Safety, potential efficacy, and pharmacokinetics of specific polyclonal immunoglobulin F(ab')<inf>2</inf> fragments against avian influenza A (H5N1) in healthy volunteers: A single-centre, randomised, double-blind, placebo-controlled, phase 1 study

The Lancet Infectious Diseases153285-29

Mucus Microrheology Measured on Human Bronchial Epithelium Culture

We describe an original method to measure mucus microrheology on human bronchial epithelium culture using optical tweezers. We probed rheology on the whole thickness of mucus above the epithelium and showed that mucus gradually varies in rheological response, from an elastic behavior close to the epithelium to a viscous one far away. Microrheology was also performed on mucus collected on the culture, on ex vivo mucus collected by bronchoscopy, and on another epithelium model. Differences are discussed and are related to mucus heterogeneity, adhesiveness, and collection method

Father’s perceptions and care involvement for their very preterm infants at French neonatal intensive care units

ObjectivesWe aimed to evaluate (1) fathers’ perceptions and care involvement for their very premature infants and their views of the hospitalization period based on parental reports and (2) their evolution over time.MethodsWe used an online parental survey to assess answers from parents of very preterm infants who were successfully discharged from French neonatal units. We analysed answers from February 2014 to January 2019 to an anonymous internet-based survey from the GREEN committee of the French Neonatal Society. Responses were compared for period 1 (P1, 1998 to 2013) and period 2 (P2, 2014 to 2019).ResultsWe analyzed 2,483 surveys, 124 (5%) from fathers and 2,359 (95%) from mothers. At birth, 1,845 (80%) fathers were present in the hospital, but only 879 (38%) were near the mother. The presence of fathers in the NICU increased from P1 to P2 (34.5% vs. 43.1%, p = 0.03). Nearly two thirds of fathers accompanied their infants during transfer to the NICU (1,204 fathers, 60.6%). Fathers and mothers had similar perceptions regarding relationships with caregivers and skin-to-skin contact with their infants. However, more fathers than mothers felt welcome in the NICU and in care involvement regarding requests for their wishes when they met their infant (79% vs. 60%, p = 0.02) and in the presentation of the NICU (91% vs. 76%; p = 0.03). Mothers and fathers significantly differed in the caring procedures they performed (p = 0.01), procedures they did not perform but wanted to perform (p &lt; 0.001), and procedures they did not perform and did not want to perform (p &lt; 0.01).ConclusionMost fathers were present at the births of their very preterm infants, but fewer fathers were near the mother at this time. Less than two thirds of fathers accompanied their infants to the NICU. There should be further changes to better meet the specific needs of the fathers of infants requiring care in the NICU. Continuing assessment with an online questionnaire may be useful to monitor changes over time in father’s involvement in NICUs

Genetic landscape of a large cohort of Primary Ovarian Insufficiency : New genes and pathways and implications for personalized medicine

Background Primary Ovarian Insufficiency (POI), a public health problem, affects 1-3.7% of women under 40 yield-ing infertility and a shorter lifespan. Most causes are unknown. Recently, genetic causes were identified, mostly in single families. We studied an unprecedented large cohort of POI to unravel its molecular pathophysiology.Methods 375 patients with 70 families were studied using targeted (88 genes) or whole exome sequencing with pathogenic/likely-pathogenic variant selection. Mitomycin-induced chromosome breakages were studied in patients' lymphocytes if necessary. Findings A high-yield of 29.3% supports a clinical genetic diagnosis of POI. In addition, we found strong evidence of pathogenicity for nine genes not previously related to a Mendelian phenotype or POI: ELAVL2, NLRP11, CENPE, SPATA33, CCDC150, CCDC185, including DNA repair genes: C17orf53(HROB), HELQ, SWI5 yielding high chromo-somal fragility. We confirmed the causal role of BRCA2, FANCM, BNC1, ERCC6, MSH4, BMPR1A, BMPR1B, BMPR2, ESR2, CAV1, SPIDR, RCBTB1 and ATG7 previously reported in isolated patients/families. In 8.5% of cases, POI is the only symptom of a multi-organ genetic disease. New pathways were identified: NF-kB, post-translational regulation, and mitophagy (mitochondrial autophagy), providing future therapeutic targets. Three new genes have been shown to affect the age of natural menopause supporting a genetic link.Interpretation We have developed high-performance genetic diagnostic of POI, dissecting the molecular pathogene-sis of POI and enabling personalized medicine to i) prevent/cure comorbidities for tumour/cancer susceptibility genes that could affect life-expectancy (37.4% of cases), or for genetically-revealed syndromic POI (8.5% of cases), ii) predict residual ovarian reserve (60.5% of cases). Genetic diagnosis could help to identify patients who may benefit from the promising in vitro activation-IVA technique in the near future, greatly improving its success in treating infertility.Funding Universite? Paris Saclay, Agence Nationale de Biome?decine.Copyright (c) 2022 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)Peer reviewe

