Mitigation of TDP-43 toxic phenotype by an RGNEF fragment in amyotrophic lateral sclerosis models.

Aggregation of the RNA-binding protein TAR DNA binding protein (TDP-43) is a hallmark of TDP-proteinopathies including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). As TDP-43 aggregation and dysregulation are causative of neuronal death, there is a special interest in targeting this protein as a therapeutic approach. Previously, we found that TDP-43 extensively co-aggregated with the dual function protein GEF (guanine exchange factor) and RNA-binding protein rho guanine nucleotide exchange factor (RGNEF) in ALS patients. Here, we show that an N-terminal fragment of RGNEF (NF242) interacts directly with the RNA recognition motifs of TDP-43 competing with RNA and that the IPT/TIG domain of NF242 is essential for this interaction. Genetic expression of NF242 in a fruit fly ALS model overexpressing TDP-43 suppressed the neuropathological phenotype increasing lifespan, abolishing motor defects and preventing neurodegeneration. Intracerebroventricular injections of AAV9/NF242 in a severe TDP-43 murine model (rNLS8) improved lifespan and motor phenotype, and decreased neuroinflammation markers. Our results demonstrate an innovative way to target TDP-43 proteinopathies using a protein fragment with a strong affinity for TDP-43 aggregates and a mechanism that includes competition with RNA sequestration, suggesting a promising therapeutic strategy for TDP-43 proteinopathies such as ALS and FTD.

Does the addition of convex uniplanar screws in hybrid constructs improve 3D surgical correction in thoracic adolescent idiopathic scoliosis posterior fusion?

Purpose: Hybrid techniques using thoracic sublaminar bands have proved their efficacy in adolescent idiopathic scoliosis posterior fusion, but clinical axial correction sometimes remained disappointing. One solution found was "the frame technique" and the second alternative was the replacement of the convex sublaminar bands by periapical uniplanar screws. The goal of this study was to compare clinical and radiological outcomes of both techniques in a consecutive cohort of adolescent idiopathic scoliosis patients. Methods: All patients undergoing primary posterior fusion for thoracic adolescent idiopathic scoliosis between January 2017 and March 2020 were included. Two groups were compared: Group 1 with thoracic sublaminar bands only and Group 2 with periapical uniplanar screws. All patients underwent standing stereoradiographs. The main frontal, sagittal, and axial (apical vertebra rotation) radiological parameters of interest were analyzed. Functional outcomes were assessed using the Scoliosis Research Society 30 score. Results: A total of 147 adolescents were included (Group 1, n = 73 and Group 2, n = 74 patients). In the frontal plane, a greater reduction index was observed in Group 2 (68% versus 62%, p < 0.001) as well as a better apical axial correction (67.8% versus 46.6%, p = 0.03). The number of thoracoplasty performed was reduced (6.7% versus 20.5%, p = 0.02) in Group 2, with a significant decrease in the rate of mechanical complication. No significant loss of correction was observed during follow-up in any of the group. Conclusion: The adjunction of convex uniplanar screws at the periapical levels improved the three-dimensional surgical correction of thoracic adolescent idiopathic scoliosis treated with hybrid constructs. Level of evidence: level III, retrospective comparative study.

Umbravirus-like RNA viruses are capable of independent systemic plant infection in the absence of encoded movement proteins.

