Emphasizing responder speed or accuracy modulates but does not abolish the distractor-induced quitting effect in visual search.

When a highly salient distractor is present in a search array, it speeds target absent visual search and increases errors during target present visual search, suggesting lowered quitting thresholds (Moher in Psychol Sci 31(1):31-42, 2020). Missing a critical target in the presence of a highly salient distractor can have dire consequences in real-world search tasks where accurate target detection is crucial, such as baggage screening. As such, the current study examined whether emphasizing either accuracy or speed would eliminate the distractor-generated quitting threshold effect (QTE). Three blocks of a target detection search task which included a highly salient distractor on half of all trials were used. In one block, participants received no instructions or feedback regarding performance. In the remaining two blocks, they received instructions and trial-by-trial feedback that either emphasized response speed or response accuracy. Overall, the distractor lowered quitting thresholds, regardless of whether response speed or response accuracy was emphasized in a block of trials. However, the effect of the distractor on target misses was smaller when accuracy was emphasized. It, therefore, appears that while the distractor QTE is not easily eradicated by explicit instructions and feedback, it can be shifted. As such, future research should examine the applicability of these and similar strategies in real-world search scenarios.

Weaning practices in phenylketonuria vary between health professionals in Europe.

BACKGROUND: In phenylketonuria (PKU), weaning is considered more challenging when compared to feeding healthy infants. The primary aim of weaning is to gradually replace natural protein from breast milk or standard infant formula with solids containing equivalent phenylalanine (Phe). In addition, a Phe-free second stage L-amino acid supplement is usually recommended from around 6 months to replace Phe-free infant formula. Our aim was to assess different weaning approaches used by health professionals across Europe. METHODS: A cross sectional questionnaire (survey monkey®) composed of 31 multiple and single choice questions was sent to European colleagues caring for inherited metabolic disorders (IMD). Centres were grouped into geographical regions for analysis. RESULTS: Weaning started at 17-26 weeks in 85% (n = 81/95) of centres, >26 weeks in 12% (n = 11/95) and < 17 weeks in 3% (n = 3/95). Infant's showing an interest in solid foods, and their age, were important determinant factors influencing weaning commencement. 51% (n = 48/95) of centres introduced Phe containing foods at 17-26 weeks and 48% (n = 46/95) at >26 weeks. First solids were mainly low Phe vegetables (59%, n = 56/95) and fruit (34%, n = 32/95).A Phe exchange system to allocate dietary Phe was used by 52% (n = 49/95) of centres predominantly from Northern and Southern Europe and 48% (n = 46/95) calculated most Phe containing food sources (all centres in Eastern Europe and the majority from Germany and Austria). Some centres used a combination of both methods.A second stage Phe-free L-amino acid supplement containing a higher protein equivalent was introduced by 41% (n = 39/95) of centres at infant age 26-36 weeks (mainly from Germany, Austria, Northern and Eastern Europe) and 37% (n = 35/95) at infant age > 1y mainly from Southern Europe. 53% (n = 50/95) of centres recommended a second stage Phe-free L-amino acid supplement in a spoonable or semi-solid form. CONCLUSIONS: Weaning strategies vary throughout European PKU centres. There is evidence to suggest that different infant weaning strategies may influence longer term adherence to the PKU diet or acceptance of Phe-free L-amino acid supplements; rendering prospective long-term studies important. It is essential to identify an effective weaning strategy that reduces caregiver burden but is associated with acceptable dietary adherence and optimal infant feeding development.

Early feeding practices in infants with phenylketonuria across Europe.

