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In his recent book, Spanning the Theory-Practice Divide in Library and Information Science, Bill Crowley (2005) examined the divide between published research from library school (LIS) faculty and the use [...]

Introduction In recent decades, institutions have been moving away from the positivism evident in many disciplines in the earlier years of the 20th century. Instead of seeking for a single [...]

The rise of antimicrobial resistance has led to renewed interest in evaluating phage therapy. In murine models highly effective treatment of acute pneumonia caused by Pseudomonas aeruginosa relies on the synergistic antibacterial activity of bacteriophages with neutrophils. Here, we show that depletion of alveolar macrophages (AM) shortens the survival of mice without boosting the P . aeruginosa load in the lungs. Unexpectedly, upon bacteriophage treatment, pulmonary levels of P. aeruginosa were significantly lower in AM-depleted than in immunocompetent mice. To explore potential mechanisms underlying the benefit of AM-depletion in treated mice, we developed a mathematical model of phage, bacteria, and innate immune system dynamics. Simulations from the model fitted to data suggest that AM reduce bacteriophage density in the lungs. We experimentally confirmed that the in vivo decay of bacteriophage is faster in immunocompetent compared to AM-depleted animals. These findings demonstrate the involvement of feedback between bacteriophage, bacteria, and the immune system in shaping the outcomes of phage therapy in clinical settings., Competing Interests: DECLARATION OF INTERESTS The authors declare no competing interests.

Cochleovestibular dysfunctions are rare conditions misrecognized. A homozygous pathogenic variation c.1561C > T (p.Arg521*) in RIPOR2 (RHO family interacting cell polarization regulator 2) has been identified by WES in Tunisian siblings suffering from congenital bilateral profound hearing and vestibular dysfunctions. In contrast to the vestibular areflexia observed in our patients, deaf Ripor2 KO mouse model and our zebrafish model have normal vestibular function., (© 2023 The Authors. Clinical Genetics published by John Wiley & Sons Ltd.)

Background: Generalised convulsive status epilepticus (GCSE) is a medical emergency. Guidelines recommend a stepwise strategy of benzodiazepines followed by a second-line anti-seizure medicine (ASM). However, GCSE is uncontrolled in 20-40% patients and is associated with protracted hospitalisation, disability, and mortality. The objective was to determine whether valproic acid (VPA) as complementary treatment to the stepwise strategy improves the outcomes of patients with de novo established GCSE., Methods: This was a multicentre, double-blind, randomised controlled trial in 244 adults admitted to intensive care units for GCSE in 16 French hospitals between 2013 and 2018. Patients received standard care of benzodiazepine and a second-line ASM (except VPA). Intervention patients received a 30 mg/kg VPA loading dose, then a 1 mg/kg/h 12 h infusion, whilst the placebo group received an identical intravenous administration of 0.9% saline as a bolus and continuous infusion. Primary outcome was proportion of patients discharged from hospital by day 15. The secondary outcomes were seizure control, adverse events, and cognition at day 90., Results: A total of 126 (52%) and 118 (48%) patients were included in the VPA and placebo groups. 224 (93%) and 227 (93%) received a first-line and a second-line ASM before VPA or placebo infusion. There was no between-group difference for patients hospital-discharged at day 15 [VPA, 77 (61%) versus placebo, 72 (61%), adjusted relative risk 1.04; 95% confidence interval (0.89-1.19); p = 0.58]. There were no between-group differences for secondary outcomes., Conclusions: VPA added to the recommended strategy for adult GCSE is well tolerated but did not increase the proportion of patients hospital-discharged by day 15., Trial Registration No: NCT01791868 (ClinicalTrials.gov registry), registered: 15 February 2012., (© 2023. The Author(s).)