The signature feature of all plant viruses is the encoding of movement proteins (MPs) that supports the movement of the viral genome into adjacent cells and through the vascular system. The recent discovery of umbravirus-like viruses (ULVs), some of which only encode replication-associated proteins, suggested that they, as with umbraviruses that lack encoded capsid proteins (CPs) and silencing suppressors, would require association with a helper virus to complete an infection cycle. We examined the infection properties of 2 ULVs: citrus yellow vein associated virus 1 (CY1), which only encodes replication proteins, and closely related CY2 from hemp, which encodes an additional protein (ORF5CY2) that was assumed to be an MP. We report that both CY1 and CY2 can independently infect the model plant Nicotiana benthamiana in a phloem-limited fashion when delivered by agroinfiltration. Unlike encoded MPs, ORF5CY2 was dispensable for infection of CY2, but was associated with faster symptom development. Examination of ORF5CY2 revealed features more similar to luteoviruses/poleroviruses/sobemovirus CPs than to 30K class MPs, which all share a similar single jelly-roll domain. In addition, only CY2-infected plants contained virus-like particles (VLPs) associated with CY2 RNA and ORF5CY2. CY1 RNA and a defective (D)-RNA that arises during infection interacted with host protein phloem protein 2 (PP2) in vitro and in vivo, and formed a high molecular weight complex with sap proteins in vitro that was partially resistant to RNase treatment. When CY1 was used as a virus-induced gene silencing (VIGS) vector to target PP2 transcripts, CY1 accumulation was reduced in systemic leaves, supporting the usage of PP2 for systemic movement. ULVs are therefore the first plant viruses encoding replication and CPs but no MPs, and whose systemic movement relies on a host MP. This explains the lack of discernable helper viruses in many ULV-infected plants and evokes comparisons with the initial viruses transferred into plants that must have similarly required host proteins for movement.

Ten years of hand hygiene excellence: a summary of outcomes, and a comparison of indicators, from award-winning hospitals worldwide.

BACKGROUND: Hand hygiene is a crucial measure for the prevention of healthcare-associated infections (HAIs). The Hand Hygiene Excellence Award (HHEA) is an international programme acknowledging healthcare facilities for their leadership in implementing hand hygiene improvement programmes, including the World Health Organisation's Multimodal Improvement Strategy. This study aimed at summarising the results of the HHEA campaign between 2010 and 2021 and investigating the relationship between different hand hygiene parameters based on data from participating healthcare facilities. METHODS: A retrospective analysis was performed on datasets from HHEA forms, including data on hand hygiene compliance, alcohol-based handrub (ABHR) consumption, and Hand Hygiene Self-Assessment Framework (HHSAF) scores. Descriptive statistics were reported for each variable. The correlation between variables was inspected through Kendall's test, while possible non-linear relationships between hand hygiene compliance, ABHR consumption and HHSAF scores were sought through the Locally Estimated Scatterplot Smoothing or logistic regression models. A tree-structured partitioning model was developed to further confirm the obtained findings. RESULTS: Ninety-seven healthcare facilities from 28 countries in three world regions (Asia-Pacific, Europe, Latin America) were awarded the HHEA and thus included in the analysis. HHSAF scores indicated an advanced hand hygiene promotion level (median 445 points, IQR 395-480). System change (100 [95-100] points) and institutional safety climate (85 [70-95] points) showed the highest and lowest score, respectively. In most cases, hand hygiene compliance was above 70%, with heterogeneity between countries. ABHR consumption above 20 millilitres per patient-day (ml/PD) was widely reported, with overall increasing trends. HHSAF scores were positively correlated with hand hygiene compliance (τ = 0.211, p = 0.007). We observed a positive correlation between compliance rates and ABHR consumption (τ = 0.193, p < 0.001), although the average predicted consumption was stable around 55-60 ml/PD for compliance rates above 80-85%. Logistic regression and partitioning tree analyses revealed that higher HHSAF scores were more likely in the high-ABHR consumption group at cut-offs around 57-59 ml/PD. CONCLUSION: Ten years after its inception, the HHEA proves to be a valuable hand hygiene improvement programme in healthcare facilities worldwide. Consistent results were provided by the different hand hygiene indicators and the HHSAF score represents a valuable proxy measure of hand hygiene compliance.

A Disintegrin And Metalloprotease 10 expression within the murine central nervous system.

