Muscle coactivation during gait in children with and without cerebral palsy.

BACKGROUND: Children with Cerebral Palsy (CP) walk with an uncoordinated gait compared to Typically Developing (TD) children. This behavior may reflect greater muscle co-activation in the lower limb; however, findings are inconsistent, and the determinants of this construct are unclear. RESEARCH OBJECTIVES: (i) Compare lower-limb muscle co-activation during gait in children with, and without CP, and (ii) determine the extent to which muscle co-activation is influenced by electromyography normalization procedures and Gross Motor Function Classification System (GMFCS) class. METHODS: An electromyography system measured muscle activity in the rectus femoris, semitendinosus, gastrocnemius, and tibialis anterior muscles during walking in 46 children (19 CP, 27 TD). Muscle co-activation was calculated for the tibialis anterior-gastrocnemius (TA-G), rectus femoris-gastrocnemius (RF-G), and rectus femoris-semitendinosus (RF-S) pairings, both using root mean squared (RMS)-averaged and dynamically normalized data, during stance and swing. Mann-Whitney U and independent t-tests examined differences in muscle co-activation by group (CP vs. TD) and GMFCS class (CP only), while mean difference 95% bootstrapped confidence intervals compared electromyography normalization procedures. RESULTS: Using dynamically normalized data, the CP group had greater muscle co-activation for the TA-G and RF-G pairs during stance (p < 0.01). Using RMS-averaged data, the CP group had greater muscle co-activation for TA-G (stance and swing, p < 0.01), RF-G (stance, p < 0.05), and RF-S (swing, p < 0.01) pairings. Muscle co-activation calculated with dynamically normalized, compared to RMS-averaged data, were larger in the RF-S and RF-G (stance) pairs, but smaller during swing (RF-G). Children with CP classified as GMFCS II had greater muscle co-activation during stance in the TA-G pair (p < 0.05). SIGNIFICANCE: Greater muscle co-activation observed in children with CP during stance may reflect a less robust gait strategy. Although data normalization procedures influence muscle co-activation ratios, this behavior was observed independent of normalization technique.

The effect of uneven surfaces on inter-joint coordination during walking in children with cerebral palsy.

Clinical gait analysis on uneven surfaces contributes to the ecological assessment of gait deviations of children with spastic cerebral palsy (CP). Walking on uneven surfaces requires specific motor strategies, which can be assessed by lower-limb kinematic and inter-joint coordination analyses. This study aimed to assess and compare kinematics and inter-joint coordination between children with CP and their typically developing (TD) peers when walking on even and two levels of uneven surfaces (medium and high). A total of 17 children with CP and 17 TD children (11.5 ± 3.5 and 10.4 ± 4.5 years old, respectively) were asked to complete 6-8 gait trials on a 4-m walkway of each surface (n = 3) in randomized blocks while fit with retro-reflective markers on their lower-limbs. Children with CP showed proximal gait adaptations (i.e., hip and knee) on uneven surfaces. Compared with the TD group, the CP group showed decreased hip extension during late stance (49-63%, d = 0.549, p < 0.001), and a more in-phase knee-hip coordination strategy during swing phase (75-84% of gait cycle, d = 1.035, p = 0.029 and 92-100%, d = 1.091, p = 0.030) when walking on an uneven (high), compared to even surface. This study provides a better understanding of kinematic strategies employed by children with spastic CP when facing typical daily life gait challenges. Further studies are needed to evaluate the benefits of integrating uneven surfaces in rehabilitation care.

Muscle co-contraction and co-activation in cerebral palsy during gait: A scoping review.

