Investigation of the relationship between transcranial impedance and intracranial pressure.

Studies on piglets have shown that cranial bioimpedance (Z) measurements correlate well with invasively measured intracranial pressure (ICP). We have tested the feasibility of collecting transcranial impedance from a clinical device for measuring whole-body water content (ImpediMed SFB7). In the clinical study, 50 normal healthy volunteers had transcranial impedance measured using nine different head montages (forehead to mastoid (left/right), temporal to mastoid (left/right), forehead to temporal (left/right), forehead to occipital (left/right) and temporal to temporal). Impedance was measured 20 times over a frequency range per montage and ANOVA used to test for effects of electrode position upon recorded value. For the experimental study, five sedated and ventilated Marino sheep were instrumented for intraventricular ICP and transcranial impedance measurement. Measures of ICP were recorded while ICP was increased from baseline to greater than 50 mmHg in five steps using an intraventricular infusion of mock CSF. There is a significant effect of electrode position and gender upon transcranial impedance (p < 0.001). The temporal-mastoid electrode position had significantly lower impedance values in keeping with its shorter path length. ICP correlated with craniospinal compliance measurements and Impedance vs Freq by ICP step shows a clear ICP dependence (p = 0.007) across the sheep.

Fluorine Is a Major Constituent of the Marine Sponge Halichondria moorei.

Fluorine constitutes about 10 percent of the dry weight of the marine sponge Halichondria moorei. The fluorine occurs as potassium fluorosilicate, which is a potent anti-inflammatory agent. A closely related sponge living in the same habitat does not contain any fluorine. The habitat was found to be free of fluorine except for the small amount naturally present in seawater.

CRISPR/Cas9 mediated generation of an ovine model for infantile neuronal ceroid lipofuscinosis (CLN1 disease).

The neuronal ceroid lipofuscinoses (NCLs) are a group of devastating monogenetic lysosomal disorders that affect children and young adults with no cure or effective treatment currently available. One of the more severe infantile forms of the disease (INCL or CLN1 disease) is due to mutations in the palmitoyl-protein thioesterase 1 (PPT1) gene and severely reduces the child's lifespan to approximately 9 years of age. In order to better translate the human condition than is possible in mice, we sought to produce a large animal model employing CRISPR/Cas9 gene editing technology. Three PPT1 homozygote sheep were generated by insertion of a disease-causing PPT1 (R151X) human mutation into the orthologous sheep locus. This resulted in a morphological, anatomical and biochemical disease phenotype that closely resembles the human condition. The homozygous sheep were found to have significantly reduced PPT1 enzyme activity and accumulate autofluorescent storage material, as is observed in CLN1 patients. Clinical signs included pronounced behavioral deficits as well as motor deficits and complete loss of vision, with a reduced lifespan of 17 ± 1 months at a humanely defined terminal endpoint. Magnetic resonance imaging (MRI) confirmed a significant decrease in motor cortical volume as well as increased ventricular volume corresponding with observed brain atrophy and a profound reduction in brain mass of 30% at necropsy, similar to alterations observed in human patients. In summary, we have generated the first CRISPR/Cas9 gene edited NCL model. This novel sheep model of CLN1 disease develops biochemical, gross morphological and in vivo brain alterations confirming the efficacy of the targeted modification and potential relevance to the human condition.

Simultaneous measurement of force and respiratory profiles during chest physiotherapy in ventilated children.

There are currently no objective means of quantifying chest wall vibrations during manual physiotherapy. The aims of the study were to (i) develop a method to quantify physiotherapy-applied forces and simultaneous changes in respiratory flow and pressure, (ii) assess the feasibility of using this method in ventilated children and (iii) characterize treatment profiles delivered by physiotherapists in the paediatric intensive care unit. Customized sensing mats were designed and used in combination with a respiratory profile monitor. Software was developed to align force and flow data streams. Force and respiratory data were successfully collected in 55 children (median age 1.6 years (range 0.02-13.7 years)). Physiotherapists demonstrated distinctive variations in the pattern of force applied and manual lung inflations. The maximum applied force ranged from 15 to 172 N, and was correlated with the child's age (r = 0.76). Peak expiratory flow increased significantly during manual inflations both with and without chest wall vibrations (p < 0.05). This method provides the basis for objective assessments of the direct and independent effects of vibration forces and manual lung inflations as an essential precursor to developing evidence-based practice.

Falls and health status in elderly women following first eye cataract surgery: a randomised controlled trial.

