Willingness to participate in research among black patients with liver disease: A national cross-sectional study.

In the United States, Black people are disproportionately diagnosed with hepatitis C virus (HCV) compared with White people but are under-represented in HCV studies. In this US-based cross-sectional telephone survey study, we assessed willingness to participate (WTP) in health/medical research and attitudes and beliefs that may influence WTP among Black patients with HCV. Two hundred participants who had current or prior HCV diagnosis and self-identified as Black or African American were recruited from a national HCV cohort study and an outpatient hepatology clinic. WTP responses ranged from 1 (not at all willing) to 5 (very willing). Multivariable models were used to identify factors associated with the overall mean WTP score. In addition, an open-ended question solicited strategies to help increase research participation from the Black community. Overall, participants reported moderate WTP in research (Mean [95% Confidence Interval (CI)] = 3.78 [3.68, 3.88]). Of 13 types of research presented, participants reported lowest WTP for randomized controlled trials of medications (Mean [95% CI] = 2.31 [2.11, 2.50]). The initial multivariable model identified higher subjective knowledge of research as positively associated with WTP (Parameter estimate [95% CI] = 0.15 [0.02, 0.27]). Sensitivity analyses also identified higher perceived benefits of research as an additional factor associated with WTP. Qualitative findings indicate that greater community-based outreach efforts would increase accessibility of research opportunities. When given the opportunity to participate, Black participants with HCV reported moderate WTP in health/medical research. Research sponsors and investigators should employ community-based outreach to expand access and awareness of research opportunities.

Evaluation of a new genetic family history screening questionnaire for identifying Lynch syndrome.

Family history is essential when screening for hereditary cancer syndromes. This article explores if a detailed genetic family history questionnaire is more effective in identifying at-risk individuals for Lynch syndrome than a basic family health questionnaire.

Hearing loss mediates executive function impairment in sleep-disordered breathing.

BACKGROUND: Sleep-disordered breathing (SDB) is often co-morbid with conductive hearing loss in early childhood due to a shared aetiology of adenotonsillar hypertrophy. Hearing loss is independently associated with impairment of executive function and behavioural difficulties. We hypothesised that these impairments in children with SDB may be mediated through hearing loss. METHODS: Fifty-eight children including 37 snorers awaiting adenotonsillectomy and 21 healthy non-snoring controls, aged 3-5 years, were assessed with pure tone audiometry, Strengths and Difficulties (SDQ), Behaviour Rating of Executive Function (BRIEF-P), and Childhood Middle Ear Disease and Hearing questionnaires. Polysomnography in snoring children generated an obstructive apnoea/hypopnea index (OAHI). Two regression models examined the effect of SDB and the mediating impact of hearing loss on BRIEF and SDQ. RESULTS: Snoring children had significantly poorer hearing, greater past exposure to hearing loss, and higher total SDQ and BRIEF-P scores than non-snoring controls. The first regression model, including all children, demonstrated that the impact of snoring on BRIEF_P, but not SDQ, was entirely mediated by a history of hearing loss exposure but not same-day audiometry. The second model examined snoring children only, categorising the group into 12 with obstructive sleep apnoea (OSA) (OAHI ≥ 5) and 25 without OSA. OSA had a direct effect on SDQ scores, but this was not mediated by a history of hearing loss. CONCLUSION: In early childhood, conductive hearing loss mediates the relationship between SDB, irrespective of severity, and parent report of executive function but not behaviour. Treatment of hearing loss in pre-school SDB might improve executive function.

A Method for the Preparation of Chicken Liver Pâté that Reliably Destroys Campylobacters.

