Neurofilament Light (NF-L) Chain Protein from a Highly Polymerized Structural Component of the Neuronal Cytoskeleton to a Neurodegenerative Disease Biomarker in the Periphery.

Neurofilaments (NFs) are critical scaffolding components of the axoskeleton of healthy neurons interacting directly with multiple synaptic-phosphoproteins to support and coordinate neuronal cell shape, cytoarchitecture, synaptogenesis and neurotransmission. While neuronal presynaptic proteins such as synapsin-2 (SYN II) degrade rapidly via the ubiquitin-proteasome pathway, a considerably more stable neurofilament light (NF-L) chain protein turns over much more slowly, and in several neurological diseases is accompanied by a pathological shift from an intracellular neuronal cytoplasmic location into various biofluid compartments. NF-L has been found to be significantly elevated in peripheral biofluids in multiple neurodegenerative disorders, however it is not as widely appreciated that NF-L expression within neurons undergoing inflammatory neurodegeneration exhibit a significant down-regulation in these neuron-specific intermediate-filament components. Down-regulated NF-L in neurons correlates well with the observed axonal and neuronal atrophy, neurite deterioration and synaptic disorganization in tissues affected by Alzheimer's disease (AD) and other progressive, age-related neurological diseases. This Review paper: (i) will briefly assess the remarkably high number of neurological disorders that exhibit NF-L depolymerization, liberation from neuron-specific compartments, mobilization and enrichment into pathological biofluids; (ii) will evaluate how NF-L exhibits compartmentalization effects in age-related neurological disorders; (iii) will review how the shift of NF-L compartmentalization from within the neuronal cytoskeleton into peripheral biofluids may be a diagnostic biomarker for neuronal-decline in all cause dementia most useful in distinguishing between closely related neurological disorders; and (iv) will review emerging evidence that deficits in plasma membrane barrier integrity, pathological transport and/or vesicle-mediated trafficking dysfunction of NF-L may contribute to neuronal decline, with specific reference to AD wherever possible.

Gastrointestinal (GI)-Tract Microbiome Derived Neurotoxins and their Potential Contribution to Inflammatory Neurodegeneration in Alzheimer's Disease (AD).

The human gastrointestinal (GI)-tract microbiome is a rich, complex and dynamic source of microorganisms that possess a staggering diversity and complexity. Importantly there is a significant variability in microbial complexity even amongst healthy individuals-this has made it difficult to link specific microbial abundance patterns with age-related neurological disease. GI-tract commensal microorganisms are generally beneficial to human metabolism and immunity, however enterotoxigenic forms of microbes possess significant potential to secrete what are amongst the most neurotoxic and pro-inflammatory biopolymers known. These include toxic glycolipids such as lipopolysaccharide (LPS), enterotoxins, microbial-derived amyloids and small non-coding RNA. One major microbial species of the GI-tract microbiome, about ~100-fold more abundant than Escherichia coli in deep GI-tract regions is Bacteroides fragilis, an anaerobic, rod-shaped Gram-negative bacterium. B. fragilis can secrete: (i) a particularly potent, pro-inflammatory and unique LPS subtype (BF-LPS); and (ii) a zinc-metalloproteinase known as B. fragilis-toxin (BFT) or fragilysin. Ongoing studies indicate that BF-LPS and/or BFT disrupt paracellular-and transcellular-barriers by cleavage of intercellular-proteins resulting in 'leaky' barriers. These barriers: (i) become defective and more penetrable with aging and disease; and (ii) permit entry of microbiome-derived neurotoxins into the systemic-circulation from which they next transit the blood-brain barrier and gain access to the CNS. Here LPS accumulates and significantly alters homeostatic patterns of gene expression. The affinity of LPS for neuronal nuclei is significantly enhanced in the presence of amyloid beta 42 (Aß42) peptides. Recent research on the appearance of the brain thanatomicrobiome at the time of death and the increasing likelihood of a complex brain microbiome are reviewed and discussed. This paper will also highlight some recent advances in this extraordinary research area that links the pro-inflammatory exudates of the GI-tract microbiome with innate-immune disturbances and inflammatory-signaling within the CNS with reference to Alzheimer's disease (AD) wherever possible.

The Psychological Impact of First Burn Camp in Nicaragua.

