The evolving continuum of dysglycaemia: Non-diabetic hyperglycaemia in older adults.

Identifying non-diabetic hyperglycaemia (NDH) and intervening to halt the progression to type 2 diabetes has become an essential component of cardiovascular and cerebrovascular risk reduction. Diabetes prevention programs have been instigated to address the increasing prevalence of NDH and type 2 diabetes by targeting lifestyle modifications. Evidence suggests that the risk of progression from NDH to type 2 diabetes declines with age, and that a diagnosis of type 2 diabetes in older adults is not associated with the same risk of adverse consequences as it is in younger age groups. The current definition of NDH is not adjusted based on a person's age. Therefore, there is debate about the emphasis that should be placed upon a diagnosis of NDH in older adults. This article will explore the evidence and current clinical practice surrounding dysglycaemia through the spectrum of different age ranges, and the potential implications this has for older adults.

Factors influencing clinical outcome in vestibular neuritis - A focussed review and reanalysis of prospective data.

Following vestibular neuritis (VN), long term prognosis is not dependent on the magnitude of the residual peripheral function as measured with either caloric or the video head-impulse test. Rather, recovery is determined by a combination of visuo-vestibular (visual dependence), psychological (anxiety) and vestibular perceptual factors. Our recent research in healthy individuals has also revealed a strong association between the degree of lateralisation of vestibulo-cortical processing and gating of vestibular signals, anxiety and visual dependence. In the context of several functional brain changes occurring in the interaction between visual, vestibular and emotional cortices, which underpin the aforementioned psycho-physiological features in patients with VN, we re-examined our previously published findings focusing on additional factors impacting long term clinical outcome and function. These included: (i) the role of concomitant neuro-otological dysfunction (i.e. migraine and benign paroxysmal positional vertigo (BPPV)) and (ii) the degree to which brain lateralisation of vestibulo-cortical processing influences gating of vestibular function in the acute stage. We found that migraine and BPPV interfere with symptomatic recovery following VN. That is, dizziness handicap at short-term recovery stage was significantly predicted by migraine (r = 0.523, n = 28, p = .002), BPPV (r = 0.658, n = 31, p < .001) and acute visual dependency (r = 0.504, n = 28, p = .003). Moreover, dizziness handicap in the long-term recovery stage continued to be predicted by migraine (r = 0.640, n = 22, p = .001), BPPV (r = 0.626, n = 24, p = .001) and acute visual dependency (r = 0.667, n = 22, p < .001). Furthermore, surrogate measures of vestibulo-cortical lateralisation were predictive of the amount of cortical suppression exerted over vestibular thresholds. That is, in right-sided VN patients, we observed a positive correlation between visual dependence and acute ipsilesional oculomotor thresholds (R2 0.497; p < .001), but not contralateral thresholds (R2 0.017: p > .05). In left-sided VN patients, we observed a negative correlation between visual dependence and ipsilesional oculomotor thresholds (R2 0.459; p < .001), but not for contralateral thresholds (R2 0.013; p > .05). To surmise, our findings illustrate that in VN, neuro-otological co-morbidities retard recovery, and that measures of the peripheral vestibular system are an aggregate of residual function and cortically mediated gating of vestibular input.

Factors associated with the development of paediatric chronic otitis media by age nine: a prospective longitudinal cohort study of 6560 children.

OBJECTIVE: This study aimed to analyse social, health and environmental factors associated with the development of chronic otitis media by age nine. METHOD: This was a prospective, longitudinal, birth cohort study of 6560 children, reviewed at age nine. Chronic otitis media defined as previous surgical history or video-otoscopic changes of tympanic membrane retraction, perforation or cholesteatoma. Non-affected children were used as the control group. RESULTS: Univariate analysis demonstrated an association between chronic otitis media and otorrhoea, snoring, grommet insertion, adenoidectomy, tonsillectomy, hearing loss, abnormal tympanograms and preterm birth. Multivariate analysis suggests many of these factors may be interrelated. CONCLUSION: The association between chronic otitis media and otorrhoea, abnormal tympanograms and grommets supports the role of the Eustachian tube and otitis media (with effusion or acute) in the pathogenesis of chronic otitis media. The role of snoring, adenoidectomy and tonsillectomy is unclear. Associations suggested by previous studies (sex, socioeconomic group, parental smoking, maternal education, childcare, crowding and siblings) were not found to be significant predictors in this analysis.

