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Glycosylation plays a critical role during inflammation and glial scar formation upon spinal cord injury (SCI) disease progression. Astrocytes and microglia are involved in this cascade to modulate the inflammation and tissue remodeling from acute to chronic phases. Therefore, understating the glycan changes in these glial cells is paramount.A lectin microarray was undertaken using a cytokine-driven inflammatory mixed glial culture model, revealing considerable differential glycosylation from the acute to the chronic phase in a cytokine-combination generated inflamed MGC model. It was found that several N- and O-linked glycans associated with glia during SCI were differentially regulated. Pearson's correlation hierarchical clustering showed that groups were separated into several clusters, illustrating the heterogenicity among the control, cytokine combination, and LPS treated groups and the day on which treatment was given. Control and LPS treatments were observed to be in dense clusters. This was further confirmed with lectin immunostaining in which GalNAc, GlcNAc, mannose, fucose and sialic acid-binding residues were detected in astrocytes and microglia. However, the sialyltransferase inhibitor inhibited this modification (upregulation of the sialic acid expression), which indeed modulates the mitochondrial functions.The present study is the first functional investigation of glycosylation modulation in a mixed glial culture model, which elucidates the role of the glycome in neuroinflammation in progression and identified potential therapeutic targets for future glyco therapeutics in neuroinflammation.

BACKGROUND Encouraging older adults to use physical activity monitors can augment efforts to promote increased physical activity. However, little is known about the frequency and type of technical assistance needed during long-term physical activity monitor (PAM) use. OBJECTIVE The objective of this study was to examine PAM-related technical problems reported and assistance received by a sample of older adults in an 18-month community-based, physical activity trial, Ready Steady 3.0 (RS3). METHODS This was an ad-hoc, longitudinal analysis of process variables representing technical problems reported and assistance received by 113 study participants in the 18 months after their orientation to PAMs. Variables included date of contact, problem(s) reported, mode of technical assistance, and equipment replacement. Analysis was descriptive including frequencies and incidence rates of distinct contacts, types of problems, and modes of technical assistance. RESULTS On average, participants were 77 years old (+ 5.2). Most identified as female (77%), reported experience using smart phones (81.4%), and used the PAM between 2 and 18 months. Eighty-two participants (73%) reported 1 to 9 problems with using PAMs, resulting in a total of 150 technical assistance contacts with a mean of 1.3 (SD=1.3). The incidence rate of new, distinct contact for technical assistance was 99, per 100 persons, per year from 2018 to 2021. The most common problems were wearing the PAM (28.7%), reading its display (15.3%), logging into its app (13.3%), charging the PAM (12%), and synchronizing the PAM to the app (10.7%). The modalities of technical assistance were in-person (35%), telephone (34%), email (17%), and U.S. mail (14%). CONCLUSIONS Results provide a detailed description of the types and quantity of technical assistance needs to expect when planning supportive structures to facilitate the long-term use of PAMs among older adults. Health promotion programs and researchers should further examine technical assistance for PAM problems experienced by older adults, such as proactive and responsive support, variations by PAM models, and expanded assistance strategies, such as the use of short graphics interchange formats and video calls. CLINICALTRIAL Clinical Trials.gov NCT03326141

