Conditioned pain modulation identifies altered sensitivity in extremely preterm young adult males and females.

BACKGROUND: Conditioned pain modulation is a potential biomarker for risk of persistent pain. As early-life experience can alter subsequent somatosensory processing and pain response, we evaluated conditioned pain modulation after extremely preterm birth. METHODS: This observational study recruited extremely preterm (<26 weeks gestation; n=98) and term-born control (n=48) young adults (19-20 yr) from the longitudinal EPICure cohort. Pressure pain threshold (PPT; variable test stimulus lower leg) was measured before, during, and after a conditioning stimulus (contralateral hand immersion; 5°C water; 30 s). Questionnaires assessed current pain, medication use, anxiety, and pain catastrophising. RESULTS: For participants tolerating conditioning, there were significant main effects of extremely preterm status, sex, and time on PPT during and after hand immersion. Inhibitory modulation was evoked in 64/98 extremely preterm (3, no change) and 38/48 term-born control (3, facilitation) subjects. The conditioned pain modulation effect (percentage change in PPT) did not differ between the extremely preterm and term-born control groups {53% [95% confidence interval (CI): 41-65] vs 57% [95% CI: 42-71]}. Reduced cold tolerance (<20 s) hampered conditioned pain modulation quantification in a higher proportion of extremely preterm participants [extremely preterm vs term-born control: 31/98 (32%) vs 7/48 (15%); P=0.03]. One-third of extremely preterm females withdrew the hand before parallel PPT (<15 s), and had lower baseline PPT than term-born control females [4.9 (95% CI: 4.8-5.1) vs 5.3 (95% CI: 5.1-5.5) ln kPa; P=0.02]. Higher anxiety, pain catastrophising, and medication use correlated with pain intensity, but not conditioned pain modulation effect. CONCLUSIONS: Cold conditioning evoked inhibitory modulation in the majority of young adults and identified a subgroup of extremely preterm females with increased baseline sensitivity. Early-life experience and sex/gender should be considered when evaluating persistent pain risk with conditioned pain modulation.

Somatosensory function and pain in extremely preterm young adults from the UK EPICure cohort: sex-dependent differences and impact of neonatal surgery.

BACKGROUND: Surgery or multiple procedural interventions in extremely preterm neonates influence neurodevelopmental outcome and may be associated with long-term changes in somatosensory function or pain response. METHODS: This observational study recruited extremely preterm (EP, <26 weeks' gestation; n=102, 60% female) and term-born controls (TC; n=48) aged 18-20 yr from the UK EPICure cohort. Thirty EP but no TC participants had neonatal surgery. Evaluation included: quantitative sensory testing (thenar eminence, chest wall); clinical pain history; questionnaires (intelligence quotient; pain catastrophising; anxiety); and structural brain imaging. RESULTS: Reduced thermal threshold sensitivity in EP vs TC participants persisted at age 18-20 yr. Sex-dependent effects varied with stimulus intensity and were enhanced by neonatal surgery, with reduced threshold sensitivity in EP surgery males but increased sensitivity to prolonged noxious cold in EP surgery females (P<0.01). Sex-dependent differences in thermal sensitivity correlated with smaller amygdala volume (P<0.05) but not current intelligence quotient. While generalised decreased sensitivity encompassed mechanical and thermal modalities in EP surgery males, a mixed pattern of sensory loss and sensory gain persisted adjacent to neonatal scars in males and females. More EP participants reported moderate-severe recurrent pain (22/101 vs 4/48; χ2=0.04) and increased pain intensity correlated with higher anxiety and pain catastrophising. CONCLUSIONS: After preterm birth and neonatal surgery, different patterns of generalised and local scar-related alterations in somatosensory function persist into early adulthood. Sex-dependent changes in generalised sensitivity may reflect central modulation by affective circuits. Early life experience and sex/gender should be considered when evaluating somatosensory function, pain experience, or future chronic pain risk.

'Emotiplay': a serious game for learning about emotions in children with autism: results of a cross-cultural evaluation.

Children with autism spectrum conditions (ASC) experience difficulties recognizing others' emotions and mental states. It has been shown that serious games (SG) can produce simplified versions of the socio-emotional world. The current study performed a cross-cultural evaluation (in the UK, Israel and Sweden) of Emotiplay's SG, a system aimed to teach emotion recognition (ER) to children with ASC in an entertaining, and intrinsically motivating way. Participants were 6-9 year olds with high functioning ASC who used the SG for 8-12 weeks. Measures included face, voice, body, and integrative ER tasks, as well as parent-reported level of autism symptoms, and adaptive socialization. In the UK, 15 children were tested before and after using the SG. In Israel (n = 38) and Sweden (n = 36), children were randomized into a SG or a waiting list control group. In the UK, results revealed that 8 weeks of SG use significantly improved participants' performance on ER body language and integrative tasks. Parents also reported their children improved their adaptive socialization. In Israel and Sweden, participants using the SG improved significantly more than controls on all ER measures. In addition, parents in the Israeli SG group reported their children showed reduced autism symptoms after using the SG. In conclusion, Emotiplay's SG is an effective and motivating psycho-educational intervention, cross-culturally teaching ER from faces, voices, body language, and their integration in context to children with high functioning ASC. Local evidence was found for more generalized gains to socialization and reduced autism symptoms.

