Amino acid 138 in the HA of a H3N2 subtype influenza A virus increases affinity for the lower respiratory tract and alveolar macrophages in pigs.

Influenza A virus (FLUAV) infects a wide range of hosts and human-to-swine spillover events are frequently reported. However, only a few of these human viruses have become established in pigs and the host barriers and molecular mechanisms driving adaptation to the swine host remain poorly understood. We previously found that infection of pigs with a 2:6 reassortant virus (hVIC/11) containing the hemagglutinin (HA) and neuraminidase (NA) gene segments from the human strain A/Victoria/361/2011 (H3N2) and internal gene segments of an endemic swine strain (sOH/04) resulted in a fixed amino acid substitution in the HA (A138S, mature H3 HA numbering). In silico analysis revealed that S138 became predominant among swine H3N2 virus sequences deposited in public databases, while 138A predominates in human isolates. To understand the role of the HA A138S substitution in the adaptation of a human-origin FLUAV HA to swine, we infected pigs with the hVIC/11A138S mutant and analyzed pathogenesis and transmission compared to hVIC/11 and sOH/04. Our results showed that the hVIC/11A138S virus had an intermediary pathogenesis between hVIC/11 and sOH/04. The hVIC/11A138S infected the upper respiratory tract, right caudal, and both cranial lobes while hVIC/11 was only detected in nose and trachea samples. Viruses induced a distinct expression pattern of various pro-inflammatory cytokines such as IL-8, TNF-α, and IFN-ß. Flow cytometric analysis of lung samples revealed a significant reduction of porcine alveolar macrophages (PAMs) in hVIC/11A138S-infected pigs compared to hVIC/11 while a MHCIIlowCD163neg population was increased. The hVIC/11A138S showed a higher affinity for PAMs than hVIC/11, noted as an increase of infected PAMs in bronchoalveolar lavage fluid (BALF), and showed no differences in the percentage of HA-positive PAMs compared to sOH/04. This increased infection of PAMs led to an increase of granulocyte-monocyte colony-stimulating factor (GM-CSF) stimulation but a reduced expression of peroxisome proliferator-activated receptor gamma (PPARγ) in the sOH/04-infected group. Analysis using the PAM cell line 3D4/21 revealed that the A138S substitution improved replication and apoptosis induction in this cell type compared to hVIC/11 but at lower levels than sOH/04. Overall, our study indicates that adaptation of human viruses to the swine host involves an increased affinity for the lower respiratory tract and alveolar macrophages.

Impact of sex on humoral immunity with live influenza B virus vaccines in mice.

Influenza B virus (FLUBV) poses a significant infectious threat, with frequent vaccine mismatch limiting its effectiveness. Our previous work investigated the safety and efficacy of modified live attenuated FLUBV vaccines with rearranged genomes (FluB-RAM and FluB-RANS) or a temperature-sensitive PB1 segment with a C-terminal HA tag (FluB-att). In this study, we compared the immune responses of female and male DBA/2J mice vaccinated with these vaccines, including versions containing a chimeric HA segment with an N-terminal IgA-inducing peptide (IGIP). Importantly, both recombinant viruses with and without IGIP remained genetically stable during egg passage. We found that introducing IGIP strengthened vaccine attenuation, particularly for FluB-RAM/IGIP. Prime-boost vaccination completely protected mice against lethal challenge with a homologous FLUBV strain. Notably, recombinant viruses induced robust neutralizing antibody responses (hemagglutination inhibition titers ≥40) alongside antibodies against NA and NP. Interestingly, female mice displayed a consistent trend of enhanced humoral and cross-reactive IgG and IgA responses against HA, NA, and NP compared to male counterparts, regardless of the vaccine used. However, the presence of IGIP generally led to lower anti-HA responses but higher anti-NA and anti-NP responses, particularly of the IgA isotype. These trends were further reflected in mucosal and serological responses two weeks after challenge, with clear distinctions based on sex, vaccine backbone, and IGIP inclusion. These findings hold significant promise for advancing the development of universal influenza vaccines.

