Dyskinésie ciliaire primitive chez l’adulte : étude rétrospective sur 78 patients

Introduction : Primary ciliary dyskinesia (PCD) is a genetic disease characterized by anomalies in ciliary structure, responsible for chronic pulmonary and rhinosinus disease. No study involving only adults has been published.Methods : Retrospective study in two French tertiary hospitals, focusing on adults with a diagnosis of PCD based on presence of bronchiectasis with typical ultrastructural defect of cilia and/or situs inversus (SI).Results : 78 patients (18-77 yrs, median follow-up 8.1 yrs) were included. FEV1 was significantly lower in women (median 60% pred vs. 77.5%, p<0.05) and in patients with chronic airway P. aeruginosa (PA, n=21) infection (median 60.5% vs. 75.5%, p<0.05). FEV1 (% pred) correlated with age (p=0.03), chest CT score (p<0.001) but not with age at diagnosis, SI or ultramicroscopy. FEV1 decline was -11mL/year and was greater in women (-28.3mL/ yr vs -3.8mL/yr p=0.01, although age and PA status were similar) but not in patients with chronic PA (-22mL/yr vs -9 mL/yr, p=0.14).Conclusions : PCD in adults is more severe in women and in patients with chronic PA infection.Introduction : La dyskinésie ciliaire primitive (DCP) est caractérisée par une pathologie sino-pulmonaire chronique. Il n’existe pas d’étude ayant porté spécifiquement sur l’adulte.Méthodes : Etude rétrospective bicentrique sur des patients adultes avec DCP certaine (DDB avec anomalie des cils typique et/ou situs inversus).Résultats : 78 patients (âge 18-77 ans, durée médiane de suivi 8,1 ans) ont été inclus. Le VEMS était significativement plus bas chez les femmes (médiane=60%th, vs. 77,5%, p<0,05) et chez les patients colonisés à P. aeruginosa (PA, n=21, médiane=60.5% vs. 75.5%, p<0.05). Le VEMS (%th) était corrélé à l’âge (p=0,03) et au score scanographique (p<0,001) mais pas à l’âge au diagnostic, ni à la présence d’un situs inversus, ni aux anomalies microscopiques. Le déclin du VEMS était de -11mL/an et était plus important chez les femmes (-28,3mL vs. -3,8mL, p=0,01) malgré un âge et un statut pour PA identiques. Le déclin du VEMS n’était pas différent chez les patients colonisés ou non à PA (-22 mL/an vs -9 mL/an, p=0,14).Conclusion : La DCP à l’âge adulte est plus sévère chez la femme et en cas de colonisation à PA

Effect of a reading aloud program on reading rate and reading prosody in a group of sixth-grade low achievement language minority readers with low SES

Language minority (LM) students’ reading comprehension remains less proficient than that of their native peers in the upper elementary grades, even if they develop proficient word decoding skills in the primary grades. Given the link between reading comprehension and reading fluency, a way of addressing LM student’s reading difficulties is to attempt to improve their reading fluency. The purpose of this study was to investigate if a group of sixth-grade low achievement LM students’ reading skills could be improved by an intervention designed to train reading fluency, a critical component of reading development, defined as integrating speed and accuracy (reading rate) as well as prosody. The study included 54 sixth-grade LM students attending a school with a low socio-economic index. Two groups matched on different reading and control (vocabulary, arithmetic, non-verbal intelligence, socio-demographic characteristics) measures were randomly assigned to an intervention condition, which consisted of a tutored reading aloud intervention combining repeated reading, assisted wide reading and modeling prosody or to a control condition, where students achieved their usual classroom activities. Reading rate (number of words correctly read per minute), prosody and comprehension were assessed. Students who received the intervention scored better on measures of reading prosody but not on reading rate and comprehension measures than students from the control group. The present study provides empirical support that LM struggling students can benefit from a reading fluency intervention to develop important reading prosody skills, not only on practiced texts but also on new texts

