The effect of early mobilisation (< 14 days) on pathophysiological and functional outcomes in animals with induced spinal cord injury: a systematic review with meta-analysis.

INTRODUCTION: The optimum time to mobilise (standing, walking) following spinal cord injury (SCI) is unknown but may have implications for patient outcomes. There are no high-quality experimental studies that examine this issue, with a paucity of guidance for clinicians. Pre-clinical studies lead research in this field and can contribute to knowledge and support future clinical practice. OBJECTIVE: to evaluate the effect of early compared to no mobilisation on pathophysiological and functional outcomes in animals with induced SCI. METHODS: A systematic review with meta-analysis was conducted by searching pre-clinical literature in MEDLINE (PubMed), Embase (Ovid), Web of Science, OpenGrey, and EThOS (June 2023). Studies were included of any research method giving numerical results comparing pathophysiological and functional outcomes in rats and mice mobilised within 14-days of induced SCI to those that did not mobilise. Data were synthesised using random-effects meta-analyses. The quality of the evidence was assessed using the CAMARADES checklist. The certainty of findings was reported using the GRADE approach. This study is registered on PROSPERO (CRD42023437494). RESULTS: Seventeen studies met the inclusion criteria. Outcomes found that Brain Derived Neurotrophic Factor levels were greater in those that initiated mobilisation within 14-days of SCI compared to the groups that did not. Mobilisation initiated within 14-days of SCI was also associated with statistically significant functional gains: (Basso, Beattie and Bresnahan locomotor rating score (BBB) = 2.13(0-21), CI 1.43, 2.84, Ladder Rung Walking Task = - 12.38(0-100), CI 20.01, - 4.76). Meta-analysis identified the greatest functional gains when mobilisation was initiated within 3 days of SCI (BBB = 3.00, CI 2.31-3.69, p < 0.001), or when delivered at low intensity (BBB = 2.88, CI 2.03-3.70, p < 0.001). Confidence in the findings from this review was low to moderate due to the risk of bias and mixed methodological quality. CONCLUSION: Mobilisation instigated within 14-days of injury, may be an effective way of improving functional outcomes in animal models following SCI, with delays potentially detrimental to recovery. Outcomes from this study support further research in this field to guide future clinical practice.

Complete genome sequence of Mycobacterium smegmatis phage Rummer, a subcluster A3 actinophage.

Bacteriophage Rummer is a siphovirus morphology actinophage isolated from Mycobacterium smegmatis. Rummer has a 50,908 base pair genome encoding 89 predicted protein-coding genes and three tRNAs. Based on gene content similarity to sequenced actinobacteriophages, Rummer is assigned to phage subcluster A3.

Fluorine in Complex Alumino-Boro-Silicate Glasses: Insight into Chemical Environment and Structure.

Fluorine incorporation into silicate glasses is important for technical fields as diverse as geophysics, extractive metallurgy, reconstructive dentistry, optical devices, and radioactive waste management. In this study, we explored the structural role of fluorine in alkaline alumino-borosilicate glass, with increasing amounts of fluorine up to 25 mol % F while maintaining the glass composition. Glasses were characterized by X-ray diffraction (XRD), 27Al and 19F magic angle spinning nuclear magnetic resonance (MAS NMR) spectroscopy, and electron probe microanalysis. Results showed that essentially all F was retained; however, between 12 and 15 mol % F (∼3.6 and 4.5 wt % F), excess fluorine partitions to CaF2 and then NaF and Na-Al-F crystalline phases. Even prior to crystallization, there exist five distinct F sites, three of which evolve into crystalline phases. The two persistent glassy sites likely involve [4]Al-F-Ca/Na local structures. We propose a general understanding of the expected chemical shift of 19F NMR in systems containing Al, Ca, and Na.

Density Gradient Centrifugation-Independent Purification of Human Basophils.

Basophils represent the rarest type of granulocyte in human peripheral blood. Thus, researching basophils has historically been challenging and has often been reliant on enrichment protocols using density gradient centrifugation. This article describes a novel, fast, and cost-effective method to purify highly viable human basophils from peripheral blood through negative immunomagnetic selection, foregoing the density centrifugation step in the Basic Protocol. The technique is easy to use and consistently produces purities >96%. Furthermore, the Support Protocols describe procedures to determine basophil yield, purity, and viability, and how to investigate functional activity of the purified basophils through flow cytometry and visualize the basophils through microscopy. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol: Gradient centrifugation-independent basophil isolation Support Protocol 1: Flow cytometry staining to assess basophil yield, purity, and viability Support Protocol 2: Giemsa staining Support Protocol 3: Calcium flux analysis Support Protocol 4: Basophil activation test.