FLUAV RAM-IGIP: A modified live influenza virus vaccine that enhances humoral and mucosal responses against influenza.

Current influenza A vaccines fall short, leaving both humans and animals vulnerable. To address this issue, we have developed attenuated modified live virus (MLV) vaccines against influenza using genome rearrangement techniques targeting the internal gene segments of FLUAV. The rearranged M2 (RAM) strategy involves cloning the M2 ORF downstream of the PB1 ORF in segment 2 and incorporating multiple early stop codons within the M2 ORF in segment 7. Additionally, the IgA-inducing protein (IGIP) coding region was inserted into the HA segment to further attenuate the virus and enhance protective mucosal responses. RAM-IGIP viruses exhibit similar growth rates to wild type (WT) viruses in vitro and remain stable during multiple passages in cells and embryonated eggs. The safety, immunogenicity, and protective efficacy of the RAM-IGIP MLV vaccine against the prototypical 2009 pandemic H1N1 strain A/California/04/2009 (H1N1) (Ca/04) were evaluated in Balb/c mice and compared to a prototypic cold-adapted live attenuated virus vaccine. The results demonstrate that the RAM-IGIP virus exhibits attenuated virulence in vivo. Mice vaccinated with RAM-IGIP and subsequently challenged with an aggressive lethal dose of the Ca/04 strain exhibited complete protection. Analysis of the humoral immune response revealed that the inclusion of IGIP enhanced the production of neutralizing antibodies and augmented the antibody-dependent cellular cytotoxicity response. Similarly, the RAM-IGIP potentiated the mucosal immune response against various FLUAV subtypes. Moreover, increased antibodies against NP and NA responses were observed. These findings support the development of MLVs utilizing genome rearrangement strategies in conjunction with the incorporation of immunomodulators. IMPORTANCE: Current influenza vaccines offer suboptimal protection, leaving both humans and animals vulnerable. Our novel attenuated MLV vaccine, built by rearranging FLUAV genome segments and incorporating the IgA-inducing protein, shows promising results. This RAM-IGIP vaccine exhibits safe attenuation, robust immune responses, and complete protection against lethal viral challenge in mice. Its ability to stimulate broad-spectrum humoral and mucosal immunity against diverse FLUAV subtypes makes it a highly promising candidate for improved influenza vaccines.

Heterogeneity of Tasks and Outcome Measures in Dual Tasking Studies in Children With Cerebral Palsy: A Scoping Review.

OBJECTIVE: The aims of this scoping review are to examine the available literature regarding dual tasking in children with cerebral palsy (CP) and to identify and categorize both the motor and cognitive tasks and outcome measures used primarily through the International Classification of Functioning, Disability, and Health model. METHODS: Five electronic databases were searched. Studies were included if they: (1) were published in English; (2) included at least 1 group of children or adolescents with a diagnosis of CP; (3) assessed dual tasking as part of the study; (4) reported the method for performing the dual task; and (5) reported the outcome measures utilized. RESULTS: Twenty-three studies with 439 children with CP were included. All studies utilized motor activities as the primary task, including walking, balance, and a functional transition. Motor secondary tasks occurred in 10 studies, cognitive secondary tasks in 12 studies, and 1 study used both. Forty-one outcome measures over 23 studies assessed the body structure and function domain, 7 measures over 6 studies assessed activity limitations, and 2 outcomes over 2 studies assessed participation. CONCLUSION: The 23 included studies demonstrated heterogeneity in the age and function of participants, secondary tasks, and outcome measures. Future studies on dual tasking in children with CP should consider the difficulty of the primary motor or cognitive task and compare secondary tasks to establish this contribution to motor performance. Studies should incorporate activity and participation measures to assess meaningful functional outcomes. IMPACT: Children with CP experience challenges when exposed to dual task situations. This scoping review highlights the importance of considering multiple factors when designing dual tasking studies involving children with CP to facilitate results translation, improved participation, and enhanced function. Similarly, studies should utilize activity and participation outcomes to assess quality of life.

Use of Reverse Genetics for the Generation of Recombinant Influenza Viruses Carrying Nanoluciferase.