A Disintegrin And Metalloprotease 10 (ADAM10), is able to control several important physiopathological processes through the shedding of a large number of protein substrates. Although ADAM10 plays a crucial role in the central nervous system (CNS) development and function, its protein distribution in the CNS has not been fully addressed. Here, we described the regional and cellular ADAM10 protein expression in C57BL/6 mice examined by immunofluorescence 1) throughout the adult mouse brain, cerebellum and spinal cord in vivo and 2) in different cell types as neurons, astrocytes, oligodendrocytes and microglia in vitro. We observed ADAM10 expression through the whole CNS, with a strong expression in the hippocampus, in the hypothalamus and in the cerebral and piriform cortex in the brain, in the Purkinje and in granular cell layers in the cerebellum and in the spinal cord to a lower extent. In vivo, ADAM10 protein expression was mainly found in neurons and in some oligodendroglial cell populations. However, in primary cultures we observed ADAM10 expression in neurons, oligodendrocytes, astrocytes and microglia. Interestingly, ADAM10 was not only found in the membrane but also in cytoplasmic vesicles and in the nucleus of primary cultured cells. Overall, this work highlights a wide distribution of ADAM10 throughout the CNS. The nuclear localization of ADAM10, probably due to its intracellular domain, emphasizes its role in cell signalling in physiological and pathological conditions. Further investigations are required to better elucidate the role of ADAM10 in glial cells.

Distal femoral osteotomy and patellar tendon advancement for the treatment of crouch gait in patients with bilateral spastic cerebral palsy.

BACKGROUND: Crouch gait, or flexed knee gait, represents a common gait pattern in patients with spastic bilateral cerebral palsy (CP). Distal femoral extension and/or shortening osteotomy (DFEO/DFSO) and patellar tendon advancement (PTA) can be considered as viable options when knee flexion contractures are involved. Better outcomes have been reported after a combination of both, independently of the presence of knee extensor lag. In this study, we evaluated the clinical and kinematic outcomes of these procedures. PATIENTS AND METHODS: We reviewed a cohort of 52 limbs (28 patients) who were treated for crouch gait by DFEO/DFSO alone (group 1, n = 15) or DFEO/DFSO + PTA (group 2, n = 37) as a part of single event multilevel surgery (SEMLS). The mean age at surgery was 14 years, and the mean follow-up time was 18 months. The physical examination data and three-dimensional standardized gait analysis were collected and analyzed before the surgery and postoperatively. RESULTS: Overall knee range of motion improved in all limbs. The knee flexion decreased significantly in both groups at initial, mid, and terminal stance. Hip flexion significantly decreased in mid-stance for limbs in group 2. Both clinical and gait parameters were most improved in limbs who underwent DFEO/DFSO + PTA. Increased pelvic tilt was observed in both groups after surgery. CONCLUSION: Although DFEO/DFSO alone was successful in correcting knee flexion contractures, PTA has helped to improve knee extensor lag and knee extension during gait. LEVEL OF EVIDENCE: Therapeutic level IV.

Is scoliosis a source of pain?

Purpose: Pain in scoliosis is definitely a hot topic with growing popularity. The literature remains very controversial, with a pain prevalence ranging from 23% to 90%, but this can be explained by the great heterogeneity of the numerous series. The aim of this review was to report results from the literature regarding pain in relation to scoliosis regardless of the etiology. Methods: A bibliographic search in Medline and Google database from 2003 to March 2023 was performed. Relevant literature was analyzed, summarized, and discussed based on authors' experience. A 1-year prospective series of adolescent idiopathic scoliosis patients was also included to compare with the existing literature. Results: A total of 126 adolescent idiopathic scoliosis patients were included, with a mean preoperative Cobb angle of 64.5° (range, 45°-112°). Reported pain prevalence was 34.1%. Pain and no-pain groups were very different in their self-reported experience, with a very low mean visual analogue scale score of 0.5 (± 0.6) in the no pain group, while visual analogue scale averaged 5.6 (± 1.2) in the pain group (p < 0.001). No significant difference was found between groups regarding the most relevant demographic and radiological parameters. Conclusion: Evidence-based literature on "scoliosis as a source of pain" remains ambiguous. There seems to be a consensus on the lack of direct relationship between deformity magnitude and back pain intensity. A comprehensive evaluation of the patient is therefore necessary before any treatment, including medical history, clinical examination, and relevant imaging for any child with scoliosis and back pain. Level of evidence: Level VI.