Goals: To perform a medical analysis of the contribution of sialendoscopy in the treatment of non-tumoral pathologies of the main salivary glands, in Reunion Island, a French overseas territory., Material and Method: A multicenter retrospective observational study was conducted for an 8-year period, before and after introduction of sialendoscopy (2011-2014 and 2015-2018), following STROBE guidelines., Objectives: To compare populations treated before (period A) and after (period B) the introduction of sialendoscopy in terms of clinical characteristics, and analyze the characteristics of patients treated by sialendoscopy., Results: Two hundred and sixty-five patients were included: 74 in 2011-2014 and 191 in 2015-2018; 139 had sialendoscopy. Populations A and B were comparable except for the proportion of parotids treated (9% vs. 31%, respectively; P<0.0001), and smaller stones (11mm vs. 7.4mm, respectively; P=0.003). One hundred and ten pure sialendoscopies and 29 combined routes (20.8%) were performed: 63% submandibular and 37% parotid. Median age was 46 years. The M/F sex ratio was 0.96. Thirty-seven patients presented stenosis. There were 10 cases of papillary catheterization failure (7.1%), and 16 false routes or creation of false channels (11.5%), including 9 during the learning period. The rate of crossover to gland resection decreased: 10.45% for 2015-2016 and 5.56% for 2017-2018., Conclusion: Although follow-up ranged between 12 and 55months (median, 30months), sialendoscopy appeared to be a useful and reliable technique, with a role in therapeutic strategy for the management of non-tumoral salivary pathologies in Reunion Island., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Aim: This study explored the systemic vascular effects of local cryotherapy with a focus on endothelial changes and arterial inflammation in the model of rat adjuvant-induced arthritis (AIA)., Methods: Cryotherapy was applied twice a day on hind paws of AIA rats from the onset of arthritis to the acute inflammatory phase. Endothelial activation was studied in the aorta by measuring the mRNA levels of chemokines (CXCL-1, MCP-1 (CCL-2), MIP-1α (CCL-3)) and adhesion molecules (ICAM-1, VCAM-1) by qRT-PCR. Endothelial dysfunction was measured in isolated aortic and mesenteric rings. Aortic inflammation was evaluated via the mRNA expression of pro-inflammatory cytokines (TNF-α, IL-6) by qRT-PCR and leucocyte infiltration analysis (flow cytometry). Plasma levels of TNF-α, IL-6, IL-1β, IL-17A, and osteoprotegerin (OPG) were measured using Multiplex/ELISA., Results: AIA was associated with an increased aortic expression of CXCL-1 and ICAM-1 as well as an infiltration of leucocytes and increased mRNA expression of IL-6, IL-1β, and TNF-α. Local cryotherapy, which decreased arthritis score and structural damages, reduced aortic mRNA expression of CXCL-1, IL-6, IL-1β, and TNF-α, as well as aortic infiltration of leucocytes (T lymphocytes, monocytes/macrophages, neutrophils) and improved acetylcholine-induced vasorelaxation in the aorta and mesenteric arteries. Plasma levels of IL-17A and OPG were significantly reduced by cryotherapy, while the number of circulating leucocytes was not. IL-17A levels positively correlated with endothelial activation and dysfunction., Conclusion: In the AIA model, local cryotherapy reduced systemic endothelial activation, immune cell infiltration, and endothelial dysfunction. Mechanistically, the reduction of circulating levels of IL-17A appears as the possible link between joint cooling and the remote vascular effects., (© 2022. The Author(s).)

