Home as place for healing

Although environment is a core concept in nursing, it has had little theoretical or empirical attention, especially related to healing. This article explores the following aspects of the meaning of healing as they relate to environment as place: (a) healing is grounded in suffering; (b) healing is active and requires presence of the patient and the nurse; and (c) healing is private, spiritual, and profound. Home is explored as a place for healing. The article explores implications for the study of meaning of home, when home is not a place for healing, and future directions for theory and research.     

Dextrin–rhEGF conjugates as bioresponsive nanomedicines for wound repair

Growth factors are known to act in concert to promote wound repair, but their topical application rarely leads to a significant clinical improvement of chronic wounds due to premature inactivation in wound environment. The aim of this study was to synthesise a polymer–growth factor conjugate and investigate whether the novel concept called Polymer-masking-UnMasking-Protein Therapy (PUMPT) might be used to generate bioresponsive polymer therapeutics as nanomedicines able to promote tissue repair. Succinoylated dextrin ( 85,000 g/mol;  19 mol% succinoylation), and rhEGF were chosen as a first model combination. The conjugate synthesised contained  16%wt rhEGF and < 1% free protein. It exhibited increased stability towards proteolytic degradation by trypsin and the clinically relevant enzyme neutrophil elastase. The dextrin component was degraded on addition of α-amylase leading to sustained release of free rhEGF over time (52.7% release after 168 h). When biological activity was assessed (± α-amylase) in proliferation assays using epidermoid carcinoma (HEp2) cells and HaCaT keratinocytes, as anticipated, polymer conjugation reduced rhEGF bioactivity (p = 0.0035). However, exposure to physiological concentrations of α-amylase triggered dextrin degradation and this led to protein unmasking with restoration of bioactivity to the level seen for unmodified rhEGF. Indeed, prolongation of HEp2 proliferation was observed over 8 days. The inability of dextrin, succinoylated dextrin or α-amylase alone to induce proliferative effects, and the ability of α-amylase-exposed dextrin–rhEGF to induce phosphorylation of the epidermal growth factor receptor (EGFR) in HEp2 cells confirmed a mechanism of action by stimulation of classical signal transduction pathways. These observations suggest that this dextrin–rhEGF, and other dextrin-growth factor conjugates have potential for further development as bioresponsive nanomedicines for tissue repair.     

Derivation and testing of an interval-level score for measuring locomotor disability in epidemiological studies of middle and old age

Purpose

Locomotor disability is prevalent in middle and old age and although interval-level measurement instruments have been developed that relate to locomotor disability, there is currently no brief, interval-level score developed specifically to measure the severity of locomotor disability in the general population. We aimed to create such a score from five items of the SF-36 Physical Functioning subscale (PF-10): three walking- and two stair-climbing-related, and assess the scoring mechanism’s measurement properties.

Methods

Data were collected from postal surveys of adults aged 50 years and over. The walking and stair-climbing items were formed into two super-items to remove response dependency. The Rasch measurement model was used to form an interval-level score and fit to this model was assessed. The scoring mechanism was applied to three external data sets and fit to the Rasch model was assessed. Repeatability, construct validity, and responsiveness of the new interval scale were examined.

Results

Overall, the fit of the super-items to the Rasch model was good, with little evidence of misfit. Our analyses broadly support the generalisability, repeatability, construct validity, and responsiveness of this new interval-level score.

Conclusions

An interval-level score for locomotor disability was created from five items of the PF-10 completed in a general population of adults aged 50 years and over. Further work is needed to assess the generalisability of this Rasch score to other populations and to determine a clinically meaningful change score.     

Electrical status epilepticus in sleep

Electrical status epilepticus in sleep (ESES) describes an electroencephalographic pattern showing significant activation of epileptiform discharges in sleep. The terms continuous spike wave in slow-wave sleep (CSWS) and Landau-Kleffner syndrome (LKS) describe the clinical epileptic syndromes seen with ESES. Although there is an overlap between these 2 syndromes, children with CSWS present with a more global regression have more problematic epilepsy and have EEG foci located predominantly in frontotemporal or frontocentral regions. In contrast, children with LKS present with an acquired auditory agnosia, fewer seizures, and EEG foci in the posterotemporal regions. ESES requires a high degree of clinical suspicion because slow-wave sleep must be recorded to confirm this diagnosis. Treatment of ESES extends beyond just control of the seizures; amelioration of the continuous epileptiform discharge must occur to improve neuropsychological outcome. Although there is little evidence to guide treatment, conventional antiepileptic drugs play only a minimal role. Steroid therapy and high-dose benzodiazepines are most commonly used, but other therapies including intravenous gamma-globulin, the ketogenic diet, and surgical therapy with multiple subpial transaction have shown efficacy in small case series. Although epilepsy resolves with time in most cases, many children are left with significant cognitive or language impairment. Longer duration of ESES appears to be the major predictor of poor outcome; markedly abnormal neuronal activity during a critical period for synaptogenesis may result in aberrant synapse formation, explaining the poorer neuropsychological outcome. Early recognition and effective therapy are necessary to improve long-term prognosis in this condition.     

