A randomised controlled trial of interventions for taxane-induced nail toxicity in women with early breast cancer.

Onycholysis and paronychia has been associated with chemotherapy treatment for women with breast cancer. Our primary aim was to investigate the effectiveness of different topical interventions to ameliorate nail toxicity. Secondary aims were to explore the full range and severity of possible nail changes associated with taxane-based chemotherapy and the specific impact this had on quality of life, using two novel measures. This was an exploratory randomised controlled trial of three topical interventions (standard care, nail polish or specialist nail drops) for the prevention or reduction of nail changes induced by taxane-based chemotherapy. Outcomes included nail toxicity assessed at three time points (baseline, 3 weeks and 3 months post completion of chemotherapy) using two novel clinical tools (NToX-G12, NToX-QoL) and the Common Terminology Criteria for Adverse Events (CTCAE v3) and EQ-5D-5L. A total of 105 women were recruited (35 in each arm) and monitored up to three months post completion of chemotherapy. Almost 20% of patients were over the age of 60 years. There were 26 withdrawals, the majority from the nail polish arm. Residual Maximum Likelihood REML analysis indicated a significant arm, time and interaction effect for each intervention (p < 0.001). Less nail toxicity was observed in patients receiving specialist nail drops or standard care arms in comparison to those using nail polish. This study provides evidence to support clinicians' suggestions on nail care recommendations based on the patients' needs and preferences. Future investigations into comparing or combining cryotherapy and topical solutions that can support patient's decisions are warranted.

Epidemiology of End-Stage Kidney Disease on Renal Replacement Therapy: 35 Years Analysis Study Nephrologists.

Incidence and prevalence of end-stage kidney disease (ESKD) population on renal replacement therapy (RRT) for some of the nations are well published. Oman's publication on this aspect is limited and therefore, this study was conducted. This study analyzed the data obtained from the RRT register in Oman. The main measurements and aim are to identify the incidence and prevalence of Oman's treated RRT population (1983-2018) with a major focus on the hemodialysis (HD) cohort. The year 1983 is the year when renal care was started in Oman. The total number of patients registered on Oman's RRT register of the central renal dialysis center from 1983 to 2010 was 3524, distributed among the following treatment cohorts; HD, 2328 patients (66%); kidney transplant, 1,144 patients (32.5%); peritoneal dialysis, 52 patients (1.5%). However, the treated patients alive on HD by end of 2018 were 2023. The dialysis sub-population increased from 35 patients in 1983 to 2023 patients in 2018. The recorded incidence registered in 1983 was 34 patients, in 1986 was 33, in 2013 was 168, in 2015 was 230, and in 2018 was 350 RRT treated patients per million population of Oman. There is a progressive rise of the incidence and prevalence of Oman's RRT population. This rise is similar to many nations, especially developing countries that are being faced with the rising trend of noncommunicable diseases (NCD). The health system and other stakeholders ought to take various stringent policies to ameliorate the progressive increase of NCD and hence, reduce the burden of chronic kidney disease and ESKD.

An Arabic Translation, Reliability, Validity, and Feasibility of the Richards-Campbell Sleep Questionnaire for Sleep Quality Assessment in ICU: Prospective-Repeated Assessments.

BACKGROUND AND PURPOSE: To translate Richards-Campbell Sleep Questionnaire (RCSQ) into the Arabic language (RCSQ-A), to assess content validity of the translated tool, to analyze the internal consistency, and to evaluate its feasibility. METHODS: A rigorous translation was completed using the process of translation by World Health Organization. Cognitive debriefing interviews were performed. Repeated assessments using RCSQ-A was conducted in critical care patients in Saudi Arabia. RESULT: Cronbach's alpha of .89 was seen in the RCSQ-A. The cognitive interviews showed that the RCSQ-A well understood and interpreted correctly and consistently. Fifty-seven participants reported their sleep using RCSQ-A a total of 110 times. CONCLUSION: RCSQ-A has adequate translation validity, provided good internal consistency and content validity, making it suitable for use as a measurement tool in practice and research in Arabic-speaking countries.