Megalencephaly-CApillary malformation-Polymicrogyria (MCAP) syndrome results from somatic mosaic gain-of-function variants in PIK3CA. Main features are macrocephaly, somatic overgrowth, cutaneous vascular malformations, connective tissue dysplasia, neurodevelopmental delay, and brain anomalies. The objectives of this study were to describe the clinical and radiological features of MCAP, to suggest relevant clinical endpoints applicable in future trials of targeted drug therapy. Based on a French collaboration, we collected clinical features of 33 patients (21 females, 12 males, median age of 9.9 years) with MCAP carrying mosaic PIK3CA pathogenic variants. MRI images were reviewed for 21 patients. The main clinical features reported were macrocephaly at birth (20/31), postnatal macrocephaly (31/32), body/facial asymmetry (21/33), cutaneous capillary malformations (naevus flammeus 28/33, cutis marmorata 17/33). Intellectual disability was present in 15 patients. Among the MRI images reviewed, the neuroimaging findings were megalencephaly (20/21), thickening of corpus callosum (16/21), Chiari malformation (12/21), ventriculomegaly/hydrocephaly (10/21), cerebral asymmetry (6/21) and polymicrogyria (2/21). This study confirms the main known clinical features that defines MCAP syndrome. Taking into account the phenotypic heterogeneity in MCAP patients, in the context of emerging clinical trials, we suggest that patients should be evaluated based on the main neurocognitive expression on each patient., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: Patients with acute severe asthma (ASA) may in rare cases require invasive mechanical ventilation (IMV). However, recent data on this issue are lacking., Materials and Methods: In this retrospective and bicentric study conducted on a 10 year period, we investigate the in-hospital mortality in patients with ASA requiring IMV. We compare this mortality to that of patients with other types of respiratory distress using a standardized mortality ratio (SMR) model., Results: Eighty-one episodes of ASA requiring IMV were evaluated. Factors significantly associated with in-hospital mortality were cardiac arrest on day of admission, cardiac arrest as the reason for intubation, absence of decompensation risk factors, need for renal replacement therapy on day of admission, and intubation in pre-hospital setting. Non-survivors had higher SAPS II, SOFA, creatinine and lactate levels as well as lower blood pressure, pH, and HCO3 on day of admission. In-hospital mortality was 15% (n = 12). Compared to a reference population of 2,670 patients, the SMR relative to the SAPS II was very low at 0.48 (95% CI, 0.25-0.84). The only factor independently associated with in-hospital mortality was cardiac arrest on day of admission. In-hospital mortality was 69% in patients with cardiac arrest on day of admission and 4% in others (p < 0.01). Salvage therapies were given to 7 patients, sometimes in combination with each other: ECMO (n = 6), halogenated gas (n = 1) and anti-IL5 antibody (n = 1). Death occurred in only 2 of these 7 patients, both of whom had cardiac arrest on day of admission., Conclusion: Nowadays, the mortality of patients with ASA requiring IMV is low. Death is due to multi-organ failure, with cardiac arrest on day of admission being the most important risk factor. In patients who did not have cardiac arrest on day of admission the mortality is even lower (4%) which allows an aggressive management., Competing Interests: The authors have declared that no competing interests exist.