Asociacion Pro-Ninos Quemados de Nicaragua (APROQUEN) is a comprehensive burn center that provides a holistic and integrated approach to treating burns. APROQUEN has set the standards internationally with acute treatment for burns, intensive care, reconstructive surgeries, nutritional care, rehabilitation, occupational therapy, and psychological treatment. APROQUEN is excelling within Central and South America with life-saving techniques and quality of care. It is imperative that burn centers in Central America recognize that the treatment of a child with a burn injury surpasses physical care to include psychological treatment for the complete well-being of the child. It is necessary to provide the tools necessary to reintegrate the child back into their environment. APROQUEN developed and implemented the first burn camp in Latin America, "Confio en Mi" (I trust myself). The camp theme focused on self-esteem. The camp program included theory (educational) and practice (applied) components where the campers through "classroom type" activities had the opportunity to reflect and share with other campers and camp staff on self-esteem, depression, and anxiety. Participants were children who survived major burns (N = 33; 58% women; ages 12-25; 61% <18) and were shown to have difficulty socializing. Comprehensive interviews were conducted to ensure fit for camp. Forty-two percent of the campers had not slept away from home since the burn injury. Mean TBSA = 20% and mean age at time of burn injury was 13. The majority of campers (46%) endured flame burn injuries, with 24% having scald injuries. Mean years postburn = 4.8 + 3.2. Most campers (40%) were enrolled in secondary school, 30% in elementary school, and 21% in college. Standardized measures (CDI-2 Parent Form and Child Form, Rosenberg Scale, APROQUEN Burn Camp Measure Parent and Child Form, Beck Anxiety Inventory, and Beck Depression Inventory) were given to all campers prior to attending camp. The same measures were given 2 weeks after the camp and again at 6 months. Paired samples' t-tests were conducted and significance was set at P <.05. The results indicate that Camp Confio en Mi had a significant impact on campers' level of anxiety, depression, and self-esteem. Future burn camps are an important part of the continued advancement of postpediatric burn care in Nicaragua. This study reveals the importance of future researches necessity to focus on generalizing the results of this study to other children who have experienced similar burn injuries.

Effects of a hospital based Wellness and Exercise program on quality of life of children with severe burns.

OBJECTIVE: To examine the effect of a 12-week Wellness and Exercise (W&E) program on the quality of life of pediatric burn survivors with burns of ≥40% total body surface area. We hypothesized this comprehensive regimen would improve physical and psychosocial outcomes. METHODS: Children were recruited for participation upon their discharge from the ICU. They were not taking anabolic/cardiovascular agents. Seventeen children participated in the W&E group and 14 children in the Standard of Care (SOC) group. Quality of life was assessed with the Child Health Questionnaire (CHQ) at discharge and 3 months. Children completed the CHQ-CF 87 and caregivers completed the CHQ-PF 28. RESULTS: The mean age of children in the W&E group was 14.07±3.5 years and mean TBSA was 58±11.8%. The mean age of children in the SOC group was 13.9±3.1 years and mean TBSA was 49±7.8%. ANOVA did not reveal statistically significant differences between the groups. Matched paired t-tests revealed that parents with children in the W&E group reported significant improvements with their children's physical functioning, role/social physical functioning, mental health, overall physical and psychosocial functioning after exercise. CONCLUSIONS: These results are clinically relevant in that a comprehensive W&E program may be beneficial in promoting physical and psychosocial outcomes.

Children with burn injuries--assessment of trauma, neglect, violence and abuse.

Burns are an important cause of injury to young children, being the third most frequent cause of injury resulting in death behind motor vehicle accidents and drowning. Burn injuries account for the greatest length of stay of all hospital admissions for injuries and costs associated with care are substantial. The majority of burn injuries in children are scald injuries resulting from hot liquids, occurring most commonly in children aged 0-4 years. Other types of burns include electrical, chemical and intentional injury. Mechanisms of injury are often unique to children and involve exploratory behavior without the requisite comprehension of the dangers in their environment. Assessment of the burnt child includes airway, breathing and circulation stabilization, followed by assessment of the extent of the burn and head to toe examination. The standard rule of 9s for estimating total body surface area (TBSA) of the burn is inaccurate for the pediatric population and modifications include utilizing the Lund and Browder chart, or the child's palm to represent 1% TBSA. Further monitoring may include cardiac assessment, indwelling catheter insertion and evaluation of inhalation injury with or without intubation depending on the context of the injury. Risk factors and features of intentional injury should be known and sought and vital clues can be found in the history, physical examination and common patterns of presentation. Contemporary burn management is underscored by several decades of advancing medical and surgical care however, common to all injuries, it is in the area of prevention that the greatest potential to reduce the burden of these devastating occurrences exists.

Virtual reality as an adjunctive non-pharmacologic analgesic for acute burn pain during medical procedures.