Slipped Capital Femoral Epiphysis in Adolescents: Functional Outcomes and Return to Physical Activity after Surgical Treatment.

Background: Slipped capital femoral epiphysis (SCFE) represents a relatively common hip disorder in adolescents. The present retrospective study analyzes the correlation between age, severity of the slip and physeal stability and the functional outcomes, as well as the ability to return to previous physical activity (PA) of patients surgically treated with either pining in situ (PIS) or the modified Dunn (MD) procedure (anatomical reduction of the slipped epiphysis). Methods:The present research is a retrospective observational study of patients surgically treated for SCFE from 2010 to 2015. The sample was divided into two groups: those treated with PIS and those with the MD procedure. Univariate and multivariate logistic regression analyses were performed to determine the relationship between age, Loder classification (stable/unstable), as well as Southwick slip angle (severity of the slip) to return to previous PA. Furthermore, linear regression was used to investigate the association of the above predictor variables to Oxford and Harris hip scores (HHS). Results:A total of 32 patients were identified (16 treated with PIS and 16 with the MD procedure). None of the examined predictor variables (age, Southwick slip angle, Loder classification) had statistically significant effect on the ability to return to previous PA in either the in situ or Dunn group. Univariate analysis showed that higher patients' age at the time of surgery was related to worse HHS and Oxford scores in both the PIS and MD groups. Unstable hips seem to affect unfavorably the HHS. Conclusion:The present study did not reveal any relationship between the age, degree of the Southwick slip angle, the stability of the physis, and the return to PA. Exploration of additional confounding factors are warranted to better understand the physis-related impact on the functional outcomes in both groups.

Complete patient exposure during paediatric brain cancer treatment for photon and proton therapy techniques including imaging procedures.

Background: In radiotherapy, especially when treating children, minimising exposure of healthy tissue can prevent the development of adverse outcomes, including second cancers. In this study we propose a validated Monte Carlo framework to evaluate the complete patient exposure during paediatric brain cancer treatment. Materials and methods: Organ doses were calculated for treatment of a diffuse midline glioma (50.4 Gy with 1.8 Gy per fraction) on a 5-year-old anthropomorphic phantom with 3D-conformal radiotherapy, intensity modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT) and intensity modulated pencil beam scanning (PBS) proton therapy. Doses from computed tomography (CT) for planning and on-board imaging for positioning (kV-cone beam CT and X-ray imaging) accounted for the estimate of the exposure of the patient including imaging therapeutic dose. For dose calculations we used validated Monte Carlo-based tools (PRIMO, TOPAS, PENELOPE), while lifetime attributable risk (LAR) was estimated from dose-response relationships for cancer induction, proposed by Schneider et al. Results: Out-of-field organ dose equivalent data of proton therapy are lower, with doses between 0.6 mSv (testes) and 120 mSv (thyroid), when compared to photon therapy revealing the highest out-of-field doses for IMRT ranging between 43 mSv (testes) and 575 mSv (thyroid). Dose delivered by CT ranged between 0.01 mSv (testes) and 72 mSv (scapula) while a single imaging positioning ranged between 2 µSv (testes) and 1.3 mSv (thyroid) for CBCT and 0.03 µSv (testes) and 48 µSv (scapula) for X-ray. Adding imaging dose from CT and daily CBCT to the therapeutic demonstrated an important contribution of imaging to the overall radiation burden in the course of treatment, which is subsequently used to predict the LAR, for selected organs. Conclusion: The complete patient exposure during paediatric brain cancer treatment was estimated by combining the results from different Monte Carlo-based dosimetry tools, showing that proton therapy allows significant reduction of the out-of-field doses and secondary cancer risk in selected organs.

-1 Programmed ribosomal frameshifting in Class 2 umbravirus-like RNAs uses multiple long-distance interactions to shift between active and inactive structures and destabilize the frameshift stimulating element.