Influenza A (FLUAV) and influenza B (FLUBV) viruses are human and/or animal pathogens widely studied due to their importance to public health and animal production. Both FLUAV and FLUBV possess a genome composed of eight viral gene segments. For reverse genetics of influenza viruses, transcription of the mRNA for the viral proteins is typically done from a plasmid encoding an RNA polymerase II (pol II) promoter element upstream of cloned viral cDNA and expressed like host mRNA. On the other side, the synthesis of the negative-sense, single-stranded, uncapped vRNAs can be accomplished by the host's RNA polymerase I (pol I). The reverse genetics for influenza has allowed the manipulation of influenza genomes incorporating heterogeneous sequences into different segments of the influenza genome, such as reporter genes. In this chapter, we outline the protocol from the generation of reverse genetic plasmid that can be applied for the cloning of any of the segments of FLUAV or FLUBV. Furthermore, we describe a protocol for generating FLUAV or FLUBV recombinant viruses carrying Nanoluciferase (NLuc) in the PB1 gene using reverse genetics. Finally, we delineate a microneutralization protocol using FLUAV-NLuc or FLUBV-NLuc viruses optimized for the use of antibodies from different sources (mice, ferrets, avian, etc.), which provides a more sensitive, reliable, and avidity-independent method to assess the presence of neutralizing antibodies against FLUAV or FLUBV.

Concurrent and predictive validity of the Alberta Infant Motor Scale and the Peabody Developmental Motor Scales-2 administered to infants born preterm in Norway.

BACKGROUND: The correlation between the Alberta Infant Motor Scale (AIMS) and the Peabody Developmental Motor Scales-2 (PDMS-2) has not previously been assessed in Norwegian infants. Our purpose was to investigate the concurrent validity of the AIMS and the PDMS-2 in a group of high-risk infants, and to investigate the predictive validity of the two tests for atypical motor function at 24 months post term age (PTA). METHODS: This is a retrospective study of the AIMS and the PDMS-2 administered to infants born preterm with gestational age ≤ 32 weeks (n = 139) who had participated in a randomized controlled trial of early parent-administered physiotherapy. The infants' motor development had been assessed using the AIMS and the PDMS-2 at 6- and 12-months. The primary outcome was PDMS-2 at 24-months PTA. To explore the correlation between the two tests we used Spearman's rho. Bland Altman plots were used to detect if there were systematic differences between the measurements. Receiver-operating characteristics curves were used to calculate area under the curve as an estimate of diagnostic accuracy of the AIMS and the PDMS- with respect to motor outcome at 24 months. RESULTS: The correlation between the AIMS and the PDMS-2 (total motor and locomotion subscale), at 6 months, was r = 0.44 and r = 0.76, and at 12 months r = 0.56 and r = 0.80 respectively. The predictive validity for atypical motor function at 24 months, assessed using the area under the curve at 6- and at 12- months, was for the AIMS 0.87 and 0.86, respectively, and for the PDMS-2 locomotion subscale 0.82 and 0.76 respectively. CONCLUSION: The correlation between the AIMS and the PDMS-2 locomotion subscale, at 6- and 12- months PTA, was good to excellent in a group of infants born preterm in Norway. And the AIMS and the locomotion subscale of the PDMS-2 were equally good predictors for atypical motor outcomes at 24 months PTA. These findings indicate that the AIMS and the locomotion subscale of the PDM-2, could be used interchangeable when assessing motor development in infants at 6- or 12 months of age. TRIAL REGISTRATION: ClinicalTrials.gov NCT01089296.

Motor control and skill acquisition in pediatric physical therapy: an enactive proposal.