TRPV1 Channel in Human Eosinophils: Functional Expression and Inflammatory Modulation.

The transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel expressed on sensory neurons and immune cells. We hypothesize that TRPV1 plays a role in human eosinophil function and is modulated by inflammatory conditions. TRPV1 expression on human eosinophils was examined by qPCR, flow cytometry, and immunohistochemistry, respectively. TRPV1 functionality was analyzed by investigating calcium flux, apoptosis, modulation by cytokines and acidic pH, and CD69 externalization using flow cytometry. Activation of TRPV1 induced calcium influx and prolonged survival. Although eosinophils were not directly activated by TRPV1 agonists, activation by IL-3 or GM-CSF was mainly restricted to TRPV1-positive eosinophils. TRPV1 surface content was increased by acidic pH, IL-3, IL-31, IL-33, TSLP, TNF-α, BDNF, and NGF-ß. Interestingly, TRPV1 was also expressed by eosinophils located in proximity to peripheral nerves in atopic dermatitis (AD) skin. In conclusion, eosinophils express functional TRPV1 channels which are increased by extracellular acidification and AD-related cytokines. Since eosinophils also express TRPV1 in AD skin, our results indicate an important role of TRPV1 for neuroimmune interaction mechanisms in itchy, inflammatory skin diseases, like AD.

Eosinophils, Basophils, and Neutrophils in Bullous Pemphigoid.

Bullous pemphigoid (BP) is an autoimmune blistering skin disease, of which the incidence has increased in recent years. BP is characterized by circulating IgG and IgE autoantibodies against the hemidesmosomal proteins BP180 and BP230. Although autoantibodies trigger inflammatory cascades that lead to blister formation, effector cells and cell-mediated autoimmunity must also be considered as important factors in the pathogenesis of BP. The aim of this review is to outline the current knowledge on the role of eosinophils, basophils, and neutrophils in BP.

Basophils in pruritic skin diseases.

Basophils are rare cells in the peripheral blood which have the capability to infiltrate into the skin. Invasion of basophils has been detected in pruritic skin diseases, including atopic dermatitis, bullous pemphigoid, chronic spontaneous urticaria and contact dermatitis. In the skin, basophils are important players of the inflammatory immune response, as they release Th2 cytokines, including interleukin (IL)-4 and IL-13, subsequently inducing the early activation of T-cells. Further, basophils release a multitude of mediators, such as histamine and IL-31, which both play an important role in the initiation of the pruritic response via activation of sensory nerves. Chronic pruritus significantly affects the quality of life and the working capability of patients, though its mechanisms are not fully elucidated yet. Since basophils and neurons share many receptors and channels, bidirectional interaction mechanisms, which drive the sensation of itch, are highlighted in this review.

Omega-3 Fatty Acids during Pregnancy in Indigenous Australian Women of the Gomeroi Gaaynggal Cohort.

Higher dietary intakes of Omega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs) have been linked to lower rates of preterm birth and preeclampsia. The aim of this analysis was to describe dietary intake and fractions of red blood cell (RBC) membrane LC-PUFAs during pregnancy in a cohort of Indigenous Australian women. Maternal dietary intake was assessed using two validated dietary assessment tools and quantified using the AUSNUT (Australian Food and Nutrient) 2011-2013 database. Analysis from a 3-month food frequency questionnaire indicated that 83% of this cohort met national n-3 LC-PUFA recommendations, with 59% meeting alpha-linolenic acid (ALA) recommendations. No nutritional supplements used by the women contained n-3 LC-PUFAs. Over 90% of women had no detectable level of ALA in their RBC membranes, and the median Omega-3 Index was 5.5%. This analysis appears to illustrate a decline in concentrations of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) across gestation in women who had preterm birth. However, there was no visible trend in LC-PUFA fractions in women who experienced hypertension during pregnancy. Further research is needed to better understand the link between dietary intake of n-3 LC-PUFA-rich foods and the role of fatty acids in preterm birth and preeclampsia.