Prospective repeated assessment of self-reported sleep quality and sleep disruptive factors in the intensive care unit: acceptability of daily assessment of sleep quality.

INTRODUCTION: Despite the importance of sleep, the assessment of sleep quality does not form part of standard clinical care in intensive care unit (ICU). Continuous assessment of self-reported quality of ICU patients' sleep has been strongly recommended. Prior to implementing such an assessment in the ICU, it is important to assess the acceptability of this method of assessment to the ICU's patients. The aims of this study were to assess the acceptability to ICU patients of completing daily self-reports on sleep quality during their ICU stay and to assess ICU patients' self-reported sleep quality and sleep disruptive factors during their time in ICU. METHODS: An observational prospective-repeated assessment was conducted on n=120 patients in an ICU in Saudi Arabia. The participants were both intubated and non-intubated. OUTCOMES MEASURES: Over a 3-month period, sleep quality was assessed using the Arabic version of the Richards-Campbell Sleep Questionnaire (RCSQ-A), and self-reported sleep disruptive factors were identified. Clinical factors, such as ICU interventions, and previously administered sedatives were also examined. The patients' acceptance of completing daily RCSQ-A reports was assessed using various indicators of acceptability. RESULTS: A total of 381 self-reports (RCSQ-A) were collected for this analysis. The patients reported 34.4±5.60, indicating that sleep quality was poor on average. The group of intubated patients reported much poorer sleep quality during intubation than after extubation. In the multivariate analysis, factors which most significantly affected sleep (exp(b), p value) were midazolam (-6.424, p<0.0005), propofol (-3.600, p<0.05), noise (-1.033, p<0.05), gender (1.836, p<0.05), daytime sleepiness (0.856, p<0.05) and the presence of mechanical ventilation (-1.218, p<0.05). CONCLUSION: The acceptability and feasibility of using daily RCSQ-A for sleep quality assessment was demonstrated. Sleep quality was reported as poor by all participants and the factors affecting sleep were varied. This study provided various recommendations for healthcare providers and researchers in terms of evaluating and improving sleep quality in ICU patients.

Assessment of APOE in atypical parkinsonism syndromes.

Atypical parkinsonism syndromes are a heterogeneous group of neurodegenerative disorders that include corticobasal degeneration (CBD), Lewy body dementia (LBD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP). The APOE ε4 allele is a well-established risk factor for Alzheimer's disease; however, the role of APOE in atypical parkinsonism syndromes remains controversial. To examine the associations of APOE ε4 and ε2 alleles with risk of developing these syndromes, a total of 991 pathologically-confirmed atypical parkinsonism cases were genotyped using the Illumina NeuroChip array. We also performed genotyping and logistic regression analyses to examine APOE frequency and associated risk in patients with Alzheimer's disease (n = 571) and Parkinson's disease (n = 348). APOE genotypes were compared to those from neurologically healthy controls (n = 591). We demonstrate that APOE ε4 and ε2 carriers have a significantly increased and decreased risk, respectively, of developing Alzheimer's disease (ε4: OR: 4.13, 95% CI: 3.23-5.26, p = 3.67 × 10-30; ε2: OR: 0.21, 95% CI: 0.13-0.34; p = 5.39 × 10-10) and LBD (ε4: OR: 2.94, 95% CI: 2.34-3.71, p = 6.60 × 10-20; ε2: OR = OR: 0.39, 95% CI: 0.26-0.59; p = 6.88 × 10-6). No significant associations with risk for CBD, MSA, or PSP were observed. We also show that APOE ε4 decreases survival in a dose-dependent manner in Alzheimer's disease and LBD. Taken together, this study does not provide evidence to implicate a role of APOE in the neuropathogenesis of CBD, MSA, or PSP. However, we confirm association of the APOE ε4 allele with increased risk for LBD, and importantly demonstrate that APOE ε2 reduces risk of this disease.

Initial characterization of behavior and ketamine response in a mouse knockout of the post-synaptic effector gene Anks1b.