BACKGROUND: In infants with phenylketonuria (PKU), dietary management is based on lowering and titrating phenylalanine (Phe) intake from breast milk or standard infant formula in combination with a Phe-free infant formula in order to maintain blood Phe levels within target range. Professionals use different methods to feed infants with PKU and our survey aimed to document practices across Europe. METHODS: We sent a cross sectional, survey monkey® questionnaire to European health professionals working in IMD. It contained 31 open and multiple-choice questions. The results were analysed according to different geographical regions. RESULTS: Ninety-five centres from 21 countries responded. Over 60% of centres commenced diet in infants by age 10 days, with 58% of centres implementing newborn screening by day 3 post birth. At diagnosis, infant hospital admission occurred in 61% of metabolic centres, mainly in Eastern, Western and Southern Europe. Breastfeeding fell sharply following diagnosis with only 30% of women still breast feeding at 6 months.53% of centres gave pre-measured Phe-free infant formula before each breast feed and 23% alternated breast feeds with Phe-free infant formula. With standard infant formula feeds, measured amounts were followed by Phe-free infant formula to satiety in 37% of centres (n = 35/95), whereas 44% (n = 42/95) advised mixing both formulas together. Weaning commenced between 17 and 26 weeks in 85% centres, ≥26 weeks in 12% and < 17 weeks in 3%. DISCUSSION: This is the largest European survey completed on PKU infant feeding practices. It is evident that practices varied widely across Europe, and the practicalities of infant feeding in PKU received little focus in the PKU European Guidelines (2017). There are few reports comparing different feeding techniques with blood Phe control, Phe fluctuations and growth. Controlled prospective studies are necessary to assess how different infant feeding practices may influence longer term feeding development.

Working while unwell: Workplace impairment in people with severe asthma.

BACKGROUND: Severe asthma affects quality of life; however, its impact on workplace productivity is poorly understood. OBJECTIVE: To compare workplace productivity-absenteeism and presenteeism-and impairment in daily activities in severe and non-severe asthma over time and identify characteristics associated with presenteeism in severe asthma. METHODS: The Severe Asthma Web-based Database is an ongoing observational registry from Australia, New Zealand and Singapore. At April 2017, 434 patients with severe asthma and 102 with non-severe asthma were enrolled (18-88 years; 59% female). Participants provided comprehensive clinical and questionnaire data at baseline and were followed-up every 6 months for 24 months. Absenteeism (percentage of time not at work), presenteeism (self-reported impairment at work) and impairment in daily activities outside work due to health problems in the last week were calculated. RESULTS: At baseline, 61.4% of participants with severe asthma and 66.2% with non-severe asthma under 65 years were employed. At younger ages (30-50 years), fewer severe asthma participants were employed (69% vs 100%). Presenteeism and impairment in daily activity were more frequently reported in severe asthma and in participants with poorer asthma control, poorer lung function and more past-year exacerbations (P < .01). Over time, deteriorating asthma control was associated with increasing presenteeism. Although absenteeism was not different between severe and non-severe asthma, worse asthma control was associated with absenteeism (P < .001). In participants with severe asthma, presenteeism was reported more frequently in those with poorer asthma control, poorer asthma-related quality of life and symptoms of depression or anxiety (P < .01). CONCLUSION AND CLINICAL RELEVANCE: Severe asthma was associated with impairment at work and outside the workplace. Improving asthma control and mental health may be important targets for optimizing workplace productivity in severe asthma. Presenteeism and absenteeism may represent key metrics for assessing intervention efficacy in people with severe asthma of working age.

International practices in the dietary management of fructose 1-6 biphosphatase deficiency.

BACKGROUND: In fructose 1,6 bisphosphatase (FBPase) deficiency, management aims to prevent hypoglycaemia and lactic acidosis by avoiding prolonged fasting, particularly during febrile illness. Although the need for an emergency regimen to avoid metabolic decompensation is well established at times of illness, there is uncertainty about the need for other dietary management strategies such as sucrose or fructose restriction. We assessed international differences in the dietary management of FBPase deficiency. METHODS: A cross-sectional questionnaire (13 questions) was emailed to all members of the Society for the Study of Inborn Errors of Metabolism (SSIEM) and a wide database of inherited metabolic disorder dietitians. RESULTS: Thirty-six centres reported the dietary prescriptions of 126 patients with FBPase deficiency. Patients' age at questionnaire completion was: 1-10y, 46% (n = 58), 11-16y, 21% (n = 27), and >16y, 33% (n = 41). Diagnostic age was: <1y, 36% (n = 46); 1-10y, 59% (n = 74); 11-16y, 3% (n = 4); and >16y, 2% (n = 2). Seventy-five per cent of centres advocated dietary restrictions. This included restriction of: high sucrose foods only (n = 7 centres, 19%); fruit and sugary foods (n = 4, 11%); fruit, vegetables and sugary foods (n = 13, 36%). Twenty-five per cent of centres (n = 9), advised no dietary restrictions when patients were well. A higher percentage of patients aged >16y rather than ≤16y were prescribed dietary restrictions: patients aged 1-10y, 67% (n = 39/58), 11-16y, 63% (n = 17/27) and >16y, 85% (n = 35/41). Patients classified as having a normal fasting tolerance increased with age from 30% in 1-10y, to 36% in 11-16y, and 58% in >16y, but it was unclear if fasting tolerance was biochemically proven. Twenty centres (56%) routinely prescribed uncooked cornstarch (UCCS) to limit overnight fasting in 47 patients regardless of their actual fasting tolerance (37%). All centres advocated an emergency regimen mainly based on glucose polymer for illness management. CONCLUSIONS: Although all patients were prescribed an emergency regimen for illness, use of sucrose and fructose restricted diets with UCCS supplementation varied widely. Restrictions did not relax with age. International guidelines are necessary to help direct future dietary management of FBPase deficiency.

