2‐deoxy D‐glucose treatment does not elicit a hair growth response in alopecia areata

2‐deoxy D‐glucose (2DG) was tested for efficacy in treating alopecia areata using the C3H/HeJ skin graft model. 2DG has proven to be efficacious in treatment of various mouse models of autoimmunity with minimal serious side effects noted. This agent has been shown to normalize abnormally activated T‐cell populations while also preventing cell surface expression of NKG2D; key factors defining alopecia areata disease progression. Daily oral ingestion of 2DG via drinking water to mice with patchy or diffuse alopecia areata for 16 weeks failed to prevent expansion of alopecia or cause regrowth of hair in treated mice. Histologically, there were no differences between treated and control groups. These results indicate that, while 2DG is effective for some autoimmune diseases, it was not efficacious for the cell‐mediated autoimmune mouse disease, alopecia areata.     

Effectiveness and Prognostic Factors of Radiotherapy for Painful Plantar Heel Spurs

BACKGROUND AND PURPOSE: The efficacy of radiation treatment (RT) for plantar heel pain has been reported repeatedly. Yet, the results referring to the pain relief rate, to long-term effects and prognostic factors are not consistent. In this paper, the effectiveness (pain relief rate and long-term results) and prognostic factors of RT for plantar heel pain have been investigated. PATIENTS AND METHODS: From January 2000 to October 2000, 62 patients (73 heels) with painful plantar heel spurs and a minimum pain history of 3 months were treated and evaluated in a prospective study. Mean age was 54 years (range 28-84 years). All patients were treated with a total dose of 5 Gy in seven fractions (= one series), given twice a week at a single-dose sequence of 0.25-0.25-0.5-1.0-1.0-1.0-1.0 Gy (10-MV photons, source-skin distance [SSD] 100 cm, direct portal, field size 12 x 17 cm). The mean duration of heel pain before RT was 26 weeks (= 6.5 months; range 3-120 months). By means of a visual analog scale (VAS) the patients had to self-assess the quantity of their heel pain once before, three times during and four times after RT at a longterm median follow-up of 28 and 40 months. Additionally, the patients had to assess their mechanical heel stress extent during RT. Effectiveness was estimated according to the patients' judgment of pain reduction. RESULTS: A significant reduction of heel pain extent measured by VAS has been observed already during the RT series (before RT: 6.3 +/- 1.5 vs. 3.8 +/- 2.1 at the end of RT; p < 0.001). 6 weeks after RT (FU 1) pain reduction (> 20%) was achieved in 60 heels (82.3%; n = 73), in 64 heels (91.4%; n = 70) after a mean follow-up of 28 months (FU 2), and in 61 heels (89.7%; n = 68) after a mean follow-up of 40 months (FU 3), respectively. Sufficient pain relief (> 80% compared to initial extent) was observed in 18/73 heels (24.6%) at FU 1 (FU 2: 42/70; 60.0%; FU 3: 37/68; 54.4%), including 13/73 heels (17.8%) with complete pain relief (FU 2: 39/70; 55.7%; FU 3: 36/68; 52.9%). Partial improvement (50-80% pain reduction) was observed in 27/73 heels (37.0%) at FU 1 (FU 2: 14/70; 20.0%; FU 3: 15/68; 22.1%), and minor partial improvement (20-50% pain reduction) in 15/73 heels (20.5%) at FU 1 (FU 2: 8/70; 11.4%; FU 3: 9/68; 13.2%), respectively. No change was seen in 13/73 heels (17.8%) at FU 1 (FU 2: 6/70; 8.6%; FU 3: 7/68; 10.3%). Older patients (p = 0.04) and patients who avoided heel stress during the period of RT (p < 0.01) demonstrated a better short-term response (FU 1); both effects were lost 28 and 40 months after RT. Moreover, significant differences in the extent of heel pain reduction by RT were observed in dependence on previous pain duration (at FU 2-3). CONCLUSION: The results confirm the high efficacy of RT in painful plantar spur and add new aspects to formerly published data concerning the time course of changes in heel pain reduction. Pain relief can be expected during and shortly after RT. In addition, the initial success can be transformed into effective long-term results > 2 years after RT; however, further improvement is not to be expected. As a new prognostic factor, the reduction of mechanical heel stress during RT may ameliorate the short-term results, whereas short heel pain history improves the long-term results. Especially for older patients, RT should be taken into consideration as primary treatment.     