Plus-strand RNA viruses frequently employ -1 programmed ribosomal frameshifting (-1 PRF) to maximize their coding capacity. Ribosomes can frameshift at a slippery sequence if progression is impeded by a frameshift stimulating element (FSE), which is generally a stable, complex, dynamic structure with multiple conformations that contribute to the efficiency of -1 PRF. As FSE are usually analyzed separate from the viral genome, little is known about cis-acting long-distance interactions. Using full-length genomic RNA of umbravirus-like (ula)RNA citrus yellow vein associated virus (CY1) and translation in wheat germ extracts, six tertiary interactions were found associated with the CY1 FSE that span nearly three-quarters of the 2.7 kb genomic RNA. All six tertiary interactions are conserved in other Class 2 ulaRNAs and two are conserved in all ulaRNAs. Two sets of interactions comprise local and distal pseudoknots that involve overlapping FSE nucleotides and thus are structurally incompatible, suggesting that Class 2 FSEs assume multiple conformations. Importantly, two long-distance interactions connect with sequences on opposite sides of the critical FSE central stem, which would unzip the stem and destabilize the FSE. These latter interactions could allow a frameshifting ribosome to translate through a structurally disrupted upstream FSE that no longer blocks ribosome progression.

D'Ann Rochon (1955-2022), a life of passion for plant virology.

D'Ann Rochon passed away on November 29th 2022. She is remembered for her outstanding contributions to the field of plant virology, her strong commitment to high quality science and her dedication to the training and mentorship of the next generation of scientists. She was a research scientist for Agriculture and Agri-Food Canada and an Adjunct Professor for the University of British Columbia. Her research program provided new insights on the infection cycle of tombusviruses and related viruses, including ground-breaking research on the structure of virus particles, the mechanisms of virus transmission by fungal zoospores, and the complexity of plant-virus interactions. She also developed diagnostic antibodies for plum pox virus and little cherry virus 2 that have had a significant impact on the management of these viruses.

Whole-Genome Sequencing-Based Screening of MRSA in Patients and Healthcare Workers in Public Hospitals in Benin.

Methicillin-resistant Staphylococcus aureus (MRSA) constitutes a serious public health concern, with a considerable impact on patients' health, and substantial healthcare costs. In this study, patients and healthcare workers (HCWs) from six public hospitals in Benin were screened for MRSA. Strains were identified as MRSA using conventional microbiological methods in Benin, and confirmed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry in Belgium. Whole-genome sequencing (WGS) was used on the confirmed MRSA isolates, to characterize their genomic content and study their relatedness. Amongst the 305 isolates (304 wound swabs and 61 nasal swabs) that were collected from patients and HCWs, we detected 32 and 15 cases of MRSA, respectively. From this collection, 27 high-quality WGS datasets were obtained, which carried numerous genes and mutations associated with antimicrobial resistance. The mecA gene was detected in all the sequenced isolates. These isolates were assigned to five sequence types (STs), with ST8 (55.56%, n = 15/27), ST152 (18.52%, n = 5/27), and ST121 (18.52%, n = 5/27) being the most common. These 27 isolates carried multiple virulence genes, including the genes encoding the Panton-Valentine leukocidin toxin (48.15%, n = 13/27), and the tst gene (29.63%, n = 8/27), associated with toxic shock syndrome. This study highlights the need to implement a multimodal strategy for reducing the risk of the cross-transmission of MRSA in hospitals.

Differences in carbonate chemistry up-regulation of long-lived reef-building corals.

With climate projections questioning the future survival of stony corals and their dominance as tropical reef builders, it is critical to understand the adaptive capacity of corals to ongoing climate change. Biological mediation of the carbonate chemistry of the coral calcifying fluid is a fundamental component for assessing the response of corals to global threats. The Tara Pacific expedition (2016-2018) provided an opportunity to investigate calcification patterns in extant corals throughout the Pacific Ocean. Cores from colonies of the massive Porites and Diploastrea genera were collected from different environments to assess calcification parameters of long-lived reef-building corals. At the basin scale of the Pacific Ocean, we show that both genera systematically up-regulate their calcifying fluid pH and dissolved inorganic carbon to achieve efficient skeletal precipitation. However, while Porites corals increase the aragonite saturation state of the calcifying fluid (Ωcf) at higher temperatures to enhance their calcification capacity, Diploastrea show a steady homeostatic Ωcf across the Pacific temperature gradient. Thus, the extent to which Diploastrea responds to ocean warming and/or acidification is unclear, and it deserves further attention whether this is beneficial or detrimental to future survival of this coral genus.

