Early-Treated Phenylketonuria: Neuropsychologic Consequences.

ERIC Educational Resources Information Center

Brunner, Robert L.; And Others

1983-01-01

The neuropsychologic performance of 27 children (about 6 to 13 years old) with early-treated phenylketonuria (PKU) was evaluated and correlated with their serum phenylalanine concentrations at several ages. (Author/SEW) Journal Availability: The Journal of Pediatrics; The C. V. Mosby Company, 11830 Westline Industrial Drive, St. Louis, MO 63141.

Classroom Demonstration of a Spot Test for Pbenylpyruvic Acid and Its Relationship to Phenylketonuria

ERIC Educational Resources Information Center

Halkides, Christopher J.

2004-01-01

Classical phenylketonuria (PKU) is caused by a lack activity in the enzyme phenylalanine hydroxylase, leading to elevated concentrations of phenylalanine in the blood. A simple demonstration and three advanced demonstrations of a spot test for phenylpyruvic acid and its relationship to phenylketonuria are given.

Psychiatric symptoms and disorders in phenylketonuria.

PubMed

Brumm, V L; Bilder, D; Waisbren, S E

2010-01-01

Psychological and psychiatric problems are well documented across the lifespan of individuals with early-treated phenylketonuria (PKU). Early-treated children and adolescents tend to display attentional problems, school problems, lower achievement motivation, decreased social competence, decreased autonomy, and low-self-esteem. As they enter adulthood, early-treated individuals may carry forward low self-esteem and lack of autonomy but also tend to develop depressed mood, generalized anxiety, phobias, decreased positive emotions, social maturity deficits, and social isolation. The correlation between level of metabolic control and severity of symptoms suggests a biological basis of psychiatric dysfunction. Additionally, psychosocial factors such as the burden of living with a chronic illness may contribute to psychological and psychiatric outcomes in PKU. The lack of a PKU-specific psychiatric phenotype combined with the observation that not everyone with PKU is affected highlights the complexity of the problem. More research on psychiatric and psychological outcomes in PKU is required. Of particular importance is the routine monitoring of emotional, behavioral, and psychosocial symptoms in individuals with this metabolic disorder. Longitudinal studies are required to evaluate the impact of new and emerging therapies on psychiatric and psychosocial functioning in PKU. Unidentified or untreated emotional and behavioral symptoms may have a significant, lifelong impact on the quality of life and social status of patients. Copyright 2009 Elsevier Inc. All rights reserved.

[National screening for phenylketonuria, congenital hypothyroidism and congenital adrenal hyperplasia].

PubMed

Osório, R V; Vilarinho, L; Soares, J P

1992-03-01

In Portugal the screening for phenylketonuria (PKU) and congenital hypothyroidism (CH) was begun towards the end of 1979, and by 1990 59 cases of PKU and 227 cases of CH had been detected. The early initiation of treatment and the observed mental and motor development, point towards a normal development in these children. A trial screen for congenital adrenal hyperplasia was carried out in 100.000 newborns, from which it was concluded that, under the present conditions, screening at a national level is not justified. A similar study is currently being undertaken for biotinidase deficiency and cystic fibrosis. The results ares discussed, as are the cost/benefits evaluations.

Implications of resolving the diagnosis of PKU for parents and children.

PubMed

Lord, Bruce; Ungerer, Judy; Wastell, Colin

2008-09-01

To examine resolution of the diagnosis among parents of children with phenylketonuria (PKU) as a mechanism of adjustment for parents and children. Reaction to diagnosis interviews were conducted with 52 mothers and 47 fathers of 55 children with PKU aged 2-12 years. The parents also completed questionnaires assessing their personal adjustment (stress symptoms), their child's adjustment (behavior problems), and coping variables (personal hopefulness and coping strategies). Most mothers (69%) and fathers (77%) were resolved to their child's diagnosis. Lower levels of parent stress were explained by higher personal hopefulness (14% of the variance for mothers and 21% for fathers) and resolution of the diagnosis (15% of the variance for mothers and 6% for fathers) after taking account of demographic variables and severity of the child's PKU. Parent resolution, however, did not contribute independently to the variance explained in child behavior problems after taking account of coping variables and severity of PKU. Resolution of the diagnosis of PKU is a strong indicator of parent adjustment, and assessment of parent reactions should be considered an integral component of clinical care. Further research is warranted in relation to the implications of parent resolution for the child's response to PKU through different development stages and the effectiveness of interventions in aiding parent resolution.

Phenylketonuria in adulthood: a collaborative study.