BACKGROUND: Cerebral palsy (CP) results from an injury to a developing brain. Muscle activation patterns during walking are disrupted in individuals with CP. Indeed, excessive muscle co-contraction or co-activation (MCo/MCa) is one of the characteristics of pathological gait. Although some researchers have studied MCo/MCa in individuals with CP during gait, inconsistent results limit our understanding of this literature. Increased knowledge of MCo/MCa patterns in individuals with CP may help the development of improved gait management approaches. RESEARCH QUESTION: This review aims to summarize MCo/MCa patterns while walking in individuals with CP across the existing literature and compare them with their healthy peers. METHODS: This study follows the Joanna Briggs Institute (JBI) guidelines and the recommendations presented in PRISMA Extension for Scoping Reviews (PRISMA-ScR). The recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for scoping Reviews statement were respected. The following databases were searched: MEDLINE (Ovid), EMBASE (Ovid), CINAHL Plus with Full Text (Ebsco), SPORTDiscus with Full Text (Ebsco), and Web of Science. RESULTS: Among 2545 identified studies, 21 studies remained after screening. In total, 337 participants with CP and 249 healthy participants were included. Both MCo and MCa terminologies are used for describing simultaneous muscle activation; however, when it is measured by electromyography (EMG), MCa terminology should be preferred to facilitate interpretation. A wide range of MCo/MCa patterns has been found across studies using different methodologies (e.g., gait protocol, computation methods). Finally, most of the included studies confirm that MCo/MCa is increased in individuals with CP during walking compared to controls. SIGNIFICANCE: This review identified missing concepts and common limitations in the literature which could be addressed in future research such as the association between MCo/MCa and gait deviations, and the most appropriate MCo/MCa computation method.

IVIg therapy in the management of BK virus infections in pediatric kidney transplant patients.

BK virus-associated nephropathy (BKPyVAN) induces kidney allograft dysfunction. Although decreasing immunosuppression is the standard for managing BK virus (BKPyV) infection, this strategy is not always effective. The use of polyvalent immunoglobulins (IVIg) may be of interest in this setting. We performed a retrospective single-center evaluation of the management of BKPyV infection in pediatric kidney transplant patients. Among the 171 patients who underwent transplantation between January 2010 and December 2019, 54 patients were excluded (combined transplant n = 15, follow-up in another center n = 35, early postoperative graft loss n= 4). Thus, 117 patients (120 transplants) were included. Overall, 34 (28%) and 15 (13%) transplant recipients displayed positive BKPyV viruria and viremia, respectively. Three had biopsy-confirmed BKPyVAN. The pre-transplant prevalence of CAKUT and HLA antibodies was higher among BKPyV-positive patients compared to non-infected patients. After the detection of BKPyV replication and/or BKPyVAN, the immunosuppressive regimen was modified in 13 (87%) patients: either by decreasing or changing the calcineurin inhibitors (n = 13) and/or switching from mycophenolate mofetil to mTor inhibitors (n = 10). Starting IVIg therapy was based on graft dysfunction or an increase in the viral load despite reduced immunosuppressive regimen. Seven of 15(46%) patients received IVIg. These patients had a higher viral load (5.4 [5.0-6.8]log vs. 3.5 [3.3-3.8]log). In total, 13 of 15 (86%) achieved viral load reduction, five of seven after IVIg therapy. As long as specific antivirals are not available for the management of BKPyV infections in pediatric kidney transplant patients, polyvalent IVIg may be discussed for the management of severe BKPyV viremia, in combination with decreased immunosuppression.

[Follow-up strategies for lung transplant recipients in France]. / Suivi partagé des patients transplantés pulmonaires.

BACKGROUND: Lung transplantation (LT) requires sustained care for a frequently polypathological condition. Follow-up is focused on three main issues: 1/stability of respiratory function; 2/comorbidity management; 3/preventive medicine. About 3000 LT patients in France are treated in 11 LT centers. Given the increased size of the LT recipient cohort, follow-up might be partially shared with peripheral centers. METHODS: This paper presents the suggestions of a working group of the SPLF (French-speaking respiratory medicine society) on possible modalities of shared follow-up. RESULTS: While the main LT center is tasked with centralizing follow-up, particularly the choice of optimal immunosuppression, an identified peripheral center (PC) may serve as an alternative to deal with acute events, comorbidities and routine assessment. Communication between the different centers should be free-flowing. Shared follow-up may be offered from the 3rd postoperative year to stable and consenting patients, whereas unstable and non-observant patients are poor candidates. CONCLUSION: These guidelines may serve as a reference for any pneumologist wishing to effectively contribute to follow-up, even and especially subsequent to lung transplant.