The human ANKS1B gene encodes an activity-dependent effector of post-synaptic signaling. It was recently associated with neuropsychiatric phenotypes in genome-wide studies. While the biological function of ANKS1B has been partly elucidated, its role in behavior is poorly understood. Here, we breed and characterize a full knockout (KO) for murine Anks1b. We found that the homozygous KO genotype was partially lethal, showing significant deviation from expected segregation ratios at weaning. Behaviorally, KOs exhibited no difference in baseline acoustic startle response, but showed deficits in prepulse inhibition (PPI). KOs also exhibited locomotor hyperactivity and increased stereotypy at baseline. Administration of ketamine, a non-competitive NMDA-receptor antagonist, greatly exacerbated locomotor activity in the KOs at lower doses, but genotype groups were almost indistinguishable as dose increased. Stereotypy showed a complex response to ketamine in the KOs, with elevated stereotypy at lower doses and markedly less at high doses, compared to wild type. Our study is the first to probe the behavioral phenotypes associated with ablation of Anks1b. Deficits in PPI, locomotor hyperactivity, elevated stereotypy and altered response to NMDA receptor antagonism are murine behavioral outcomes with translational relevance for psychiatric disorders. These findings are also consistent with the role of Anks1b as an effector of glutamatergic signaling. As an intermediary between post-synaptic receptor stimulation and long-term changes to neuronal protein expression, further investigation of Anks1b is warranted.

Postmortem Alzheimer's Disease Hippocampi Show Oxidative Phosphorylation Gene Expression Opposite that of Isolated Pyramidal Neurons.

Causes of initiation and progression of sporadic Alzheimer's disease (sAD) are likely multiple and include impairment of mitochondrial bioenergetics. We analyzed RNA expression levels of multiple mitochondrial oxidative phosphorylation (OXPHOS) and biogenesis (mitobiogenesis) genes in unfixed hippocampal (WH) frozen sections (10 sAD; 9 CTL) and laser-captured hippocampal pyramidal neurons (PyNs, ~1000 neurons from each case) from 8 sAD and 7 CTL cases. Nuclear-encoded OXPHOS genes in WH were significantly increased in sAD, whereas in isolated sAD PyNs, these same genes were significantly decreased. Mitochondrial DNA-encoded genes were increased in sAD PyNs but showed a non-significant downward trend in sAD WH. Relationships among WH and PyN gene expression levels in sAD distributed in a different population compared to CTL. Principal component analysis (PCA) revealed clustering of CTL but widespread heterogeneity of sAD samples. In sAD, mitochondrial bioenergetics at the gene expression level are depressed in vulnerable PyNs. PCA revealed that CTL samples clustered together, whereas sAD samples varied widely. From the perspective of OXPHOS bioenergetics, sAD is a heterogeneous syndrome and not likely due to a single abnormality. Increased stimulation of nuclear-encoded OXPHOS gene expression in PyNs is a rational therapeutic approach for most but not all cases of sAD.

Mitochondrial DNA copy numbers in pyramidal neurons are decreased and mitochondrial biogenesis transcriptome signaling is disrupted in Alzheimer's disease hippocampi.

Alzheimer's disease (AD) is the major cause of adult-onset dementia and is characterized in its pre-diagnostic stage by reduced cerebral cortical glucose metabolism and in later stages by reduced cortical oxygen uptake, implying reduced mitochondrial respiration. Using quantitative PCR we determined the mitochondrial DNA (mtDNA) gene copy numbers from multiple groups of 15 or 20 pyramidal neurons, GFAP(+) astrocytes and dentate granule neurons isolated using laser capture microdissection, and the relative expression of mitochondrial biogenesis (mitobiogenesis) genes in hippocampi from 10 AD and 9 control (CTL) cases. AD pyramidal but not dentate granule neurons had significantly reduced mtDNA copy numbers compared to CTL neurons. Pyramidal neuron mtDNA copy numbers in CTL, but not AD, positively correlated with cDNA levels of multiple mitobiogenesis genes. In CTL, but not in AD, hippocampal cDNA levels of PGC1α were positively correlated with multiple downstream mitobiogenesis factors. Mitochondrial DNA copy numbers in pyramidal neurons did not correlate with hippocampal Aß1-42 levels. After 48 h exposure of H9 human neural stem cells to the neurotoxic fragment Aß25-35, mtDNA copy numbers were not significantly altered. In summary, AD postmortem hippocampal pyramidal neurons have reduced mtDNA copy numbers. Mitochondrial biogenesis pathway signaling relationships are disrupted in AD, but are mostly preserved in CTL. Our findings implicate complex alterations of mitochondria-host cell relationships in AD.