PubMed

Koch, R; Burton, B; Hoganson, G; Peterson, R; Rhead, W; Rouse, B; Scott, R; Wolff, J; Stern, A M; Guttler, F; Nelson, M; de la Cruz, F; Coldwell, J; Erbe, R; Geraghty, M T; Shear, C; Thomas, J; Azen, C

2002-09-01

During 1967-1983, the Maternal and Child Health Division of the Public Health Services funded a collaborative study of 211 newborn infants identified on newborn screening as having phenylketonuria (PKU). Subsequently, financial support was provided by the National Institute of Child Health and Human Development (NICHD). The infants were treated with a phenylalanine (Phe)-restricted diet to age 6 years and then randomized either to continue the diet or to discontinue dietary treatment altogether. One hundred and twenty-five of the 211 children were then followed until 10 years of age. In 1998, NICHD scheduled a Consensus Development Conference on Phenylketonuria and initiated a study to follow up the participants from the original Collaborative Study to evaluate their present medical, nutritional, psychological, and socioeconomic status. Fourteen of the original clinics (1967-1983) participated in the Follow-up Study effort. Each clinic director was provided with a list of PKU subjects who had completed the original study (1967-1983), and was asked to evaluate as many as possible using a uniform protocol and data collection forms. In a subset of cases, magnetic resonance imaging and spectroscopy (MRI/MRS) were performed to study brain Phe concentrations. The medical evaluations revealed that the subjects who maintained a phenylalanine-restricted diet reported fewer problems than the diet discontinuers, who had an increased rate of eczema, asthma, mental disorders, headache, hyperactivity and hypoactivity. Psychological data showed that lower intellectual and achievement test scores were associated with dietary discontinuation and with higher childhood and adult blood Phe concentrations. Abnormal MRI results were associated with higher brain Phe concentrations. Early dietary discontinuation for subjects with PKU is associated with poorer outcomes not only in intellectual ability, but also in achievement test scores and increased rates of medical and behavioural

Implications of Resolving the Diagnosis of PKU for Parents and Children

PubMed Central

Ungerer, Judy; Wastell, Colin

2008-01-01

Objective To examine resolution of the diagnosis among parents of children with phenylketonuria (PKU) as a mechanism of adjustment for parents and children. Methods Reaction to diagnosis interviews were conducted with 52 mothers and 47 fathers of 55 children with PKU aged 2–12 years. The parents also completed questionnaires assessing their personal adjustment (stress symptoms), their child's adjustment (behavior problems), and coping variables (personal hopefulness and coping strategies). Results Most mothers (69%) and fathers (77%) were resolved to their child's diagnosis. Lower levels of parent stress were explained by higher personal hopefulness (14% of the variance for mothers and 21% for fathers) and resolution of the diagnosis (15% of the variance for mothers and 6% for fathers) after taking account of demographic variables and severity of the child's PKU. Parent resolution, however, did not contribute independently to the variance explained in child behavior problems after taking account of coping variables and severity of PKU. Conclusions Resolution of the diagnosis of PKU is a strong indicator of parent adjustment, and assessment of parent reactions should be considered an integral component of clinical care. Further research is warranted in relation to the implications of parent resolution for the child's response to PKU through different development stages and the effectiveness of interventions in aiding parent resolution. PMID:18339641

How Do Health Care Providers Diagnose Phenylketonuria (PKU)?

MedlinePlus

... born with PKU. To perform this test, a health care provider takes some cells, either through a needle inserted into the abdomen or a small tube inserted into the vagina. A genetic counselor who understands the risks and benefits of genetic testing can help explain the choices available for testing. ...

Developmental Trajectories of Executive and Verbal Processes in Children with Phenylketonuria.

PubMed

Hawks, Zoë W; Strube, Michael J; Johnson, Neco X; Grange, Dorothy K; White, Desirée A

2018-01-01

Phenylketonuria (PKU) is a hereditary disorder characterized by disrupted phenylalanine metabolism and cognitive impairment. However, the precise nature and developmental trajectory of this cognitive impairment remains unclear. The present study used a verbal fluency task to dissociate executive and verbal processes in children with PKU (n = 23; 7-18 years) and controls (n = 44; 7-19 years). Data were collected at three longitudinal timepoints over a three-year period, and the contributions of age, group, and their interaction to fluency performance were evaluated. Results indicated impairments in executive processes in children with PKU, which were exacerbated by declining metabolic control.

The Long-Term Use of a Low-Phenylalanine Diet in Late-Treated Phenylketonuria: A Single Case Report

ERIC Educational Resources Information Center

Hewitt, Philippa; Cottle, Mandy; Coleman, Carol

2006-01-01

Background: When phenylketonuria (PKU) is not diagnosed and long-term treatment commenced within the first few weeks of life, permanent brain damage will occur. There is some evidence to show that late diagnosed or untreated people with PKU who have severe challenging behaviours may benefit from a low phenylalanine diet [Harper & Reid (1987)…

Breastfeeding infants with phenylketonuria in the United States and Canada.

