 and EV-C105 genotypes circulating in Switzerland.

Determinants of total incapacity to work duration among 231 victims of school violence in France.

INTRODUCTION: This study aimed to identify the factors that may influence the duration of the total incapacity to work (TIW) among victims of school violence from the perspective of clinical forensics practice. METHODS: It used a cross-sectional design to collect data from school violence victims examined at a French forensic unit following a judicial requisition. Logistic regression models were used to identify whether the victim's characteristics, the circumstances of the violence, or the evaluation itself could predict a TIW duration equal to or greater than 2 days. RESULTS: Among 231 victims of school violence, the presence of traumatic injuries such as sprains or broken bones (OR=19.8; 95% CI, 1.7-23.4, p = 0.018), bruises (OR=6.3; 95% CI, 1.5-26.8, p = 0.007), and muscle contractures (OR=7.3; 95% CI, 2.0-26.2, p = 0.007) were the main risk determinants for a longer TIW. Factors with a mild impact were the presence of ecchymosis (OR=3.8; 95% CI, 1.4-9.9, p = 0.007), anxiety (OR=3.4, 95% CI, 1.6-7.1, p = 0.001), female physician (OR=2.5, 95% CI, 1.2-5.1, p = 0.016), and the presence of a psychological follow-up for the victim or the need for a psychological consultation (OR=3.6, 95% CI, 1.2-10.7 and OR=4.7, 95% CI, 1.9-11.5, p = 0.001). CONCLUSION: These results highlight the importance of developing a more uniform model in determining TIW, whatever the physician's characteristics, through screening and reporting methods for both physical and psychological symptoms.

[SARS-CoV-2 infections and the autonomic nervous system]. / SARS-CoV-2 Infektionen und das autonome Nervensystem.

Investigations of the heart rate variability (HRV) in an 11-year-old boy with multisystemic inflammation syndrome in children (MIS-C) and a 16-year-old girl with postural orthostatic tachycardia syndrome (POTS) after SARS-CoV­2 infections are presented. Results: The MIS­C is characterized by a maximum suppression of the HRV during ECG monitoring on the pediatric intensive care unit. After intravenous administration of immunoglobulins HRV supppression is rapidly reversible. The POTS is characterized by a heart rate increase of more than 40 bpm and the complete collapse of the HRV in the active standing test that can probably explain some chronic problems after SARS-CoV­2 infections. In the MIS­C patient we found autoantibodies against receptors of the autonomic nervous system. Summary: The examination of HRV in patients with COVID-19 are initial descriptions,which can enrich our knowledge of the pathophysiology of this new disease.

[The practice of telemedicine by French internal medicine physicians in 2019]. / La pratique de la télémédecine par les médecins internistes français en 2019.

INTRODUCTION: Telemedicine has been developing in France since 2018. The objective of this survey was to assess the knowledge, attitudes, practices and training of internal physicians regarding telemedicine. MATERIAL AND METHODS: A national descriptive observational study carried out between July and October 2019, via an online self-questionnaire with members of the National Society of Internal Medicine and the Association of Young Internists, included a descriptive and comparative analysis by subgroups of age. RESULTS: Analysis of 309 responses from physicians qualified in internal medicine or practicing in an internal medicine service (61,8%) and residents in internal medicine (38%) showed that 34.6% had notions or a good knowledge of regulation of telemedicine. For 62,1%, 72.5% and 74.1% respectively, it could improve patient care, access to care and exchanges between internists and other doctors. The main obstacles to this practice were the absence of face-to-face with the patient (57.3%) and computer dysfunctions (55%). Only 23.3% practiced it, including 88.9% tele-expertise. Telemedicine was performed informally (telephone and email) in 70.8% of the cases. Doctors over the age of 50 were better acquainted with the regulations and more practiced official telemedicine. In total, 54% wanted to practice telemedicine and 72.8% wanted to train there. CONCLUSION: Attitudes towards telemedicine were positive, but few internists knew about it and practiced it formally, warranting appropriate training.

Beam Energy and Centrality Dependence of Direct-Photon Emission from Ultrarelativistic Heavy-Ion Collisions.