Lower-limb joint-coordination and coordination variability during gait in children with cerebral palsy.

BACKGROUND: Children with cerebral palsy present with poor motor control, altering their ability to perform tasks such as walking. Continuous relative phase analysis is a popular method to quantify motor control impairments via inter-joint coordination and coordination variability; however, it has not been explored in children with cerebral palsy. METHODS: 45 children with cerebral palsy and 45 typically developing children walked while fit with retroreflective markers. Continuous relative phase analysis for knee-hip and ankle-knee joint pairs quantified inter-joint coordination and coordination variability. The Gait Profile Score estimated gait pathology. Group differences were assessed with unpaired t-tests for coordination amplitude and variability (knee-hip, ankle-knee) across gait events. For the cerebral palsy group, correlations assessed the relation between the gait profile score and coordination metrics. FINDINGS: The cerebral palsy group showed more in-phase patterns for knee-hip coupling compared to the typically developing group (initial contact, loading response, mid-stance, terminal swing) (p ≤ 0.03). The cerebral palsy group showed lower knee-hip coordination variability (mid-stance, mid-swing) (p ≤ 0.037) and lower ankle-knee coordination variability (initial contact, loading response, terminal swing) (p < 0.001). The gait profile score correlated weakly to moderately (r = [0.323-0.472]), and negatively with the knee-hip inter-joint coordination (initial contact, loading response, mid-stance, terminal swing) (p ≤ 0.042). INTERPRETATION: Children with cerebral palsy showed a more in-phase gait strategy during challenging transitional gait cycle phases (beginning and end) and less flexible and adaptable motor behaviors. Moreover, the correlation between in-phase joint patterns and increased gait deviations (gait profile score) reinforces the relevance of coordination analysis to assess motor control impairment.

[Autoinflammatory diseases associated with RIPK1 mutations: A review of the literature]. / Revue de la littérature sur les maladies auto-inflammatoires associées aux mutations du gène RIPK1.

Autoinflammatory diseases related to RIPK1 mutations have been recently described. Two distinct clinical phenotypes have been reported and depend on the type and location of the mutation. When the mutation is recessive with loss of function, patients develop a combined phenotype of immune deficiency with recurrent bacterial and fungal infections and signs of early inflammatory bowel disease, non-erosive polyarthritis and growth retardation. On the other hand, when the mutation is dominant, gain of function, the manifestations are only auto-inflammatory with extensive lymphoproliferation, oral lesions such as aphthosis or ulcers, abdominal pain and hepatosplenomegaly. The mutations described for the dominant form affect only the cleavage site of caspase 8 and the clinical phenotype is called CRIA for Cleavage-Resistant RIPK1-Induced Autoinflammatory syndrome. The recessive form is severe and life-threatening requiring hematopoietic stem cell transplantation while the dominant form responds well to interleukin-6 receptor antagonists. Thus, RIPK1 mutations can induce various clinical manifestations with two distinct phenotypes. Although still rare, because of their recent description, these diseases can be suspected by an internist, in front of recurrent digestive features and will be increasingly diagnosed in the future through the integration of this gene in the diagnostic chips dedicated to autoinflammatory diseases and early inflammatory bowel diseases, using next generation sequencing.

Gait adaptations of individuals with cerebral palsy on irregular surfaces: A scoping review.