Sleep paralysis and trauma, psychiatric symptoms and disorders in an adult African American population attending primary medical care

The occurrence of sleep paralysis (SP) absent narcolepsy appears to not be uncommon in African Americans and probably other non-European groups. Prior research has linked SP to trauma and psychiatric disorders and suggested a specific relationship to panic disorder in African Americans. The objective of our study was to evaluate relationships of SP with trauma, concurrent psychiatric symptoms and lifetime psychiatric diagnoses in an adult African American population recruited from primary care. Cross sectional study with surveys and diagnostic interviews; Patients attending primary care clinics filled out a survey that determined the 6 month prevalence and associated features of SP, a panic disorder screen, the self-rated Hamilton Depression Scale, and an inventory of trauma exposure. A subset of trauma-exposed participants (N = 142) received comprehensive diagnostic interviews that incorporated the Structured Clinical Interview for DSM-IV and the Clinician Assessed PTSD Scale. Four hundred and forty-one adults participated (mean age-40.0 SD = 13.3, 68% female, 95% African American). Fourteen percent endorsed recent SP. In approximately 1/3 of those with SP, episodes also featured panic symptoms. SP was strongly associated with trauma history, and concurrent anxiety and mood symptoms. SP was not associated with specific psychiatric disorders other than lifetime (but not current) alcohol or substance use disorders. Our findings suggest that SP is not uncommon in adult African Americans and is associated with trauma and concurrent distress but not with a specific psychiatric diagnosis.     

Multiple SNPs within and surrounding the apolipoprotein E gene influence cerebrospinal fluid apolipoprotein E protein levels

The epsilon4 allele of the apolipoprotein E gene (APOE) is associated with increased risk and earlier age at onset in late onset Alzheimer's disease (AD). Other factors, such as expression level of apolipoprotein E protein (apoE), have been postulated to modify the APOE related risk of developing AD. Multiple loci in and outside of APOE are associated with a high risk of AD. The aim of this exploratory hypothesis generating investigation was to determine if some of these loci predict cerebrospinal fluid (CSF) apoE levels in healthy non-demented subjects. CSF apoE levels were measured from healthy non-demented subjects 21-87 years of age (n=134). Backward regression models were used to evaluate the influence of 21 SNPs, within and surrounding APOE, on CSF apoE levels while taking into account age, gender, APOE epsilon4 and correlation between SNPs (linkage disequilibrium). APOE epsilon4 genotype does not predict CSF apoE levels. Three SNPs within the TOMM40 gene, one APOE promoter SNP and two SNPs within distal APOE enhancer elements (ME1 and BCR) predict CSF apoE levels. Further investigation of the genetic influence of these loci on apoE expression levels in the central nervous system is likely to provide new insight into apoE regulation as well as AD pathogenesis.     

Family function in cognitively normal children with epilepsy: impact on competence and problem behaviors

A cross-sectional cohort of 82 cognitively normal children with epilepsy attending the pediatric neurology clinic, who were aged 6-17 years and who had a similarly aged sibling without seizures or cognitive delay, were identified. The parent was asked to complete the Family Assessment Measure III (FAM-III) as well as the Child Behavior Checklist (CBCL) for both the child with epilepsy and his or her sibling. The Overall Rating Score on FAM-III did not differ significantly from the normative mean, although families scored significantly better on the Involvement subscale and significantly worse on the Role Performance subscale. Moderate correlations were found between competence and behavior problems and family function in both children with epilepsy and their siblings. In families functioning at the highest level, both cohorts did well. In those at the lowest level, approximately half of the children in either cohort had problems. For average functioning families, behavior and competence issues were more frequent in children with epilepsy than their siblings.     

Depression, anxiety, and quality of life in siblings of children with intractable epilepsy

Thirty-seven siblings (aged 6-18) of children with intractable epilepsy were surveyed regarding their anxiety, depression, and quality of life, by both self-report (Revised Children's Manifest Anxiety Scale, RCMAS; Children's Depression Inventory, CDI; and Peds QL) and parental report (Child Behavior Checklist, CBCL). Completed forms were returned by 37 of 58 (64%) eligible families. No sibling had a score in the clinical range on the CDI, and only 2 of 37 (6%) scored in the clinical range on the RCMAS, a proportion similar to the normative population. In contrast, 25% were rated by their parents to have elevated Internalizing Behaviors scores on the CBCL. There was a trend for PedsQL scores to be lower than the normative mean. Comorbid behavior and attention problems in the child with epilepsy and sibling CDI and RCMAS scores correlated significantly with self-reported quality of life. However, other epilepsy, child, and family variables (income, parental education, family function, maternal depression) did not correlate. We conclude that siblings of children with intractable epilepsy are functioning well overall and have a good quality of life.