Visual Vertigo, Motion Sickness, and Disorientation in Vehicles.

Environmental circumstances that result in ambiguity or conflict with the patterns of sensory stimulation may adversely affect the vestibular system. The effect of this conflict in sensory information may be dizziness, a sense of imbalance, nausea, and motion sickness sometimes even to seemingly minor daily head movement activities. In some, it is not only exposure to motion but also the observation of objects in motion around them such as in supermarket aisles or other places with visual commotion; this can lead to dizziness, nausea, or a feeling of motion sickness that is referred to as visual vertigo. All people with normal vestibular function can be made to experience motion sickness, although individual susceptibility varies widely and is at least partially heritable. Motorists learn to interpret sensory stimuli in the context of the car stabilized by its suspension and guided by steering. A type of motorist's disorientation occurs in some individuals who develop a heightened awareness of perceptions of motion in the automobile that makes them feel as though they may be rolling over on corners and as though they are veering on open highways or in streaming traffic. This article discusses the putative mechanisms, consequences and approach to managing patients with visual vertigo, motion sickness, and motorist's disorientation syndrome in the context of chronic dizziness and motion sensitivity.

Attenuated cortisol reactivity to psychosocial stress is associated with greater visual dependency in postural control.

Despite known anatomical links between the hypothalamic-pituitary-adrenal (HPA) axis and the vestibular system, there are no studies on the relationship between postural control and HPA axis function. Visual dependence in postural control, often measured by increased postural sway on exposure to visual motion, is an indication of altered visual-vestibular integration with greater weighting towards visual cues for balance. Visual dependence is more common in older age and a range of vestibular and non-vestibular health conditions. The relationship between visual dependence in postural control was investigated in relation to cortisol reactivity to psychosocial stress (using the Trier Social Stress Test for groups: TSST-G), as an index of HPA axis function, in healthy young females. In those who exhibited a cortisol response (>2 nmol/l), a negative relationship between stress-induced cortisol reactivity and visual dependence in postural control was observed, since those with the largest cortisol response showed less visual motion induced postural sway (measured by force platform). This finding in healthy females indicates that subtle non-clinical differences in vestibular function are associated with dysregulated HPA axis activity as indicated by lower cortisol reactivity to psychosocial stress. It adds to the growing body of evidence linking blunted cortisol reactivity to stress to poor homeostatic regulation and potential negative health and behavioural outcomes.

The birth experience and subsequent maternal caregiving attitudes and behavior: a birth cohort study.

Optimal maternal caregiving is critical for children's healthy development, yet quality of maternal caregiving may be influenced by a negative birth experience. We examined whether the birth experience was associated with maternal caregiving attitudes and behavior throughout the first year. We conducted secondary analysis of the Avon Longitudinal Study of Parents and Children birth cohort on perinatal data. The birth experience was assessed using self-report data on level of support in labor. Maternal caregiving variables were self-report maternal attitudes at one and eight postnatal months, and observed maternal behavior at 12 postnatal months. Data were analyzed using multivariable logistic regression models adjusting for critical covariates at one (N = 4389), eight (N = 4580), and 12 (N = 842) postnatal months. Feeling supported in labor was associated with a report of "immediately falling in love" with one's baby after birth, surveyed at 1 month (adjusted OR 1.41 [95% CI 1.20-1.65]), and with more positive parenting scores at 8 months (adjusted OR 1.56 [95% CI 1.36-1.79]), but not with more positive observed maternal behavior at 12 months. Additional risk factors were identified. Our findings suggest that we may be able to modify the risk of poor postnatal maternal caregiving by supporting women in labor and facilitating a positive birth experience.