Surgery for posterior fossa tumours (PFTs) in children is associated with bulbar palsy and swallowing difficulties although this risk is not well defined in the literature and issues contributing to dysphagia following surgery are not fully understood.This study aims to study the eating, drinking and swallowing function of children following PFT resection in a specialist paediatric neurosurgery centre. This included the frequency and duration of dysphagia, the risk of aspiration and the link between tumour type and dysphagia.This is a retrospective review of children undergoing surgery for PFT between 2014 and 2019. Information was obtained from the patients' hospital and speech and language therapy (SLT) notes, oncology database and clinical letters. The International Dysphagia Diet Standardisation Initiative (IDDSI) Framework was used to describe food and fluid modifications.Seventy children had surgery to resect a posterior fossa tumour at Alder Hey from 2014 to 2019. Thirty-one children were included in the study following referral to SLT. Videofluoroscopy (VF) was undertaken at our institution in 68% (21/31) of cases. Fifty-two percent (11/21) of children aspirated or were considered at risk, and 55% (6/11) of those who aspirated showed silent aspiration. After 3 months, 43% (13/30) still required modified food and/or fluid textures, with this proportion reducing as time progressed. By tumour type, VF was performed in 5/7 medulloblastoma patients with 3/5 showing aspiration and 3/3 silently aspirating; in 8/9 patients with ependymoma with 4/8 patients aspirating with 2/4 showing silent aspiration; and 6/12 glioma patients with 4/6 aspirating with 1/4 showing silent aspiration.Swallowing difficulties, including silent aspiration, are an important complication of PFT resection. A proportion of children will need ongoing food and/or fluid modification. Further study into dysphagia following PFT resection is indicated.

OBJECTIVES To assess whether dental arch relationship scores are associated with speech, audiological and psychology outcomes in patients with complete unilateral cleft lip and palate (UCLP) and bilateral cleft lip and palate (BCLP). SETTING AND SAMPLE POPULATION One hundred 5-year-old children with non-syndromic complete UCLP and forty-two 5-year-olds with non-syndromic complete BCLP from the United Kingdom. MATERIAL AND METHODS Data were collected from five-year audit clinics for dental arch relationships, speech, hearing and psychology outcomes. Associations were assessed between ordinal prognostic covariates and the dental arch relationship outcome using a Cochrane-Armitage test for trend and comparisons with binary prognostic covariates using chi-square/Fisher's exact test. This was extended to assess associations between five-year audit outcomes and a measure of deprivation. RESULTS There was no evidence of associations between dental arch relationships and outcomes for audiology and speech. Individual domain analysis of the psychology outcomes within the UCLP cohort reported a poor outcome for Pro-social score to be associated with a poor 5-year-old index score (P = .018). For the BCLP sample, a good outcome for the BCLP Deciduous Dentition Yardstick was associated with a good conduct score (P = .01). CONCLUSION There was no association with the 5-year-old index/BCLP Deciduous Dentition Yardstick score and outcomes reported for audiology and speech. For the UCLP and BCLP cohorts, a poor dental arch relationship outcome may be associated with issues with some aspects of psychological well-being, associated with peer interactions and conduct. The deprivation index of samples had no association with the outcomes assessed.

Canonical babbling (CB) is commonly defined as present when at least 15% of all syllables produced are canonical, in other words a canonical babbling ratio (CBR) ≥0.15. However, there is limited knowledge about inter-rater reliability in classification of CB status based on CBR and inter-rater differences in assessment of CBR. We investigated inter-rater reliability of experienced Speech Language Therapists (SLTs) on: classification of CB status based on CBR ≥ 0.15, CBRs and the total number of syllables per infant used to calculate CBR.Each infant (n = 484) was video-recorded at a clinical site in play interaction with their parent as part of the randomised controlled trial Timing of Primary Surgery for Cleft Palate. Each recording was subsequently assessed by three independent SLTs, from a pool of 29 SLTs. They assessed the recordings in real time.The three assessing SLTs agreed in classification of CB status in 423 (87.4%) infants, with higher complete agreement for canonical (91%; 326/358) than non-canonical (77%; 97/126). The average difference in CBR and total number of syllables identified between the SLT assessments of each infant was 0.12 and 95, respectively.This study provided new evidence that one trained SLT can reliably classify CB status (CBR ≥ 0.15) in real time when there is clear distinction between the observed CBR and the boundary (0.15); however, when the observed CBR approaches the boundary multiple SLT assessments are beneficial. Thus, we recommend to include assessment of inter-rater reliability, if the purpose is to compare CBR and total syllable count across infants or studies.Trial registration number here: www.clinicaltrials.gov, identifier NCT00993551

