Measuring the digital divide among people with severe mental ill health using the essential digital skills framework.

AIMS: Amid the vast digitalisation of health and other services during the pandemic, people with no digital skills are at risk of digital exclusion. This risk might not abate by the end of the pandemic. This article seeks to understand whether people with severe mental ill health (SMI) have the necessary digital skills to adapt to these changes and avoid digital exclusion. METHODS: Two hundred and forty-nine adults with SMI across England completed a survey online or offline. They provided information on their digital skills based on the Essential Digital Skills (EDS) framework, sociodemographic information, and digital access. This is the first time that the EDS is benchmarked in people with SMI. RESULTS: 42.2% had no Foundation Skills, and 46.2% lacked skills for daily life (lacking Foundation or Life Skills). 23.0% of those working lacked skills for professional life (lacking Foundation or Work Skills). The most commonly missing skills were handling passwords and using the device settings (Foundation Skills) and online problem solving (Skills for Life). People were interested in learning more about approximately half of the skills they did not have. People were more likely to lack Foundation Skills if they were older, not in employment, had a psychosis-spectrum disorder, or had no Internet access at home. CONCLUSION: A significant portion of people with SMI lacked Foundation Skills in this objective and benchmarked survey. This points to a high risk for digital exclusion and the need for focused policy and tailored health sector support to ensure people retain access to key services and develop digital skills and confidence. To our knowledge, this is the first time this has been described using the EDS framework. Services, including the National Health Service (NHS), need to be aware of and mitigate the risks.

Localized gene expression of axon guidance molecules in neuronal co-cultures.

Axonal growth cones are guided to their targets by contact-dependent mechanisms or by diffusible chemotropic factors. Axon guidance by these factors typically involves culturing neurons on an acellular substrate which may not represent the in vivo biological environment. We developed two novel in vitro methods to create patterned gene expression of guidance molecules in a physiologically-relevant cellular environment. In the Matrigel assay, a droplet of adenovirus-Matrigel suspension was placed on astrocytes grown in Matrigel. The adenovirus diffused through the gel and transduced underlying astrocytes, creating a radial infection gradient within a localized area. In the second model, recombinant adenovirus was bound to an anti-hexon antibody adsorbed onto stripe patterns of nitrocellulose. Once the cells were added, only those contacting the adenovirus were infected. The outgrowth pattern of chick DRG neurons on NGF, semaphorin 3A and brevican were studied. As expected, results showed robust axonal growth toward NGF as opposed to either secreted Sema 3A or membrane bound brevican, however subtle differences in axonal growth responses were observed in comparison to those obtained with less physiologically-relevant methods. Novel to this technology, the location and area of molecule expression can be controlled and manipulated in an intricate cellular environment.

Initial effect of smoke inhalation injury on oxygen consumption (response to positive pressure ventilation).

BACKGROUND: Our purpose was to determine the effect of a smoke inhalation injury on initial oxygen demands measured as oxygen consumption. In addition, we wanted to determine the effect of positive pressure ventilation (PPV) on this process. METHODS: Adult sheep were insuffated with cotton toweling smoke to a carboxyhemoglobin level of 45% +/- 3% and then monitored unanesthetized for 24 hours. Oxygen delivery was maintained at a constant state. RESULTS: A significant increase in oxygen consumption (VO2), indicating increased metabolic demands, occurred during the first 2 hours after smoke with peak increase of 75% +/- 10% above baseline. A second increase occurred peaking at 18 hours with a 40% +/- 11% increase. Both increases were due to increased O2 extraction from hemoglobin rather than increased cardiac output. Use of PPV during the first 2 hours had no effect on VO2 but did correct impaired lung function manifested by an increased shunt fraction. Use of PPV during the later increased VO2 totally reversed the process but had less effect on improving lung function. CONCLUSIONS: We concluded that the initial increase in oxygen demands is likely due to an acute release of inflammatory mediators from the airway injury. The PPV response is to reexpand airways and alveoli, but it has no effect on the metabolic response. The late increase is likely due to increased work of breathing, which is removed by PPV. However, lung dysfunction from established airway edema at this stage is less reversible with PPV.