BACKGROUND: Individuals with cerebral palsy (CP) have a reduced ability to perform motor tasks such as walking. During daily walking, they are confronted with environmental constraints such as irregular surfaces (e.g., relief and uneven surfaces) which may require adaptations to maintain stability and avoid falls. Laboratory gait assessments are conventionally conducted under ideal conditions (e.g., regular and even surfaces) and may overlook subtle problems which may only present in challenging walking environments. Increased knowledge of adaptations to successfully navigate irregular surfaces may contribute to a better understanding of everyday walking barriers. RESEARCH QUESTION: This scoping review aims to describe gait adaptations to irregular surfaces in individuals with CP and contrast adaptations with those of healthy individuals. METHODS: This review followed the 6-stage Joanna Briggs Institute methodology and respected the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews statement. The MEDLINE, EMBASE, CINAHL, SPORTDiscus, and Web of Science databases were searched on March 2021. RESULTS: The research strategy identified 1616 studies published between 2014 and 2020, of which 10 were included after abstract and full-text screening. This review reported on 152 individuals with CP (diplegia: n = 117, hemiplegia: n = 35) and 159 healthy individuals. The included studies focused on spatial-temporal, kinematic, kinetic, and muscle activity parameters over relief, inclined, and staircase surfaces. 7/10 studies were conducted in laboratories, often using surfaces that are not representative of the real-world. The results suggest that for individuals with CP, adaptations on irregular surfaces differ from flat surface walking and across CP subtype. Moreover, individuals with CP present with typical and pathology-specific adaptations to irregular surfaces compared to healthy individuals. SIGNIFICANCE: This review highlights the clinical and research interest of focusing future studies on more ecologically valid data collection approaches and provides important recommendations to overcome research gaps in the existing literature.

Homing of granulocytes transfused in perineal cellulitis in a RAC2 deficiency child monitored by chimerism quantification methods.

Granulocyte transfusions can be used to treat infections when appropriate antibiotic and anti-fungal drugs have proved ineffective. We report a case of clinical efficacy of 18 granulocyte transfusions for perineal cellulitis in a 3-week-old RAC2-deficient newborn girl. This RAC2 deficiency is characterized by severe phagocyte defects including defective superoxide formation, adhesion and chemotaxis deficiency. In order to check that the granulocytes infused had reached the lesion site, the infiltration of donor cells was quantified by next generation sequencing (NGS) and digital droplet PCR after identification of DNA specific markers for donor and patient. After the 6th transfusion, 20% circulating cells and 55% cells isolated by swabbing from the lesion site were donor cells, confirming the infiltration of polynuclear cells in the perineal lesion site. These results strengthen the indication of granulocyte transfusions, and its continuation until the healing process of the skin is complete. This clinical case report highlights the potential efficacy of granulocyte transfusions to treat skin lesions in RAC2-deficient patients, a process which could be monitored by molecular biology tools for chimerism quantification.

Long-term safety and efficacy of lentiviral hematopoietic stem/progenitor cell gene therapy for Wiskott-Aldrich syndrome.

Patients with Wiskott-Aldrich syndrome (WAS) lacking a human leukocyte antigen-matched donor may benefit from gene therapy through the provision of gene-corrected, autologous hematopoietic stem/progenitor cells. Here, we present comprehensive, long-term follow-up results (median follow-up, 7.6 years) (phase I/II trial no. NCT02333760 ) for eight patients with WAS having undergone phase I/II lentiviral vector-based gene therapy trials (nos. NCT01347346 and NCT01347242 ), with a focus on thrombocytopenia and autoimmunity. Primary outcomes of the long-term study were to establish clinical and biological safety, efficacy and tolerability by evaluating the incidence and type of serious adverse events and clinical status and biological parameters including lentiviral genomic integration sites in different cell subpopulations from 3 years to 15 years after gene therapy. Secondary outcomes included monitoring the need for additional treatment and T cell repertoire diversity. An interim analysis shows that the study meets the primary outcome criteria tested given that the gene-corrected cells engrafted stably, and no serious treatment-associated adverse events occurred. Overall, severe infections and eczema resolved. Autoimmune disorders and bleeding episodes were significantly less frequent, despite only partial correction of the platelet compartment. The results suggest that lentiviral gene therapy provides sustained clinical benefits for patients with WAS.