ASD and schizophrenia show distinct developmental profiles in common genetic overlap with population-based social communication difficulties.

Difficulties in social communication are part of the phenotypic overlap between autism spectrum disorders (ASD) and schizophrenia. Both conditions follow, however, distinct developmental patterns. Symptoms of ASD typically occur during early childhood, whereas most symptoms characteristic of schizophrenia do not appear before early adulthood. We investigated whether overlap in common genetic influences between these clinical conditions and impairments in social communication depends on the developmental stage of the assessed trait. Social communication difficulties were measured in typically-developing youth (Avon Longitudinal Study of Parents and Children, N⩽5553, longitudinal assessments at 8, 11, 14 and 17 years) using the Social Communication Disorder Checklist. Data on clinical ASD (PGC-ASD: 5305 cases, 5305 pseudo-controls; iPSYCH-ASD: 7783 cases, 11 359 controls) and schizophrenia (PGC-SCZ2: 34 241 cases, 45 604 controls, 1235 trios) were either obtained through the Psychiatric Genomics Consortium (PGC) or the Danish iPSYCH project. Overlap in genetic influences between ASD and social communication difficulties during development decreased with age, both in the PGC-ASD and the iPSYCH-ASD sample. Genetic overlap between schizophrenia and social communication difficulties, by contrast, persisted across age, as observed within two independent PGC-SCZ2 subsamples, and showed an increase in magnitude for traits assessed during later adolescence. ASD- and schizophrenia-related polygenic effects were unrelated to each other and changes in trait-disorder links reflect the heterogeneity of genetic factors influencing social communication difficulties during childhood versus later adolescence. Thus, both clinical ASD and schizophrenia share some genetic influences with impairments in social communication, but reveal distinct developmental profiles in their genetic links, consistent with the onset of clinical symptoms.

Ultrasound-guided wire localisation to facilitate removal of an abnormal neck lymph node - a technical note.

BACKGROUND: Ultrasound-guided wire localisation is a technique that is well established in breast surgery, but is not well described in head and neck practice. It can be used to locate impalpable lesions for surgical removal, without the need for more extensive surgery. METHOD: This paper describes a case where the technique was used to assist in the removal of an impalpable but radiologically abnormal lymph node. CONCLUSION: The technique offers a safe and effective method for removing lesions within the head and neck.

Glycolysis inhibition improves photodynamic therapy response rates for equine sarcoids.

Photodynamic therapy (PDT) holds great promise in treating veterinary and human dermatological neoplasms, including equine sarcoids, but is currently hindered by the amount of photosensitiser and light that can be delivered to lesions thicker than around 2 mm, and by the intrinsic antioxidant defences of tumour cells. We have developed a new PDT technique that combines an efficient transdermal penetration enhancer solution, for topical delivery of 5-aminolevulinic acid (ALA) photosensitiser, with acute topical post-PDT application of the glycolysis inhibitor lonidamine. We show that the new PDT combination treatment selectively kills sarcoid cells in vitro, with repeated rounds of treatment increasing sarcoid sensitisation to PDT. In vivo, ALA PDT followed by 600 µM lonidamine substantially improves treatment outcomes for occult, verrucous, nodular and fibroblastic sarcoids after 1 month (93% treatment response in 27 sarcoids), compared with PDT using only ALA (14% treatment response in 7 sarcoids).

Motion sickness.