Theories of motor control and skill acquisition strongly influence and guide various fields of clinical practice. In last decades, changes in theoretical frameworks related to the conceptualization of brain plasticity, functional structures within the child, and environment have led to a revision of therapy approaches progressing from therapist-driven to child-initiated approaches. Even though theoretical frameworks and clinical practice are closely linked to the child's body, the profession has paid less attention to theories concerning the body's role and status in interpersonal relationships when fostering motor control and skill acquisition in children. In this theoretical paper we discuss the theoretical frameworks of motor control and skill acquisition that currently guide clinical practice. Through highlighting valuable contributions of these theories, we explore theoretical and practical benefits pediatric physical therapy can acquire by taking an enactive approach as a means to bring the child as a subject into focus. We rely on enactive concepts of embodiment, autonomy, and participatory sense-making in our exploration to provide an extended understanding of motor control and skill acquisition shaping our beliefs about what counts in therapeutic encounters in pediatric physical therapy.

Antigenic mapping of the hemagglutinin of the H9 subtype influenza A viruses using sera from Japanese quail (Coturnix c. japonica).

IMPORTANCE: Determining the relevant amino acids involved in antigenic drift on the surface protein hemagglutinin (HA) is critical to understand influenza virus evolution and efficient assessment of vaccine strains relative to current circulating strains. We used antigenic cartography to generate an antigenic map of the H9 hemagglutinin (HA) using sera produced in one of the most relevant minor poultry species, Japanese quail. Key antigenic positions were identified and tested to confirm their impact on the antigenic profile. This work provides a better understanding of the antigenic diversity of the H9 HA as it relates to reactivity to quail sera and will facilitate a rational approach for selecting more efficacious vaccines against poultry-origin H9 influenza viruses in minor poultry species.

Association between post-operative hPG80 (circulating progastrin) detectable level and worse prognosis in glioblastoma.

BACKGROUND: Patients with glioblastomas have a dismal prognosis, and there is no circulating predictive or prognostic biomarker. Circulating progastrin, hPG80, is a tumor-promoting peptide present in the blood of patients with various cancers that has been shown to have prognostic value. We evaluated the prognostic value of plasma hPG80 in patients with isocitrate dehydrogenase-wild type glioblastoma after surgery. PATIENTS AND METHODS: A multicentric retrospective study in glioblastoma patients treated with standard radio-chemotherapy was conducted. The hPG80 levels were measured in plasma EDTA samples collected after surgery with an ELISA DxPG80.lab kit (Biodena Care, Montpellier, France), which has a detection threshold of 1.2 pM. The relationship between post-operative hPG80 plasma levels, in combination with other known prognostic factors, and patients' progression-free survival (PFS) and overall survival (OS) was evaluated. RESULTS: Sixty-nine patients were assessable. Plasma samples were collected after tumor biopsy (B), partial resection (PR), and complete resection (CR) for 22, 25, and 22 patients, respectively. At a median concentration of 5.37 pM (interquartile range 0.00-13.90 pM), hPG80 was detected in 48 (70%) patients (hPG80+). CR was associated with significant lower values of hPG80 levels: the median value was 0.7 versus 9.1 pM for PR (P = 0.02) and 8.3 pM for B (P = 0.004). The hPG80 detection rate was also significantly lower: 50% (CR) versus 72% (PR) versus 86% (B) (P = 0.005). The median follow-up was 39 months [22.4 months-not reached]. hPG80 post-operative detection was associated with numerically shorter PFS (6.4 versus 9.4 months, P = 0.13) and OS (14.5 versus 20.9 months, P = 0.11). In multivariate analysis, hPG80 was a prognostic factor for OS (P = 0.034). CONCLUSIONS: Circulating hPG80 could serve as a new prognostic biomarker after surgery in patients with glioblastoma treated with radio-chemotherapy.

A systematic synthesis of qualitative studies on parents' experiences of participating in early intervention programs with their infant born preterm.