This study devised a protocol for the manufacture of commercial quantities of chicken liver pâté that reliably destroyed campylobacters. A literature search identified 40 pâté manufacture recipes. Recipes stages with a potential to be antimicrobial were assembled to form a new protocol that included washing with organic acid, freeze-thaw and flambé in alcohol. Naturally-contaminated, high-risk livers were obtained from clearance flocks at slaughter and the effect of each stage of the protocol on Campylobacter populations was determined. Organic acid washing changed the color of the liver surfaces. However, there were no significant differences between liver surface color changes when a range of concentrations of lactic acid and ethanoic acid washes were compared by reflective spectrophotometry. A 5% (w/v) acid wash reduced numbers of indigenous campylobacters by around 1.5 log10 CFU/g for both acids. The use of a Bain Marie was found to more reproducibly apply heat compared with pan-frying. Antimicrobial recipe stages reduced the numbers of campylobacters, but not significantly if thermal processing was ineffective. Cooking to 63°C was confirmed to be a critical control point for campylobacters cooked in a Bain Marie. Organoleptic and sensory assessment of pâté determined an overall preference for pâté made from frozen livers.

A factor analysis of the SSQ (Speech, Spatial, and Qualities of Hearing Scale).

OBJECTIVE: The speech, spatial, and qualities of hearing questionnaire (SSQ) is a self-report test of auditory disability. The 49 items ask how well a listener would do in many complex listening situations illustrative of real life. The scores on the items are often combined into the three main sections or into 10 pragmatic subscales. We report here a factor analysis of the SSQ that we conducted to further investigate its statistical properties and to determine its structure. DESIGN: Statistical factor analysis of questionnaire data, using parallel analysis to determine the number of factors to retain, oblique rotation of factors, and a bootstrap method to estimate the confidence intervals. STUDY SAMPLE: 1220 people who have attended MRC IHR over the last decade. RESULTS: We found three clear factors, essentially corresponding to the three main sections of the SSQ. They are termed "speech understanding", "spatial perception", and "clarity, separation, and identification". Thirty-five of the SSQ questions were included in the three factors. There was partial evidence for a fourth factor, "effort and concentration", representing two more questions. CONCLUSIONS: These results aid in the interpretation and application of the SSQ and indicate potential methods for generating average scores.

Injectable polyHIPEs as high-porosity bone grafts.

Polymerization of high internal phase emulsions (polyHIPEs) is a relatively new method for the production of high-porosity scaffolds. The tunable architecture of these polyHIPE foams makes them attractive candidates for tissue engineered bone grafts. Previously studied polyHIPE systems require either toxic diluents or high cure temperatures which prohibit their use as an injectable bone graft. In contrast, we have developed an injectable polyHIPE that cures at physiological temperatures to a rigid, high-porosity foam. First, a biodegradable macromer, propylene fumarate dimethacrylate (PFDMA), was synthesized that has appropriate viscosity and hydrophobicity for emulsification. The process of surfactant selection is detailed with particular focus on the key structural features of both polymer (logP values, hydrogen bond acceptor sites) and surfactant (HLB values, hydrogen bond donor sites) that enable stable HIPE formation. Incubation of HIPEs at 37 °C was used to initiate radical cross-linking of the unsaturated double bond of the methacrylate groups to polymerize the continuous phase and lock in the emulsion geometry. The resulting polyHIPEs exhibited ~75% porosity, pore sizes ranging from 4 to 29 µm, and an average compressive modulus and strength of 33 and 5 MPa, respectively. These findings highlight the great potential of these scaffolds as injectable, tissue engineered bone grafts.

The age-related failure of adaptive responses to contractile activity in skeletal muscle is mimicked in young mice by deletion of Cu,Zn superoxide dismutase.