Practices in prescribing protein substitutes for PKU in Europe: No uniformity of approach.

BACKGROUND: There appears little consensus concerning protein requirements in phenylketonuria (PKU). METHODS: A questionnaire completed by 63 European and Turkish IMD centres from 18 countries collected data on prescribed total protein intake (natural/intact protein and phenylalanine-free protein substitute [PS]) by age, administration frequency and method, monitoring, and type of protein substitute. Data were analysed by European region using descriptive statistics. RESULTS: The amount of total protein (from PS and natural/intact protein) varied according to the European region. Higher median amounts of total protein were prescribed in infants and children in Northern Europe (n=24 centres) (infants <1 year, >2-3g/kg/day; 1-3 years of age, >2-3 g/kg/day; 4-10 years of age, >1.5-2.5 g/kg/day) and Southern Europe (n=10 centres) (infants <1 year, 2.5 g/kg/day, 1-3 years of age, 2 g/kg/day; 4-10 years of age, 1.5-2 g/kg/day), than by Eastern Europe (n=4 centres) (infants <1 year, 2.5 g/kg/day, 1-3 years of age, >2-2.5 g/kg/day; 4-10 years of age, >1.5-2 g/kg/day) and with Western Europe (n=25 centres) giving the least (infants <1 year, >2-2.5 g/kg/day, 1-3 years of age, 1.5-2 g/kg/day; 4-10 years of age, 1-1.5 g/kg/day). Total protein prescription was similar in patients aged >10 years (1-1.5 g/kg/day) and maternal patients (1-1.5 g/kg/day). CONCLUSIONS: The amounts of total protein prescribed varied between European countries and appeared to be influenced by geographical region. In PKU, all gave higher than the recommended 2007 WHO/FAO/UNU safe levels of protein intake for the general population.

A questionnaire survey on the usage of low protein staple foods by people with phenylketonuria in Scotland.

BACKGROUND: There is scarce evidence available with respect to an evaluation of the role of low protein staple foods (LPSF) in the management of phenylketonuria (PKU). The present study explored beliefs, acceptability and issues around the use of LPSF by people with PKU or their carers. METHODS: A semi-anonymous questionnaire was posted to 178 people with PKU in Scotland (104 children, aged 2-17 years, and 74 adults). Questions explored were: the type and amount of LPSF ordered; perceptions on use and usefulness of LPSF; acceptability of the LPSF sensory properties (i.e. taste, smell, texture, appearance); support for the supply and use of LPSF; and comments from primary healthcare professionals regarding dispensing and prescription. RESULTS: Eighty-two individuals responded (46% response rate): 97% perceived that LPSF were useful for PKU management; more than 85% reported that LPSF were important for phenylalanine control, satisfying appetite, and diet variety. The most common LPSF ordered were pasta/rice/cous cous, flour, biscuits and bread. Fifty percent of respondents ordered <51% of the recommended unit allowance of LPSF. The sensory properties of LPSF were well perceived. Forty-nine percent (n = 39) had received a comment from primary healthcare staff regarding the prescription or dispensing of LPSF; 59% (n = 23) received negative comments, the majority of which came within general practitioner surgeries. CONCLUSIONS: There is a positive attitude and perception on the use and usefulness of LPSF in the management of PKU. Issues with respect to the supply and provision of LPSF within primary health care may indicate poor communication between specialists and primary healthcare professionals or a lack of scientific evidence demonstrating their clinical effectiveness.

The oncogenic GLI transcription factors facilitate keratinocyte survival and transformation upon exposure to genotoxic agents.