Over 2000 years ago the Greek physician Hippocrates wrote, "sailing on the sea proves that motion disorders the body." Indeed, the word "nausea" derives from the Greek root word naus, hence "nautical," meaning a ship. The primary signs and symptoms of motion sickness are nausea and vomiting. Motion sickness can be provoked by a wide variety of transport environments, including land, sea, air, and space. The recent introduction of new visual technologies may expose more of the population to visually induced motion sickness. This chapter describes the signs and symptoms of motion sickness and different types of provocative stimuli. The "how" of motion sickness (i.e., the mechanism) is generally accepted to involve sensory conflict, for which the evidence is reviewed. New observations concern the identification of putative "sensory conflict" neurons and the underlying brain mechanisms. But what reason or purpose does motion sickness serve, if any? This is the "why" of motion sickness, which is analyzed from both evolutionary and nonfunctional maladaptive theoretic perspectives. Individual differences in susceptibility are great in the normal population and predictors are reviewed. Motion sickness susceptibility also varies dramatically between special groups of patients, including those with different types of vestibular disease and in migraineurs. Finally, the efficacy and relative advantages and disadvantages of various behavioral and pharmacologic countermeasures are evaluated.

Childbirth and symptoms of postpartum depression and anxiety: a prospective birth cohort study.

We investigated associations between aspects of childbirth and elevated postpartum symptoms of depression and anxiety. We employed secondary analysis of perinatal data (N = 4657-4946) from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. Multivariable logistic regression models (adjusted for covariates) examined predictors of elevated symptoms of postpartum depression and anxiety. Predictors included the following: type of delivery (normal physiological vs. interventive non-physiological), immediate postpartum complications, and maternal perception of the recent birth experience. The Edinburgh Postnatal Depression Scale assessed elevated symptoms of depression (score ≥ 13), and the Crown-Crisp Experiential Index assessed elevated symptoms of anxiety (score ≥ 9) at 2 and 8 months after delivery. A more negative perception of the recent birth experience was associated with elevated symptoms of anxiety at 2 months [odds ratio (OR) 1.52, 95 % confidence interval (CI) 1.25-1.85] and 8 months (OR 1.30, 95 % CI 1.06-1.60) postpartum but was not associated with elevated symptoms of depression at either time point. Type of delivery (physiological vs. non-physiological) and immediate postpartum complications were not associated with elevated symptoms of depression or anxiety. Our findings suggest that improving women's childbirth experience may decrease the likelihood of postpartum anxiety, but not postpartum depression.

Adverse effects of maternal lead levels on birth outcomes in the ALSPAC study: a prospective birth cohort study.

OBJECTIVE: To study the associations of prenatal blood lead levels (B-Pb) with pregnancy outcomes in a large cohort of mother-child pairs in the UK. DESIGN: Prospective birth cohort study. SETTING: Avon area of Bristol, UK. POPULATION: Pregnant women enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC). METHODS: Whole blood samples were collected and analysed by inductively coupled plasma dynamic reaction cell mass spectrometry (n = 4285). Data collected on the infants included anthropometric variables and gestational age at delivery. Linear regression models for continuous outcomes and logistic regression models for categorical outcomes were adjusted for covariates including maternal height, smoking, parity, sex of the baby and gestational age. MAIN OUTCOME MEASURES: Birthweight, head circumference and crown-heel length, preterm delivery and low birthweight. RESULTS: The mean blood lead level (B-Pb) was 3.67 ± 1.47 µg/dl. B-Pb ≥ 5 µg/dl significantly increased the risk of preterm delivery (adjusted odds ratio [OR] 2.00 95% confidence interval [95% CI] 1.35-3.00) but not of having a low birthweight baby (adjusted OR 1.37, 95% CI 0.86-2.18) in multivariable binary logistic models. Increasing B-Pb was significantly associated with reductions in birth weight (ß -13.23, 95% CI -23.75 to -2.70), head circumference (ß -0.04, 95% CI -0.07 to -0.06) and crown-heel length (ß -0.05, 95% CI -0.10 to -0.00) in multivariable linear regression models. CONCLUSIONS: There was evidence for adverse effects of maternal B-Pb on the incidence of preterm delivery, birthweight, head circumference and crown-heel length, but not on the incidence of low birthweight, in this group of women.

Lead, cadmium and mercury levels in pregnancy: the need for international consensus on levels of concern.