Bivertebral pedicle-supralaminar autostable claw for proximal fixation of magnetic growing rods in early-onset scoliosis.

BACKGROUND: The various methods for the proximal fixation of magnetic growing rods in patients with early-onset scoliosis (EOS) are associated with high rates of mechanical complications related to material failure or proximal junctional kyphosis (PJK). The bivertebral autostable claw (BAC) has been proven reliable in adolescent idiopathic scoliosis but has not been assessed when used with magnetic growing rods. The objective of this study was to describe the operative technique and outcomes of BAC proximal fixation of magnetic growing rods in children with EOS. HYPOTHESIS: The BAC provides stable and effective proximal fixation in children with early-onset scoliosis. MATERIAL AND METHODS: This retrospective observational study included 24 patients who had surgery in 2015-2019 for early-onset scoliosis with magnetic growing rod implantation and BAC proximal fixation. Radiological variables were measured in the coronal and sagittal planes before surgery, during the early postoperative period (<3months) and at last follow-up (≥2years). RESULTS: No neurological complications were recorded. At last follow-up, four patients had radiological PJK, including one patient with clinical PJK due to material failure. DISCUSSION: BAC proximal fixation is both effective and sufficiently stable (4.2% pull-out) to withstand the forces applied during distraction sessions and daily activities in children with EOS. Moreover, the polyaxial connecting rods ensure better BAC adaptation to the local proximal kyphosis, which is often marked in this population. CONCLUSION: The BAC is a reliable proximal fixation device that is well-suited to magnetic growing rod fixation in children with EOS. LEVEL OF EVIDENCE: IV, retrospective observational cohort study.

RNAcanvas: interactive drawing and exploration of nucleic acid structures.

Two-dimensional drawing of nucleic acid structures, particularly RNA structures, is fundamental to the communication of nucleic acids research. However, manually drawing structures is laborious and infeasible for structures thousands of nucleotides long. RNAcanvas automatically arranges residues into strictly shaped stems and loops while providing robust interactive editing features, including click-and-drag layout adjustment. Drawn elements are highly customizable in a point-and-click manner, including colours, fonts, size and shading, flexible numbering, and outlining of bases. Tertiary interactions can be drawn as draggable, curved lines. Leontis-Westhof notation for depicting non-canonical base-pairs is fully supported, as well as text labels for structural features (e.g. hairpins). RNAcanvas also has many unique features and performance optimizations for large structures that cannot be correctly predicted and require manual refinement based on the researcher's own analyses and expertise. To this end, RNAcanvas has point-and-click structure editing with real-time highlighting of complementary sequences and motif search functionality, novel features that greatly aid in the identification of putative long-range tertiary interactions, de novo analysis of local structures, and phylogenetic comparisons. For ease in producing publication quality figures, drawings can be exported in both SVG and PowerPoint formats. URL: https://rnacanvas.app.

ADAR1 Biology Can Hinder Effective Antiviral RNA Interference.