Traumatic spinal cord injury (SCI) results in complex neurological dysfunction. Astrocytes react in response to SCI by undergoing proliferation and migrating to the injury site, resulting in astrogliosis. Neural stem cells (NSCs) have been proposed as a promising therapeutic strategy to promote neurogenesis following transplantation post SCI. In this study the antigenic and morphological phenotype of astrocytes, and the pattern of galectin expression was examined following SCI. Female Sprague Dawley rats were contused at thoracic (T) level T9 and treated with Cyclosporin-A (CsA) and/or NSCs 1 week post-injury. CsA and NSC treatment led to increased glial fibrillary acidic protein (GFAP), brain lipid binding protein (BLBP) and vimentin expression. Quiescent and reactive astrocytes were the most abundant cell morphology observed. Astrocytes co-localised with galectin-1 (Gal-1) and galectin-3 (Gal-3). Gal-1 expression was increased in both CsA and CSA + NSC treated animals 2 weeks post-treatment. Treatment with CsA and/or NSCs offers many prospective beneficial effects. A detailed revelation of how astrocytes are heterogeneously responsive to SCI, in addition to their affinity to galectins and response to CsA and NSCs is shown in this study. The current study’s findings support the potential application of NSCs as a novel therapeutic tool in the treatment of SCI.

Cellular signalling processes can exhibit pronounced cell-to-cell variability in genetically identical cells. This affects how individual cells respond differentially to the same environmental stimulus. However, the origins of cell-to-cell variability in cellular signalling systems remain poorly understood. Here we measure the temporal evolution of phosphorylated MEK and ERK dynamics across populations of cells and quantify the levels of population heterogeneity over time using high-throughput image cytometry. We use a statistical modelling framework to show that upstream noise is the dominant factor causing cell-to-cell variability in ERK phosphorylation, rather than stochasticity in the phosphorylation/dephosphorylation of ERK. In particular, the cell-to-cell variability during sustained phosphorylation stems from random fluctuations in the background upstream signalling processes, while during transient phosphorylation, the heterogeneity is primarily due to noise in the intensity of the upstream signal(s). We show that the core MEK/ERK system uses kinetic proof-reading to faithfully and robustly transmits these variable inputs. The MAPK cascade thus propagates cell-to-cell variability at the population level, rather than attenuating or increasing it.

Increased physical activity and exercise have been found to reduce falls and decrease mortality and age-related morbidity in older adults. However, a large percentage of this population fail to achieve the necessary levels of activity needed to support health living. In this work, we present a mobile app developed on the iOS platform that monitors activity levels using accelerometry. The data captured by the sensor is utilized to provide real-time motivational feedback to enable reinforcement of positive behaviors in older adults. Pilot experiments (conducted with younger adults) performed to assess validity of activity measurement showed that system accurately measures sedentary, light, moderate and vigorous activities in a controlled lab setting. Pilot tests (conducted with older adults) in the user setting showed that while the app is adept at capturing gross body activity (such as sitting, walking and jogging), additional sensors may be required to capture activities involving the extremities.

To appraise the external validity of physical activity interventions designed to reduce falls among community-dwelling older adults, using the reach, efficacy/effectiveness, adoption, implementation, and maintenance framework.Falls are a globally common, important, and a preventable problem. The efficacy of physical activity interventions to reduce falls among older adults is well established. Translation of this research into practice is slow as evidenced by persistently low proportions of older adults who engage in physical activities and the rising incidence of falls.Four electronic databases were searched for relevant studies published between 2000-2010. Studies that examined the effects of physical activity interventions designed to reduce falls among community-dwelling older adults were included in this review (n = 46).This was a quantitative systematic review with narrative synthesis. The reach, efficacy/effectiveness, adoption, implementation, and maintenance framework guided the identification, appraisal, and synthesis of indicators representing study validity.The majority of studies in this review described indicators representing internal validity. Details about indicators representing external validity were reported infrequently, limiting the generalizability of fall-preventive physical activity interventions in diverse cultures and social contexts over time.To foster translational research in real world settings, additional programmatic intervention research is needed that: (i) targets diverse populations; (ii) incorporates theories of behavioural change; (iii) describes and operationalizes critical content that enables replication and translation; (iv) tests innovative measures of fall risk and physical activity; and (v) evaluates feasibility and acceptability.