In muscle, aging is associated with a failure of adaptive responses to contractile activity, and this is hypothesized to play an important role in age-related loss of muscle mass and function. Mice lacking the Cu,Zn superoxide dismutase (Cu,ZnSOD, SOD1) show an accelerated, age-related loss of muscle mass and function. This work determined whether adult mice lacking Cu,ZnSOD (Sod1(-/-) mice) show a premature failure of adaptive responses to contractions in a similar manner to old wild-type (WT) mice. Adult Sod1(-/-) mice (6-8 months of age) had a ∼30% reduction in gastrocnemius muscle mass compared with age-matched WT mice. This lower muscle mass was associated with an activation of DNA binding by NFκB and AP-1 at rest. Measurements of the activity of reactive oxygen species (ROS) in single fibres from the muscles of Sod1(-/-) mice at rest indicated an elevation in activity compared with fibres from WT mice. Following 15 min of isometric contractions, muscle fibres from WT mice showed an increase in the intracellular ROS activities and activation of NFκB and AP-1, but no changes in either ROS activity or NFκB and AP-1 activation were seen in the muscles of Sod1(-/-) mice following contractions. This pattern of changes mimics that seen in the muscles of old WT mice, suggesting that the attenuated responses to contractile activity seen in old mice result from chronic exposure to increased oxidant activity. Data support the use of the Sod1(-/-) mouse model to evaluate potential mechanisms that contribute to the loss of muscle mass and function in the elderly.

Beta-carotene conversion to vitamin A decreases as the dietary dose increases in humans.

It has been suggested that high doses of beta-carotene limit its conversion to vitamin A, yet this effect has not been well established in humans. A feeding study was conducted in a randomized crossover design in which volunteers consumed 2 doses of deuterium-labeled beta-carotene on 2 occasions, with beta-carotene and vitamin A response assessed by plasma area under the concentration time curve (AUC). Seven volunteers (4 men, 3 women) consumed each of 2 doses of beta-carotene-d8 and provided serial blood samples for 37 d after each dose. beta-Carotene doses were 20 and 40 mg. Plasma beta-carotene-d8 was assessed by HPLC-MS. Plasma retinol (ROH)-d4, which was derived from the beta-carotene-d8, was evaluated by GC-MS after saponification to convert retinyl esters to ROH prior to the formation of the trimethylsilylether. The plasma AUC for beta-carotene-d8 increased 2-fold from the 20-mg dose to the 40-mg dose. The plasma AUC for ROH-d4 increased 36% from the 20-mg dose to the 40-mg dose. These results establish that, in humans, beta-carotene conversion to vitamin A decreases as the dietary dose increases.

Bioavailability of anthocyanins from purple carrot juice: effects of acylation and plant matrix.

Absorption of cyanidin-based anthocyanins is not fully understood with respect to dose or anthocyanin structure. In feeding studies using whole foods, nonacylated anthocyanins are more bioavailable than their acylated counterparts, but the extent to which plant matrix determines relative bioavailability of anthocyanins is unknown. Using juice of purple carrots to circumvent matrix effects, a feeding trial was conducted to determine relative bioavailability of acylated and nonacylated anthocyanins and to assess dose-response effects. Appearance of anthocyanins in plasma was measured in 10 healthy adults for 8 h following consumption of purple carrot juice. Each subject consumed 50, 150, and 250 mL of juice containing 76 micromol (65 mg), 228 micromol (194 mg), and 380 micromol (323 mg) of total anthocyanins, respectively. Acylated anthocyanins comprised 76% of total anthocyanins in the juice, yet their bioavailability was found to be significantly less than that of nonacylated anthocyanins. Peak plasma concentrations of nonacylated anthocyanins were 4-fold higher than that for acylated anthocyanins. Absorption efficiency declined across the doses administered. Because the treatments were consumed as juice, it could be discerned that the difference in bioavailability of acylated versus nonacylated anthocyanins was not primarily caused by interactions with the plant matrix.

Cerebral blood flow velocity and cognition in children before and after adenotonsillectomy.