Effect of increasing the tidal volume of smoke breaths on smoke-induced lung dysfunction.

We determined the effect of a graded increase in lung exposure to a toxic smoke by increasing smoke tidal volume (VT) or the number of smoke breaths. Sheep were anesthetized and then insufflated with cooled cotton toweling smoke; VT was 5, 10, or 20 ml/kg, and smoke breaths were varied from 12 to 48. The smoke had a uniform particle size (3 +/- 0.4 microns diam). Peak carboxyhemoglobin levels varied from 8 +/- 2 to 45 +/- 4% in the lowest to highest exposure groups, respectively. Animals were monitored unanesthetized for 24 h, and then they were killed. Oxygenation (ratio of arterial PO2 to fraction of inspire O2) decreased from 480 +/- 21 to 200 Torr, and compliance decreased by approximately 50% in the highest smoke exposure groups, whereas only a modest decrease in oxygenation and no compliance changes were seen with lesser exposures. A moderate tracheobronchitis, some atelectasis, and no alveolar edema were noted in the lower smoke exposure groups, whereas severe tracheobronchitis, airway edema, and alveolar atelectasis were observed in the highest exposure group. Only modest alveolar flooding was noted. Impaired oxygenation and anatomic injury correlated best with the total smoke delivered (r = 0.59). Increasing VT from 5 to 20 ml/kg did not increase airway or alveolar injury if the total smoke mass delivered was maintained constant. The degree of impaired oxygenation did not correlate with measured lung water (r = 0.27) or lung lymph flow (r = 0.31).

Paradoxical effects of copper and manganese on brain mitochondrial function.

Defects in the mitochondrial genome have been associated with Parkinson's and Alzheimer's disease, and apoptosis can be triggered by the presence of energetically compromised mitochondria. Thus, in this study we have examined whether the divalent cations Cu2+ and Mn2+ could influence mitochondrial function in vitro. Mitochondrial electron transport was dose and time dependently reduced by Cu2+ to a greater extent with succinate as a substrate. Following a 60 min preincubation period, Mn2+ dose dependently inhibited electron transport to a greater extent with lactate and malate. In contrast, paradoxical effects were seen following a 5 min preincubation period with Mn2+. Cu2+ dose-dependently reduced NADH-dependent lactate dehydrogenase (LDH) activity, with almost complete inhibition apparent at 10 microM. An initial induction of LDH by 10 microM Mn2+ was partially reversed by higher concentrations of the metal. Cu2+ dose-dependently reduced flavin adenine dinucleotide (FAD)-dependent monoamine oxidase A (MAO-A) activity in a time-independent manner, with an IC50 value approximately 20 microM, whereas Mn2+ had no effect. In conclusion, it is proposed that Cu2+ and Mn2+ have differential effects on nicotinamide adenine dinucleotide (NAD) and FAD-dependent mitochondrial enzymes at the level of the essential cofactors. Cu2+ appears to exert an inhibitory effect on both NAD and FAD-dependent enzymes, but predominantly against the latter, including MAO-A and succinate dehydrogenase. The complex responses to Mn2+ may be due to dose-related effects on the interconversion of NAD and NADH and reversible enzymatic reactions employing this nucleotide cofactor.

Stimulus omission and recovery of the electrodermal and digital vasoconstrictive components of the orienting response.

Three experiments are reported which investigated Sokolov's (1968) hypothesis that, after a number of stimulus presentations, complete omission of a stimulus leads to increased responsiveness of the orienting response (OR). The skin conductance response (SCR) and finger pulse volume (FPV) response components of the OR were studied. In experiment 1 (N=60), the effect of number of pre-omission training trials on response recovery was investigated, while experiment 2 (N=120) investigated the effects of stimulus intensity (70 or 90 dB) and interstimulus interval (12 or 21 sec) on recovery to stimulus omission following a fixed number of training trials. In experiment 3 (N=40), an attempt was made to control for possible below-zero habituation effects by training each subject to a habituation criterion before stimulus omission. All experiments employed a 1000 Hz tone of 3 sec duration which was presented at a constant interstimulus interval. Although recovery of the SCR did occur under some conditions, the results were largely negative. Manipulation of the number of training trials, training stimulus intensity and interstimulus interval had little effect on response recovery. A consistent finding, however, was that subjects who displayed SCR recovery also displayed significantly more spontaneous fluctuations in skin conductance during the pre-stimulus period and required significantly more training trials to reach the criterion of habituation than did subjects displaying no recovery. Moreover, the SCRs displayed by 'labile' subjects on omission trials were significantly larger than those displayed on either the last training trial or during a control interval just prior to stimulus omission.