Viruses constantly evolve and adapt to the antiviral defenses of their hosts. The biology of viral circumvention of these selective pressures can often be attributed to the acquisition of novel antagonistic gene products or by rapid genome change that prevents host recognition. To study viral evasion of RNA interference (RNAi)-based defenses, we established a robust antiviral system in mammalian cells using recombinant Sendai virus designed to be targeted by endogenous host microRNAs (miRNAs) with perfect complementarity. Using this system, we previously demonstrated the intrinsic ability of positive-strand RNA viruses to escape this selective pressure via homologous recombination, which was not observed in negative-strand RNA viruses. Here, we show that given extensive time, escape of miRNA-targeted Sendai virus was enabled by host adenosine deaminase acting on RNA 1 (ADAR1). Independent of the viral transcript targeted, ADAR1 editing resulted in disruption of the miRNA-silencing motif, suggesting an intolerance for extensive RNA-RNA interactions necessary for antiviral RNAi. This was further supported in Nicotiana benthamiana, where exogenous expression of ADAR1 interfered with endogenous RNAi. Together, these results suggest that ADAR1 diminishes the effectiveness of RNAi and may explain why it is absent in species that utilize this antiviral defense system. IMPORTANCE All life at the cellular level has the capacity to induce an antiviral response. Here, we examine the result of imposing the antiviral response of one branch of life onto another and find evidence for conflict. To determine the consequences of eliciting an RNAi-like defense in mammals, we applied this pressure to a recombinant Sendai virus in cell culture. We find that ADAR1, a host gene involved in regulation of the mammalian response to virus, prevented RNAi-mediated silencing and subsequently allowed for viral replication. In addition, the expression of ADAR1 in Nicotiana benthamiana, which lacks ADARs and has an endogenous RNAi system, suppresses gene silencing. These data indicate that ADAR1 is disruptive to RNAi biology and provide insight into the evolutionary relationship between ADARs and antiviral defenses in eukaryotic life.

A gait functional classification of adolescent idiopathic scoliosis (AIS) based on spatio-temporal parameters (STP).

BACKGROUND: Therapeutic decisions for patients with adolescent idiopathic scoliosis (AIS) are mostly based on static measurements performed on two-dimensional standing full-spine radiographs. However, the trunk plays an essential role in the human locomotion, and the functional consequences during daily activities of this specific and common spinal deformity are not factored in. RESEARCH QUESTION: Does patients with AIS have specific gait patterns based on spatio-temporals parameters measurements ? METHODS: 90 AIS patients (aged 10-18 years) with preoperative simplified gait analysis were retrospectively included for analysis between 2017 and 2020. Spatio-temporal parameters (STP) were measured on a 3-m baropodometric gaitway and included the measurement of 15 normalized gait parameters. A hierarchical cluster analysis was performed to identify group of patients based on the similarities of their gait patterns, and functional variables' inter-group differences were also measured. The subject distribution was calculated to identify the structural characteristics of the subjects according to their gait patterns. RESULTS: Three gait patterns were identified. Cluster 1 (46%) was defined by asymmetry, Cluster 2 (16%) by instability, and Cluster 3 (36%) by variability. Each cluster was significantly different from the other ones on at least 6 different parameters (p < 0.05). Furthermore, each cluster was associated with one type of curve: Lenke 1 for Cluster 1 (57.5%), Lenke 6 for Cluster 2 (40%) and Lenke 5 for Cluster 3 (43.5%). SIGNIFICANCE: Patients with severe AIS have a dynamic signature during gait identified on STP. Understanding consequences of this deformity on gait may be an interesting avenue to study the pathological mechanisms involved in their dynamic motor organization. Furthermore, these results might also be a first step to study the effectiveness of the different therapies.

Conserved Structure Associated with Different 3'CITEs Is Important for Translation of Umbraviruses.