Ustekinumab in Hidradenitis Suppurativa: A Systematic Review and Meta-analysis

IntroductionHidradenitis suppurativa (HS) is a frequently debilitating, inflammatory skin condition. Patients may have a limited response to adalimumab, currently the only Food and Drug Administration (FDA)-approved biologic treatment for HS. Ustekinumab is an interleukin-12/23 inhibitor that has been utilized in HS, but there is a lack of an updated systematic review on its efficacy and safety. The aim of this study is to perform a systematic review and meta-analysis of the literature on the efficacy and safety of ustekinumab for HS.MethodsIn October 2022, MEDLINE and Embase databases were searched for articles on ustekinumab in HS. Data extraction was performed on relevant articles by two reviewers. The primary study outcome was the pooled response rate of HS to ustekinumab. A fixed-effects meta-analysis was performed, and Cochran's Q statistic and I squared index were used to assess heterogeneity. Statistical significance was determined at p &lt; 0.05. This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.ResultsFrom 2012 to 2022, ten articles (nine case series and one prospective trial) with 88 patients met the inclusion criteria. Patients with reported disease severity had Hurley stage II (17.6%, 12/68) or III (82.4%, 56/68) disease. The majority (80.7%, 71/88) had previously failed at least one biologic treatment. A meta-analysis of all ten studies showed a pooled response rate of 67% (95% CI 0.57-0.76). Study limitations include a small number of patients and randomized controlled trials (RCTs).ConclusionsUstekinumab may be a helpful treatment option to consider for HS that is recalcitrant to first-line biologic therapies, but RCTs are needed to determine optimal dosing regimens and the specific patient populations that would benefit the most from this agent

Idea evaluation as a design process: understanding how experts develop ideas and manage fixations

Idea evaluation is used to identify and select ideas for development as future innovations. However, approaching idea evaluation as a decision gate can limit the role of the person evaluating ideas, create fixation bias, and underutilise the person’s creative potential. Although studies show that during evaluation experts are able to engage in design activities, it is still not clear how they design and develop ideas. The aim of this study was to understand how experts develop ideas during evaluation. Using the think-aloud technique, we identify different ways in which experts develop ideas. Specifically, we show how experts transform initial idea concepts using iterative steps of elaboration and transformation of different idea components. Then, relying on concept-knowledge theory (C-K theory), we identify six types of reasoning that the experts use during idea evaluation. This helps us to distinguish between three different roles that experts can move between during evaluation: gatekeeper, designer managing fixation, and designer managing defixation. These findings suggest that there is value in viewing idea evaluation as a design process because it allows us to identify and leverage the experts’ knowledge and creativity to a fuller extent

Genetic Pharmacotherapy as an Early CNS Drug Development Strategy: Testing Glutaminase Inhibition for Schizophrenia Treatment in Adult Mice

Genetic pharmacotherapy is an early drug development strategy for the identification of novel CNS targets in mouse models prior to the development of specific ligands. Here for the first time, we have implemented this strategy to address the potential therapeutic value of a glutamate-based pharmacotherapy for schizophrenia involving inhibition of the glutamate recycling enzyme phosphate-activated glutaminase. Mice constitutively heterozygous for GLS1, the gene encoding glutaminase, manifest a schizophrenia resilience phenotype, a key dimension of which is an attenuated locomotor response to propsychotic amphetamine challenge. If resilience is due to glutaminase deficiency in adulthood, then glutaminase inhibitors should have therapeutic potential. However, this has been difficult to test given the dearth of neuroactive glutaminase inhibitors. So, we used genetic pharmacotherapy to ask whether adult induction of GLS1 heterozygosity would attenuate amphetamine responsiveness. We generated conditional floxGLS1 mice and crossed them with global CAGERT2cre∕+ mice to produce GLS1 iHET mice, susceptible to tamoxifen induction of GLS1 heterozygosity. One month after tamoxifen treatment of adult GLS1 iHET mice, we found a 50% reduction in GLS1 allelic abundance and glutaminase mRNA levels in the brain. While GLS1 iHET mice showed some recombination prior to tamoxifen, there was no impact on mRNA levels. We then asked whether induction of GLS heterozygosity would attenuate the locomotor response to propsychotic amphetamine challenge. Before tamoxifen, control and GLS1 iHET mice did not differ in their response to amphetamine. One month after tamoxifen treatment, amphetamine-induced hyperlocomotion was blocked in GLS1 iHET mice. The block was largely maintained after 5 months. Thus, a genetically induced glutaminase reduction—mimicking pharmacological inhibition—strongly attenuated the response to a propsychotic challenge, suggesting that glutaminase may be a novel target for the pharmacotherapy of schizophrenia. These results demonstrate how genetic pharmacotherapy can be implemented to test a CNS target in advance of the development of specific neuroactive inhibitors. We discuss further the advantages, limitations, and feasibility of the wider application of genetic pharmacotherapy for neuropsychiatric drug development

The Effect of Elective Ligation of the Arteriovenous Fistula on Cardiac and Renal Functions in Kidney Transplant Recipients.