Neurotrophins: Neuroimmune Interactions in Human Atopic Diseases.

Allergic diseases are accompanied by a variety of symptoms such as pruritus, coughing, sneezing, and watery eyes, which can result in severe physiological and even psychological impairments. The exact mechanisms of these conditions are not yet completely understood. However, recent studies demonstrated a high relevance of neurotrophins in allergic inflammation, as they induce cytokine release, mediate interaction between immune cells and neurons, and exhibit different expression levels in health and disease. In this review, we aim to give an overview of the current state of knowledge concerning the role of neurotrophins in atopic disorders such as atopic dermatitis, allergic asthma, and allergic rhinitis.

Protocol for the development of a multidisciplinary clinical practice guideline for the care of patients with chronic subdural haematoma.

Introduction: A common neurosurgical condition, chronic subdural haematoma (cSDH) typically affects older people with other underlying health conditions. The care of this potentially vulnerable cohort is often, however, fragmented and suboptimal. In other complex conditions, multidisciplinary guidelines have transformed patient experience and outcomes, but no such framework exists for cSDH. This paper outlines a protocol to develop the first comprehensive multidisciplinary guideline from diagnosis to long-term recovery with cSDH. Methods: The project will be guided by a steering group of key stakeholders and professional organisations and will feature patient and public involvement. Multidisciplinary thematic working groups will examine key aspects of care to formulate appropriate, patient-centered research questions, targeted with evidence review using the GRADE framework. The working groups will then formulate draft clinical recommendations to be used in a modified Delphi process to build consensus on guideline contents. Conclusions: We present a protocol for the development of a multidisciplinary guideline to inform the care of patients with a cSDH, developed by cross-disciplinary working groups and arrived at through a consensus-building process, including a modified online Delphi.

Differential Upregulation and Functional Activity of S1PR1 in Human Peripheral Blood Basophils of Atopic Patients.

Basophils are key effector cells in atopic diseases, and the signaling sphingolipid Sphigosine-1-phosphate (S1P) is emerging as an important mediator in these conditions. The possible interaction of S1P and basophils and the resulting biological effects have not yet been studied. We hypothesize that S1P influences the function of basophils in atopy and aim to elucidate the modes of interaction. S1P receptor (S1PR) expression in human peripheral blood basophils from atopic and non-atopic patients was assessed through qRT-PCR and flow cytometry analysis. Functional effects of S1P were assessed through a basophil activation test (BAT), calcium flux, apoptosis, and chemotaxis assays. Immunofluorescence staining was performed to visualize intracellular S1P. Human basophils express S1PR1, S1PR2, S1PR3, and S1PR4 on the mRNA level. 0.1 µM S1P have anti-apoptotic, while 10 µM exhibits apoptotic effects on basophils. Basophils from atopic patients show less chemotactic activity in response to S1P than those from healthy donors. Protein expression of S1PR1 is downregulated in atopic patients, and basophils in lesional AD skin possess intracellular S1P. These findings suggest that the interaction of S1P and basophils might be an important factor in the pathophysiology of atopy.

Association of Chemotherapy Regimen Intensity and Use of Psychotropic Medications in Pediatric Oncology Patients.

OBJECTIVE: Pediatric oncology patients endure treatments that may include chemotherapy, surgery, radiation, and transplant. These treatment modalities often have an effect on a patient's mental health. To date, little is known or published about the association between certain cancer treatment regimens and the use of psychotropic medications. The goal of this study is to identify associations between the use of psychotropic medications in pediatric oncology patients in relation to the intensity of their oncologic treatment regimen. METHODS: A retrospective chart review was completed for pediatric oncology patients seen between the years of 2009 and 2019 with prescriptions and/or inpatient orders for specific psychotropic medications. The intensity of the oncologic regimen was categorized using the Intensity of Treatment Rating Scale (ITR-3) tool. Association between the intensity of therapy and use of psychotropic medications were compared using Pearson χ2 and Fisher exact tests as appropriate. RESULTS: There were 172 patients identified as having inpatient and/or outpatient orders for psychotropic medications during the study period. Ninety-one pediatric oncology patients were included in data analysis. It was found that psychotropic medications were used consistently in pediatric oncology patients despite a specific ITR-3 score. There were no statistically significant associations found when comparing ITR-3 scores to psychotropic medication use or to age at diagnosis. CONCLUSIONS: Significance was not obtained in this study; however, we found that psychotropic medications were used across the spectrum of diagnoses, age, and oncologic treatment intensity. This suggests that all pediatric oncology patients should be evaluated for psychiatric needs throughout their course of oncologic treatment.