Heterogeneous Microscopic Dynamics of Intruded Water in a Superhydrophobic Nanoconfinement: Neutron Scattering and Molecular Modeling.

With their strong confining porosity and versatile surface chemistry, zeolitic imidazolate frameworks-including the prototypical ZIF-8-display exceptional properties for various applications. In particular, the forced intrusion of water at high pressure (∼25 MPa) into ZIF-8 nanopores is of interest for energy storage. Such a system reveals also ideal to study experimentally water dynamics and thermodynamics in an ultrahydrophobic confinement. Here, we report on neutron scattering experiments to probe the molecular dynamics of water within ZIF-8 nanopores under high pressure up to 38 MPa. In addition to an overall confinement-induced slowing down, we provide evidence for strong dynamical heterogeneities with different underlying molecular dynamics. Using complementary molecular simulations, these heterogeneities are found to correspond to different microscopic mechanisms inherent to vicinal molecules located in strongly adsorbing sites (ligands) and other molecules nanoconfined in the cavity center. These findings unveil a complex microscopic dynamics, which results from the combination of surface residence times and exchanges between the cavity surface and center.

Dynamics of heterogeneous wetting in periodic hybrid nanopores.

We present experimental and theoretical results concerning the forced filling and spontaneous drying of hydrophobic cylindrical mesopores in the dynamical regime. Pores are structured with organic/inorganic moieties responsible for a periodicity of the surface energy along their axis. We find that the forced intrusion of water in these hydrophobic pores presents a slow dynamics: the intrusion pressure decreases as the logarithm of the intrusion time. We find that this slow dynamics is well described quantitatively by a classical model of activated wetting at the nanoscale, giving access to the structural length scales and surface energies of the mesoporous material.

Investigation of primary immune deficiency after severe bacterial infection in children: A population-based study in western France.

BACKGROUND: Infectious diseases are still an important cause of morbidity and mortality in high-income countries and may preferentially affect predisposed children, especially immunocompromised children. We aimed to evaluate the frequency of recommended immunological tests in children with community-onset severe bacterial infection (COSBI) admitted to a pediatric intensive care unit. We also assessed the frequency and described the typology of diagnosed primary immune deficiency (PID). METHODS: We conducted a retrospective observational epidemiological study in six university hospitals in western France. All children from 1 month to 16 years of age admitted to hospital for bacterial meningitis, purpura fulminans, or meningococcal disease between August 2009 and January 2014 were included. We analyzed the frequency, type, and results of the immunological tests performed on children with meningitis, purpura fulminans, or a meningococcemia episode. RESULTS: Among the 143 children included (144 episodes), 84 (59%) and 60 (41%) had bacterial meningitis and purpura fulminans or meningococcemia, respectively: 72 (50%) had immunological tests and 8% had a complete immunological investigation as recommended. Among the 72 children examined for PID, 11 (15%) had at least one anomaly in the immunological test results. Two children had a diagnosis of PID (one with C2 deficit and the other with C8 deficit) and seven other children had possible PID. Thus, the prevalence of a definite or possible diagnosis of PID was 12% among the children examined. CONCLUSION: PID is rarely investigated after COSBI. We raise awareness of the need for immunological investigations after a severe infection requiring PICU admission.

Evaluation of timolol maleate gel for management of hard-to-heal chronic venous leg ulcers. Phase II randomised-controlled study.

