Ambulatory pediatricians: how to bridge the gaps in diagnosis and care coordination for neurodevelopmental disorders in France.

Introduction and aims: The organization of healthcare pathways for neurodevelopmental disorders (NDD) relies on different levels of expertise depending on the complexity of these disorders. NDDs affect between 8% and 15% of children. Historically, national recommendations and healthcare planning measures were initially devoted to autism spectrum disorders and were gradually extended to Attention deficit hyperactivity disorder (ADHD) and specific learning and development disorders. Private doctors play an increasing role in these pathways at different levels of care due to difficulties in organization, particularly in the health and social sector. The aim of this work was to evaluate the contribution of second-line private doctors in the diagnosis and care of children affected by NDD. Methods: A first series of surveys in 2016 evaluated the level of commitment of primary care pediatricians; this online national survey was repeated in 2023 among 1,430 members of the French Association of Ambulatory Pediatrics (Association Française de Pédiatrie Ambulatoire: AFPA) to assess their training, current and future involvement, and activity in NDD care. Analysis was performed by the main author using Epi-Info software. Results: The study identified in 2023 214 second-line private doctors (14% of all pediatricians in activity), of which 185 agreed to appear in a directory published the same year by the AFPA to facilitate referrals from other professionals. Sex ratio of responders is usual for paediatricians: 79.5%/20.5% (F/M), with a distribution among ages showing a slight increase of the age range between age 51-60 (30.5%). Our data indicate that in France in 2022, second-line private doctors made 48%-53% of NDD diagnoses, 24%-26.4% of follow-up consultations and declare to be accountable for 21% of initial prescriptions for Methylphenidate. Among these second-line doctors, 40% had completed a post-university degree on NDD, 74.3% had completed professional development training (PDT) and 85.2% had completed either or both types of training. Most doctors participating in the survey wanted to improve their level of practice, suggesting that in five years, the number of second-line private doctors will increase by 20% to 244 despite 24 planned retirements within the same period. This data probably underestimates the role of private doctors in NDD diagnosis, follow-up, and initial Methylphenidate prescriptions given the unfavourable working conditions (no financial compensation for long appointments, difficulty accessing paramedical and psychological assessments). Conclusions: Our data confirms that diagnosis and care coordination in the various presentations of NDD may rely on different types of practices and specializations: medical and social professionals, mental health professionals, but also a growing body of medical doctors involved in developmental and behavioural pediatrics. This data and reflection will be helpful for organizing healthcare in France or in other countries. Main study limitation relies in the self-declaration of MD's involvement in NDD and could not evaluate the activity of employed MD's from the social and medico social sector, nor be based on the national databases for prescription. It remains however the first attempt of characterization of medical activity at the national level in France for NDD.

Natural antisense transcripts as versatile regulators of gene expression.

Long non-coding RNAs (lncRNAs) are emerging as a major class of gene products that have central roles in cell and developmental biology. Natural antisense transcripts (NATs) are an important subset of lncRNAs that are expressed from the opposite strand of protein-coding and non-coding genes and are a genome-wide phenomenon in both eukaryotes and prokaryotes. In eukaryotes, a myriad of NATs participate in regulatory pathways that affect expression of their cognate sense genes. Recent developments in the study of NATs and lncRNAs and large-scale sequencing and bioinformatics projects suggest that whether NATs regulate expression, splicing, stability or translation of the sense transcript is influenced by the pattern and degrees of overlap between the sense-antisense pair. Moreover, epigenetic gene regulatory mechanisms prevail in somatic cells whereas mechanisms dependent on the formation of double-stranded RNA intermediates are prevalent in germ cells. The modulating effects of NATs on sense transcript expression make NATs rational targets for therapeutic interventions.

XPR1: a regulator of cellular phosphate homeostasis rather than a Pi exporter.