"These issues aren't talked about at home": a qualitative study of the sexual and reproductive health information preferences of adolescents in Vanuatu.

BACKGROUND: Onset of sexual activity during adolescence is common in Vanuatu, however access to comprehensive sexual and reproductive health (SRH) information is limited. Improving adolescents' knowledge about SRH is necessary to improve health outcomes, however little is known about the information needs and preferences of adolescents in the Pacific to inform policy and programs in this region. METHODS: Sixty-six focus group discussions were conducted with 341 male and female adolescents aged 15-19 years from rural and urban communities on two islands of Vanuatu. Twelve key-informant interviews were also conducted with policymakers and health service providers. Data were analysed thematically using an inductive approach. RESULTS: Much of the SRH information targeting adolescents focused on sexually transmitted infections and HIV. While this information was valued, important gaps were identified including prevention of pregnancy, condom use, puberty, sexuality and relationships. Peer educators and health workers were adolescents' preferred sources of information because they were considered knowledgeable and trustworthy. Parents were not a common source but were preferred, particularly by girls, despite considerable socio-cultural barriers. Schools were an important but underutilised source of information, as were a range of media sources. CONCLUSIONS: Providing adolescents with comprehensive SRH information can have life-long protective benefits, however there are important content gaps in information currently provided in Vanuatu. The broad range of sources preferred by adolescents highlights the need to strengthen information provision through multiple channels to reach in and out-of-school youth and respond to individual needs and contexts.

The effect of continuous intrathecal baclofen on sitting in children with severe cerebral palsy.

AIM: To investigate the effect of intrathecal baclofen (ITB) on sitting in children with cerebral palsy with severe spasticity; and identify potential sub-groups of patients at particular risk of deterioration. METHOD: Twenty three children with cerebral palsy, mean age 10 yrs 10 mo were assessed before and after ITB treatment using the Sitting dimension of the Gross Motor Function Measure. Sitting prior to treatment was compared to sitting following ITB treatment in the same children. Exploration of sub groups was also attempted to investigate affects of ITB on sitting according to age and severity of motor impairment. RESULTS: No significant difference was found in sitting before ITB treatment compared to sitting following insertion of an ITB pump (p = 0.09). No specific age group or classification of motor impairment demonstrated significant deterioration in sitting following ITB treatment. CONCLUSION: Sitting does not improve or deteriorate in children following treatment with ITB, independent of age or severity of motor impairment.

"Be kind to young people so they feel at home": a qualitative study of adolescents' and service providers' perceptions of youth-friendly sexual and reproductive health services in Vanuatu.

BACKGROUND: Sexual activity during adolescence is common in Vanuatu, however many adolescents lack access to sexual and reproductive health (SRH) services and subsequently suffer a disproportionate burden of poor SRH. There is limited peer-reviewed research describing adolescents' SRH service delivery preferences in Vanuatu to inform policy and programs. The aim of this qualitative study was to explore the barriers preventing adolescents from accessing SRH services in Vanuatu and the features of a youth-friendly health service as defined by adolescents. METHODS: Sixty-six focus group discussions were conducted with 341 male and female adolescents aged 15-19 years in rural and urban communities. Additionally, 12 semi-structured interviews were undertaken with policymakers and service providers. Data were analysed using thematic analysis. RESULTS: Socio-cultural norms and taboos regarding adolescent sexual behaviour were the most significant factors preventing adolescents from accessing services. These contributed to adolescents' own fear and shame, judgmental attitudes of service providers, and disapproval from parents and community gate-keepers. Lack of confidentiality and privacy, costs, and adolescents' lack of SRH knowledge were also important barriers. Adolescents and service providers identified opportunities to make existing services more youth-friendly. The most important feature of a youth-friendly health service described by adolescents was a friendly service provider. Free or affordable services, reliable commodity supply, confidentiality and privacy were also key features. The need to address socio-cultural norms and community knowledge and attitudes was also highlighted. CONCLUSIONS: There are significant demand and supply-side barriers contributing to low utilisation of SRH services by adolescents in Vanuatu. However, there are many opportunities to make existing SRH services more youth-friendly, such as improving service provider training. Investment is also required in strategies that aim to create a more supportive environment for adolescent SRH.