Early intervention programs involving both the parent and the infant born preterm have demonstrated positive effects on developmental outcomes for the children. However, studies have also shown that parental engagement and adherence when implementing intervention programs can be challenging. The aim of this review was to provide a comprehensive description and new insights into key messages gleaned from the parent reports on participating in early intervention with their infant born preterm; knowledge vital to facilitate implementation of early interventions into clinical practice when using a model of direct parent involvement. Early intervention is broadly defined as a multi-interdisciplinary field provided to children from birth to five years of age to foster child health, wellbeing, development, adapting parenting and family function. For this systematic synthesis we define early intervention as programs with specific activities completed with the infant during the first year after birth. We assembled qualitative interview studies on parents' experiences with participation in early intervention and applied Malterud's qualitative systematic meta-synthesis to synthesize and translate the original findings across studies. In the analysis we applied enactive concepts of embodiment, autonomy, participatory sensemaking, and agency. 10 qualitative studies were identified and included. The systematic synthesis reveals how parents' successful and meaningful participation in early intervention programs were facilitated by their "active embodied doing." The "embodied doing" appeared as the basis for the parents' sense-making processes, development of confidence, and the ability for parents to see new possibilities for actions within themselves, with and in the child. In that respect, a perception of mutuality in the interaction between parent, infant and interventionist was central. Consequently, an important consideration when implementing early intervention into clinical practice is to promote embodied parent-infant interactions as well as trust between the parent and the interventionist.

Eating and Drinking Ability Classification System to detect aspiration risk in children with cerebral palsy: a validation study.

This prospective study has two aims. The first aim is to assess the concurrent validity of the Eating and Drinking Ability Classification System (EDACS) as a means of identifying aspiration risk in children with cerebral palsy by using the Pediatric version of the Eating Assessment Tool (PEDI-EAT-10) as the reference test. The second aim is to investigate the relationship between the aspiration and non-aspiration groups using both the EDACS and the PEDI-EAT-10. Data were collected and analyzed from the EDACS and PEDI-EAT-10 using a convenience sample of 131 children with cerebral palsy and feeding problems (77 males, 54 females; median age 4.4 years [IQR 2.5 years]). Risk of aspiration was identified in 118 individuals using the PEDI-EAT-10 scores of ≥ 5 points. The EDACS proved to be a valid tool in identifying aspiration risk in children who are classified in EDACS levels III-V. There was a significant correlation between the EDACS and PEDI-EAT-10 (rs = 0.597, p < 0.001). The EDACS had 78% (95% CI = 71-86%) sensitivity and 92% (95% CI = 88-97%) specificity in identifying aspiration risk a positive predictive value of 0.99, a negative predictive value of 0.32, a positive likelihood ratio of 9.75, and a negative likelihood ratio of 0.24.   Conclusion: The EDACS is a useful clinical tool to identify aspiration risk in children with cerebral palsy. Children in EDACS levels III to V are at risk of aspiration. As time permits, we recommend the use of both tools, the EDACS and the PEDI-EAT-10, when making decisions regarding referral for an instrumented swallowing study. What is Known: • Approximately 50% of children with cerebral palsy have dysphagia. • The Eating and Drinking Ability Classification System (EDACS) can be used to classify eating and drinking efficiency and safety in children with cerebral palsy. What is New: • Based on ROC analysis, EDACS demonstrates sensitivity of 78% and specificity of 92% in clinical identification of aspiration risk. • The combined use of the EDACS and the Pediatric version of the Eating Assessment Tool is recommended to make decisions about referral for an instrumented swallow study.

Epistasis reduces fitness costs of influenza A virus escape from stem-binding antibodies.

The hemagglutinin (HA) stem region is a major target of universal influenza vaccine efforts owing to the presence of highly conserved epitopes across multiple influenza A virus (IAV) strains and subtypes. To explore the potential impact of vaccine-induced immunity targeting the HA stem, we examined the fitness effects of viral escape from stem-binding broadly neutralizing antibodies (stem-bnAbs). Recombinant viruses containing each individual antibody escape substitution showed diminished replication compared to wild-type virus, indicating that stem-bnAb escape incurred fitness costs. A second-site mutation in the HA head domain (N129D; H1 numbering) reduced the fitness effects observed in primary cell cultures and likely enabled the selection of escape mutations. Functionally, this putative permissive mutation increased HA avidity for its receptor. These results suggest a mechanism of epistasis in IAV, wherein modulating the efficiency of attachment eases evolutionary constraints imposed by the requirement for membrane fusion. Taken together, the data indicate that viral escape from stem-bnAbs is costly but highlights the potential for epistatic interactions to enable evolution within the functionally constrained HA stem domain.