Neuromas as the cause of pain in the residual limbs of amputees. An ultrasound study.

AIM: To explore the morphology of neuromas and to determine the differences, if any, between asymptomatic and symptomatic neuromas using ultrasound. MATERIALS AND METHODS: Eighty patients with symptomatic neuromas were included in this retrospective review. High-resolution ultrasound examination was performed. Transducer pressure allowed real-time analysis of both symptomatic and asymptomatic neuromas. Quantifiable assessment of pain by the patient assigned a pain score of 0, 1, 2, or 3, to each neuroma. RESULTS: One hundred and fifty-nine neuromas were identified in total. Fifty-three neuromas were asymptomatic (pain score=0), very severe pain was recorded in 54 (pain score=3), 16 neuromas were mildly painful (pain score=1) and 36 were moderately painful (pain score=2). The average number of neuromas per patient was 1.98, and the average number of symptomatic neuromas per patient was 1.3. There was no correlation between pain score and patient age, neuroma volume, amputation type, and time since amputation. CONCLUSIONS: High-resolution ultrasound can distinguish between asymptomatic and symptomatic neuromas. Patient age, time since amputation, the type of amputation, and the neuroma volume were not related to the presence of pain.

Heart rate passivity of cerebral tissue oxygenation is associated with predictors of poor outcome in preterm infants.

AIM: Near-infrared spectroscopy (NIRS) and transcranial Doppler (TCD) allow non-invasive assessment of cerebral haemodynamics. We assessed cerebrovascular reactivity in preterm infants by investigating the relationship between NIRS- and TCD-derived indices and correlating them with severity of clinical illness. METHODS: We recorded the NIRS-derived cerebral tissue oxygenation index (TOI) and TCD-derived flow velocity (Fv), along with other physiological variables. Moving correlation coefficients between measurements of cerebral perfusion (TOI, Fv) and heart rate were calculated. We presumed that positivity of these correlation coefficients - tissue oxygenation heart rate reactivity index (TOHRx) and flow velocity heart rate reactivity index (FvHRx) - would indicate a direct relationship between cerebral perfusion and cardiac output representing impaired cerebrovascular autoregulation. RESULTS: We studied 31 preterm infants at a median age of 2 days, born at a median gestational age of 26 + 1 weeks. TOHRx was significantly correlated with gestational age (R = -0.57, p = 0.007), birth weight (R = -0.58, p = 0.006) and the Clinical Risk Index for Babies II (R = 0.55, p = 0.0014). TOHRx and FvHRx were significantly correlated (R = 0.39, p = 0.028). CONCLUSION: Heart rate has a key influence on cerebral haemodynamics in preterm infants, and TOHRx may be of diagnostic value in identifying impaired cerebrovascular reactivity leading to adverse clinical outcome.

Transient haemodynamic events in neurologically compromised infants: a simultaneous EEG and diffuse optical imaging study.

We describe a series of novel simultaneous EEG and diffuse optical imaging studies of newborn infants. These experiments provide evidence of large, transient haemodynamic events which occur repeatedly and consistently within and across several infants with neurological damage, all of whom were diagnosed with seizures. A simple but independent process of rejecting artifacts and identifying events within diffuse optical imaging data is described, and this process is applied to data from 4 neurologically damaged neonates and from 19 healthy, age-matched controls. This method results in the consistent identification of events in three out of four of the neurologically damaged infant group which are dominated by a slow (>30s) and significant increase in oxyhaemoglobin concentration, followed by a rapid and significant decrease before a slow return to baseline. No comparable events are found in any of our control data sets. The importance and physiological implications of our findings are discussed, as is the suitability of a combined EEG and diffuse optical imaging approach to the study and monitoring of neonatal brain injury.

Food-deprivation-induced phase shifts in Sminthopsis macroura froggatti.

Past research has shown that there is a circadian oscillator in laboratory rats that is entrained by restricted feeding schedules. However, in laboratory rats at least, the light-dark (LD) cycle is the dominant zeitgeber in the entrainment of wheel-running activity rhythms. Given that dasyurid marsupials are predominantly carnivorous, the episodic intake of food in the wild and the high nutritive content of that food suggest that food may be an important zeitgeber in these species. Twelve Sminthopsis macroura froggatti were presented with a daily meal at 0900 hr under an LD 12:12 cycle with lights-on at 0600 hr for 37 days. Activity in anticipation of the meal was observed in most animals. Following this, all animals were exposed to periods of 12-18 days ad lib. food interspersed with 3-day periods of deprivation--a technique used previously to demonstrate persistent meal-associated rhythms. The meal-associated activity rhythms previously observed in rats during the 3-day deprivation period were not seen, but the 3-day deprivation period produced large phase-shifts in the activity rhythms of several S.m. froggatti. It is concluded that meal feeding does not dominate the LD cycle in entraining dasyurid marsupials, but that the frequent observation of phase shifts suggests a different and, perhaps, stronger role for food intake in biological rhythmicity than has been observed previously in laboratory rats.