Ultraviolet B (UVB) light is the principal aetiological factor associated with non-melanoma skin cancer, the most prevalent group of malignancies in the Caucasian population. Exposure to environmental chemicals has also been shown to promote skin carcinogenesis and, as for UVB, this is associated with the acquisition of genomic DNA damage. Cells respond to DNA damage by inducing cell cycle arrest to facilitate DNA repair, although apoptosis will occur if the damage is excessive. Oncogenes may drive carcinogenesis by disrupting the balanced control of cell cycle progression, DNA repair and apoptosis, allowing for the propagation of cells with damaged DNA. The transcription factors GLI1 and GLI2 have been implicated in both the initiation and progression of several cancers, including basal cell carcinoma. Here we show that GLI1 and an active mutant of GLI2 (ΔNGLI2) promote apoptotic resistance in N/TERT human keratinocytes upon exposure to UVB and the DNA-alkylating chemicals such as methyl methanesulphonate (MMS) and N-ethyl-N-nitrosurea. Compared with control and untreated N/TERT-GLI1 and -GLI2 cells, those that survived genotoxic insult formed significantly more colonies in soft agar and were significantly more invasive when grown in three-dimensional organotypic collagen gel cultures. Indeed, surviving N/TERT-GLI1 and -GLI2 cells expressed higher levels of the epithelial-to-mesenchymal transition markers Snail and vimentin, and a subpopulation of MMS-treated cells displayed an elongated fibroblast-like morphology with decreased levels of E-cadherin. Finally, whereas Bcl2 was strongly increased in N/TERT-GLI2 cells, the level of induction was weak in N/TERT-GLI1 cells, indicating that GLI1 may activate anti-apoptotic mechanisms(s) independently of Bcl2. In summary, our results show that GLI1 and GLI2 facilitate the propagation of cells with damaged DNA, and thus their expression may be naturally higher in cells that form the earliest precursor tumour lesions.

Dimensions of physical frailty and cognitive function in older adults with amnestic mild cognitive impairment.

OBJECTIVE: The objective of this study was to examine relationships between dimensions of physical frailty and severity of cognitive impairment in older adults with amnestic mild cognitive impairment (aMCI). PATIENTS AND METHODS: The prevalence of physical frailty dimensions including slow gait speed, low physical activity, and low grip strength was examined among 201 sedentary older adults with aMCI. Associations between dimensions of physical frailty and severity of cognitive impairment, as measured with the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and individual dimensions of cognitive function were examined using multiple linear regression models. RESULTS: Greater than 50% of participants met physical frailty criteria on dimensions of slow gait speed, low physical activity and low grip strength. Slower gait speed was associated with elevated severity of cognitive impairment. Both gait speed and physical activity were associated with individual dimensions cognitive function. CONCLUSIONS: Dimensions of physical frailty, particularly gait speed, were associated with severity of cognitive impairment, after adjusting for age, sex and age-related factors. Further studies are needed to investigate mechanisms and early intervention strategies that assist older adults with aMCI to maintain function and independence.

Weaning infants with phenylketonuria: a review.

Careful weaning is particularly important in phenylketonuria (PKU). Dietary phenylalanine intake is severely restricted, and the diet is supplemented with phenylalanine-free amino acids and special low protein foods. In PKU, there are no evidence-based weaning guidelines and no studies assessing the introduction of solid foods. We critically review the literature and examine current UK weaning practices. Ideally, weaning in PKU should closely reflect the 'model' for healthy infants. However, the requirement for optimal blood phenylalanine control and the demands of diet therapy overshadow the social aspects of weaning. Solid food intake is established with very low protein foods first, and then 50 mg phenylalanine exchanges (equivalent to 1 g of intact protein) gradually replace breast/formula feeds. Introducing solids before the recommended 6 months of age may be advantageous because there is a less persistent neophobic food response, possibly leading to better food acceptance. Infants with PKU also require a special phenylalanine-free protein substitute. Between 6 and 12 months, a second concentrated source of phenylalanine-free protein substitute is required. This is commonly given as an additional liquid, although the prescribed volume may adversely affect appetite. Alternatively, a second-stage protein substitute administered as a paste may better suit feeding development. Further research aiming to examine the weaning process in PKU with a focus on biological, maternal, infant, social and environmental factors is required. This will help provide evidence for the effect of protein substitute on appetite and help in the development of evidence-based guidelines.