The PHENIX collaboration presents first measurements of low-momentum (0.41 GeV/c) direct-photon yield dN_{γ}^{dir}/dη is a smooth function of dN_{ch}/dη and can be well described as proportional to (dN_{ch}/dη)^{α} with α≈1.25. This scaling behavior holds for a wide range of beam energies at the Relativistic Heavy Ion Collider and the Large Hadron Collider, for centrality selected samples, as well as for different A+A collision systems. At a given beam energy, the scaling also holds for high p_{T} (>5 GeV/c), but when results from different collision energies are compared, an additional sqrt[s_{NN}]-dependent multiplicative factor is needed to describe the integrated-direct-photon yield.

[Epidemiologic and etiologic patterns of uveitis in a University Hospital]. / Caractéristiques épidémiologiques et étiologiques des uvéites dans un centre hospitalier universitaire.

INTRODUCTION: The purpose of this study was to describe the epidemiologic characteristics of adult uveitis evaluated at the regional center of excellence specializing in systemic and autoimmune disease in the Nancy university medical center. The secondary objectives were to describe the progression over time of the various etiologies and to identify local specificities. MATERIALS AND METHODS: We performed a retrospective epidemiological study of patients diagnosed with uveitis. All patients were referred to the regional center of excellence of the Nancy university medical center between January 1, 2005 and December 31, 2016. Patients under 18 years of age, patients with a first episode of acute anterior uveitis, as well as patients for whom the etiological diagnosis was made by the ophthalmologist with no need of internal medicine referral, were excluded. Age, gender, laterality, site of inflammation, clinical signs, etiology (infectious, non-infectious or idiopathic, as well as diagnosis), and date of first consultation were recorded. RESULTS: Six hundred and ninetypatients were included, with 59 % women and a mean age of 49 years. The uveitis was unilateral in 53 % of cases. Panuveitis was the most common form (52 %, N=358), followed by recurrent anterior uveitis (30 %, N=205), posterior uveitis (16 %, N=107), and intermediate uveitis (3 %, N=20). Non-infectious etiologies accounted for 35 % of all uveitis (the most common being HLA-B27 uveitis, sarcoidosis, ankylosing spondylitis and Behçet's disease) and infectious etiologies for 13 % (tuberculosis, toxoplasmosis and Lyme disease were the most frequent). The uveitis was idiopathic in 52 %. A trend toward improvement in diagnostic yield was observed : 53 % of uveitides were considered idiopathic prior to 2011 compared to 50 % after 2011 (P<0,01). CONCLUSION: We identified a majority of panuveitis, which is explained by our inclusion criteria. Fifty-two percent of our series remained idiopathic, with an improvement in the diagnostic yield over time. This could be related to both repeated etiological assessments and better diagnostic performance. The study of this large cohort of patients improved our knowledge of the characteristics of uveitis in our center.

Alleviation of arrhythmia burden in children with frequent idiopathic premature ventricular contractions by omega-3-fatty acid supplementation.

BACKGROUND: Patients at our pediatric outpatient clinic were offered 24-h Holter electrocardiogram (ECG) before and after 3-month period of dietary supplementation with omega-3 fatty acids to monitor the effect on heart rate variability (HRV) and arrhythmias. METHODS: The study included 17 children (mean age: 11.6 ±â€¯4.9 years) with >1% premature ventricular contractions (PVC) at baseline. 24-h Holter ECG monitoring was performed before and after omega-3 fatty acid supplementation (mean duration: 143 days). RESULTS: Compared with 86 age-matched healthy control children, baseline HRV was significantly reduced and mean heart rate was significantly increased in children with frequent PVC. After omega-3-fatty acid supplementation, the mean heart rate decreased from 92.6 ±â€¯3.4 bpm to 83.9 ±â€¯9.9 bpm (p = 0.001), while global HRV showed a significant increase [standard deviation of all NN intervals (SDNN): 148.1 ±â€¯34.4 ms vs. 126.5 ±â€¯39.3 ms, p = 0.022)]. Enhanced vagal activity was indicated by significantly higher square root of the mean of the sum of the squares of differences between adjacent NN intervals (rMSSD) (42.3 ±â€¯12.6 vs. 33.2 ±â€¯14.8; p = 0.0003). PVC percentage significantly decreased by 45% (6.9 ±â€¯7.0% vs. 12.1 ±â€¯8.2%; p = 0.014). CONCLUSIONS: Omega-3-fatty acid supplementation caused a 45% reduction in frequent PVC in children with structurally healthy hearts. This antiarrhythmic effect was likely attributable to improved autonomic function, which is consistent with previous findings in children with obesity, attention deficit disorder, and short stature.