Albumin administration protects against bilirubin-induced auditory brainstem dysfunction in Gunn rat pups.

BACKGROUND: Free bilirubin (Bf), the unbound fraction of unconjugated bilirubin (UCB), can induce neurotoxicity, including impairment of the auditory system, which can be assessed by brainstem auditory evoked potentials (BAEPs). We hypothesized that albumin might reduce the risk of neurotoxicity by decreasing Bf and its translocation into the brain. AIM: To determine the effects of albumin on BAEPs and brain bilirubin content in two Gunn rat pup models of acute hyperbilirubinemia. METHODS: We used Gunn rat pups, which have a deficiency of the bilirubin-conjugating enzyme UGT1A1. We induced haemolysis by injection of phenylhydrazine (phz) into 14-days old pups. Subsequently, pups were treated with either i.p. human serum albumin (HSA; 2.5 g/kg; n = 8) or saline (control, n = 8). We induced acute neurotoxicity by injecting 16-days old pups with sulphadimethoxine (sulpha) and treated them with either HSA (n = 9) or saline (control, n = 10). To assess bilirubin neurotoxicity, we used the validated BAEP method and compared relevant parameters; i.e. peak latency values and interwave interval (IWI) between peak I and peak II, a marker of acute neurotoxicity. RESULTS: Phz and sulpha significantly increased IWI I-II by 26% and 29% (P < 0.05) in the haemolysis and the displacement model, respectively. Albumin completely prevented the increase of IWI I-II in either model. The beneficial effect of albumin in the displacement-model by means of normal BAEPs was in line with less bilirubin in the brain (NS). Interestingly, in the haemolysis model the accumulation of total bilirubin in the brain was unaltered, and BAEPs still appeared normal. This might advocate for a role of brain Bf which was calculated and showed that albumin treatment non-significantly reduces Bf concentrations in brain, compared with saline treatment. CONCLUSIONS: Albumin treatment is neuroprotective in acute hyperbilirubinemia in Gunn rat pups. Our present results underline the importance of functional diagnostic test of neurotoxicity above biochemical concentrations.

Provision of information about malignant spinal cord compression: perceptions of patients and staff.

BACKGROUND: Various guidelines have highlighted the importance of patients being given information on malignant spinal cord compression (MSCC), both when diagnosed with the condition and as a tool to aid early detection. AIM: To determine patient and staff views on the provision of MSCC information to patients with a diagnosis of or considered to be at high risk of developing MSCC. METHODS: Patients with MSCC admitted to a large regional cancer centre in Scotland over a 6-month period were interviewed. Staff were also surveyed using similar questions. RESULTS: Fifty-six patients and fifty staff were recruited. Only 4% of staff reported giving any written information about MSCC to patients with a confirmed diagnosis, although 20% of patients said they received it and 77% wanted it. A total of 54% of staff reported gaving prophylactic information about MSCC to patients, although the majority of the patients (86%) said they would have wanted this information. Patients generally did not access additional information about MSCC and were dependent on the limited amount provided by the health-care team. CONCLUSION: Health professionals need to ensure that patients get the information they want, which will allow them to recognize MSCC symptoms early for improved treatment outcomes or to better adapt to a diagnosis.

Multi-neuronal recordings in the Basal Ganglia in normal and dystonic rats.