Avoidable hazard to New Zealand children: case reports of haemorrhagic disease of the newborn.

Haemorrhagic disease of the newborn is preventable by the routine administration of vitamin K to newborn babies. Despite this, prophylactic administration of Vitamin K1 remains controversial and haemorrhagic disease of the newborn continues to cause significant morbidity and mortality. We present two cases of this disease occurring recently in this region of New Zealand; one resulting in an infant's death, the other baby suffering from an intraventricular haemorrhage and secondary hydrocephalus. These cases prompted us to survey major New Zealand hospitals to assess their policy as regards routine vitamin K administration to newborn infants. The results of this survey suggest that there is now a uniform policy in New Zealand hospitals of giving intramuscular vitamin K. However, intramuscular vitamin K administration may still be objected to by some parents and lead to further cases of this preventable disease. Evidence now available shows that vitamin K1 given orally in a dose of 1 mg is effective in preventing haemorrhagic disease of the newborn.

Functional distinction between NGF-mediated plasticity and regeneration of nociceptive axons within the spinal cord.

Successful regeneration after injury requires either the direct reformation of the circuit or the formation of a bridge circuit to provide partial functional return through a more indirect route. Presently, little is known about the specificity of how regenerating axons reconnect or reconstruct functional circuits. We have established an in vivo Dorsal root entry zone (DREZ) model, which in the presence of Nerve Growth Factor (NGF), shows very robust regeneration of peptidergic nociceptive axons, but not other sensory axons. Expression of NGF in normal, non-injured animals leads to robust sprouting of only the peptidergic nociceptive axons. Interestingly, NGF-induced sprouting of these axons leads to severe chronic pain, whereas, regeneration leads to protective-like pain without chronic pain. Using this model we set out to compare differences in behavioral outcomes and circuit features between these two groups. In this study, we examined pre-synaptic and post-synaptic markers to evaluate the relationship between synaptic connections and behavioral responses. NGF-induced sprouting of calcitonin gene-related peptide (CGRP) axons resulted in a significant redistribution of synapses and cFos expression into the deeper dorsal horn. Regeneration of only the CGRP axons showed a general reduction in synapses and cFos expression within laminae I and II; however, inflammation of the hindpaw induced peripheral sensitization. These data show that although NGF-induced sprouting of peptidergic axons induces robust chronic pain and cFos expression throughout the entire dorsal horn, regeneration of the same axons resulted in normal protective pain with a synaptic and cFos distribution similar, albeit significantly less than that shown by the sprouting of CGRP axons.

Social and ethnic differences in attendance for antenatal care in England.

OBJECTIVES: Evidence about sociodemographic factors associated with late attendance for antenatal care in the UK is of poor quality. This study aimed to identify any social or ethnic differences in access to antenatal care, and to quantify the effect of any such differences using data collected in a survey of women's experiences of antenatal screening. STUDY DESIGN: Cross-sectional survey using a postal questionnaire. METHODS: A stratified clustered random sampling strategy was used. Hospitals in England were stratified according to ethnic mix. In order to ensure inclusion of an adequate number of women from Black and Minority Ethnic (BME) backgrounds, hospitals with >or= 15% of women of BME origin were oversampled. Pregnant women aged >or= 16 years, receiving care in 15 participating hospitals, were sent a postal questionnaire at 27-31 weeks of gestation. Logistic regression was used to estimate odds ratios (ORs) comparing social and ethnic groups for attendance for antenatal care, adjusting for sociodemographic and clinical factors. RESULTS: In total, 839 women (57%) returned completed questionnaires. Compared with all women giving birth in 2005 in England and Wales, the survey sample contained fewer women aged <20 years (5.8% vs 6.9%), more women aged >35 years (24.1% vs 19.6%) and fewer women who were born outside the UK (14.8% vs 20.8%). Five percent of responders were late attenders for their first antenatal appointment. The odds of late initiation of antenatal care were higher for women born outside the UK [OR 4.37, 95% confidence interval (CI) 2.25-8.52; P=0.0004] and for women living without a husband/partner (OR 2.74, 95% CI 1.81-4.16; P=0.0002). In total, 2.5% of women were late attenders for their booking appointment. The odds of late booking were higher for Black women (OR 5.92, 95% CI 2.97-11.83) and women living without a husband/partner (OR 1.95, 95% CI 0.97-3.93; P=0.06). CONCLUSIONS: A small proportion of women initiate and/or book late for antenatal care. This study provides recent, good-quality evidence that women born outside the UK and those living without a husband/partner may be at particular risk of late attendance for antenatal care.