Phosphate (Pi) is an essential nutrient, and its plasma levels are under tight hormonal control. Uphill transport of Pi into cells is mediated by the two Na-dependent Pi transporter families SLC34 and SLC20. The molecular identity of a potential Pi export pathway is controversial, though XPR1 has recently been suggested by Giovannini and coworkers to mediate Pi export. We expressed XPR1 in Xenopus oocytes to determine its functional characteristics. Xenopus isoforms of proteins were used to avoid species incompatibility. Protein tagging confirmed the localization of XPR1 at the plasma membrane. Efflux experiments, however, failed to detect translocation of Pi attributable to XPR1. We tested various counter ions and export medium compositions (pH, plasma) as well as potential protein co-factors that could stimulate the activity of XPR1, though without success. Expression of truncated XPR1 constructs and individual domains of XPR1 (SPX, transmembrane core, C-terminus) demonstrated downregulation of the uptake of Pi mediated by the C-terminal domain of XPR1. Tethering the C-terminus to the transmembrane core changed the kinetics of the inhibition and the presence of the SPX domain blunted the inhibitory effect. Our observations suggest a regulatory role of XPR1 in cellular Pi handling rather than a function as Pi exporter. Accordingly, XPR1 senses intracellular Pi levels via its SPX domain and downregulates cellular Pi uptake via the C-terminal domain. The molecular identity of a potential Pi export protein remains therefore elusive.

SARS-CoV-2 infection prevalence and associated factors among primary healthcare workers in France after the third COVID-19 wave.

Data on the SARS-CoV-2 infection among primary health care workers (PHCWs) are scarce but essential to reflect on policy regarding prevention and control measures. We assessed the prevalence of PHCWs who have been infected by SARS-CoV-2 in comparison with modeling from the general population in metropolitan France, and associated factors. A cross-sectional study was conducted among general practitioners (GPs), pediatricians, dental and pharmacy workers in primary care between May and August 2021. Participants volunteered to provide a dried-blood spot for SARS-CoV-2 antibody assessment and completed a questionnaire. The primary outcome was defined as the detection of infection-induced antibodies (anti-nucleocapsid IgG, and for non-vaccinees: anti-Spike IgG and neutralizing antibodies) or previous self-reported infection (positive RT-qPCR or antigenic test, or positive ELISA test before vaccination). Estimates were adjusted using weights for representativeness and compared with prediction from the general population. Poisson regressions were used to quantify associated factors. The analysis included 1612 PHCWs. Weighted prevalences were: 31.7% (95% CI 27.5-36.0) for GPs, 28.7% (95% CI 24.4-33.0) for pediatricians, 25.2% (95% CI 20.6-31.0) for dentists, and 25.5% (95% CI 18.2-34.0) for pharmacists. Estimates were compatible with model predictions for the general population. PHCWs more likely to be infected were: GPs compared to pharmacist assistants (adjusted prevalence ratio [aPR] = 2.26; CI 95% 1.01-5.07), those living in Île-de-France (aPR = 1.53; CI 95% 1.14-2.05), South-East (aPR = 1.57; CI 95% 1.19-2.08), North-East (aPR = 1.81; CI 95% 1.38-2.37), and those having an unprotected contact with a COVID-19 case within the household (aPR = 1.48; CI 95% 1.22-1.80). Occupational factors were not associated with infection. In conclusion, the risk of SARS-CoV-2 exposure for PHCWs was more likely to have occurred in the community rather than at their workplace.

Significant Variations in Double-Stranded RNA Levels in Cultured Skin Cells.

Endogenous double-stranded RNA has emerged as a potent stimulator of innate immunity. Under physiological conditions, endogenous dsRNA is maintained in the cell nucleus or the mitochondria; however, if protective mechanisms are breached, it leaches into the cytoplasm and triggers immune signaling pathways. Ectopic activation of innate immune pathways is associated with various diseases and senescence and can trigger apoptosis. Hereby, the level of cytoplasmic dsRNA is crucial. We have enriched dsRNA from two melanoma cell lines and primary dermal fibroblasts, including a competing probe, and analyzed the dsRNA transcriptome using RNA sequencing. There was a striking difference in read counts between the cell lines and the primary cells, and the effect was confirmed by northern blotting and immunocytochemistry. Both mitochondria (10-20%) and nuclear transcription (80-90%) contributed significantly to the dsRNA transcriptome. The mitochondrial contribution was lower in the cancer cells compared to fibroblasts. The expression of different transposable element families was comparable, suggesting a general up-regulation of transposable element expression rather than stimulation of a specific sub-family. Sequencing of the input control revealed minor differences in dsRNA processing pathways with an upregulation of oligoadenylate synthase and RNP125 that negatively regulates the dsRNA sensors RIG1 and MDA5. Moreover, RT-qPCR, Western blotting, and immunocytochemistry confirmed the relatively minor adaptations to the hugely different dsRNA levels. As a consequence, these transformed cell lines are potentially less tolerant to interventions that increase the formation of endogenous dsRNA.