The role of adrenocorticotropin and norepinephrine in appetitive learning in the rat.

This study examines the involvement of ACTH/4-10 and norepinephrine during training and testing of a complex maze task. Hormones were administered post-trial to eliminate effects on processes other than learning and memory during training and testing sessions. ACTH/4-10, but not NE, facilitates acquisition of an appetitive maze task, but neither affect test performance. Facilitation of acquisition by ACTH/4-10 is discussed within two frameworks. ACTH/4-10 may enhance memory, presumably via a direct action on certain brain cells, resulting in stimulated protein synthesis and modified synaptic transmission. An interaction with serotonin synthesis and metabolism may be involved. Alternatively, during training and testing of a complex maze task, an ACTH-opiate receptor interaction may modify reinforcing properties, thus facilitating acquisition.

Restricted feeding and circadian activity rhythms of a predatory marsupial, Dasyuroides byrnei.

There is considerable disagreement as to whether food availability entrains circadian activity rhythms in omnivorous laboratory rodents. However, in carnivorous mammals a restricted feeding regime could act as a zeitgeber because the predator should hold a periodism correlated to that of the prey. Nevertheless, a restricted feeding schedule does not dominate the LD cycle for entrainment of circadian activity rhythms of the nocturnal predator Dasyuroides byrnei, nor does it entrain the free-running activity rhythms in DD. Anticipatory wheel running prior to food availability was observed in most animals. Some evidence for weak coupling between LD-entrained and meal-associated oscillators was indicated by occurrences of relative coordination. This species does not appear to have a dominance hierarchy of zeitgebern different to that reported for laboratory rodents. One would have predicted that it would have been ecologically adaptive for cycles of food availability to be more important than the LD cycle in this species.

Verbal conditioning of stimulus significance in the orienting response context: an exploration demonstrating a new personality effect.

The manipulation of stimulus significance, by instructions from the experimenter, may be taken as an example of verbal conditioning. Consideration of such a mechanism suggested that personality effects previously found in conditioning studies should be apparent in instructional manipulations of significance in a study of the orienting response (OR) to words. Because of recent changes in dimensioning of the personality structure, some of the items originally used to define Eysenck's extraversion (E) dimension are now used to assess the new dimension of psychoticism (P), suggesting that at least some of the established effects of E upon conditioning may be associated now with P. Hence the P scale was focused on in this study. Words differing on the evaluative dimension of the semantic differential were presented in three blocks, the first under indifferent instructions, the second under instructions to rate the words for their affective impact, and the third under indifferent instructions again. These blocks correspond to baseline, conditioning, and extinction conditions respectively. Electrodermal activity indicated enhanced conditioning, together with greater carry-over effects in the extinction phase, for low-P compared with high-P subjects. The results indicate the importance of personality effects in studies of stimulus significance and illustrate the value of the verbal conditioning mechanism in this area of the OR field. They also suggest the need to re-examine previously obtained E-effects in conditioning studies in light of changing personality tests.

Asbestos, dental X-rays, tobacco, and alcohol in the epidemiology of laryngeal cancer.

A case-control study of 47 laryngeal cancers in males of three counties of Washington State was conducted. Personal interview was used to obtain information on smoking, alcohol use, exposure to asbestos, and other substances, and x-rays of the head and neck area. Smoking and alcohol consumption were found to increase risk of laryngeal cancer independently, with a clear dose-response relationship. Neither asbestos exposure nor exposure to other substances was found to significantly increase the risk of laryngeal cancer, although the relative risk with asbestos exposure was 1.75. Lifetime history of exposure to dental x-rays on five or more occasions was associated with significantly increased risk of laryngeal cancer among heavy smokers but not among light smokers. The importance of tobacco and alcohol in the epidemiology of laryngeal cancer was re-affirmed, the importance of asbestos exposure was brought into question, and a possible relationship of laryngeal cancer with exposure to dental x-rays among heavy smokers was demonstrated.

In vitro fertilisation in a small unit in the NHS.

In vitro fertilisation is one of the most effective new treatments for infertility, but financial restrictions have made it impossible for it to be widely carried out in the National Health Service. We report on the establishment of a small, largely self funded, unit that was set up with the help of the local health service management. All cycles are programmed so that most work is carried out during the working week; oocyte recoveries are performed as outpatient procedures without general anaesthesia and guided by ultrasound. Roughly a tenth of treatment cycles and roughly a fifth of embryo transfers resulted in a clinical pregnancy.

Diagnóstico de la vivienda de bajo costo y su relación con la vulnerabilidad sísmica en la República Dominicana

Este trabajo se inicia describiendo las características que definen la sismicidad del país, así como también cómo se distribuye la población. Define la producción de viviendas de bajo costo, tanto del sector público, como el informal. Las características estructurales, materiales usados en este tipo de viviendas y el comportamiento esperado cuando ocurra un evento sísmcio, en la República Dominicana