Hospital characteristics associated with nurse staffing during labor and birth: Inequities for the most vulnerable maternity patients.

BACKGROUND: Evidence is limited on nurse staffing in maternity units. PURPOSE: To estimate the relationship between hospital characteristics and adherence with Association of Women's Health, Obstetric and Neonatal Nurses nurse staffing guidelines. METHODS: We enrolled 3,471 registered nurses in a cross-sectional survey and obtained hospital characteristics from the 2018 American Hospital Association Annual Survey. We used mixed-effects linear regression models to estimate associations between hospital characteristics and staffing guideline adherence. FINDINGS: Overall, nurses reported strong adherence to AWHONN staffing guidelines (rated frequently or always met by ≥80% of respondents) in their hospitals. Higher birth volume, having a neonatal intensive care unit, teaching status, and higher percentage of births paid by Medicaid were all associated with lower mean guideline adherence scores. DISCUSSION AND CONCLUSIONS: Important gaps in staffing were reported more frequently at hospitals serving patients more likely to have medical or obstetric complications, leaving the most vulnerable patients at risk.

Characterizing a century of genetic diversity and contemporary antigenic diversity of N1 neuraminidase in influenza A virus from North American swine.

Influenza A viruses (IAVs) of the H1N1 classical swine lineage became endemic in North American swine following the 1918 pandemic. Additional human-to-swine transmission events after 1918, and a spillover of H1 viruses from wild birds in Europe, potentiated a rapid increase in genomic diversity via reassortment between introductions and the endemic classical swine lineage. To determine mechanisms affecting reassortment and evolution, we conducted a phylogenetic analysis of N1 and paired HA swine IAV genes in North America between 1930 and 2020. We described fourteen N1 clades within the N1 Eurasian avian lineage (including the N1 pandemic clade), the N1 classical swine lineage, and the N1 human seasonal lineage. Seven N1 genetic clades had evidence for contemporary circulation. To assess antigenic drift associated with N1 genetic diversity, we generated a panel of representative swine N1 antisera and quantified the antigenic distance between wild-type viruses using enzyme-linked lectin assays and antigenic cartography. Within the N1 genes, the antigenic similarity was variable and reflected shared evolutionary history. Sustained circulation and evolution of N1 genes in swine had resulted in a significant antigenic distance between the N1 pandemic clade and the classical swine lineage. Between 2010 and 2020, N1 clades and N1-HA pairings fluctuated in detection frequency across North America, with hotspots of diversity generally appearing and disappearing within 2 years. We also identified frequent N1-HA reassortment events (n = 36), which were rarely sustained (n = 6) and sometimes also concomitant with the emergence of new N1 genetic clades (n = 3). These data form a baseline from which we can identify N1 clades that expand in range or genetic diversity that may impact viral phenotypes or vaccine immunity and subsequently the health of North American swine.

Linking Patient Safety Climate With Missed Nursing Care in Labor and Delivery Units: Findings From the LaborRNs Survey.

OBJECTIVE: This study aimed to explore the association of nurses' perceptions of patient safety climate with missed nursing care in labor and delivery (L&D) units. METHODS: We recruited nurse respondents via email distribution of an electronic survey between February 2018 and July 2019. Hospitals with L&D units were recruited from states with projected availability of 2018 state inpatient data in the United States. Measures included the Safety Attitudes Questionnaire Safety Climate Subscale and the Perinatal Missed Care Survey. We estimated the relationship between safety climate and missed care using Kruskal-Wallis tests and mixed-effects linear regression. RESULTS: The analytic sample included 3429 L&D registered nurses from 253 hospitals (response rate, 35%). A majority of respondents (65.7%) reported a perception of good safety climate in their units, with a mean score of 4.12 (±0.73) out of 5. The mean number of aspects of care occasionally, frequently, or always missed on respondents' units was 11.04 (±6.99) out of 25. χ2 Tests showed that six mostly commonly missed aspects of care (e.g., timely documentation) and three reasons for missed care (communications, material resources, and labor resources) were associated with safety climate groups ( P < 0.001). The adjusted mixed-effects model identified a significant association between better nurse-perceived safety climate and less missed care ( ß = -2.65; 95% confidence interval, -2.97 to -2.34; P < 0.001) after controlling for years of experience and highest nursing education. CONCLUSIONS: Our findings suggest that improving safety climate-for example, through better teamwork and communication-may improve nursing care quality during labor and birth through decreasing missed nursing care. Conversely, it is also possible that strategies to reduce missed care-such as staffing improvements-may improve safety climate.