Probing non-perturbative QED with electron-laser collisions.

The vast majority of QED results are obtained in relatively weak fields and so in the framework of perturbation theory. However, forthcoming laser facilities providing extremely high fields can be used to enter not-yet-studied regimes. Here, a scheme is proposed that might be used to reach a supercritical regime of radiation reaction or even the fully non-perturbative regime of quantum electrodynamics. The scheme considers the collision of a 100 GeV-class electron beam with a counterpropagating ultraintense electromagnetic pulse. To reach these supercritical regimes, it is unavoidable to use a pulse with ultrashort duration. Using two-dimensional particle-in-cell simulations, it is therefore shown how one can convert a next-generation optical laser to an ultraintense (I ≈ 2.9 × 1024 Wcm-2) attosecond (duration ≈ 150 as) pulse. It is shown that if the perturbation theory persists in extreme fields, the spectrum of secondary particles can be found semi-analytically. In contrast, a comparison with experimental data may allow differentiating the contribution of high-order radiative corrections if the perturbation theory breaks.

Prospect of Studying Nonperturbative QED with Beam-Beam Collisions.

We demonstrate the experimental feasibility of probing the fully nonperturbative regime of quantum electrodynamics with a 100 GeV-class particle collider. By using tightly compressed and focused electron beams, beamstrahlung radiation losses can be mitigated, allowing the particles to experience extreme electromagnetic fields. Three-dimensional particle-in-cell simulations confirm the viability of this approach. The experimental forefront envisaged has the potential to establish a novel research field and to stimulate the development of a new theoretical methodology for this yet unexplored regime of strong-field quantum electrodynamics.

[Diagnostic vitrectomy in intraocular inflammations: A retrospective series]. / Vitrectomie diagnostique dans les inflammations intraoculaires : étude d'une série rétrospective.

PURPOSE: To determine the diagnostic and functional yield of vitrectomy in patients with uveitis of unknown origin. METHODS: A single-centered retrospective study was performed on patients who underwent a diagnostic vitrectomy for uveitis in the Department of Ophthalmology of the Nancy University Hospital from January 2011 to December 2016. Vitreous samples were analyzed in the cytology laboratory by cytological and immunohistochemical techniques, and in the microbiological laboratory by culture and bacterial, fungal and viral PCR, depending on clinical findings. Preoperative and one- and six-month postoperative visual acuity were collected and compared. RESULTS: Thirty-four patients (39 vitrectomies) were included. Vitreous testing led to a diagnosis in 14 out of 39 cases (36 %): 10 intraocular lymphoma, 2 amyloidosis, 1 CMV retinitis, and 1 choroidal metastasis of cutaneous melanoma with vitreous dissemination. Vitrectomy was negative in 20 patients. Visual acuity improved from 1.2±0.7 logMAR preoperatively to 0.8±0.7 logMAR at 1 month (p<0.001) and 0.9±0.8 logMAR at 6 months (p=0.054). CONCLUSION: In our study, diagnostic vitrectomy and vitreous fluid analysis were useful to diagnose uveitis of unknown origin, most of which were found to be intraocular lymphomas. Visual acuity improved for the majority of patients. Diagnostic vitrectomy with appropriate vitreous analysis related to clinical examination must be considered in the evaluation of uveitis of unknown origin.

[How to proceed after a failed vacuum delivery]. / Quelle voie d'accouchement choisir après échec d'extraction par ventouse.