The cap-independent translation of plus-strand RNA plant viruses frequently depends on 3' structures to attract translation initiation factors that bind ribosomal subunits or bind directly to ribosomes. Umbraviruses are excellent models for studying 3' cap-independent translation enhancers (3'CITEs), as umbraviruses can have different 3'CITEs in the central region of their lengthy 3'UTRs, and most also have a particular 3'CITE (the T-shaped structure or 3'TSS) near their 3' ends. We discovered a novel hairpin just upstream of the centrally located (known or putative) 3'CITEs in all 14 umbraviruses. These CITE-associated structures (CASs) have conserved sequences in their apical loops and at the stem base and adjacent positions. In 11 umbraviruses, CASs are preceded by two small hairpins joined by a putative kissing loop interaction (KL). Converting the conserved 6-nt apical loop to a GNRA tetraloop in opium poppy mosaic virus (OPMV) and pea enation mosaic virus 2 (PEMV2) enhanced translation of genomic (g)RNA, but not subgenomic (sg)RNA reporter constructs, and significantly repressed virus accumulation in Nicotiana benthamiana. Other alterations throughout OPMV CAS also repressed virus accumulation and only enhanced sgRNA reporter translation, while mutations in the lower stem repressed gRNA reporter translation. Similar mutations in the PEMV2 CAS also repressed accumulation but did not significantly affect gRNA or sgRNA reporter translation, with the exception of deletion of the entire hairpin, which only reduced translation of the gRNA reporter. OPMV CAS mutations had little effect on the downstream BTE 3'CITE or upstream KL element, while PEMV2 CAS mutations significantly altered KL structures. These results introduce an additional element associated with different 3'CITEs that differentially affect the structure and translation of different umbraviruses.

Occurrence of focal myositis during Behçet's disease: The identification of a specific vasculitis-associated focal myopathy.

AIMS: This study aimed to report the association of focal myositis (FM) and Behçet's disease (BD) and to analyse the main characteristics of such an association. METHODS: This is a retrospective multicentre study of patients with BD and FM (BD + FM+ group) and those without FM (BD - FM+ group). Clinical, laboratory, radiological, pathological, treatment and outcome data were analysed. RESULTS: The BD + FM+ group included 10 patients; the median [interquartile range] age at BD diagnosis was 25 [16-35] years, and at FM diagnosis, it was 30 [26-42] years. The diagnosis of BD preceded FM in the majority of cases (n = 8/10). FM occurrence was associated with BD flare-ups in three cases. The creatine kinase levels remained normal or slightly increased. Histological analyses identified relatively preserved muscle tissue, associated with vasculitis (n = 5/6). All patients required treatment; most patients relapsed (n = 9/10). The BD - FM+ group included 35 patients. A comparison of the groups identified a trend towards a younger median age at diagnosis of FM among those with BD (p = 0.063) and more frequent focal muscle swelling in the BD + FM+ group (p = 0.029). The pathological analysis identified significantly less frequent muscle alterations in the BD + FM+ group (muscle fibre size heterogeneity, p = 0.021; necrosis, p = 0.007; and fibrosis, p = 0.027). BD + FM+ patients had a higher frequency of relapse (p = 0.003) and systematic treatment (p = 0.042). CONCLUSIONS: FM occurring during BD appears to be part of the systemic vasculitis process and presents as a vasculitis-associated focal myopathy with a specific clinico-histological pattern. Patients with this association require long-term follow-up and adapted management. This case series also highlights the need for research on BD diagnostic criteria in cases of FM.

Nursery outbreak caused by enteroaggregative Escherichia coli serogroup O111:H21.

This study describes, for the first time, the occurrence of an epidemic of enteroaggregative Escherichia coli (EAEC) O111:H21 in a Belgian nursery and describes a practical approach concerning its management. Few data exist in the literature on this type of outbreak. Clinical and microbiological investigations were needed to find a link between the cases and identify the causative agent. The microbiological procedure followed was first based on conventional analyses: isolation using selective cultures, identification by MALDI-TOF MS, antibiogram, determination of the serogroup by agglutination, then whole genome sequencing. A total of 7/21 children were infected with this pathogen. Four cases could be confirmed by a molecular technique, wgMLST, as belonging to the same bacterial clone. The action plan put in place focused on symptomatic case eviction, strict general hygiene precaution as well as specific cleaning and disinfection measures. The epidemic did last only a few days. It appears important, in the context of an epidemic, that clinical laboratories standardize their practice by equipping themselves with molecular techniques such as a multiplex which does not focus only on the serotype O157:H7 and which make it possible to distinguish the different pathotypes of E. coli by targeting several virulence genes (stx, aggR…). However, cost/effectiveness studies are awaited to confirm the interest of a systematic search by molecular method for the pathogen involved in a suspected outbreak occurring in a nursery.