Age-Specific Resurgence in Invasive Pneumococcal Disease Incidence in the COVID-19 Pandemic Era and Its Association With Respiratory Virus and Pneumococcal Carriage Dynamics: A Time-Series Analysis.

Using multiple national surveillance systems, we found an increase in the incidence of invasive pneumococcal disease during after the relaxation of non-pharmaceutical interventions against COVID-19, which strongly varied by age. Age groups with higher incidence of respiratory syncytial virus and influenza also experienced higher increase in invasive pneumococcal disease incidence, with no change in pneumococcal carriage.

Antibiotic Resistance of Haemophilus influenzae in Nasopharyngeal Carriage of Children with Acute Otitis Media and in Middle Ear Fluid from Otorrhea.

Haemophilus influenzae (Hi) is one of the leading bacteria implicated in childhood acute otitis media (AOM). Recent concerns have been raised about the emergence of Hi-resistant strains. We aimed to analyze the evolution of ß-lactam resistance to Hi among strains isolated from nasopharyngeal carriage in children with AOM and in mild ear fluid (MEF) after the spontaneous perforation of the tympanic membrane (SPTM) in France. In this national ambulatory-based cohort study over 16 years, we analyzed the rate of Hi nasopharyngeal carriage and the proportion of ß-lactam-resistant Hi strains over time using a segmented linear regression model. Among the 13,865 children (median [IQR] age, 12.7 [9.3-17.3] months; 7400 [53.4%] male) with AOM included from November 2006 to July 2022, Hi was isolated in 7311 (52.7%) children by nasopharyngeal sampling. The proportion of ß-lactamase-producing and ß-lactamase-negative, ampicillin-resistant (BLNAR) Hi strains in nasopharyngeal carriage remained stable during the study period. Among the 783 children (median [IQR] age, 20 [12.3-37.8] months; 409 [52.2%] male) with SPTM included from October 2015 to July 2022, Hi was isolated in 177 (22.6%) cases by MEF sampling. The proportions of ß-lactamase-producing and BLNAR Hi strains did not significantly differ between nasopharyngeal (17.6% and 8.8%, respectively) and MEF (12.6% and 7.4%) samples. Accordingly, amoxicillin remains a valid recommendation as the first-line drug for AOM in France.

Anti-infective treatment of gastro-intestinal tract infections in children.

Gastroenteritis is most often viral in origin and Rotavirus and Norovirus most frequently implicated in young children. Stool-based multiplex Polymerase Chain Reaction (PCR) can detect bacteria, viruses or parasites that may or may not be responsible for gastroenteritis (colonization). While the etiological profile of these digestive infections has greatly benefited from PCR, in the absence of underlying pathologies the presence of potential pathogens does not justify anti-infectious treatment. Indeed, very few bacterial causes require antibiotic treatment, apart from shigellosis, severe forms of salmonellosis and a few Campylobacter sp. infections. The development of antibiotic resistance in Salmonella sp., Shigella sp. and Campylobacter sp. is a cause for concern worldwide, limiting therapeutic options. The antibiotics proposed in this guide are in line with the joint recommendations of the European Society of Pediatric Infectious Diseases and the European Society of Pediatric Gastroenterology and Nutrition. Azithromycin is preferentially used to treat infections with Shigella sp. or Campylobacter sp. Ceftriaxone and ciprofloxacin are recommended for salmonellosis requiring antibiotic therapy. Empirical treatments without bacterial identification are not indicated except in cases of severe sepsis or in subjects at risk (e.g., sickle-cell disease). Metronidazole should be prescribed only for acute intestinal amebiasis after microbiological confirmation.

Antimicrobial treatment of urinary tract infections in children.