peer reviewed[en] KEY POINTS: Surgical AVF ligation in KTRs is associated with a significant increase in diastolic BP while systolic BP remains stable. AVF closure in KTRs leads to an improvement of LV and LA morphology and a decrease in serum NT-proBNP levels. There is no significant effect of AVF ligation on kidney allograft function: The eGFR remains stable over time. BACKGROUND: Kidney transplantation is considered as the best kidney replacement therapy, and arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis. The systematic ligation of a functioning AVF in stable kidney transplant recipients (KTRs) remains debatable. METHODS: In this prospective study, we investigated the hemodynamic effect of the surgical closure of AVF in KTRs. Forty-three KTRs underwent an ambulatory BP monitoring before surgical closure of AVF (T0) and 12 months later (M12), as well as measurement of serum cardiac biomarkers (i.e., soluble suppression of tumorigenicity 2, N-terminal pro b-type natriuretic peptide [NT-proBNP], and galectin-3). Serum tests were also performed 6 months after AVF closure (M6). An echocardiographic examination was performed at each time point. All serum creatinine values were collected to compare the individual eGFR slopes before versus after AVF closure. The latest measure of the AVF flow before kidney transplantation was recorded. RESULTS: Diastolic BP significantly rose from T0 to M12: +4.4±7.3 mm Hg (P = 0.0003) for 24h, +3.8±7.4 mm Hg (P = 0.0018) during the day, and +6.3±9.9 mm Hg (P = 0.0002) during the night, leading to an increased proportion of KTRs with European Society of Hypertension (ESH)-defined arterial hypertension after AVF ligation. No change was observed for systolic BP. NT-proBNP significantly dropped between T0 and M6 (345 [190; 553] to 230 [118; 458] pg/ml, P = 0.0001) and then remained stable from M6 to M12 while suppression of tumorigenicity 2 and galectin-3 levels did not change from T0 to M12. We observed a significant decrease in left ventricular (LV) end-diastolic volume, LV end-systolic volume, LV mass, interventricular septum diameter, left atrial volume, and tricuspid annular plane systolic excursion from T0 to M6 and then a stability from M6 to M12. LV ejection fraction and eGFR slope remained stable during the whole study. These observations remained unchanged after adjustment for AVF flow. CONCLUSION: The closure of a patent AVF in KTRs is associated with elevation of diastolic BP, drop in serum NT-proBNP levels, reduction of left ventricular and atrial dimensions, and stability of eGFR slope

Characteristics and correlates of seclusion and mechanical restraint measures in a Parisian psychiatric hospital group

IntroductionSeclusion or restraint (S/R) are last-resort measures used in psychiatry to ensure the safety of the patient and the staff. However, they have harmful physical and psychological effects on patients, and efforts to limit their use are needed. We describe the characteristics and correlates of S/R events in four Parisian psychiatric centers.MethodsWithin a 3-month period, November 5, 2018 to February 3, 2019, we recorded data for patients experiencing an S/R measure as well as characteristics of the measures. We studied the mean duration of a S/R event, the time between hospital admission and the occurrence of the event, as well as correlates of these durations. We also examined factors associated with use of a restraint versus a seclusion measure.ResultsFor the 233 patients included, we recorded 217 seclusion measures and 64 mechanical restraints. Seclusion measures mostly occurred after the patient’s transfer from the emergency department. The duration of a seclusion measure was about 10 days. Patients considered resistant to psychotropic treatments more frequently had a longer seclusion duration than others. The mean duration of a mechanical restraint measure was 4 days. Male sex and younger age were associated with experiencing mechanical restraint.DiscussionS/R measures mostly occur among patients perceived as resistant to psychotropic drugs who are arriving from the emergency department. Developing specific emergency department protocols might be useful in limiting the use of coercive measures

Serotonin in retina.

International audienceThe expression of serotonin (5-HT) in the retina was first reported in the sixties. The detection of vesicular monoamine transporter and serotonin receptors in several retinal cells confirm that 5-HT is playing a neuromodulatory role in this structure. Whereas signaling pathways activated by 5-HT receptor binding has been poorly investigated so far, numerous data demonstrated that 5-HT is involved in retinal physiology, retinal physiopathology and photoreceptor survival

Néogenèse lymphoïde induite par l'infection bactérienne bronchopulmonaire chronique