Doctoral Education in Nursing for Practitioner Knowledge and for Academic Knowledge: The University of Adelaide, Australia

Australian nursing has undergone rapid academization in the past 10 years and this radical change has tended to meld the somewhat different academic traditions of North America and Britain. The introduction of doctoral education in nursing in 1987 has led to a massive increase in scholarly activity and to the preparation of talented leaders. We concur with the view expressed by Henry (1997), "I am convinced that the problems we face in the nursing services would be much more creatively solved if the majority of our doctoral programs prepared young, energetic nurses, early in their career, for clinical practice, not for research and teaching" (p. 162).     

Leukocyte Depletion of Blood Cardioplegia Attenuates Reperfusion Injury

Background. Leukocytes are associated with myocardial injury during reperfusion after ischemia. Short periods of leukocyte depletion during reperfusion result in persistent attenuation of postischemic myocardial dysfunction.

Methods. Leukocyte depletion was examined in a canine model of regional myocardial ischemia and reperfusion. The extracorporeal circuit and cardioplegia circuits underwent leukocyte depletion by mechanical filtration. Animals were instrumented for baseline global function before 90-minute occlusion of the left anterior descending coronary artery. Global function during ischemia and at 5, 30, 60, and 90 minutes after a 60-minute cardioplegic arrest using continuous blood cardioplegia was assessed in leukocyte-depleted (n = 9) and control (n = 10) groups.

Results. No significant difference between groups was seen for systemic leukocyte counts, global function, or water content. Endothelial function was significantly protected as assessed by response to both calcium ionophore (endothelial-dependent, receptor-independent relaxation: leukocyte-depleted, 72% ± 19% of endothelin-induced constriction versus control, 46% ± 14%; p < 0.05) and acetylcholine (endothelial-dependent, receptor-dependent relaxation: leukocyte-depleted, 83% ± 11% versus control, 44% ± 15%; p < 0.05).

Conclusions. Leukocyte-mediated endothelial reperfusion injury can be attenuated by leukocyte depletion during reperfusion.     

Integration from proteins to organs: the IUPS Physiome Project

The IUPS Physiome Project is an internationally collaborative open source project intended to provide a public domain framework for computational physiology, including the development of modeling standards, computational tools and web-accessible databases of models of structure and function at all spatial scales and across all organ systems. Here, we illustrate the application of this multi-scale modeling approach to three organ systems: the heart, the lungs and the musculo-skeletal system, and in each case we show how the organ level models incorporate tissue and cell-level physiology. Although the computational physiology framework presented here does not yet incorporate models of ageing processes, the model-based approach is certainly capable of describing ageing and disease-related processes both via parameter changes within the models of normal physiological processes and via models of additional processes added to the framework.     

Difficulties in navigating the intersection of generalist and specialist palliative care services: A cross-sectional study of bereaved family's experiences of care at home in New Zealand

A generalist–specialist model of palliative care is well established as a framework for the provision of community care in resource-rich countries. However, evidence is lacking regarding how the model is experienced by family carers and the extent to which access to both generalist and specialist palliative care is equitable. A cross-sectional postal survey was undertaken to explore bereaved family's experiences of generalist palliative care and its intersection with hospice services in the last 3 months of life. A modified version of the Views of Informal Carers—Evaluation of Services survey was sent to 4,778 bereaved family. Data were collected between February 2017 and October 2018. Chi-square was utilised to identify factors that impacted on experiences of generalist palliative care; analysis of free text data comprising 45,823 words was undertaken using a directed content analysis approach. Eight hundred and twenty-six questionnaires were returned (response rate = 21%). Seventy per cent of people (n = 579) spent some time at home in the last 3 months prior to death. People who received support from hospice were more likely to receive support from multiple other services. Those who received no community services were less likely to feel supported by their general practitioner, less likely to spend the last 2 days of life or die at home. Feeling supported had a strong association with services working well together, being involved in decision-making and being aware of the poor prognosis. The provision of palliative care is complicated by a lack of integration with specialist palliative care and may be the basis of continuing inequities in the provision of community care at the end of life. The assumption at a policy level that “generalists” are willing and able to play a key role in palliative care provision needs to be further challenged.     