OBJECTIVE: The goal was to determine whether amelioration of sleep-disordered breathing through adenotonsillectomy would reduce middle cerebral artery velocity in parallel with improvements in cognition and behavior. METHODS: For 19 children (mean age: 6 years) with mild sleep-disordered breathing, and 14 healthy, ethnically similar and age-similar, control subjects, parents repeated the Pediatric Sleep Questionnaire an average of 12 months after adenotonsillectomy. Children with sleep-disordered breathing underwent repeated overnight measurement of mean oxyhemoglobin saturation. Neurobehavioral tests that yielded significant group differences preoperatively were readministered. Middle cerebral artery velocity measurements were repeated with blinding to sleep study and neuropsychological results, and mixed-design analyses of variance were performed. RESULTS: The median Pediatric Sleep Questionnaire score significantly improved postoperatively, and there was a significant increase in mean overnight oxyhemoglobin saturation. The middle cerebral artery velocity decreased in the sleep-disordered breathing group postoperatively, whereas control subjects showed a slight increase. A preoperative group difference was reduced by the postoperative assessment, which suggests normalization of middle cerebral artery velocity in those with sleep-disordered breathing. The increase in mean overnight oxyhemoglobin saturation postoperatively was associated with a reduction in middle cerebral artery velocity in a subgroup of children. A preoperative group difference in processing speed was reduced postoperatively. Similarly, a trend for a preoperative group difference in visual attention was reduced postoperatively. Executive function remained significantly worse for the children with sleep-disordered breathing, compared with control subjects, although mean postoperative scores were lower than preoperative scores. CONCLUSIONS: Otherwise-healthy young children with apparently mild sleep-disordered breathing have potentially reversible cerebral hemodynamic and neurobehavioral changes.

Increased cerebral blood flow velocity in children with mild sleep-disordered breathing: a possible association with abnormal neuropsychological function.