Assessing sensory processing differences in children with idiopathic toe walking: A pilot study.

Idiopathic toe-walking (ITW) refers to persistent walking without heel contact for unknown reasons. An underexplored area is the relationship of sensory processing to ITW. This study presents methods to assess sensory differences in individuals with ITW and summarizes results from a pilot testing of the measures. This pilot study included nine children and one young adult with ITW. Ten age-matched controls were recruited to provide a comparison group when norms were not available in the literature. The measures included in this study were as follows: sensory questionnaires; electrodermal activity response to sensory stimuli; monofilaments; biothesiometer; gait on different surfaces; NeuroCom® SMART Balance Master® Sensory Organization Test and Adaptation Test; and ankle position matching. All study procedures were completed in about 3 hours. Children as young as 4 years were able to complete the measures. We observed overall differences in sensory processing, specifically, higher Sensory Processing Measure scores (p = .011), higher resting electrodermal activity (p = .012), increases in heel-toe walking on novel surfaces (p = .034), and more falls with balance perturbation (p = .007) in individuals with ITW. A subset of individuals also showed tactile hyposensitivity (5 out of 10 in the ITW group) and poor equilibrium scores in the Sensory Organization Test (4 out of 9 in the ITW group, 1 unable to complete the test). Our results confirmed the heterogeneity in the etiology of ITW. We propose that further testing in sensory modulation, tactile processing, and vestibular processing is needed to fully explore the impact of sensory processing on children with ITW.

Can items on the TIMP aide in determining the motor performance of children with severe cerebral palsy? A pilot study.

BACKGROUND: Assessing the functional level of children with severe cerebral palsy (CP) requires sensitive tools. In this study, an 'assessment tool' was developed based on the Test of Infant Motor Performance (TIMP) for this population and the reliability and validity evaluated. METHODS: Five physical therapists administered the 'assessment tool' to six children (3-6 years old with a diagnosis of CP, GMFCS Level V). Subtest I of the Gross Motor Function Measure (GMFM-88) was also administered. Intra- and inter-rater reliability were assessed, and the concurrent validity between the 'assessment tool' and GMFM-88 calculated. RESULTS: The intra-rater reliability, a comparison of the total scores on the 'assessment tool' (live test) and the videotaped rescoring of the same test one month later showed consistency among four of the five therapists (ICC = 0.7545 to 0.979). The inter-rater reliability varied on some of the items but the total score on the 'assessment tool' showed good reliability (ICC2,5 0.816). Scores of children with dyskinesia were less stable. The Spearman's rank correlation coefficient was not significant. Therapists provided recommendations for item revisions. CONCLUSION: Further development of an 'assessment tool' appears justified; a larger study using a version with revised administration guidelines and items should be undertaken to re-verify the psychometrics properties of the 'assessment tool.'

The Significance of Touch in Pediatric Physiotherapy.

Change in theoretical framework over the last decades and recent research in pediatric physiotherapy, has created a debate surrounding therapeutic touch. What is the role of or is there a need for handling and hands-on facilitated guidance (facilitation)? Does it limit and/or interfere with children's learning and development? It is frequently argued that therapeutic touch represents a passive and/or static approach that restricts disabled children's participation during interaction and activity in clinical encounters leading to decreased home, school and community participation. Touch may even appear as coercive and controlling. In this context, therapeutic touch is largely associated with physical hands-on activities. However, therapeutic touch can also be understood as an intersubjective phenomenon that arises from a deep connection between movement, perception, and action. We believe the significance of therapeutic touch and its impact on physiotherapy for children has not been considered from this broader, holistic perspective. In this theoretical paper, we will apply enactive concepts of embodiment, sensory-motor agency, coordination, and emergence to explore the concept and importance of touch in physiotherapists' clinical face-to face encounters with children. We will frame the discussion within the context of the typical sensorimotor development of children from the fetal stage to birth on and into adulthood. Moreover, we will rely on biological, physiological, and phenomenological insights to provide an extended understanding of the importance of touch and the significance of touch in clinical practice.