BACKGROUND/AIM: A third of elderly people fall each year. Poor vision is associated with increased risk of falls. The authors aimed to determine if first eye cataract surgery reduces the risk of falling, and to measure associated health gain. METHODS: 306 women aged over 70, with cataract, were randomised to expedited (approximately 4 weeks) or routine (12 months wait) surgery. Falls were ascertained by diary, with follow up every 3 months. Health status was measured after 6 months. RESULTS: Visual function improved in the operated group (corrected binocular acuity improved by 0.25 logMAR units; 8% had acuity worse than 6/12 compared with 37% of controls). Over 12 months of follow up, 76 (49%) operated participants fell at least once, and 28 (18%) fell more than once. 69 (45%) unoperated participants fell at least once, 38 (25%) fell more than once. Rate of falling was reduced by 34% in the operated group (rate ratio 0.66, 95% confidence interval 0.45 to 0.96, p = 0.03). Activity, anxiety, depression, confidence, visual disability, and handicap all improved in the operated group compared with the control group. Four participants in the operated group had fractures (3%), compared with 12 (8%) in the control group (p = 0.04). CONCLUSION: First eye cataract surgery reduces the rate of falling, and risk of fractures and improves visual function and general health status.

Future time perspective in current and previous injecting drug users.

Future time perspective (FTP) is a measure of an individual's ability to conceptualise the future which has been shown to be foreshortened in drug addicts. We studied 100 opiate injecting drug users (IDUs) in New South Wales, Australia, of which half were currently injecting and half were not. There was a significant difference between the two groups on FTP, with those currently injecting having a truncated FTP extension. Factor analysis of the FTP scale suggested that the dimensions of future time may differ between groups, with current injectors having a perspective of loss and isolation compared to the dimension of self-evaluation and self-acceptance in those not currently injecting. These data support previous studies which demonstrated truncated FTP, also demonstrating a difference in currently (as opposed to previously) IDUs and suggest that both extension of FTP and an alteration of the dimensions of FTP are associated with cessation of injecting and entry into treatment.

Aspects of the immunotoxicity of chronic tobacco smoke exposure of the rat.

One hundred and eighty Wistar-strain rats were exposed to differing concentrations of tobacco smoke, for periods of up to 20 months, in order to examine the response of the pulmonary immune system. The amount of bronchus-associated lymphoid tissue (BALT) in the lungs of exposed rats increased initially over the first 5 weeks of exposure, subsequently falling to below control levels by the fourteenth week and eventually increasing again to a level slightly higher than that of the controls by the twelfth month, at which level it was maintained until the twentieth month. Quantitative immunohistochemical assay of bronchial immunoglobulin levels (only assessed over the initial 14 weeks of exposure) revealed a transitory enhancement of levels followed by a depression, the speed of response being apparently dose-related. Alveolar macrophage activity, indicated by lysosomal enzyme activity, increased relative to the control animals over the same 14-week exposure period. The significance of these observations is discussed and a tentative explanatory hypothesis is advanced.

The toxicity of beta-carotene.

The safety of beta-carotene, a widely distributed food colorant was assessed in tests with cells and in sub-chronic and chronic experiments with animals. Mutagenicity evaluations which included the standard Ames test and the micro-nucleus test of bone marrow cells from mice showed that beta-carotene exerted no mutagenic properties. Embryotoxicity studies in rats and rabbits showed that there was no evidence of embryotoxicity and a multiple generation study in rats showed that there was no interference with the reproductive function in rats given oral doses of up to 1000 mg/kg/day. Chronic toxicity was studied in a 2-year study with dogs in a toxicity/tumorigenicity study in rats and in a mouse carcinogenicity study. Histological findings in the livers of treated dogs and mice, but not in rats, included vacuolated cells with eccentric nuclei which were distributed in periportal areas and which were frequently associated with minimal lipid deposition. There was no evidence that the vacuolisation was dose-related. It was considered that the vacuolated cells were fat storage cells. There was no effect on the tumor profiles in the rat and the mouse studies.

Assessment of the continued supervision and asthma management knowledge of patients possessing home nebulizers.