For heavy metals that have any degree of transfer though the placenta to the fetus, it is unlikely that there are safe limits for maternal blood levels. The only means of reducing fetal exposure is to minimise maternal exposure. There are few recommendations for levels of concern. With the exception of US recommendations for maternal Pb levels, but there are no international levels of concern or cut-off levels specifically for pregnancy for heavy metals, so that comparisons can generally only be made with national reference values relating to similar physiological statuses or age groups. These include recommendations for Cd levels by Germany (reference value for non-smoking adults aged 18-69 years, 1 µg/l) and for Hg by Germany (reference value for adults age 18-60 years with fish intake < or =3 times per month, 2.0 µg/l) and the USA (cut-off level for women, 5.8 µg/dl). To illustrate the lack of cohesion, we present data on blood Pb, Cd and Hg levels from pregnant women enroled in the UK Avon Longitudinal Study of Parents and Children study and compare the values with present levels of concern and recommended cut-off values. We also compare the levels with those found in other groups of pregnant women worldwide to strengthen the database for the development of levels of concern in pregnancy. The need for clarity of terminology in describing levels of concern is discussed. There is a pressing need for international consensus on levels of concern for all age groups and physiological statuses, particularly for pregnancy.

Girl or boy? Prenatal lead, cadmium and mercury exposure and the secondary sex ratio in the ALSPAC study.

The aim of this study was to evaluate the effect of prenatal exposure to lead, cadmium and mercury levels on the secondary sex ratio. Whole blood samples were collected from pregnant women enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC) study at a median gestational age of 11 weeks and were analyzed for lead, cadmium and mercury. Regression analysis was used to identify associations between maternal lead, cadmium and mercury levels and the secondary sex ratio with adjustment for confounders. There was no evidence for associations between maternal lead, cadmium or mercury levels and the secondary sex ratio in this sample. It appears unlikely that alterations in the secondary sex ratio are influenced by exposure to heavy metals, but further work should be done in large cohorts in other countries to confirm these findings.

Effects of prochlorperazine on normal vestibular ocular and perceptual responses: a randomised, double-blind, crossover, placebo-controlled study.

BACKGROUND: The present study investigated whether prochlorperazine affects vestibulo-ocular reflex (VOR) and vestibulo-perceptual function. METHODS: We studied 12 healthy naïve subjects 3 h after a single dose of oral prochlorperazine 5 mg in a randomised, placebo-controlled, double-blind, crossover study in healthy young subjects. Two rotational tests in yaw were used: (1) a threshold task investigating perceptual motion detection and nystagmic thresholds (acceleration steps of 0.5°/s(2)) and (2) suprathreshold responses to velocity steps of 90°/s in which vestibulo-ocular and vestibuloperceptual time constants of decay, as well as VOR gain, were measured. RESULTS: Prochlorperazine had no effect upon any measure of nystagmic or perceptual vestibular function compared to placebo. This lack of effects on vestibular-mediated motion perception suggests that the drug is likely to act more as an anti-emetic than as an antivertiginous agent.

Motion sickness susceptibility in healthy subjects and vestibular patients: effects of gender, age and trait-anxiety.

Several studies have suggested that anxiety may play a role in motion sickness susceptibility (MSS) variability. This study aimed to assess motion sickness susceptibility in healthy subjects and chronic vestibular patients and to investigate its relationship to gender, age and trait-anxiety. Healthy subjects (n=167) and chronic dizzy patients with various vestibulopathies (n=94), aged from 20 to 92 years old, were asked to complete Motion Sickness Susceptibility questionnaire (MSSQ) and trait-anxiety questionnaire (STAI-B). When patients were divided into those who had vestibular loss (n=51) vs. patients without vestibular loss (n=43), the MSSQ scores (mean ± SD) for patients with vestibular loss (18.8 ± 30.9) were lower than healthy subjects (36.4 ± 34.8), who were lower than vestibular patients without vestibular loss (59.0 ± 39.7). These significant differences could not be explained by gender, age, trait-anxiety, or interaction. Women had higher MSS than men, and MSS declined with age for healthy subjects and vestibular patients. The overall relationship between anxiety and MSS scores was weak and only reached significance in healthy subjects. These results support the conclusion that the vestibular system is heavily involved in MSS and that trait-anxiety may play a role in MSS but only in healthy subjects.