Urinary tract infections are the most frequently proven bacterial infections in pediatrics. The treatment options proposed in this guide are based on recommendations published by the Groupe de Pathologie Infectieuse de Pédiatrique (GPIP-SFP). Except in rare situations (newborns, neutropenia, sepsis), a positive urine dipstick for leukocytes and/or nitrites should precede a urine culture examination and any antibiotic therapy. After rising steadily between 2000 and 2012, the proportion of Escherichia coli strains resistant to extended-spectrum ß-lactamases (E-ESBL) has remained stable over the last ten years (between 7% and 10% in pediatrics). However, in many cases no oral antibiotic is active on E-ESBL leading either to prolonged parenteral treatment, or to use of a non-orthodox combination such as cefixime + clavulanate. With the aim of avoiding penem antibiotics and encouraging outpatient management, this guide favors initial treatment of febrile urinary tract infections (suspected or actual E-ESBL infection), with amikacin. Amikacin remains active against the majority of E-ESBL strains. It could be prescribed as monotherapy for patients in pediatric emergency departments or otherwise hospitalized patients.

Clinical and Functional Assessment of Digenicity in Renal Phosphate Wasting.

Apart from increased fluid intake, patients with kidney stone disease (KSD) due to renal phosphate wasting require specific metaphylaxis. NaPi2a, NaPi2c, and NHERF1 regulate plasma phosphate concentration by reabsorbing phosphate in proximal kidney tubules and have been found altered in monogenic hypophosphatemia with a risk of KSD. In this study, we aimed at assessing the combined genetic alterations impacting NaPi2a, NaPi2c, and NHERF1. Therefore, we screened our hereditary KSD registry for cases of oligo- and digenicity, conducted reverse phenotyping, and undertook functional studies. As a result, we identified three patients from two families with digenic alterations in NaPi2a, NaPi2c, and NHERF1. In family 1, the index patient, who presented with severe renal calcifications and a bone mineralization disorder, carried digenic alterations affecting both NaPi transporter 2a and 2c. Functional analysis confirmed an additive genetic effect. In family 2, the index patient presented with kidney function decline, distinct musculature-related symptoms, and intracellular ATP depletion. Genetically, this individual was found to harbor variants in both NaPi2c and NHERF1 pointing towards genetic interaction. In summary, digenicity and gene dosage are likely to impact the severity of renal phosphate wasting and should be taken into account in terms of metaphylaxis through phosphate substitution.

Surveillance of noninvasive group A Streptococcus infections in French ambulatory pediatrics before and during the COVID-19 pandemic: a prospective multicenter study from 2018-2022.

OBJECTIVES: We evaluated the burden of noninvasive group A Streptococcus (GAS) infections in ambulatory pediatrics before and during the COVID-19 pandemic in France. METHODS: We analyzed data from a national network of ambulatory pediatricians between 2018 and 2022. Clinicians evaluating children ≤15 years old for tonsillopharyngitis, perianal infections, paronychia/blistering dactylitis, and scarlet fever were invited to perform a rapid antigen detection test (RADT) for GAS. Monthly incidence of noninvasive GAS infections per 10,000 visits was modeled using time series analysis, considering two breakpoints: March 2020 (first national lockdown) and March 2022 (end of mandatory mask-wearing in schools). RESULTS: Over the study period, 125 pediatricians recorded 271,084 infectious episodes. GAS-related illnesses represented 4.3% of all infections. In March 2020, the incidence of GAS diseases decreased by 84.5% (P <0.001), with no significant trend until March 2022. After March 2022, the incidence significantly increased (+23.8% per month, P <0.001), with similar patterns across all monitored GAS-related diseases. CONCLUSION: By using routine clinical data and RADTs, we have monitored changes in the incidence of noninvasive GAS infections in ambulatory pediatrics. COVID-19 mitigation measures have had a major impact on the epidemiology of noninvasive GAS infections, but their relaxation was followed by a surge above baseline levels.

Midterm clinical outcome of uncemented short-stem reversed shoulder arthroplasty.