This paper describes the results of a questionnaire survey on some aspects of nebulizer use, nebulizer instruction, and features relating to the recognition and management of deteriorating asthma. The study population consisted of 90 children with home nebulizers attending a paediatric asthma clinic, and 200 asthmatic children and 200 asthmatic adults whose nebulizers had been purchased directly from a manufacturer in the U.K. The results suggest that follow-up supervision of the patients who bought their own nebulizers occurred in only approximately 25% of cases. Written information focusing on the management of symptoms was also lacking. Peak flow meters were being under-used. Although the majority (77-100%) of patients were aware of the '4 h rule' for repeat use of bronchodilator therapy at home, there was still some confusion about the acceptable time interval and action to be taken should the dose be required more frequently. Very few (32%) in the nationwide adult group had a crisis action plan should the nebulizer fail to produce relief. This paper recommends that a simple treatment and crisis plan should be included with the purchased nebulizer, highlighting the key areas to be discussed by the patients with the doctor or other medical professionals. Such a package may prevent the occasional disaster that can occur with unsupervised nebulized bronchodilator usage.

Antarctic wintering--over, suggestion and transient olfactory stimulation: EEG evoked potential and electrodermal responses.

EEG evoked potential and electrodermal responses to real and suggested olfactory stimulation were recorded on a team of nine men who wintered-over at Scott Base, Antarctica. Multi-variate analysis of variance findings indicated some consistent trends despite adverse conditions and marked inter-individual differences. Consistent with studies of secondary afferentation olfaction-related EEGs were evidenced in the occipital area (O1 and O2) as well as the temporal area (T3 and T4). Skin conductance (SC) showed significant responses for real and suggested odorants pre and post wintering-over. Suppression of EEG amplitudes for real and suggested stimuli was evidenced prior to wintering-over. Following wintering-over experience suppression of EEG amplitudes for real stimuli showed a decrease while suppression increased for suggested stimuli. The implications of the suggestion findings are discussed in possible explanation of the apparent conflict between different sources of information about human responses to isolation in the Antarctic environment.

Cognitive load as a determinant of the dimensionality of the electroencephalogram: a replication study.

A sequel study to that reported by Gregson, Britton, Campbell and Gates (1990), partially replicating and extending findings which relate estimates of the dimensionality of the EEG to the complexity of task load in a visual scanning task, is described. The correlation dimensionality D2 of the attractor was computed using a variant of the Grassberger-Procaccia algorithm, and was shown to change in the expected direction, increasing as the task became more complicated. The effects are slight but consistent, and may be attenuated by nonstationarity over time, and by idiosyncratic factors. The results are numerically and qualitatively compatible with other recent reported studies, and support an interpretation linking brain dynamics to implied cognitive processes.

Comparisons of the nonlinear dynamics of electroencephalograms under various task loading conditions: a preliminary report.

Comparison of the characteristics of electroencephalogram (EEG) records treated as realizations from a nonlinear process were compared under four different conditions: eyes shut resting, and three silent observation instructions to predict the patterns of randomly generated lights which illuminated every 10 seconds. The correlation dimension of the EEG was calculated by a method involving finding the correlation integral in m-dimensional space, and found to show some variations within time series. The degree and directions of changes in the dimensionality of the process varied between observers and did not clearly confirm some earlier reported findings, but it is demonstrable that the measures of nonlinear brain dynamics can be correlated with psychological variables. Reasons for this are discussed.

Severe retinopathy of prematurity and its association with different rates of survival in infants of less than 1251 g birth weight.

BACKGROUND: There is controversy over whether improved survival of preterm infants has resulted in a higher incidence of severe (grade 3 or greater) retinopathy of prematurity (ROP). AIM: To compare survival rates and rates of > or = stage 3 ROP-that is, with a high risk of sequelae-in preterm infants in five English cities where, anecdotally, the incidence of ROP is reported to show considerable variation. METHODS: All infants of birth weight < 1500 g and or gestational age < 32 weeks, born in 1994 in one of the cities or transferred in within 48 hours, were studied. The populations were adjusted for case mix variation using CRIB (clinical risk index for babies, a disease severity scoring system). The incidence of severe ROP, the actual death rate, and that adjusted for disease severity were determined. RESULTS: The rate of severe ROP per 1000 births was higher in city 1 than in all the other cities. This increase in comparison with city 2 and city 4 was significant (city 1, 167 (95% confidence interval (CI) 96 to 260); city 2, 24 (6 to 59); city 4, 16 (1 to 84)). A significant difference was not seen between city 1 and cities 3 (23 (1 to 120)) and 5 (74 (21 to 79)). The relative risk of developing severe ROP in city 1 compared with all the other cities was 5.5 (2.5 to 11.9). The actual death rate per 1000 births in city 1 was significantly lower than that predicted by modelling death against CRIB score (city 1: actual 270; predicted 385 (95% CI 339 to 431)). In contrast, the other cities had actual death rates as predicted, or worse than predicted, by CRIB. INTERPRETATION: A significantly higher incidence of severe ROP was identified in one of the five cities studied. Variation in survival rates among high risk infants may explain this observation.