Reduction in Maternal Energy Intake during Lactation Decreased Maternal Body Weight and Concentrations of Leptin,Insulin and Adiponectin in Human Milk without Affecting Milk Production,Milk Macronutrient Composition or Infant Growth

Maternal diet has the potential to affect human milk (HM) composition, but very few studies have directly assessed the effect of maternal diets on HM composition. The primary aim of this study was to assess the effect of improving dietary quality in lactating women over 2 weeks on the concentrations of macronutrients and metabolic hormones in HM. The secondary aims were to assess the impact of the dietary intervention on 24 h milk production, maternal body composition and infant growth. Fifteen women completed a 1-week baseline period followed by a 2-week dietary intervention phase targeted towards reducing fat and sugar intake. Maternal anthropometric and body composition and infant growth measurements were performed weekly. Total 24 h milk production was measured before and after the dietary intervention, and HM samples were collected daily. Maternal intakes of energy (−33%), carbohydrate (−22%), sugar (−29%), fat (−54%) and saturated fat (−63%) were significantly reduced during the dietary intervention. HM insulin, leptin and adiponectin concentrations were 10–25% lower at the end of the dietary intervention, but HM concentrations of macronutrients were unaffected. Maternal body weight (−1.8%) and fat mass (−6.3%) were significantly reduced at the end of the dietary intervention, but there were no effects on 24 h milk production or infant growth. These results suggest that reducing maternal energy, carbohydrate, fat and sugar intake over a 2-week period is associated with significant reductions in HM insulin, leptin and adiponectin concentrations. These changes may be secondary to decreases in maternal weight and fat mass. The limited studies to date that have investigated the association between metabolic hormone concentrations in HM and infant growth raise the possibility that the changes in HM composition observed in the current study could impact infant growth and adiposity, but further studies are required to confirm this hypothesis.     

Serum neuron-specific enolase in the major subtypes of status epilepticus

OBJECTIVES: To determine the relative magnitudes of neuron-specific enolase (NSE) levels after complex partial status epilepticus (SE), absence SE, generalized convulsive SE, and subclinical generalized convulsive SE (frequently referred to as acute symptomatic myoclonic status epilepticus). BACKGROUND: NSE is a marker of acute brain injury and blood-brain barrier dysfunction, which is elevated in SE. METHODS: Serum NSE levels were drawn in 31 patients 1, 2, 3, and 7 days after SE. Patients were classified as acute symptomatic or remote symptomatic, and the duration and outcome of SE were determined and correlated with the peak NSE level. RESULTS: NSE was elevated significantly in all four subtypes of SE, but NSE levels were highest in complex partial and subclinical SE. The mean peak NSE level for the complex partial SE group was 23.88 ng/mL (n = 12), 21.5 ng/mL for absence SE (n = 1), 14.10 ng/mL for the generalized convulsive SE group (n = 12), and 37.83 ng/mL for the subclinical SE group (n = 6), all of which was significantly higher than normal control subjects (5.02 ng/mL). Outcome was significantly different between the three groups (p = 0.0007), and was significantly worse for subclinical SE (p = 0.0005, subclinical versus generalized convulsive SE). CONCLUSION: Serum NSE levels were highest in complex partial and subclinical generalized convulsive SE. The extremely high levels of NSE in subclinical SE reflect the severity of the acute neurologic insults and poor outcome common to subclinical SE. High NSE levels in complex partial SE reflects the long duration of SE in this subgroup, and potential for brain injury.     

P300 auditory event-related potentials in nontraumatic coma. Association with Glasgow Coma Score and awakening.

Auditory event-related potentials (ERPs) were performed in 20 patients with nontraumatic coma to determine the presence of a P300 ERP in coma and its association with the Glasgow Coma Score and awakening (Glasgow Outcome Score, > or = 3). A standard "oddball" paradigm was used: frequent tone, 1 kHz; rare tone, 2 kHz and 4 Hz; probability, 20%. The Glasgow Coma Score was determined concurrently with the P300 ERP. Thirty percent (6/20) of the comatose patients had a P300 ERP. The mean Glasgow Coma Score was significantly higher for those with a P300 ERP. Eighty-three percent (5/6) of those with a P300 ERP awoke. Presence of a P300 ERP was associated significantly with awakening, but absence of a P300 ERP did not preclude it.