INTRODUCTION: While the incidence of reverse total shoulder arthroplasty (rTSA) is increasing constantly, newer implants with designs other than the classic Grammont geometry are gaining importance. More anatomic inclination angles and lateralization are supposed to have a positive impact on clinical results and complication rates. Presentation of midterm results therefore is important to support these assumptions. The aim of this study was to report the midterm clinical outcome of primary rTSA with an uncemented humeral short-stem prosthesis (USSP) with a humeral inclination angle of 145° and the analysis of different variables on the outcome. METHODS: This is a retrospective study of all patients with primary rTSA using an USSP and a combined humeral inclination angle of 145° (Ascend™ flex, Stryker) with a minimum clinical follow-up of 2 years. The implant combines a 132.5° inclination for the humeral stem with an additional 12.5° for the polyethylene inlay. Primary outcomes were patient-reported outcome measures: ASES score, simple shoulder test (SST) and subjective shoulder value (SSV). Secondary outcomes were complication and revision rates. We analyzed different variables: preoperatively gender, age, indication for surgery and status of rotator cuff. Also, the glenoid morphology was classified according to Walch and a proximal humerus cortical bone thickness measurement (CBT avg) of 6 mm was used as a threshold for osteoporosis. Postoperatively, we analyzed different radiologic parameters: filling ratio, distalization and lateralization angles according to Boutsiadis. RESULTS: A total of 84 out of 99 (85%) patients with a mean FU of 46.7 months (range 24-80 months) could be included: 62 women and 22 men with a mean age of 74.7 years. Mean ASES score significantly increased from 47 preoperatively to 85.8 at the last follow-up (p = 0.001). The postoperative SST reached an average of 65.3 and the mean SSV was 83%. None of the variable parameters analyzed could be identified as a risk factor for a lower outcome defined as a SSV < 70. Three patients (3.6%) had a complication: one incomplete lower plexus lesion, one dislocation and one major hematoma. Surgical revision was needed in two cases (2.4%). CONCLUSION: The midterm clinical outcome of primary reverse total shoulder arthroplasty (rTSA) with an uncemented humeral short stem and a humeral inclination angle of 145° showed good-to-excellent results with a low complication and revision rate independent from a wide range of pre- and postoperative variables. PROMs are comparable to those reported for anatomic TSA with a low complication rate, different to historical studies especially with the Grammont design. LEVEL OF EVIDENCE: Treatment study, Level IV.

Overview of meningococcal epidemiology and national immunization programs in children and adolescents in 8 Western European countries.

Background: In Europe, meningococcal (Men) vaccines are available against 5 of the 6 serogroups responsible of nearly all cases of invasive meningococcal disease (IMD). Meningococcal vaccination has been introduced in the national immunization programs (NIPs) for children and adolescents of numerous European countries, but with no consistent strategy across countries. Objectives: To describe IMD epidemiology, NIPs, and vaccination coverage rates (VCRs) in children and adolescents in 8 Western European countries. Methods: Epidemiological data (from 1999 to 2019), NIPs regarding meningococcal vaccination status, and VCRs were collected from the European Centre for Disease Prevention and Control (ECDC) and/or national websites. Results: MenB was the most common serogroup. In Belgium, Spain, France, the Netherlands, the United Kingdom (UK), and Portugal, incidence was greater for MenW than MenC. In 2019, MenB risk was covered in 2 countries (Italy, UK). MenC risk was covered in all countries, via MenC only (countries: N = 3), MenACWY only (N = 2), or MenC (infants/children) and MenACWY (adolescents) (N = 3) vaccination. VCRs were higher in children than adolescents. Conclusion: Our study confirmed the diversity of NIPs, including in neighboring European countries with similar factors like economic resources and epidemiological risk, thus indicating that other factors underlie NIPs. Convergence toward a more common immunization program including MenACWY and MenB vaccination would promote equity and safe travel regarding infectious diseases for young people, and possibly improve the understanding of vaccination by patients and healthcare professionals.

[The professional ear user-implications for the prevention, diagnosis, and treatment of ear diseases]. / Der "Professional Ear User" ­ Implikationen für die Prävention, Diagnostik und Therapie von Ohrerkrankungen.

BACKGROUND: Perfect hearing is crucial to the practice of various professions, such as instrument makers, musicians, sound engineers, and other professions not related to music, such as sonar technicians. For people of these occupational groups, we propose the term "professional ear user" (PEU) in analogy to "professional voice user". PEUs have special requirements for their hearing health, as they have well-known above-average auditory perceptual abilities on which they are professionally dependent. OBJECTIVE: The purpose of this narrative review is to summarize selected aspects of the prevention, diagnosis, and treatment of ear disorders in PEUs. RESULTS AND CONCLUSION: Prevention of hearing disorders and other ear diseases includes protection from excessive sound levels, avoidance of ototoxins and nicotine, and a safe manner of cleaning the outer auditory canal. Diagnosing hearing disorders in PEUs can be challenging, since subclinical but relevant changes in hearing cannot be reliably objectified by conventional audiometric methods. Moreover, the fact that a PEU is affected by an ear disease may influence treatment decisions. Further, physicians must be vigilant for non-organic ear diseases in PEUs. Lastly, measures to promote comprehensive ear health in PEUs as part of an educational program and to maintain ear health by means of a specialized otolaryngology service are discussed. In contrast to existing concepts, we lay the attention on the entirety of occupational groups that are specifically dependent on their ear health in a professional setting. In this context, we suggest avoiding a sole focus on hearing disorders and their prevention, but rather encourage the maintenance of a comprehensive ear health.