Targeting tumour energy metabolism potentiates the cytotoxicity of 5-aminolevulinic acid photodynamic therapy.

BACKGROUND: Cancerous cells usually exhibit increased aerobic glycolysis, compared with normal tissue (the Warburg effect), making this pathway an attractive therapeutic target. METHODS: Cell viability, cell number, clonogenic assay, reactive oxygen (ROS), ATP, and apoptosis were assayed in MCF-7 tumour cells and corresponding primary human mammary epithelial cells (HMEC). RESULTS: Combining the glycolysis inhibitors 2-deoxyglucose (2DG; 180 mM) or lonidamine (300 µM) with 10 J cm(-2) 5-aminolevulinic acid (ALA) photodynamic therapy (PDT) increases MCF-7 cytotoxicity (by 3.5-fold to 70% death after 24 h, and by 10-fold in 9-day clonogenic assays). However, glycolysis inhibition only slightly increases HMEC PDT cytotoxicity (between two-fold and three-fold to a maximum of 9% death after 24 h). The potentiation of PDT cytotoxicity only occurred if the glycolysis inhibitors were added after ALA incubation, as they inhibited intracellular accumulation of photosensitiser if coincubated with ALA. CONCLUSION: As 2DG and lonidamine are already used as cancer chemotherapeutic agents, our results are directly translatable to combination therapies with existing topical PDT.

Parent-infant vocalisations at 12 months predict psychopathology at 7 years.

This study investigated the utility of adult and infant vocalisation in the prediction of child psychopathology. Families were sampled from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. Vocalisation patterns were obtained from 180 videos (60 cases and 120 randomly selected sex-matched controls) of parent-infant interactions when infants were one year old. Cases were infants who had been subsequently diagnosed aged seven years, with at least one psychiatric diagnostic categorisation using the Development and Wellbeing Assessment. Psychopathologies included in the case group were disruptive behaviour disorders, oppositional-conduct disorders, Attention Deficit Hyperactivity Disorder, pervasive development disorder, and emotional disorders. Associations between infant and parent vocalisations and later psychiatric diagnoses were investigated. Low frequencies of maternal vocalisation predicted later development of infant psychopathology. A reduction of five vocalisations per minute predicted a 44% (95%CI: 11-94%; p-value=0.006) increase in the odds of an infant being a case. No association was observed between infant vocalisations and overall case status. In sum, altered vocalisation frequency in mother-infant interactions at one year is a potential risk marker for later diagnosis of a range of child psychopathologies.

Predictors of diagnosis of child psychiatric disorder in adult-infant social-communicative interaction at 12 months.

To establish which social interactive behaviours predict later psychiatric diagnosis, we examined 180 videos of a parent-infant interaction when children were aged one year, from within the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. Sixty of the videos involved infants who were later diagnosed with a psychiatric disorder at seven years, and 120 were a randomly selected sex-matched control group. Interactive behaviours for both the caregiver and the one year old infant were coded from the videos according to eight holistic categories of interpersonal engagement: Well-being, Contingent Responsiveness, Cooperativeness, Involvement, Activity, Playfulness, Fussiness, and Speech. Lower levels of adult activity and speech in interaction at one year significantly predicted overall diagnosis of child psychiatric disorder.

Can psychopathology at age 7 be predicted from clinical observation at one year? Evidence from the ALSPAC cohort.

One of the challenges of developmental psychopathology is to determine whether identifiable pathways to developmental disorders exist in the first months or years of life. Early identification of such disorders poses a similar challenge for clinical services. Using data from a large contemporary birth cohort, we examined whether psychopathology at age seven can be predicted from clinician observation at one year. Two groups of clinical raters observed videos of caregiver-infant interaction. Neither group of raters could reliably identify any precursors of later development of psychopathology in the one-year-old infants in this setting.