17Beta-estradiol protects against quinolinic acid-induced lipid peroxidation in the rat brain.

The neurotoxin quinolinic acid has been identified as a causative agent in Huntington's disease and is a metabolite of the tryptophan pathway in the brain. In the present study, the in vivo and in vitro effect of 17beta-estradiol on lipid peroxidation induced by quinolinic acid was investigated. For the in vivo experiments ovariectomized female rats were administered with 100 microg 17beta-estradiol daily for seven days prior to and seven days following the intrahippocampal injection of 1 micromol quinolinic acid. The level of lipid peroxidation in brain homogenate was investigated using the thiobarbituric acid test. The in vitro experiments were performed in brain homogenates of ovariectomized female rats. The homogenate was treated with quinolinic acid alone or in combination with 17beta-estradiol. Quinolinic acid increased lipid peroxidation in a dose dependent manner in vitro, while homogenate co-treated with 17beta-estradiol showed a significant reduction in lipid peroxidation. 17Beta-estradiol was also shown to be protective against quinolinic acid in vivo. These results could explain the neuroprotective effect of 17beta-estradiol.

Insulin infusions in infants of birthweight less than 1250 g and with glucose intolerance.

Fifteen preterm babies (mean gestation: 26.7 weeks; mean birthweight 860 g) with significant glucose intolerance were treated with insulin infusions. During the insulin infusions there was a significant increase in both the mean energy intake (60.8 +/- 25.1 cal/kg per day to 79.9 +/- 24.5 cal/kg per day; P less than 0.001) and the mean amount of intravenous dextrose tolerated (7.0 +/- 2.7 mg/kg per min to 9.2 +/- 2.6 mg/kg per min; P less than 0.01). The infusions were initiated at a mean postnatal age of 5.3 days (range: 2-12 days) and were continued for 1.5-17.5 days. Of the 998 blood glucose estimations performed during the insulin infusions, 28 (2.8%) were less than 2 mmol/l and 216 (21.6%) greater than 8 mmol/l. We conclude that continuous insulin infusion is a safe and effective way of managing glucose intolerance in very low birthweight infants, provided adequate means for continuous monitoring of blood glucose are available.

17Beta-estradiol attenuates quinolinic acid insult in the rat hippocampus.

A number of studies have shown that 17beta-estradiol has neuroprotective properties. In this study the neuroprotective effect of 17beta-estradiol against quinolinic-acid-induced neuronal damage was investigated. Ovariectomized rats were separated into three groups of five animals each. Rats received daily subcutaneous injections of either olive oil or 17beta-estradiol in olive oil for 7 days prior to and following a single intrahippocampal injection of 1 micromol quinolinic acid in 2 microL phosphate-buffered saline. The brains were removed and the hippocampi either sectioned and stained for microscopic examination or used in glutamate receptor saturation binding studies. Glutamate receptor displacement binding studies were also performed using concentrations of 0.05 nM-5 microM 17beta-estradiol or quinolinic acid. The results show that 17beta-estradiol protects hippocampal neurons from quinolinic-acid-induced neurodegeneration by competing with quinolinic acid to bind to the N-methyl-D-aspartate (NMDA) receptor. This would result in a decrease in intracellular free-calcium influx and resultant neuronal swelling.