Classical rate-based pathway models are invaluable for conceptualizing direct/indirect basal ganglia pathways, but cannot account for many aspects of normal and abnormal motor control. To better understand the contribution of patterned basal ganglia signaling to normal and pathological motor control, we simultaneously recorded multi-neuronal and EMG activity in normal and dystonic rats. We used the jaundiced Gunn rat model of kernicterus as our experimental model of dystonia. Stainless steel head fixtures were implanted on the skulls and EMG wires were inserted into antagonistic hip muscles in nine dystonic and nine control rats. Under awake, head-restrained conditions, neuronal activity was collected from up to three microelectrodes inserted in the principal motor regions of the globus pallidus (GP), subthalamic nucleus, and entopeduncular nucleus (EP). In normal animals, most neurons discharged in regular or irregular patterns, without appreciable bursting. In contrast, in dystonic animals, neurons discharged in slow bursty or irregular, less bursty patterns. In normal rats, a subset of neurons showed brief discharge bursts coinciding with individual agonist or antagonist EMG bursts. In contrast, in dystonics, movement related discharges were characterized by more prolonged bursts which persist over multiple dystonic co-contraction epics. The pattern of movement related decreases in discharge activity however did not differ in dystonics compared to controls. In severely dystonic rats, exclusively, simultaneously recorded units often showed abnormally synchronized movement related pauses in GP and bursts in EP. In conclusion, our findings support that slow, abnormally patterned neuronal signaling is a fundamental pathophysiological feature of intrinsic basal ganglia nuclei in dystonia. Moreover, from our findings, we suggest that excessive movement related silencing of neuronal signaling in GP profoundly disinhibits EP and in turn contributes to sustained, unfocused dystonic muscle contractions.

Successful affiliations: principles and practices.

An affiliation can help a healthcare provider prepare for the challenges of healthcare reform, the rapidly changing landscapes of the commercial insurance industry, and the public's expectations about service and quality. UC Davis Medical Center, a 645-bed tertiary hospital in Sacramento, California, with many hospital-based clinics and a community-based group of primary care clinics, has developed a number of principles for affiliation. These principles are based on its experience in legal and financial affiliations with an academic practice group, with individual and small groups of primary care physicians, and with community hospitals around oncology services linked with U.C. Davis' National Cancer Institute-designated cancer center. This article offers a process for evaluating the appropriateness of an affiliation. The chances for a successful affiliation improve if each party has indicated the value it hopes to derive and how to measure that value, has communicated with all affected constituents, and has an agreed-upon method for resolving disputes.

A novel stereotaxic apparatus for neuronal recordings in awake head-restrained rats.

A novel technique for neuronal recordings in awake head-restrained animals is presented. Our setup allows (1) daily repeat microelectrode studies in rats without use of anesthesia, (2) excellent stabilization of head using an eight point fixation, (3) painless head-restraint of the animal, (4) accurate stereotaxic localization during multiple sessions of recording, (5) to considerably reduced surgical time, (6) quick repositioning during chronic recording sessions and (7) high quality stabilized neuronal recordings during periods of rest and active movements.

Profile of minocycline neuroprotection in bilirubin-induced auditory system dysfunction.

Excessive hyperbilirubinemia in human neonates can cause permanent dysfunction of the auditory system, as assessed with brainstem auditory evoked potentials (BAEPs). Jaundiced Gunn rat pups (jjs) exhibit similar BAEP abnormalities as hyperbilirubinemic neonates. Sulfadimethoxine (sulfa) administration to jjs, which displaces bilirubin from serum albumin into tissues including brain, exacerbates acute toxicity. Minocycline administered prior to sulfa in jjs protects against BAEP abnormalities. This study evaluates the neuroprotective capabilities of minocycline HCl (50 mg/kg) administered 30 or 120 min after sulfa (200 mg/kg) in 16 days old jjs. BAEPs are recorded at 6 or 24 h post-sulfa. Abnormal BAEP waves exhibit increased latency and decreased amplitude. The sulfa/saline treated jjs exhibited a significantly increased interwave interval between waves I and II (I-II IWI) and significantly decreased amplitudes of waves II and III compared to the saline/saline jjs. The minocycline 30 min post-sulfa (sulfa/mino+30) group was not significantly different from the saline/saline control group, indicating neuroprotection. The minocycline 120 min post-sulfa (sulfa/mino+120) group had a significantly decreased amplitude of wave III at both 6 and 24h. These studies indicate that minocycline has a graded neuroprotective effect when administered after acute bilirubin neurotoxicity.