Trends in pediatric ambulatory community acquired infections before and during COVID-19 pandemic: A prospective multicentric surveillance study in France.

Background: Covid-19 pandemic control has imposed several non-pharmaceutical interventions (NPIs). Strict application of these measures has had a dramatic reduction on the epidemiology of several infectious diseases. As the pandemic is ongoing for more than 2 years, some of these measures have been removed, mitigated, or less well applied. The aim of this study is to investigate the trends of pediatric ambulatory infectious diseases before and up to two years after the onset of the pandemic. Methods: We conducted a prospective surveillance study in France with 107 pediatricians specifically trained in pediatric infectious diseases. From January 2018 to April 2022, the electronic medical records of children with an infectious disease were automatically extracted. The annual number of infectious diseases in 2020 and 2021 was compared to 2018-2019 and their frequency was compared by logistic regression. Findings: From 2018 to 2021, 185,368 infectious diseases were recorded. Compared to 2018 (n=47,116) and 2019 (n=51,667), the annual number of cases decreased in 2020 (n=35,432) by about a third. Frequency of scarlet fever, tonsillopharyngitis, enteroviral infections, bronchiolitis, and gastroenteritis decreased with OR varying from 0·6 (CI95% [0·5;0·7]) to 0·9 (CI95% [0·8;0·9]), p<0·001. In 2021, among the 52,153 infectious diagnoses, an off-season rebound was observed with increased frequency of enteroviral infections, bronchiolitis, gastroenteritis and otitis with OR varying from 1·1 (CI95% [1·0;1·1]) to 1·5 (CI95% [1·4;1·5]), p<0·001. Interpretation: While during NPIs strict application, the overall frequency of community-acquired infections was reduced, after relaxation of these measures, a rebound of some of them (enteroviral infections, bronchiolitis, gastroenteritis, otitis) occurred beyond the pre-pandemic level. These findings highlight the need for continuous surveillance of infectious diseases, especially insofar as future epidemics are largely unpredictable. Funding: ACTIV, AFPA, GSK, MSD, Pfizer and Sanofi.

Prediction of Acute and Chronic Mastitis in Dairy Cows Based on Somatic Cell Score and Mid-Infrared Spectroscopy of Milk.

Monitoring for mastitis on dairy farms is of particular importance, as it is one of the most prevalent bovine diseases. A commonly used indicator for mastitis monitoring is somatic cell count. A supplementary tool to predict mastitis risk may be mid-infrared (MIR) spectroscopy of milk. Because bovine health status can affect milk composition, this technique is already routinely used to determine standard milk components. The aim of the present study was to compare the performance of models to predict clinical mastitis based on MIR spectral data and/or somatic cell count score (SCS), and to explore differences of prediction accuracies for acute and chronic clinical mastitis diagnoses. Test-day data of the routine Austrian milk recording system and diagnosis data of its health monitoring, from 59,002 cows of the breeds Fleckvieh (dual purpose Simmental), Holstein Friesian and Brown Swiss, were used. Test-day records within 21 days before and 21 days after a mastitis diagnosis were defined as mastitis cases. Three different models (MIR, SCS, MIR + SCS) were compared, applying Partial Least Squares Discriminant Analysis. Results of external validation in the overall time window (-/+21 days) showed area under receiver operating characteristic curves (AUC) of 0.70 when based only on MIR, 0.72 when based only on SCS, and 0.76 when based on both. Considering as mastitis cases only the test-day records within 7 days after mastitis diagnosis, the corresponding areas under the curve were 0.77, 0.83 and 0.85. Hence, the model combining MIR spectral data and SCS was performing best. Mastitis probabilities derived from the prediction models are potentially valuable for routine mastitis monitoring for farmers, as well as for the genetic evaluation of the trait udder health.

Cardiovascular Regulation During Acute Gravitational Changes with Exhaling on Exertion.