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

Validation de l'efficacité des différentiels de pression pour lutter contre les contaminations croisées en zone de production primaire de formes sèches

LYON1-BU Santé (693882101) / SudocSudocFranceF

Microwave-assisted modifications of polysaccharides

Polysaccharides are a natural and renewable feed stock for synthesizing high performance macromolecular materials. However, their structure does not allow reaching all properties required for specific applications and chemical modifications are necessary to reach such objectives. Despite the use of natural polymers, the chemistry and processes employed are not environment-friendly due to the nature of chemicals, solvents or because the conventional chemical process are energy-consuming. On the other hand, microwave assisted processes were developed in organic chemistry since the 1980s and more recently for polymer chemistry (polymer formation and modification). Within the chemistry of natural polymers, the use of microwave irradiation has been exploited in the past two decades to alleviate limitations in the synthesis of graft modified polysaccharide materials. Microwave heating is described as more homogeneous, selective and efficient as compared to conventional heating resulting in faster reactions with fewer or no side products as example. Different results reported within the recent literature will be discussed considering the role of microwave irradiation and its consequence on the reaction parameters and properties of final materials. Grafting of polysaccharides, specific modification of polysaccharides or fibers particularly for preparing smart textiles or medical products as well as reactions of polysaccharides to valuable bio-platform molecule will be discussed

Usage des microondes pour l'extraction et la fonctionnalisation de molécules naturelles ou biosourcées (Using microwaves to extract and functionalize natural or bio-based molecules)

Faced with traditional heating techniques, microwave irradiation allows quick energy supply for instantaneous heating. Usual organic solvents may be suppressed, replaced by aqueous media, bio-based or renewable solvents⋯ These properties allow this process perfectly answering the "green chemistry" criteria. Two examples on using this process with bio-based materials are presented: the extraction of saponins from soap nuts and their applications to latex preparation, and the chemical modification of a polysaccharide, the chitosan. The first example reports the efficiency of microwaves in terms of time and yield during the extraction of bio-based molecules, a surfactant. The latter, tested for the synthesis of latex, usefully replaces non-ionic ethoxylated polyphenols-like surfactants of which degradation products may be known as priority substances in accordance with the European directive on water. The second one highlights the process to efficiently modify chitosan with a strong optimisation of reaction times

Pre-TKR isokinetic quadriceps strengthening has a positive effect which may diminish following the intervention despite pain and functional improvements: A case study

International audienceWe report a longitudinal survey of a 53-year-old man suffering from right knee osteoarthritis who has undergone total knee replacement (TKR). We aimed at evaluating the effect of a short preoperative isokinetic strengthening program on the functional status, pain, and quadriceps and hamstrings strength before and after TKR. The patient performed a 4-week (6 sessions) preoperative isokinetic strengthening program of the quadriceps and hamstrings. The findings for the concentric strength at 60 degrees/s, 6-minute walk test (6MWT), and Knee injury and Osteoarthritis Outcome Score (KOOS) were recorded. At baseline the patient presented with an overall KOOS score of 44%, a 6MWT of 444 m, a 63% and 21% strength deficits of the quadriceps and hamstrings, respectively. Following the strengthening program, the quadriceps strength of the operated limb improved ( +121 Nm; +83%), but the function as reflected by the KOOS score remained unchanged. Following the TKR, the concentric isokinetic strength of the quadriceps reappeared altered (63% of deficit) despite pain and functional improvements. This case report underlines the importance of functional evaluation rather than the maximal strength to assess the effectiveness of TKR. However, further studies are necessary to conceptualize the meaning of maximal strength measurement and the impact of associated deficits, if any