Investigating the adverse respiratory effects of ß-blocker treatment: six years of prospective longitudinal data in a cohort with cardiac disease.

BACKGROUND: Globally, cardiovascular disease (CVD) is the leading cause of death. Beta-blocker medications have well-established survival benefit for myocardial infarction and heart failure. However, CVD frequently coexists with chronic obstructive airways disease (COPD), a disease in which beta-blockers are traditionally avoided. AIM: We sought to investigate the adverse respiratory effects associated with long-term beta-blocker treatment in patients with cardiac disease, and presumed high risk of COPD. METHODS: In this prospective cohort study, patients admitted with acute cardiac disease were recruited from the cardiology unit of a tertiary referral hospital. The treating cardiologist determined beta-blocker treatment, independent of the study. Repeated measures of spirometry and respiratory symptom scores were assessed over 12 months. Respiratory exacerbations, cardiac events and survival were recorded over 6 years. Outcomes were compared according to beta-blocker exposure. RESULTS: Sixty-four subjects participated, 30 of whom received beta-blockers. Beta-blockers did not adversely affect spirometry, respiratory symptoms or survival. However, considering two categories of respiratory exacerbations (symptom-based vs treated), subjects taking beta-blockers accumulated increased annual risk (relative risk (RR) 1.30, 95% confidence interval (CI) 1.11-1.53, P= 0.001 and RR 1.37, 95% CI 1.09-1.72, P= 0.008) and concluded with overall increased risk (RR 3.67, 95% CI 1.65-8.18, P= 0.001 and RR 4.03, 95% CI 1.26-12.9, P= 0.019), when compared with the group not taking beta-blockers. CONCLUSION: Long-term beta-blocker treatment did not adversely affect lung function, respiratory symptom scores or survival, but was associated with increased risk of respiratory exacerbations.

Cardiovascular mortality and morbidity in chronic obstructive pulmonary disease: the impact of bronchodilator treatment.

Chronic obstructive pulmonary disease (COPD) is a substantial health burden. Cardiovascular disease (CVD), the leading cause of death, frequently coexists with COPD, an effect attributed to high individual disease prevalences and shared risk factors. It has long been recognized that COPD, whether stable or during acute exacerbations, is associated with an excess of cardiac arrhythmias. Bronchodilator medications have been implicated in the excess CVD seen in COPD, either as an intrinsic medication effect or related to side-effects. Despite the theory behind increased pro-arrhythmic effects in COPD, the reported results of trials investigating this for inhaled formulations at therapeutic doses are few. Methodological flaws, retrospective analysis and inadequate adjustment for concomitant medications, including short-acting 'relief' bronchodilators and non-respiratory medications with known arrhythmia propensity, mar many of these studies. For most bronchodilators at therapeutic levels in stable COPD, we can be reassured of their safety from current studies. The exception to this is ipratropium bromide, where the current data indicate an association with increased cardiovascular adverse effects. Moreover, there is no proven benefit from combining short-acting beta-agonists with short-acting anticholinergics at high doses in the acute setting, and although this practice is widespread, it is associated with increased cardiovascular risk.

Preferred and actual participation roles during health care decision making in persons with cancer: a systematic review.

The preferred and actual participation roles during decision making have been studied over the past two decades; however, there is a lack of evidence on the degree of match between patients' preferred and actual participation roles during decision making. A systematic review was carried out to identify published studies that examined preferred and actual participation roles and the match between preferred and actual roles in decision making among patients with cancer. PubMed (1966 to January 2009), PsycINFO (1967 to January 2009), and CINAHL (1982 to January 2009) databases were searched to access relevant medical, psychological, and nursing literature. Twenty-two studies involving patients with breast, prostate, colorectal, lung, gynecological, and other cancers showed discrepancies between preferred and actual roles in decision making. These groups of patients wanted a more shared or an active role versus a less passive role. Across all cancer types, patients wanted more participation than what actually occurred. Research to date documents a pervasive mismatch between patients' preferred and actual roles during decision making. Yet, there is lack of innovative interventions that can potentially increase matching of patients' preferred and actual role during decision making. Role preferences are dynamic and vary greatly during decision making, requiring regular clinical assessment to meet patients' expectations and improve satisfaction with treatment decisions.

Professionals delivering palliative care to people with COPD: qualitative study.