Quantification of gait in dystonic Gunn rats.

Spontaneously jaundiced Gunn rats exposed to sulfadimethoxine develop bilirubin encephalopathy (kernicterus) with hearing loss and dystonia, closely resembling the human syndrome. We recently characterized the electromyographic activity in this animal model supporting our clinical impression of dystonia. The objective of this study was to develop a simple, non-invasive method to quantify the motor deficits in dystonic rodents. On postnatal day 16, Gunn rats were treated with 100mg/kg of sulfadimethoxine or saline. On postnatal day 31, the ventral view of the animals was videotaped while the animals walked inside a Plexiglas chamber. Individual video frames were reviewed and specific gait parameters including hindlimb spread, step length ratio variability, stance/swing ratio and walking speed were compared between dystonic and non-dystonic jaundiced and non-jaundiced littermates. Data analysis demonstrated statistically significant increases in hindlimb spread and step length ratio variability and decreases in walking speed in dystonic animals as compared to controls. This study demonstrates a valuable technique to objectively characterize dystonia in Gunn rats, which could have wide use for other experimental movement disorders as well.

In vitro complementation of Tdp1 deficiency indicates a stabilized enzyme-DNA adduct from tyrosyl but not glycolate lesions as a consequence of the SCAN1 mutation.

A homozygous H493R mutation in the active site of tyrosyl-DNA phosphodiesterase (TDP1) has been implicated in hereditary spinocerebellar ataxia with axonal neuropathy (SCAN1), an autosomal recessive neurodegenerative disease. However, it is uncertain how the H493R mutation elicits the specific pathologies of SCAN1. To address this question, and to further elucidate the role of TDP1 in repair of DNA end modifications and general physiology, we generated a Tdp1 knockout mouse and carried out detailed behavioral analyses as well as characterization of repair deficiencies in extracts of embryo fibroblasts from these animals. While Tdp1(-/-) mice appear phenotypically normal, extracts from Tdp1(-/-) fibroblasts exhibited deficiencies in processing 3'-phosphotyrosyl single-strand breaks and 3'-phosphoglycolate double-strand breaks (DSBs), but not 3'-phosphoglycolate single-strand breaks. Supplementing Tdp1(-/-) extracts with H493R TDP1 partially restored processing of 3'-phosphotyrosyl single-strand breaks, but with evidence of persistent covalent adducts between TDP1 and DNA, consistent with a proposed intermediate-stabilization effect of the SCAN1 mutation. However, H493R TDP1 supplementation had no effect on phosphoglycolate (PG) termini on 3' overhangs of double-strand breaks; these remained completely unprocessed. Altogether, these results suggest that for 3'-phosphoglycolate overhang lesions, the SCAN1 mutation confers loss of function, while for 3'-phosphotyrosyl lesions, the mutation uniquely stabilizes a reaction intermediate.

Linking academic and clinical missions: UC Davis' integrated AHC.

Academic health centers (AHCs) rely on cross-subsidization of education and research programs by the clinical enterprise, but this is becoming more challenging as clinical reimbursements decline. These new realities provide an important opportunity to reevaluate the relationships between medical schools and academic medical centers. The authors examine the benefits of their ongoing commitment to create a fully integrated AHC at the University of California (UC) Davis, discussing strategies that serve as catalysts for continued growth. They explore how investments of proceeds from the clinical enterprise directly enhance educational and research initiatives, which, in turn, increase the success of patient-care programs. This has created a cycle of excellence that leads to an enhanced reputation for the entire health system. One strategy involves using clinical margins to "prime the pump" in anticipation of major research initiatives, resulting in rapid increases in external research funding and academic recognition. In turn, this facilitates recruitment of high-quality faculty and staff, improving the ability to deliver expert clinical care. The overall enhanced institutional reputation positions both the clinical and academic programs for further success. The authors posit that such approaches require executive-level commitment to a single strategic vision, unified leadership, and collaborative financial and operational decision making. Adopting such changes is not without challenges, which are discussed, but the authors suggest that an integrated AHC fosters optimized operations, enhanced reputation, and stronger performance across all mission areas. They also provide examples of how the UC Davis Health System has thus attracted philanthropists and investments from the private sector.