Improving adolescent reproductive health in Asia and the Pacific: do we have the data? A review of DHS and MICS surveys in nine countries.

Data on adolescent reproductive health (ARH) are required to inform evidence-based policies and programs. The reports of national-level household surveys such as the Demographic and Health Survey (DHS) and Multiple Indicator Cluster Survey (MICS) are important sources of such data in developing countries. The aim of this study was to map data on ARH from DHS and MICS reports from selected countries in the Asia and Pacific regions. The DHS and MICS reports for Bangladesh, Cambodia, Indonesia, Papua New Guinea, Philippines, Solomon Islands, Timor-Leste, Vanuatu, and Vietnam were reviewed. Data on 128 indicators, including ARH outcomes, outcomes for babies of adolescent mothers, and adolescents' access to health information and services, were mapped. Available data are limited because of the omission of cohorts such as young adolescents (10-14 years old) and, in many surveys, unmarried women; the omission of important indicators; and failure to report data disaggregated by age. DHS and MICS reports have limited capacity to inform policy and programs to improve ARH. A review of DHS and MICS sampling strategies and reporting templates, and a consideration of alternative data collection strategies, are warranted.

Goals and outcomes for non ambulant children receiving continuous infusion of intrathecal baclofen.

AIM: To evaluate the success of goals and compare these to actual outcomes in severely disabled children receiving continuous intrathecal baclofen [ITB]. METHOD: 37 non ambulant children with severe spasticity were assessed just before implantation of a pump for ITB, and 9 and 18 months afterwards. Three key goals were chosen for treatment by the family and therapist. These were reviewed at the assessments, together with caregivers' views of the outcome of treatment in 14 different aspects. At the first and last assessment, the degree of deformity of the hips and spine were reviewed, and Orthopaedic Surgeons were also asked to predict what surgery would be needed in the next 2 years. RESULTS: The most common successful outcomes were ease of nursing care, better sitting, spasm reduction, more relaxed/better mood, and improved sleep. This was reflected in the goals selected which were therefore realistic for this treatment. All 3 pre-set goals were achieved by 80% of children. Deformities of the hip and spine continued to occur. The predicted number of orthopaedic operations before and after ITB remained unchanged. INTERPRETATION: ITB is a major treatment for children with severe disability and should be undertaken with understanding of what can and cannot be achieved, therefore allowing realistic goals to be set.

Controlled study of the effects of continuous intrathecal baclofen infusion in non-ambulant children with cerebral palsy.

AIM: To measure changes in children with severe spastic cerebral palsy (CP) after continuous intrathecal baclofen (ITB) infusion over 18 months and to compare the results with those of a comparison group awaiting treatment. METHOD: Thirty-eight children with severe spastic CP considered suitable for ITB were assessed when first seen, just before insertion of an intrathecal pump, and 9 months and 18 months later. Eighteen children waited around 9 months for a pump (group 1: nine males, nine females; mean age 9y 11mo [SD 3y 7mo], nine in Gross Motor Function Classification System [GMFCS] level IV, nine in level V). This baseline period was used as a control for comparison with the first and second 9-month periods after the pump for the remaining 20 children (group 2: 11 males, nine females; mean age 10y 2mo [SD 3y 1mo], nine in GMFCS level IV, 11 in level V). The main outcome measure was the Pediatric Evaluation of Disability Inventory (PEDI); other assessments were of function, ease of care, quality of life, and costs of new equipment. RESULTS: No significant change was found in the PEDI between group 1 while awaiting treatment and group 2 in the two periods afterwards, nor in the Lifestyle Assessment Questionnaire or the cost of new equipment. Significant changes were found in group 2 in the first 9 months according to the modified Ashworth score (difference between mean values for groups -1.7, standard error 0.58; p=0.008), Penn Spasm score (-1.3, 0.37; p=0.001), mean joint range of movement (8.3°, 2.8; p=0.005), and Caregiver Questionnaire (-19.7, 5.1; p=0.01), and in the second 9 months for the Modified Ashworth Scale score (-0.62, 0.12; p=0.001). INTERPRETATION: ITB in children with severe spastic CP over the first 18 months improves their quality of life in terms of comfort and ease of care. It has less effect on function, participation in society, or the overall cost of new equipment.