OBJECTIVES: Compare maternal and neonatal morbidity in patients delivered by a second instrument versus cesarean section after failed vacuum. METHODS: We performed a retrospective study between January 2006 and December 2014. Case notes of 172 failed vacuum deliveries were studied. The studied parameters were blood loss, perineal tears, pH, Apgar score, neonatal reanimation and length of stay in neonatology. RESULTS: The frequency of vacuum failure was 8.7%. The use of the second instrument (77.9%) was associated with a higher prevalence of third degree perineal tears (13.4% vs. 0%; P=0.017) and more episiotomy (72.2% vs. 0%; P<0.0001). There was no significant difference regarding post partum hemorrhage between cesarean section and second instrument delivery. There was no significant difference regarding neonatal morbidity between cesarean section and second instrument delivery after failed vacuum. When an attempted second instrument delivery failed, the risk of adverse neonatal outcome was increased: newborns had a significantly longer stay in a neonatal unit (2.4 versus 0.6 days; P=0.026), lower pH (P=0.017), lower Apgar scores (7.4 versus 8.8; P=0.0373), needed intubation (P=0.0471) and had seizures (P=0.04) more often. CONCLUSION: Compared to cesarean section, the use of the second instrument increased maternal morbidity but doesn't seem to increase neonatal morbidity. If the second instrument fails, neonatal morbidity is significantly increased.

[Early satisfaction with care among outpatients with substance dependence]. / Satisfaction précoce vis-à-vis des soins ambulatoires chez des patients dépendants aux substances psychoactives.

BACKGROUND: Patient satisfaction with health care is an important indicator of health care quality. The main objective was to identify factors associated with early outpatient satisfaction with care 45 days after study inclusion for alcohol and opioid dependence. The secondary objective was to study the reproducibility of the satisfaction during the care. METHODS: A longitudinal study was conducted. Satisfaction was assessed during the early care process 15 and 45 days after study inclusion using the quality of care satisfaction questionnaire in outpatient consultation EQS-C. Multiple linear regression was performed to identify the variables associated with satisfaction level. The reproducibility of the questionnaire between the two measurements (15 and 45 days after inclusion) was tested by intraclass correlation coefficient. RESULTS: A total of 189 outpatients were included, and 90 patients completed the satisfaction questionnaire both at 15 and 45 days after inclusion. The level of early satisfaction with care was high. If patients without a history of previous care for substance dependence were at first more satisfied at 45 days (ß=6.8; P=0.05) than those who had received care previously, only the total score of the satisfaction with care at 15 days is associated with satisfaction with care at 45 days when taken into account in the model (ß=0,7; P<0.0001). The results indicated good total satisfaction reproducibility with an intraclass correlation coefficient ICC=0.68. CONCLUSION: We recommend an early measure of satisfaction with care among outpatients with substance dependence.

Dermatological manifestations in cardiofaciocutaneous syndrome: a prospective multicentric study of 45 mutation-positive patients.

BACKGROUND: Data on dermatological manifestations of cardiofaciocutaneous syndrome (CFCS) remain heterogeneous and almost without expert dermatological classification. OBJECTIVES: To describe the dermatological manifestations of CFCS; to compare them with the literature findings; to assess those discriminating CFCS from other RASopathies, including Noonan syndrome (NS) and Costello syndrome (CS); and to test for dermatological phenotype-genotype correlations. METHODS: We performed a 4-year, large, prospective, multicentric, collaborative dermatological and genetic study. RESULTS: Forty-five patients were enrolled. Hair abnormalities were ubiquitous, including scarcity or absence of eyebrows and wavy or curly hair in 73% and 69% of patients, respectively. Keratosis pilaris (KP), ulerythema ophryogenes (UO), palmoplantar hyperkeratosis (PPHK) and multiple melanocytic naevi (MMN; over 50 naevi) were noted in 82%, 44%, 27% and 29% of patients, respectively. Scarcity or absence of eyebrows, association of UO and PPHK, diffuse KP and MMN best differentiated CFCS from NS and CS. Oral acitretin may be highly beneficial for therapeutic management of PPHK, whereas treatment of UO by topical sirolimus 1% failed. No significant dermatological phenotype-genotype correlation was determined. CONCLUSIONS: A thorough knowledge of CFCS skin manifestations would help in making a positive diagnosis and differentiating CFCS from CS and NS.

Dermatological manifestations in Noonan syndrome: a prospective multicentric study of 129 patients positive for mutation.