During gravitational changes or changes in the direction of action in relation to the body, fluid displacements can be observed. In special cases different breathing maneuvers (e. g., exhaling on exertion; Ex-Ex) are used to counteract acute fluid shifts. Both factors have a significant impact on cardiovascular regulation. Eight healthy male subjects were tested on a tilt seat, long arm human centrifuge, and parabolic flight. The work aims to investigate the effect of exhaling on exertion on the cardiovascular regulation during acute gravitational changes compared to normal breathing. Possible interactions and differences between conditions (Ex-Ex, normal breathing) for the parameters V'O 2 , V' E , HR, and SV were analysed over a 40 s period by a three-way ANOVA. Significant (p≤0.05) effects for all main factors and interactions between condition and time as well as maneuver and time were found for all variables. The exhaling on exertion maneuver had a significant influence on the cardiovascular response during acute gravitational and positional changes. For example, the significant increase of V'O2 at the end of the exhalation on exertion maneuver indicates an increased lung circulation as a result of the maneuver.

Seroprevalence of SARS-CoV-2 IgG Antibodies and Factors Associated with SARS-CoV-2 IgG Neutralizing Activity among Primary Health Care Workers 6 Months after Vaccination Rollout in France.

We aimed to investigate the immunoglobulin G response and neutralizing activity against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) among primary health care workers (PHCW) in France and assess the association between the neutralizing activity and several factors, including the coronavirus disease 2019 (COVID-19) vaccination scheme. A cross-sectional survey was conducted between 10 May 2021 and 31 August 2021. Participants underwent capillary blood sampling and completed a questionnaire. Sera were tested for the presence of antibodies against the nucleocapsid (N) protein and the S-1 portion of the spike (S) protein and neutralizing antibodies. In total, 1612 PHCW were included. The overall seroprevalences were: 23.6% (95% confidence interval (CI) 21.6-25.7%) for antibodies against the N protein, 94.7% (93.6-95.7%) for antibodies against the S protein, and 81.3% (79.4-83.2%) for neutralizing antibodies. Multivariate regression analyses showed that detection of neutralizing antibodies was significantly more likely in PHCW with previous SARS-CoV-2 infection than in those with no such history among the unvaccinated (odds ratio (OR) 16.57, 95% CI 5.96-59.36) and those vaccinated with one vaccine dose (OR 41.66, 95% CI 16.05-120.78). Among PHCW vaccinated with two vaccine doses, the detection of neutralizing antibodies was not significantly associated with previous SARS-CoV-2 infection (OR 1.31, 95% CI 0.86-2.07), but was more likely in those that received their second vaccine dose within the three months before study entry than in those vaccinated more than three months earlier (OR 5.28, 95% CI 3.51-8.23). This study highlights that previous SARS-CoV-2 infection and the time since vaccination should be considered when planning booster doses and the design of COVID-19 vaccine strategies.

Coxsackievirus A6 Recombinant Subclades D3/A and D3/H Were Predominant in Hand-Foot-And-Mouth Disease Outbreaks in the Paediatric Population, France, 2010-2018.

Coxsackievirus A6 (CVA6) emerged as the most common enterovirus of seasonal outbreaks of hand-foot-and-mouth disease (HFMD). We investigated CVA6 genetic diversity among the clinical phenotypes reported in the paediatric population during sentinel surveillance in France between 2010 and 2018. CVA6 infection was confirmed in 981 children (mean age 1.52 years [IQR 1.17-2.72]) of whom 564 (58%) were males. Atypical HFMD was reported in 705 (72%) children, followed by typical HFMD in 214 (22%) and herpangina in 57 (6%) children. Throat specimens of 245 children were processed with a target-enrichment new-generation sequencing approach, which generated 213 complete CVA6 genomes. The genomes grouped within the D1 and D3 clades (phylogeny inferred with the P1 genomic region). In total, 201 genomes were classified among the recombinant forms (RFs) A, B, F, G, H, and N, and 12 genomes were assigned to 5 previously unreported RFs (R-V). The most frequent RFs were A (58%), H (19%), G (6.1%), and F (5.2%). The yearly number of RFs ranged between 1 (in 2012 and 2013) and 6 (2018). The worldwide CVA6 epidemic transmission began between 2005 and 2007, which coincided with the global spread of the recombinant subclade D3/RF-A.