BACKGROUND: Venous leg ulcers (VLUs) often take a very long time to heal. Timolol maleate has been reported as displaying efficacy in healing of VLUs. OBJECTIVES: To evaluate the efficacy of timolol maleate gel in the management of hard-to-heal VLUs and to assess its safety as a topical agent during 12 weeks of use in combination with conventional treatment. METHODS: A prospective, phase-II randomised-controlled trial with a sample size based on Fleming's one-stage design (P0=0.25, P1=0.45, alpha=0.1, beta=0.2) was planned. Patients with VLUs present for ≥24 weeks and with ≥50% granulation tissue were included. One drop of sustained-release timolol gel (Timoptol® LP 0.5%, Santen, Tampere, Finland) per 6 cm2 VLU area was applied every 2 days for 12 weeks in timolol-treated patients, as adjuvant therapy to the standard care protocol (interface dressing and multilayer venous compression). Controls received standard care alone. The primary endpoint was to obtain ≥40% reduction in ulcer area at week 12 (W12). RESULTS: Forty-three patients were randomised to the study, with 40 receiving at least one treatment and included in the analysis: 21 timolol-treated patients and 19 controls (females: 70%; median age: 72.5 [range 35-93] years). At W12, ≥40% ulcer-area reduction was achieved in 14/21 (67%) timolol-treated patients vs. 6/19 (32%) controls. No serious adverse events occurred. Local wound infections not requiring systemic antibiotics occurred in 5 cases in the timolol group and in one case in the controls. CONCLUSIONS: These results support the benefit and safety of using timolol maleate to manage hard-to-heal VLUs, but confirmation is required in a larger multicentre randomised phase-III study.

Effects of a dietary supplement enriched in palmitoleic acid on fatty acid composition of follicular fluid, granulosa cell metabolism, and oocyte developmental capacity in early lactation dairy cows.

In high-yielding dairy cows, some fertility traits can be influenced by the fatty acid (FA) composition of the follicular fluid during early lactation. The first objective of the current study was to evaluate the potential of dietary supplements enriched in specific FA to influence the FA composition of follicular fluid lipid classes in early lactation dairy cows. The second objective was to determine the influence of the resulting follicular fluid FA composition on the folliculogenesis, lipid and energy metabolism of granulosa cells, as well as oocyte quality and embryo development. Twenty Holstein multiparous cows in late gestation were randomly assigned to 200 g/d of FA supplements enriched in (1) palmitic acid (control treatment; 82% 16:0; PA) in the rumen or (2) palmitoleic acid (sea buckthorn oil; 27% cis-9 16:1, 28% 16:0, 22% cis-9 18:1, and 11% cis-9,cis-12 18:2; SBT) in the abomasum. The treatment period ranged from 20 ± 5 d precalving to 67 ± 2 d postcalving. Cumulus-oocyte complexes, granulosa cells, and follicular fluid were recovered from 2 sequential sessions of ovum pick-up (OPU-1 and OPU-2) at 46 and 67 ± 2 d postcalving (mean ± standard deviation). On the same days, blood samples were collected. Milk performance was recorded, and feed and milk samples were collected from d 8 to 10 ± 3 (onset of lactation), d 35 to 37 ± 2 (before OPU-1), and d 63 to 65 ± 2 (before OPU-2). Treatments did not affect milk yield or fat concentration throughout the experimental trial. Compared with PA, SBT increased the cis-9 16:1 concentration in milk fat, in plasma esterified lipid classes (phospholipids, cholesterol esters, and triacylglycerols), and in follicular fluid phospholipids and cholesterol esters at OPU-1. Abundance of mRNA for stearoyl-CoA desaturase 1 and 5, and perilipin 2 in granulosa cells was not different between treatments, but an increase in the level of stearoyl-CoA desaturase 5 was observed between the 2 OPU periods. Treatments did not affect oocyte quality and developmental capacity or embryo lipid metabolism when cultivated in vitro. These results suggest that limited modifications in the FA composition of the oocyte microenvironment via dietary lipid supplements enriched in specific FA had no major effects on granulosa cell metabolism and oocyte developmental capacity in early lactation cows.