BACKGROUND: Data on dermatological manifestations of Noonan syndrome (NS) remain heterogeneous and are based on limited dermatological expertise. OBJECTIVES: To describe the dermatological manifestations of NS, compare them with the literature findings, and test for dermatological phenotype-genotype correlations with or without the presence of PTPN11 mutations. METHODS: We performed a large 4-year, prospective, multicentric, collaborative dermatological and genetic study. RESULTS: Overall, 129 patients with NS were enrolled, including 65 patients with PTPN11-NS, 34 patients with PTPN11-NS with multiple lentigines (NSML), and 30 patients with NS who had a mutation other than PTPN11. Easy bruising was the most frequent dermatological finding in PTPN11-NS, present in 53·8% of patients. Multiple lentigines and café-au-lait macules (n ≥ 3) were present in 94% and 80% of cases of NSML linked to specific mutations of PTPN11, respectively. Atypical forms of NSML could be associated with NS with RAF1 or NRAS mutations. In univariate analysis, patients without a PTPN11 mutation showed (i) a significantly higher frequency of keratinization disorders (P = 0·001), including keratosis pilaris (P = 0·005), ulerythema ophryogenes (P = 0·0001) and palmar and/or plantar hyperkeratosis (P = 0·06, trend association), and (ii) a significantly higher frequency of scarce scalp hair (P = 0·035) and scarce or absent eyelashes (P = 0·06, trend association) than those with PTPN11 mutations. CONCLUSIONS: The cutaneous phenotype of NS with a PTPN11 mutation is generally mild and nonspecific, whereas the absence of a PTPN11 mutation is associated with a high frequency of keratinization disorders and hair abnormalities.

[Decision-making regarding treatment limitation after severe traumatic brain injury: A survey of French neurosurgeons]. / Modalités de décision de limitation thérapeutique chez les traumatisés crâniens sévères : enquête auprès des neurochirurgiens en France.

BACKGROUND/INTRODUCTION: In France, the law defines and prohibits "unreasonable obstinacy" and provides a framework for the subsequent decision to limit or to cease treatment. It also gives the person the right to appoint a trusted person and to draft advance directives regarding this issue. There have been few studies of neurosurgeons' involvement in decision-making in regard to treatment limitation after severe traumatic brain injury. AIM OF THE STUDY: The first aim of the study was to assess French neurosurgeons' adherence to the law on patients' rights and end of life which governs such decision-making. The second aim was to assess the prognostic and decision-making criteria applied by neurosurgeons. METHODS: A declarative practice and opinion survey, using a self-administered questionnaire emailed to all practising neurosurgeons members of the French Society of Neurosurgery, was conducted from April to June 2016. RESULTS: Of the 197 neurosurgeons contacted, 62 filled in the questionnaire. Discussions regarding treatment limitation were in all cases collegial, as required under the law, and the patient's neurosurgeon was always involved. The trusted person and/or family were always informed and consulted, but their opinions were not consistently taken into account. Advance directives were most often lacking (68%) [56; 80] or inappropriate (27%) [16; 38]. The most frequently used prognostic criteria were clinical parameters, intracranial pressure, cerebral perfusion pressure, and imaging, with significant interindividual variation in their use. The main decision-making criteria were foreseeable disability, expected future quality of life, and age. CONCLUSIONS: Neurosurgeons showed good compliance with legal requirements, except in the matter of calling for the opinion of an external consultant. Furthermore, this survey confirmed variability in the use of prognosis predictors, and the need for further clinical research so as to achieve more-standardized practices to minimise the subjectivity in decision-making.

Prenatally diagnosed periventricular nodular heterotopia: Further delineation of the imaging phenotype and outcome.