Background: Recommendations for management of Finnish-type congenital nephrotic syndrome (CNS) followed by many teams include daily albumin infusions, early bilateral nephrectomy, dialysis and transplantation. We aimed to assess the treatment and outcome of patients with CNS in France., Methods: We conducted a nationwide retrospective study on 55 consecutive children born between 2000 and 2014 treated for non-infectious CNS., Results: The estimated cumulative incidence of CNS was 0.5/100 000 live births. The underlying defect was biallelic mutations in NPHS1 (36/55, 65%), NPHS2 (5/55, 7%), PLCE1 (1/55, 2%), heterozygous mutation in WT1 (4/55, 7%) and not identified in nine children (16%). Fifty-three patients (96%) received daily albumin infusions from diagnosis (median age 14 days), which were spaced and withdrawn in 10 patients. Twenty children (35%) were managed as outpatients. Thirty-nine patients reached end-stage kidney disease (ESKD) at a median age of 11 months. The overall renal survival was 64% and 45% at 1 and 2 years of age, respectively. Thirteen children died during the study period including four at diagnosis, two of nosocomial catheter-related septic shock, six on dialysis and one after transplantation. The remaining 13 patients were alive with normal renal function at last follow-up [median 32 months (range 9-52)]. Renal and patient survivals were longer in patients with NPHS1 mutations than in other patients. The invasive infection rate was 2.41/patient/year., Conclusions: Our study shows: (i) a survival free from ESKD in two-thirds of patients at 1 year and in one-half at 2 years and (ii) a significant reduction or even a discontinuation of albumin infusions allowing ambulatory care in a subset of patients. These results highlight the need for new therapeutic guidelines for CNS patients., (© The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Objectives: Health literacy refers to the ability of individuals to gain access to, use, and understand health information and services in order to maintain a good health. The assessment of health literacy profiles in a population is potentially crucial to respond to health needs. The Health Literacy Questionnaire explores nine dimensions of health literacy and has been shown to display robust psychometric properties. The aim was to test the validity of the multidimensional Health Literacy Questionnaire and to describe the health literacy profiles in a French population at risk of cardiovascular disease., Methods: Data were collected using self-administered questionnaires from 175 participants attending health education and support programmes in local associations of patients in Paris. Analysis included scale reliability, confirmatory factor analysis, and health literacy profiles via descriptive statistics., Results: In confirmatory factor analysis, the nine-factor structure was close to the original Health Literacy Questionnaire. A nine-factor confirmatory factor analysis model was fitted to the 44 items with no cross-loadings or correlated residuals allowed. Given the restricted nature of the model, the fit was satisfactory: χ 2 WLSMV (866 df) = 1383.81, p = 0.0000, comparative fit index = 0.925, Tucker-Lewis index = 0.918, root mean square error of approximation = 0.058, weighted root mean square residual = 1.175. Composite reliability ranged from 0.77 to 0.91. Among the 9 scales of the Health Literacy Questionnaire, the highest scores were found for scale 1 'Feeling understood and supported by healthcare professionals' and scale 9 'Understand health information enough to know what to do' and the lowest for scale 2 'Having sufficient information to manage my health' and scale 7 'Navigating the healthcare system'., Conclusion: The French version of the Health Literacy Questionnaire was shown to be psychometrically robust with good reliability. In the context of France, the 9 scales of Health Literacy Questionnaire allow a thorough assessment of health literacy strengths and weaknesses to respond to health literacy needs and improve the accessibility of health information and services., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To describe conservative management of spontaneous intestinal perforation (SIP) in preterm infants using peritoneal needle aspiration (PNA)., Study Design: Monocentric retrospective review of SIP cases treated primarily by PNA between 1999 and 2015 (n=31)., Results: Mean gestational age was 29.2±2.4 weeks and birthweight 1149±428 g. SIP occurred at 3.7±2.2 days of life. PNA achieved definitive treatment in 18 patients (60%) with a mean of 1.8 (±0.8) procedures. All patients requiring more than three PNAs had secondary laparotomy. Two patients died and five presented severe cerebral lesions. Full enteral feeding was achieved 42±18 days after SIP. Intestinal morbidity included cholestasis (n=6), intestinal stricture (n=1) and growth restriction (n=22). On follow-up (n=25, median=4 years), no severe impairment was noted. Seventeen children (68%) had a normal development., Conclusion: PNA as primary therapy for SIP is a viable option, resulting in definitive treatment in 60% of cases, with limited mortality and morbidity.

Background: Chikungunya virus (CHIKV) is an arthritogenic member of the Alphavirus genus (family Togaviridae) transmitted by Aedes mosquitoes. CHIKV is now known to target non hematopoietic cells such as epithelial, endothelial cells, fibroblasts and to less extent monocytes/macrophages. The type I interferon (IFN) response is an early innate immune mechanism that protects cells against viral infection. Cells express different pattern recognition receptors (including TLR7 and RIG-I) to sense viruses and to induce production of type I IFNs which in turn will bind to their receptor. This should result in the phosphorylation and translocation of STAT molecules into the nucleus to promote the transcription of IFN-stimulated antiviral genes (ISGs). We herein tested the capacity of CHIKV clinical isolate to infect two different human fibroblast cell lines HS 633T and HT-1080 and we analyzed the resulting type I IFN innate immune response., Methods: Indirect immunofluorescence and quantitative RT-PCR were used to test for the susceptibility of both fibroblast cell lines to CHIKV., Results: Interestingly, the two fibroblast cell lines HS 633T and HT-1080 were differently susceptible to CHIKV infection and the former producing at least 30-fold higher viral load at 48 h post-infection (PI). We found that the expression of antiviral genes (RIG-I, IFN-β, ISG54 and ISG56) was more robust in the more susceptible cell line HS 633T at 48 h PI. Moreover, CHIKV was shown to similarly interfere with the nuclear translocation of pSTAT1 in both cell lines., Conclusion: Critically, CHIKV can control the IFN response by preventing the nuclear translocation of pSTAT1 in both fibroblast cell lines. Counter-intuitively, the relative resistance of HT-1080 cells to CHIKV infection could not be attributed to more robust innate IFN- and ISG-dependent antiviral responses. These cell lines may prove to be valuable models to screen for novel mechanisms mobilized differentially by fibroblasts to control CHIKV infection, replication and spreading from cell to cell.