OBJECTIVE: Sleep-disordered breathing describes a spectrum of upper airway obstruction in sleep from simple primary snoring, estimated to affect 10% of preschool children, to the syndrome of obstructive sleep apnea. Emerging evidence has challenged previous assumptions that primary snoring is benign. A recent report identified reduced attention and higher levels of social problems and anxiety/depressive symptoms in snoring children compared with controls. Uncertainty persists regarding clinical thresholds for medical or surgical intervention in sleep-disordered breathing, underlining the need to better understand the pathophysiology of this condition. Adults with sleep-disordered breathing have an increased risk of cerebrovascular disease independent of atherosclerotic risk factors. There has been little focus on cerebrovascular function in children with sleep-disordered breathing, although this would seem an important line of investigation, because studies have identified abnormalities of the systemic vasculature. Raised cerebral blood flow velocities on transcranial Doppler, compatible with raised blood flow and/or vascular narrowing, are associated with neuropsychological deficits in children with sickle cell disease, a condition in which sleep-disordered breathing is common. We hypothesized that there would be cerebral blood flow velocity differences in sleep-disordered breathing children without sickle cell disease that might contribute to the association with neuropsychological deficits. DESIGN: Thirty-one snoring children aged 3 to 7 years were recruited from adenotonsillectomy waiting lists, and 17 control children were identified through a local Sunday school or as siblings of cases. Children with craniofacial abnormalities, neuromuscular disorders, moderate or severe learning disabilities, chronic respiratory/cardiac conditions, or allergic rhinitis were excluded. Severity of sleep-disordered breathing in snoring children was categorized by attended polysomnography. Weight, height, and head circumference were measured in all of the children. BMI and occipitofrontal circumference z scores were computed. Resting systolic and diastolic blood pressure were obtained. Both sleep-disordered breathing children and the age- and BMI-similar controls were assessed using the Behavior Rating Inventory of Executive Function (BRIEF), Neuropsychological Test Battery for Children (NEPSY) visual attention and visuomotor integration, and IQ assessment (Wechsler Preschool and Primary Scale of Intelligence Version III). Transcranial Doppler was performed using a TL2-64b 2-MHz pulsed Doppler device between 2 pm and 7 pm in all of the patients and the majority of controls while awake. Time-averaged mean of the maximal cerebral blood flow velocities was measured in the left and right middle cerebral artery and the higher used for analysis. RESULTS: Twenty-one snoring children had an apnea/hypopnea index <5, consistent with mild sleep-disordered breathing below the conventional threshold for surgical intervention. Compared with 17 nonsnoring controls, these children had significantly raised middle cerebral artery blood flow velocities. There was no correlation between cerebral blood flow velocities and BMI or systolic or diastolic blood pressure indices. Exploratory analyses did not reveal any significant associations with apnea/hypopnea index, apnea index, hypopnea index, mean pulse oxygen saturation, lowest pulse oxygen saturation, accumulated time at pulse oxygen saturation <90%, or respiratory arousals when examined in separate bivariate correlations or in aggregate when entered simultaneously. Similarly, there was no significant association between cerebral blood flow velocities and parental estimation of child's exposure to sleep-disordered breathing. However, it is important to note that whereas the sleep-disordered breathing group did not exhibit significant hypoxia at the time of study, it was unclear to what extent this may have been a feature of their sleep-disordered breathing in the past. IQ measures were in the average range and comparable between groups. Measures of processing speed and visual attention were significantly lower in sleep-disordered breathing children compared with controls, although within the average range. There were similar group differences in parental-reported executive function behavior. Although there were no direct correlations, adjusting for cerebral blood flow velocities eliminated significant group differences between processing speed and visual attention and decreased the significance of differences in Behavior Rating Inventory of Executive Function scores, suggesting that cerebral hemodynamic factors contribute to the relationship between mild sleep-disordered breathing and these outcome measures. CONCLUSIONS: Cerebral blood flow velocities measured by noninvasive transcranial Doppler provide evidence for increased cerebral blood flow and/or vascular narrowing in childhood sleep-disordered breathing; the relationship with neuropsychological deficits requires further exploration. A number of physiologic changes might alter cerebral blood flow and/or vessel diameter and, therefore, affect cerebral blood flow velocities. We were able to explore potential confounding influences of obesity and hypertension, neither of which explained our findings. Second, although cerebral blood flow velocities increase with increasing partial pressure of carbon dioxide and hypoxia, it is unlikely that the observed differences could be accounted for by arterial blood gas tensions, because all of the children in the study were healthy, with no cardiorespiratory disease, other than sleep-disordered breathing in the snoring group. Although arterial partial pressure of oxygen and partial pressure of carbon dioxide were not monitored during cerebral blood flow velocity measurement, assessment was undertaken during the afternoon/early evening when the child was awake, and all of the sleep-disordered breathing children had normal resting oxyhemoglobin saturation at the outset of their subsequent sleep studies that day. Finally, there is an inverse linear relationship between cerebral blood flow and hematocrit in adults, and it is known that iron-deficient erythropoiesis is associated with chronic infection, such as recurrent tonsillitis, a clinical feature of many of the snoring children in the study. Preoperative full blood counts were not performed routinely in these children, and, therefore, it was not possible to exclude anemia as a cause of increased cerebral blood flow velocity in the sleep-disordered breathing group. However, hemoglobin levels were obtained in 4 children, 2 of whom had borderline low levels (10.9 and 10.2 g/dL). Although there was no apparent relationship with cerebral blood flow velocity in these children (cerebral blood flow velocity values of 131 and 130 cm/second compared with 130 and 137 cm/second in the 2 children with normal hemoglobin levels), this requires verification. It is of particular interest that our data suggest a relationship among snoring, increased cerebral blood flow velocities and indices of cognition (processing speed and visual attention) and perhaps behavioral (Behavior Rating Inventory of Executive Function) function. This finding is preliminary: a causal relationship is not established, and the physiologic mechanisms underlying such a relationship are not clear. Prospective studies that quantify cumulative exposure to the physiologic consequences of sleep-disordered breathing, such as hypoxia, would be informative.