This article describes health and social care professionals' perceptions of palliative care and facilitators and barriers to the delivery of such care for patients with advanced chronic obstructive pulmonary disease. Health professionals participated in semi structured interviews and focus groups which were analysed using content analysis. According to participants, care of patients with chronic obstructive pulmonary disease is focused upon the management of symptoms, with emphasis focused predominately on an acute model of care. Key barriers towards the delivery of palliative care included the reluctance to negotiatie end-of-life decisions and a perceived lack of understanding among patients and carers regarding the illness trajectory. Consequently the delivery of palliative care was viewed as a specialist role rather than an integral component of care. There is a need for education and training for health and social care professions to plan and provide high quality end-of-life care.

Predictors of adherence in the Women's Health Initiative Calcium and Vitamin D Trial.

The authors analyzed data from the Women's Health Initiative (WHI) Calcium and Vitamin D Supplementation Trial (CaD) to learn more about factors affecting adherence to clinical trial study pills (both active and placebo). Most participants (36,282 postmenopausal women aged 50-79 years) enrolled in CaD 1 year after joining either a hormone trial or the dietary modification trial of WHI. The WHI researchers measured adherence to study pills by weighing the amount of remaining pills at an annual study visit; adherence was primarily defined as taking > or = 80% of the pills. The authors in this study examined a number of behavioral, demographic, procedural, and treatment variables for association with study pill adherence. They found that relatively simple procedures (ie, phone contact early in the study [4 weeks post randomization] and direct social contact) later in the trial may improve adherence. Also, at baseline, past pill-use experiences, personal supplement use, and relevant symptoms may be predictive of adherence in a supplement trial.

I can not get a breath: experiences of living with advanced chronic obstructive pulmonary disease.

This study aims to explore the potential for palliative care among people living with advanced chronic obstructive pulmonary disease (COPD). Individual semi-structured interviews (n=13) were conducted with people who had a diagnosis of advanced COPD and were on optimal tolerated drug therapy, with their breathing volume (forced expiratory volume at less than 30%) or were on long-term oxygen therapy or non-invasion ventilation. Participants raised concerns about the uncertain trajectory of the illness and reported unmet palliative care needs with poor access to palliative care services. For most people, palliative care was associated with end of life; therefore, they were unwilling to discuss the issue. There was a wide acceptance that, medically, nothing more could be done. Findings also suggest that patients had unmet palliative care needs, requiring information and support. The research suggests the need for palliative care to be extended to all (regardless of diagnosis), with packages of care developed to target specific needs.

Circulating insulin-like growth factor axis and the risk of pancreatic cancer in four prospective cohorts.

Insulin-like growth factor (IGF)-I induces growth in pancreatic cancer cells and blockade of the IGF-I receptor has antitumour activity. The association of plasma IGF-I and IGF binding protein-3 (IGFBP-3) with pancreatic cancer risk has been investigated in two small studies, with conflicting results. We conducted a nested case-control study within four large, prospective cohorts to investigate whether prediagnostic plasma levels of IGF-I, IGF-II, and IGFBP-3 were associated with pancreatic cancer risk. Plasma levels in 212 cases and 635 matched controls were compared by conditional logistic regression, with adjustment for other known pancreatic cancer risk factors. No association was observed between plasma levels of IGF-I, IGF-II, or IGFBP-3 and incident diagnosis of pancreatic cancer. Relative risks for the highest vs the lowest quartile of IGF-I, IGF-II, and IGFBP-3 were 0.94 (95% confidence interval (CI), 0.60-1.48), 0.96 (95% CI, 0.61-1.52), and 1.21 (95% CI, 0.75-1.92), respectively. The relative risk for the molar ratio of IGF-I and IGFBP-3, a surrogate measure for free IGF-I, was 0.84 (95% CI, 0.54-1.31). Additionally, no association was noted in stratified analyses or when requiring longer follow-up. In four prospective cohorts, we found no association between the risk of pancreatic cancer and prediagnostic plasma levels of IGF-I, IGF-II, or IGFBP-3.

A new, low-volume protein substitute for teenagers and adults with phenylketonuria.