A new animal model of hemolytic hyperbilirubinemia-induced bilirubin encephalopathy (kernicterus).

Neonatal hyperbilirubinemia can cause bilirubin encephalopathy (kernicterus). Spontaneously jaundiced (jj) Gunn rats treated with sulfonamide (sulfa) to displace bilirubin from serum albumin, develop bilirubin encephalopathy and abnormal brainstem auditory evoked potentials (BAEPs) comparable with human newborns. We hypothesized phenylhydrazine (PHZ)-induced hemolysis would significantly elevate total plasma bilirubin (TB) in jj Gunn rat pups and produce BAEP abnormalities similar to those observed after sulfa. PHZ 0, 25, 50, or 75 mg/kg was administered intraperitonealy to 15-d-old jjs. An initial TB was recorded in each animal, and a second recorded 1-4 d postinjection to generate a dose-response curve. After PHZ 75 mg/kg, TB peaked at about 30 mg/dL at 48-72 h. A second group of jjs injected with PHZ (0, 25, 50, or 75 mg/kg) and nonjaundiced controls given PHZ 75 mg/kg had HCT and TB at baseline, and HCT, TB, and BAEPs recorded at 48 h. BAEP wave II and III amplitudes decreased, and I-II and I-III interwave intervals increased indicating abnormal central (brainstem) auditory function. PHZ-induced hemolysis in jaundiced Gunn rat pups produces sufficiently elevated TB levels to produce bilirubin encephalopathy. This new model may be a more clinically relevant experimental model of kernicterus- and bilirubin-induced neurologic disorders.

Electromyographic characterization in an animal model of dystonia.

Kernicterus is known to produce damage to the auditory system and the basal ganglia in humans. Although the Gunn rat model of kernicterus has been extensively used to characterize the auditory features, this model has not been similarly utilized to systematically investigate the movement disorder. In the present study, spontaneously jaundiced (jj) 16 day old Gunn rat pups were treated with sulfadimethoxine to exacerbate bilirubin toxicity and compared to saline treated jjs and non-jaundiced (Nj) littermates. Electromyographic (EMG) activity was recorded from antagonistic hip muscles in dystonic and in normal appearing rats. Raw EMG signals were decomposed using the Discrete Wavelet Transform based multi-resolution analysis and signal coefficients corresponding to the dominant EMG frequency band were chosen. Gunn rats exposed to sulfadimethoxine developed a stable clinical state characterized by prolonged abnormal axial and appendicular postures. Coherence plots of the separated signals coefficients revealed 4-7 Hz co-activation in antagonistic muscles that was significantly more prominent in jj sulfa treated dystonic compared to normal rats. The EMG findings support the presence of dystonia in sulfadimethoxine exposed jj Gunn rats and suggest that these animals can serve as a valuable model for experimental investigations of dystonia.

Using guidelines to support secondment: a personal experience.

BACKGROUND: Secondment is recognized as a method of staff development and can offer both individuals and organizations structure and flexibility in relation to service development. AIM: This article describes the experience of a clinical nurse specialist (CNS) seconded 3 days a week for 18 months to a Macmillan Education Unit, as an associate lecturer (the host organization). Different types of secondment are discussed, mapping this experience to Partnership Information Network guidelines. EVALUATION: A 360 degrees evaluation process involving all key stakeholders was carried out, and highlighted positive aspects. CONCLUSION: Secondment is recommended as a valuable and safe method of staff development, increasing knowledge and skills, raising motivation and aiding retention, provided guidelines are adhered to and strategies are in place to mitigate risks.