The purpose of this analysis is to examine the concept of wellness within the context of older adulthood. Identifying characteristics of wellness will clarify and develop conceptual strengths and limitations, providing a step toward evaluating its relevance in older adults and increasing utility in geriatric nursing.Rodger's evolutionary perspective.Computer and manual searches were conducted of articles in the English language from 1950 to 2010, addressing wellness across the life span or among older adult populations. An inductive analysis of articles produced descriptive themes.A historical time line traced the evolution of the wellness concept and its operationalization. Wellness has evolved from a little used concept to one commonly applied across many industries. Antecedents, attributes, and consequences of wellness are described. Concepts related to wellness are also identified.This concept analysis adds clarity to wellness in older adults. The state of wellness development as a concept in geriatric nursing is moving from conceptualization to use and testing in nursing theory and interventions. Increased knowledge of wellness will enable geriatric nurses to discover the strengths of older adults thereby promoting their ongoing growth and development while simultaneously guiding care for their changing and diverse health.

Objective To compare the outcomes for primary repair of unilateral cleft lip and palate, operating on the soft palate first versus the hard palate first. Design Randomized controlled trial. Setting The Regional Cleft Service of West Nepal. Patients Forty-seven consecutive patients with nonsyndromic unilateral cleft lip and palate, of whom 37 were assessed 4 to 6 years after completing primary surgical repair. Interventions Primary repair of unilateral cleft lip and palate by two differing sequences: (1) soft palate repair, with hard palate and lip repair 3 months later; and (2) lip and hard palate repair, followed by the soft palate repair 3 months later. Main Outcome Measures Analysis of dental study models, weight gain, and speech recordings. Results Four to 7 years after completing the cleft closure, there was no significant difference in facial growth between the two types of repair sequencing. Completing posterior repair first had no effect on anterior alveolar gap width. It narrowed the hard palate gap by reducing the intercanine distance. Anterior repair dramatically closed the anterior alveolar gap, and narrowed the intercanine distance. Comparing anterior alveolar gap width with age at first presentation demonstrated that there was no spontaneous narrowing of the cleft in older children. Completing posterior closure first had a weight gain advantage over anterior closure first. Improved oropharyngeal closure, and thus swallowing, is the likely explanation. Conclusion Changing the sequencing of cleft closure has no demonstrable difference in facial growth at 4 to 7 years after completion of the primary surgery.

Aims: Eustachian tube dysfunction affects nearly all children with cleft palate but its management is controversial. Some units perform routine prophylactic grommet insertion at the time of palate repair, whilst others are more conservative, inserting grommets only when signs and symptoms of otitis media with effusion are present. This study aims to present outcome data from one cleft team practising a conservative approach. Design: This is a retrospective study in which consecutive palate repairs over 10 years are analysed and compared with previously published data. The spectrum of clefting and severity (LAHSHAL), otological and speech outcomes were recorded. Patients were excluded if incomplete data was available, and if sensorineural deafness or syndromic clefting was present. Results: Data is presented for 72 of 109 consecutive patients and the 37 excluded patients are discussed. Following a conservative approach to otitis media with effusion, 29% of cases required grommets. The use of grommets seemed to be more common in those with more severe clefting. Despite this, the group receiving grommets had better speech results than those who did not, although this improvement was not statistically significant. Conclusions: There is no evidence of poor overall otological outcome in this series. The data demonstrates that those receiving grommets had better results despite more severe clefting.