Some older patients with phenylketonuria (PKU) fail to consume their protein substitute (with or without vitamin and mineral supplements) in prescribed amounts, which contributes to poor blood phenylalanine control. PKU Express (Vitaflo), is a new low-volume (amino acids 72 g/100 g), low-carbohydrate, phenylalanine-free protein substitute with added vitamins and minerals designed for people with PKU over 8 years of age. In an open intervention study, the aim was to investigate its acceptability and effectiveness in a group of teenagers and adults with PKU. Twenty-three subjects (15 female; 8 male) with PKU, who had a median age of 17 years (range 8-37 years) took the substitute for 8 weeks. A 3-day prospective diet diary, height, weight, plasma amino acids, biochemical and haematological nutritional analytes were measured at weeks 0 and 8. Skin-puncture bloods for plasma phenylalanine were collected every 2 weeks. The median weight of protein substitute (with or without vitamin and mineral supplements) consumed decreased by 33% from 150 g (range 140-180) daily to 100 g (range 100-125) daily ( p <0.001). Median change in energy intake decreased by a median of 10% (95% CI 2.0 to 18.0) when compared to intake on original protein substitute. On PKU Express, the intakes of all nutrients exceeded the dietary reference values but none was excessively high. Blood phenylalanine decreased by a mean of 37 micromol/L (95% CI-27 to 102) during the trial. Body mass index decreased in 40% of subjects. Changes in blood phenylalanine or body mass index were not statistically significant. Most of the nutritional, haematological and biochemical indices stayed within normal reference ranges for the analytes studied. Sixteen (70%) of the subjects had low plasma selenium at the start, but only 13 (57%) at the study end. Plasma vitamin B12 was high in 8 subjects at the start of the study and 9 at the end. Twenty-one subjects (96%) stated that the product was convenient and easy to prepare. However, 7 (32%) described the smell and 9 (46%) the texture as the same as or worse than those of previous protein substitutes. Because of the use of the premeasured sachets, some subjects were able to prepare their own protein substitute for the first time. PKU Express is a safe, efficacious, protein substitute that significantly reduces the daily volume of prescribed protein substitute.

Catalytic function of Drosophila melanogaster glutathione S-transferase DmGSTS1-1 (GST-2) in conjugation of lipid peroxidation end products.

Drosophila melanogaster glutathione S-transferase DmGSTS1-1 (earlier designated as GST-2) is related to sigma class GSTs and was previously described as an indirect flight muscle-associated protein with no known catalytic properties. We now report that DmGSTS1-1 isolated from Drosophila or expressed in Escherichia coli is essentially inactive toward the commonly used synthetic substrate 1-chloro-2,4-dinitrobenzene (CDNB), but has relatively high glutathione-conjugating activity for 4-hydroxynonenal (4-HNE), an electrophilic aldehyde derived from lipid peroxidation. 4-HNE is thought to have signaling functions and, at higher concentrations, has been shown to be cytotoxic and involved in the etiology of various degenerative diseases. Drosophila strains carrying P-element insertions in the GstS1 gene have a reduced capacity for glutathione conjugation of 4-HNE. In flies with both, one, or none of the GstS1 alleles disrupted by P-element insertion, there is a linear correlation between DmGSTS1-1 protein content and 4-HNE-conjugating activity. This correlation indicates that in adult Drosophila 70 +/- 6% of the capacity to conjugate 4-HNE is attributable to DmGSTS1-1. The high abundance of DmGSTS1-1 (approximately 2% of the soluble protein in adult flies) and its previously reported localization in tissues that are either highly aerobic (indirect flight muscle) or especially sensitive to oxidative damage (neuronal tissue) suggest that the enzyme may have a protective role against deleterious effects of oxidative stress. Such function in insects would be analogous to that carried out in mammals by specialized alpha class glutathione S-transferases (e.g. GSTA4-4). The independent emergence of 4-HNE-conjugating activity in more than one branch of the glutathione S-transferase superfamily suggests that 4-HNE catabolism may be essential for aerobic life.

Cerebrospinal fluid shunt infections in infants and children in Mobile, Alabama.

Cerebrospinal fluid shunt systems are used to treat hydrocephalus in infants and children; unfortunately, some shunt systems become infected. We sought to define the epidemiology of shunt infections and shunt survival prior to infection at our institution. We identified 268 shunt procedures performed from January 1990 to June 1996 in 145 patients. There were 29 episodes of shunt infection for an incidence of 10.8% per procedure and 13.1% per patient. Staphylococcus epidermidis was the most common isolate recovered. The probability of shunt infection was highest during the first 8 weeks after a shunt procedure and subsequent infection was less likely after 28 weeks.