OBJECTIVES: Periventricular nodular heterotopia (PNH) is a malformation of cortical development which presents with heterogeneous imaging, neurological phenotype and outcome. There is a paucity of comprehensive description detailing the prenatal diagnosis of PNH. The aim of this study is to report neuroimaging features and correlated outcomes in order to delineate the spectrum of prenatally diagnosed PNH. METHODS: It was a retrospective study over 15 years in five tertiary centers. All fetuses with prenatally diagnosed PNH were collected. Fetal ultrasound and MRI were reviewed and genetic screening collected. Prenatal findings were analyzed in correlation to fetopathological analyses and post-natal follow up. RESULTS: Thirty fetuses (22 females and 8 males) with PNH were identified. The two major ultrasound signs were ventriculomegaly associated with dysmorphic frontal horns (60%) and posterior fossa anomalies (73.3%). On MRI, two groups of PNH were identified: the contiguous and diffuse PNH (n = 15, 50%), often associated with megacisterna magna, and the non-diffuse, either anterior, posterior or unilateral PNH. FLNA mutations were found in 6/11 cases with diffuse PNH. Additional cortical malformations were exclusively observed in non diffuse PNH (9/15; 60%). Twenty-four pregnancies (80%) were terminated. Six children aged 6 months to 5 years are alive. Five have normal neurodevelopment (all had diffuse PNH) whereas one case with non diffuse PNH has developmental delay and epilepsy. CONCLUSION: PNH is heterogeneous but patients with diffuse PNH are a common subgroup with specific findings on prenatal imaging and implications for prenatal counseling.

A functional genetic variation of SLC6A2 repressor hsa-miR-579-3p upregulates sympathetic noradrenergic processes of fear and anxiety.

Increased sympathetic noradrenergic signaling is crucially involved in fear and anxiety as defensive states. MicroRNAs regulate dynamic gene expression during synaptic plasticity and genetic variation of microRNAs modulating noradrenaline transporter gene (SLC6A2) expression may thus lead to altered central and peripheral processing of fear and anxiety. In silico prediction of microRNA regulation of SLC6A2 was confirmed by luciferase reporter assays and identified hsa-miR-579-3p as a regulating microRNA. The minor (T)-allele of rs2910931 (MAFcases = 0.431, MAFcontrols = 0.368) upstream of MIR579 was associated with panic disorder in patients (pallelic = 0.004, ncases = 506, ncontrols = 506) and with higher trait anxiety in healthy individuals (pASI = 0.029, pACQ = 0.047, n = 3112). Compared to the major (A)-allele, increased promoter activity was observed in luciferase reporter assays in vitro suggesting more effective MIR579 expression and SLC6A2 repression in vivo (p = 0.041). Healthy individuals carrying at least one (T)-allele showed a brain activation pattern suggesting increased defensive responding and sympathetic noradrenergic activation in midbrain and limbic areas during the extinction of conditioned fear. Panic disorder patients carrying two (T)-alleles showed elevated heart rates in an anxiety-provoking behavioral avoidance test (F(2, 270) = 5.47, p = 0.005). Fine-tuning of noradrenaline homeostasis by a MIR579 genetic variation modulated central and peripheral sympathetic noradrenergic activation during fear processing and anxiety. This study opens new perspectives on the role of microRNAs in the etiopathogenesis of anxiety disorders, particularly their cardiovascular symptoms and comorbidities.

[Echographic diagnosis of missed early miscarriage: Assessment of image quality]. / Diagnostic échographique de grossesse arrêtée précoce : étude de la qualité des clichés.

OBJECTIVE: Ultrasound examination plays a central role in case of suspected non-viable pregnancy. A wrong diagnosis might have major consequence in terms of inadequate care, especially in cases of false positive non-viable pregnancy diagnosis. Ultrasound criterions are today well defined. Our objective was to evaluate the feasibility and reproducibility of a novel image-quoting method of first-trimester non-viable pregnancy. METHODS: Thirty images of non-viable pregnancy were twice evaluated with blinded proofreading. Two quotations were evaluated: the first for the images of gestational sacs without embryo (gestational sac score), the second for the images with embryo (embryo score). RESULTS: The ICC (interclass correlation coefficient) was>0.75 for inter- and intra-observer reproducibility both for the quotations of the gestational sac and for the embryo with a low variability. Reproducibility of quoting crown rump length measurements <5mm was low at first proofreading but after adjustment of the quoting modalities, ICC was also>0.75. CONCLUSION: The inter- and intra-observer reproducibility of our quoting methods is high with a low variability. They might be a useful tool in current practice in the future.