Eye splashes during invasive vascular procedures.

In recent years there has been an increased awareness among health care workers regarding possible risk of nosocomial transmission of blood borne pathogens. The aim of this study is to document the risk of contamination of radiologists' eyes during invasive vascular procedures. Radiologists performing these examinations were asked to wear glasses throughout. After each examination the glasses were inspected for droplets. 150 procedures were performed on 123 patients (M = 80, F = 43). 10 procedures (6.7%) resulted in splashes to glasses. In four of these cases the radiologist was not aware of the "eye splash" nor was there a spray event to account for it. Radiologists were aware of 13 spray events (8.7% of all procedures). There was a significantly increased risk of spray events and eye splashes during thrombolysis (chi 2 = 14.93, p < 0.001) and of spray events during angioplasty when compared with perfemoral arteriography (chi 2 = 8.816, p < 0.01). Procedures lasting longer than 30 min were associated with a significantly increased risk of spray events (chi 2 = 5.63, p < 0.02). Significantly more eye splashes were associated with more than two catheter changes (chi 2 = 8.912, p < 0.01). It is suggested that protective eye wear should be used routinely during invasive vascular procedures.

Prediction of relapse in men alcoholics.

Cognitive impairment, as measured by the Patterned Cognitive Impairment Test, was the best predictor of relapse in a group of patients after treatment for alcoholism.

Olfaction in Korsakoffs, alcoholics and normals.

Samples of 12 hospitalized Korsakoffs, 12 hospitalized non-Korsakoff alcoholics, and 12 controls, all groups being of comparable age range, were tested using a set of seven visual and olfactory measures which involved memory. By stepwise multiple discriminant analysis it was shown that strong separation could be effected between the three groups, solely on the basis of the olfactory recognition and recall tests, which included the Campbell-Gregson (1972) procedure. The use of of anosmia as a diagnostic indicator for Korsakoff's syndrome is discussed.

Preferential uptake of soluble antigen by respiratory tract epithelium overlying bronchus-associated lymphoid tissue in the rat.

Soluble protein antigen (Horseradish peroxidase - HRP) administered to rats intratracheally is predominantly phagocytosed by alveolar macrophages and Type-II pneumonocytes. A proportion, after localization on the lumenal surface of the bronchiolar epithelium is transported across the epithelium via the apical cytoplasm and the intercellular space to the region of the basement membrane. The rate of transfer is faster in the epithelium closer to areas of BALT than elsewhere and in these areas there is further significant penetration below the basement membrane into the BALT tissue to facilitate the contact of antigen and of lymphoid cells. No evidence of alveolar macrophage re-entry to the lymphatic system after phagocytosis of HRP could be seen.

A metastasizing cardiac rhabdomyosarcoma in a CD 1 strain mouse.

A rhabdomyosarcoma arising in the ventricular myocardium, with a renal metastasis, is described in a 95-week-old male CD 1 strain mouse. Rhabdomyosarcoma has previously been recorded only in the BALB/c strain of mouse and never arising from heart muscle.

Postnatal development of bronchus-associated lymphoid tissue (BALT) in the rat, Rattus norvegicus.

The pattern of development of bronchus-associated lymphoid tissue (BALT) in specified-pathogen-free and conventional (non-barrier maintained) rats over the initial 4 weeks of life appeared to be similar. BALT first appeared around the 2nd week of life and increased in amount over the following 2 weeks. Overlying large nodules of BALT the bronchial epithelium becomes infiltrated by lymphocytes to form a lymphoepithelium. This transformation occurs earlier in conventional rats, possibly because of the differing antigen levels to which they are exposed.

Bronchus-associated lymphoid tissue (BALT) in the laboratory-bred and wild rat, Rattus norvegicus.

In juvenile wild rats, bronchus-associated lymphoid tissue (BALT) development was similar to that seen in adult specified-pathogen-free rats. In adult wild rats the BALT was widespread. In one animal infected with a mycoplasma-like organism, a region of bronchoepithelium overlying a large BALT nodule was seen, through which lymphocytes appeared able to pass to make direct contact with the bronchial lumen: the significance of this observation is discussed. There was no evidence of infection in lungs from any of the specified-pathogen-free animals, where small foci of BALT were seen.