INTRODUCTION: Excessive pain during medical procedures is a widespread problem but is especially problematic during daily wound care of patients with severe burn injuries. METHODS: Burn patients report 35-50% reductions in procedural pain while in a distracting immersive virtual reality, and fMRI brain scans show associated reductions in pain-related brain activity during VR. VR distraction appears to be most effective for patients with the highest pain intensity levels. VR is thought to reduce pain by directing patients' attention into the virtual world, leaving less attention available to process incoming neural signals from pain receptors. CONCLUSIONS: We review evidence from clinical and laboratory research studies exploring Virtual Reality analgesia, concentrating primarily on the work ongoing within our group. We briefly describe how VR pain distraction systems have been tailored to the unique needs of burn patients to date, and speculate about how VR systems could be tailored to the needs of other patient populations in the future.

Growth curve trajectories of distress in burn patients.

Psychological adjustment after a major burn injury is a significant concern to providers and patients alike. Although efforts have been made to identify associated risk factors, little is known about heterogeneity in the levels or trajectories of adjustment in this population. This study used a novel application of Growth Mixture Modeling to identify subgroups of patients based on their longitudinal self-reported distress using the Brief Symptom Inventory (BSI). Data were drawn from the database of the Burn Model Systems project, a prospective, multisite, cohort study of major burn injury survivors. The BSI was used to assess symptoms in-hospital and at 6, 12, and 24 months postburn. Participants' T scores on the BSIs Global Severity Index provided a continuous measure of psychological distress. Analyses were conducted using participants' Global Severity Index T scores to discern distinct classes of respondents with similar trajectories across the 2-year follow-up. Results from the Growth Mixture Modeling analysis produced an ordered four-class model of psychological recovery from a major burn. Groups represented the equivalent of high, subthreshold, mild, and minimal symptom severity. Covariates significantly affected the intercept and slope of each class, as well as prediction of group assignment. These analyses demonstrate differences between individual recoveries after a major burn. Psychological distress symptoms remain largely stable over time and highlight the psychological vulnerability of this patient population.

Prospective relationship between maternal depressive symptoms and asthma morbidity among inner-city African American children.

OBJECTIVE: To examine prospective relationships between caregiver's depressive symptoms and child asthma morbidity among inner-city African American families. METHODS: Phone surveys were conducted 6 months apart with 262 African American mothers of children with asthma. Cross-lagged structural path analysis was used for data analyses. RESULTS: Using goodness-of-fit indices, the final model for asthma symptoms had a good fit to the data. Time 1 (T1) maternal depressive symptoms predicted T2 child asthma symptoms (beta =.16, p <.01); however, T1 asthma symptoms did not predict T2 maternal depressive symptoms (beta =.03, non-significant). In contrast, in the final model for emergency department (ED) visits there was no predictive association between maternal depressive symptoms and ED visits. CONCLUSION: Maternal depressive symptoms may have a detrimental effect on child asthma morbidity among inner-city African American families, rather than vice versa. Ameliorating maternal depressive symptoms may result in better asthma outcomes for inner-city children.

Treatments for common psychiatric conditions among children and adolescents during acute rehabilitation and reintegration phases of burn injury.

Advances in critical care and surgical management during the last 20 years have decreased mortality rates among children with severe burn injuries. This improved survival rate has prompted researchers to study the psychological aspects of recovering from a burn injury. Initially research focused primarily on epidemiology, prevention and descriptions of the psychological phenomenon experienced by the children and adolescents. Whereas previously interventions were often utilized during the acute phases of burn injury without knowledge of the long-term effects, more recently, priorities have shifted to include long-term treatment outcome studies. The purpose of this paper is to review and discuss the current evidence-based techniques and their efficacy in the treatment of common psychological and psychiatric conditions among children and adolescents during the three major phases of burn injury.

Confirmatory factor analysis of the Short Form McGill Pain Questionnaire with burn patients.

The Short Form McGill Pain Questionnaire (SF-MPQ) is an abbreviated version of McGill Pain Questionnaire (MPQ) developed for pragmatic reasons to improve the clinical utility of the MPQ. Although the SF-MPQ has been used in more than 250 published studies, few studies have examined the core constructs it measures. The objective of this study was to evaluate in a sample with burn injuries whether the factor structure of the SF-MPQ is consistent with the theoretic pain constructs it purports to measure. Participants (n = 338) met American Burn Association's criteria for major burn injury and had a mean total body surface area burned of 14%. They were mostly male (70.1%) and Caucasian (63.4%) with an average age of 41.25 years. There were 2 primary findings. First, confirmatory factor analysis yielded fit index values demonstrating viability of a 2-factor, oblique, solution composed of sensory and affective latent constructs. These findings were consistent with previous work and the theoretic constructs. Second, results from a relatively new model consisting of 8 SF-MPQ items demonstrated potential viability for measuring similar constructs.