Introduction: lymphoid follicles (LF) are absent in normal lungs, but are described in lungs of subjects with cystic fibrosis (CF) or non-CF bronchiectasis, suggesting a role for bacterial infection in lymphoid neogenesis. We aimed to study the dynamic of pulmonary lymphoid neogenesis (LN) during bacterial infection. Methods: C57BL/6 mice were instilled intratracheally with PAO1- or S. aureus-coated (1.106 CFU/mouse) agarose beads (which produced prolonged airway infection) and compared to controls (sterile beads or no instillation). Mice were sacrificed on day (d)1, d4, d7, and d14 after instillation. Results: chronic pulmonary infection with PAO1 or S. aureus induced organised LF in 14 days after a single challenge with PAO1- or S. aureus-coated beads. Bacteria- induced LF were exclusively localized in the subepithelium of infected airways. Staining for CXCL12 and CXCL13 was weak in airway epithelium of controls, but was positive in airway epithelium (CXCL13) at 1 day and in LF (both) of infected mice at 14 days. Treatment with anti CXCL12 or anti CXCL13 Ab did not reduce LN induced by PAO1 infection. Conclusions: chronic bacterial infection and respiratory epithelium could contribute to LN in chronic airway diseases. Our unique model allows to study mechanisms for the formation and maintenance of lung LF.Introduction: les follicules lymphoïdes (FL) sont absents du poumon normal mais ont été décrits dans les poumons de patients atteints de mucoviscidose ou de dilatations de bronches non mucoviscidosiques, suggérant un rôle pour l’infection bronchique dans la néogenèse lymphoïde (NL). Nous avons étudié la dynamique de la néogenèse lymphoïde dans l’infection bactérienne. Méthodes: les souris C57BL/6 ont reçu une instillation intratrachéale de billes d’agarose contenant du PAO1 ou du S. aureus (106 CFU/animal) permettant une infection prolongée et ont été comparées à des souris contrôles (billes stériles ou absence de billes). Les souris ont été sacrifiées à J1, J4, J7 et J14. Résultats: l’instillation unique de billes d’agarose contenant du PAO1 ou du S. aureus induit en 14 jours des FL fonctionnels situés sous l’épithélium en regard des zones d’infection. Le marquage pour CXCL12 et CXCL13 est faible chez contrôles, mais présent dans l’épithélium (CXCL13) dès J1 et présent également dans les FL (CXCL12 et CXCL13) à J14 chez les souris infectées. Le traitement des souris par un anticorps anti CXCL12 ou anti CXCL13 n’inhibe pas la formation des FL induite par l’infection à PAO1. Conclusion: nos données suggèrent un rôle pour l’infection bactérienne prolongée et l’épithélium respiratoire dans la NL des bronchopathies chroniques. Notre modèle permet d’évaluer les mécanismes de la formation et de persistance des FL dans le poumon

Intrapulmonary lymphoid neogenesis induced by prolonged bacterial airway infection in mice

Introduction: les follicules lymphoïdes (FL) sont absents du poumon normal mais ont été décrits dans les poumons de patients atteints de mucoviscidose ou de dilatations de bronches non mucoviscidosiques, suggérant un rôle pour l’infection bronchique dans la néogenèse lymphoïde (NL). Nous avons étudié la dynamique de la néogenèse lymphoïde dans l’infection bactérienne. Méthodes: les souris C57BL/6 ont reçu une instillation intratrachéale de billes d’agarose contenant du PAO1 ou du S. aureus (106 CFU/animal) permettant une infection prolongée et ont été comparées à des souris contrôles (billes stériles ou absence de billes). Les souris ont été sacrifiées à J1, J4, J7 et J14. Résultats: l’instillation unique de billes d’agarose contenant du PAO1 ou du S. aureus induit en 14 jours des FL fonctionnels situés sous l’épithélium en regard des zones d’infection. Le marquage pour CXCL12 et CXCL13 est faible chez contrôles, mais présent dans l’épithélium (CXCL13) dès J1 et présent également dans les FL (CXCL12 et CXCL13) à J14 chez les souris infectées. Le traitement des souris par un anticorps anti CXCL12 ou anti CXCL13 n’inhibe pas la formation des FL induite par l’infection à PAO1. Conclusion: nos données suggèrent un rôle pour l’infection bactérienne prolongée et l’épithélium respiratoire dans la NL des bronchopathies chroniques. Notre modèle permet d’évaluer les mécanismes de la formation et de persistance des FL dans le poumon.Introduction: lymphoid follicles (LF) are absent in normal lungs, but are described in lungs of subjects with cystic fibrosis (CF) or non-CF bronchiectasis, suggesting a role for bacterial infection in lymphoid neogenesis. We aimed to study the dynamic of pulmonary lymphoid neogenesis (LN) during bacterial infection. Methods: C57BL/6 mice were instilled intratracheally with PAO1- or S. aureus-coated (1.106 CFU/mouse) agarose beads (which produced prolonged airway infection) and compared to controls (sterile beads or no instillation). Mice were sacrificed on day (d)1, d4, d7, and d14 after instillation. Results: chronic pulmonary infection with PAO1 or S. aureus induced organised LF in 14 days after a single challenge with PAO1- or S. aureus-coated beads. Bacteria- induced LF were exclusively localized in the subepithelium of infected airways. Staining for CXCL12 and CXCL13 was weak in airway epithelium of controls, but was positive in airway epithelium (CXCL13) at 1 day and in LF (both) of infected mice at 14 days. Treatment with anti CXCL12 or anti CXCL13 Ab did not reduce LN induced by PAO1 infection. Conclusions: chronic bacterial infection and respiratory epithelium could contribute to LN in chronic airway diseases. Our unique model allows to study mechanisms for the formation and maintenance of lung LF