Pathobiology and dysbiosis of the respiratory and intestinal microbiota in 14 months old Golden Syrian hamsters infected with SARS-CoV-2.

The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS2) affected the geriatric population. Among research models, Golden Syrian hamsters (GSH) are one of the most representative to study SARS2 pathogenesis and host responses. However, animal studies that recapitulate the effects of SARS2 in the human geriatric population are lacking. To address this gap, we inoculated 14 months old GSH with a prototypic ancestral strain of SARS2 and studied the effects on virus pathogenesis, virus shedding, and respiratory and gastrointestinal microbiome changes. SARS2 infection led to high vRNA loads in the nasal turbinates (NT), lungs, and trachea as well as higher pulmonary lesions scores later in infection. Dysbiosis throughout SARS2 disease progression was observed in the pulmonary microbial dynamics with the enrichment of opportunistic pathogens (Haemophilus, Fusobacterium, Streptococcus, Campylobacter, and Johnsonella) and microbes associated with inflammation (Prevotella). Changes in the gut microbial community also reflected an increase in multiple genera previously associated with intestinal inflammation and disease (Helicobacter, Mucispirillum, Streptococcus, unclassified Erysipelotrichaceae, and Spirochaetaceae). Influenza A virus (FLUAV) pre-exposure resulted in slightly more pronounced pathology in the NT and lungs early on (3 dpc), and more notable changes in lungs compared to the gut microbiome dynamics. Similarities among aged GSH and the microbiome in critically ill COVID-19 patients, particularly in the lower respiratory tract, suggest that GSHs are a representative model to investigate microbial changes during SARS2 infection. The relationship between the residential microbiome and other confounding factors, such as SARS2 infection, in a widely used animal model, contributes to a better understanding of the complexities associated with the host responses during viral infections.

Enactive explorations of children's sensory-motor play and therapeutic handling in physical therapy.

Introduction: In pediatric physical therapy, there is an ongoing debate about the use of therapeutic handling and its potential effects on motor learning. In this study, we build on enactive theoretical perspectives to explore the role of therapeutic handling in connection to children's sensory-motor play, engagement, and performance during a single physical therapy session. Material and methods: This is a qualitative study based on video observations of therapy sessions and interviews with 15 physical therapists (PTs) each treating two different children aged 0-3. The authors utilized a framework of co-reviewing, discussing, and reflecting on the sessions. Themes were identified and used to describe the ways by which PTs' therapeutic handling unfolds, with connections to theories on sensory-motor play and learning, along with enactive perspectives on embodiment, experience, mutual incorporation, and sense-of-agency. Results: The characteristics and purposes of therapeutic handling are presented in two main themes: (1) position and support, and (2) directing movement. We found that position and support promoted sensory-motor improvement when the PTs' handling aligned with the child's play interests and engagements. As part of play, the children used new and additional support surfaces to self-initiate better posture and movement solutions and reach play goals. The PTs' ways of directing movements varied. To awaken curiosity and induce a child's self-driven motor exploration the PT needs to be subtle, flexible, and precise in the directing of movement. This entails responsiveness to the child's signals and bodily know-how in the placing of hands and direction of pressure to enable the child to actively participate in and eventually self-drive movement. Discussion: Therapeutic handling that is mutually incorporated between PT and child can enrich the child's playing-to-learn-to-move process by providing novelty and facilitating the child's sense-of-agency in the self-initiated exploration and refinement of movement possibilities. In the PTs' effort to merge therapeutic handling with children's play, the momentum of interaction can open new therapeutic windows of movement experience and learning opportunities.