PubMed

Banta-Wright, Sandra A; Press, Nancy; Knafl, Kathleen A; Steiner, Robert D; Houck, Gail M

2014-04-01

This study described the prevalence and duration of mothers' breastfeeding infants with phenylketonuria (PKU) and explored factors related to duration of breastfeeding as a surrogate for breastfeeding success. Descriptive analysis as performed from an international Internet survey of mothers (n=103) who met the inclusion criteria: (1) at least 21 years of age, (2) able to read and write in English, (3) child with PKU, and (4) living in the United States or Canada. Of the 103 mothers, 89 (86%) initiated breastfeeding immediately following delivery, whereas 14 (14%) chose bottle feeding. In comparison to breastfeeding after delivery, significantly fewer mothers breastfed after diagnosis (McNemar's χ(2)=30.33, p<0.001; n=72 vs. n=89). Breastfeeding duration ranged from less than 1 month to 24 months with one modal duration category (n=20, 22%) at less than 1 month. The timing of the addition of commercial infant formula to supplement breastfeeding or expressed mothers' milk was associated with a shorter duration of breastfeeding among infants with PKU: χ(2) (42, n=73)=88.13, p<0.001. PKU is treated with phenylalanine (Phe) restriction. Breastfeeding infants with PKU is challenging in part because Phe intake is difficult to determine precisely. We studied breastfeeding duration in infants with PKU and factors associated with success. Further research should identify the unique needs of mothers' breastfeeding infants with PKU to guide the development of interventions specific to these mothers to support their efforts to continue breastfeeding after the diagnosis of PKU.

Breastfeeding Infants with Phenylketonuria in the United States and Canada

PubMed Central

Press, Nancy; Knafl, Kathleen A.; Steiner, Robert D.; Houck, Gail M.

2014-01-01

Abstract Objective: This study described the prevalence and duration of mothers' breastfeeding infants with phenylketonuria (PKU) and explored factors related to duration of breastfeeding as a surrogate for breastfeeding success. Subjects and Methods: Descriptive analysis as performed from an international Internet survey of mothers (n=103) who met the inclusion criteria: (1) at least 21 years of age, (2) able to read and write in English, (3) child with PKU, and (4) living in the United States or Canada. Results: Of the 103 mothers, 89 (86%) initiated breastfeeding immediately following delivery, whereas 14 (14%) chose bottle feeding. In comparison to breastfeeding after delivery, significantly fewer mothers breastfed after diagnosis (McNemar's χ2=30.33, p<0.001; n=72 vs. n=89). Breastfeeding duration ranged from less than 1 month to 24 months with one modal duration category (n=20, 22%) at less than 1 month. The timing of the addition of commercial infant formula to supplement breastfeeding or expressed mothers' milk was associated with a shorter duration of breastfeeding among infants with PKU: χ2 (42, n=73)=88.13, p<0.001. Conclusions: PKU is treated with phenylalanine (Phe) restriction. Breastfeeding infants with PKU is challenging in part because Phe intake is difficult to determine precisely. We studied breastfeeding duration in infants with PKU and factors associated with success. Further research should identify the unique needs of mothers' breastfeeding infants with PKU to guide the development of interventions specific to these mothers to support their efforts to continue breastfeeding after the diagnosis of PKU. PMID:24350704

The birth prevalence of PKU in populations of European, South Asian and sub-Saharan African ancestry living in South East England.

PubMed

Hardelid, P; Cortina-Borja, M; Munro, A; Jones, H; Cleary, M; Champion, M P; Foo, Y; Scriver, C R; Dezateux, C

2008-01-01

Phenylketonuria (PKU) is an autosomal recessive inborn error of metabolism (OMIM 261600). Treatment with a low-phenylalanine diet following early ascertainment by newborn screening prevents impaired cognitive development, the major disease phenotype in PKU. The overall birth prevalence of PKU in European, Chinese and Korean populations is approximately 1/10,000. Since the human PAH locus contains PKU-causing alleles and polymorphic core haplotypes that describe and corroborate an out-of-Africa range expansion in modern human populations, it is of interest to know the prevalence of PKU in different ethnic groups with diverse geographical origin. We estimated PKU prevalence in South East England, where a sizeable proportion of the population are of Sub-Saharan African or South Asian ancestry. Over the period 1994 to 2004 167 children were diagnosed with PKU. Using birth registration and census data to derive denominators, PKU birth prevalence per 10,000 live births (95% Bayesian credible intervals) was estimated to be 1.14 (0.96-1.33) among white, 0.11 (0.02-0.37) among black, and 0.29 (0.10-0.63) among Asian ethnic groups. This suggests that PKU is up to an order of magnitude less prevalent in populations with Sub-Saharan African and South Asian ancestry that have migrated to the UK.

Costs and Outcomes over 36 Years of Patients with Phenylketonuria Who Do and Do Not Remain on a Phenylalanine-Restricted Diet

ERIC Educational Resources Information Center

Guest, J. F.; Bai, J. J.; Taylor, R. R.; Sladkevicius, E.; Lee, P. J.; Lachmann, R. H.

2013-01-01

Background: To quantify the costs and consequences of managing phenylketonuria (PKU) in the UK and to estimate the potential implications to the UK's National Health Service (NHS) of keeping patients on a phenylalanine-restricted diet for life. Methods: A computer-based model was constructed depicting the management of PKU patients over the first…

The Prevalence of Phenylketonuria in Arab Countries, Turkey, and Iran: A Systematic Review.

PubMed

El-Metwally, Ashraf; Yousef Al-Ahaidib, Lujane; Ayman Sunqurah, Alaa; Al-Surimi, Khaled; Househ, Mowafa; Alshehri, Ali; Da'ar, Omar B; Abdul Razzak, Hira; AlOdaib, Ali Nasser

2018-01-01

This paper seeks to identify the prevalence of Phenylketonuria (PKU) in Arab countries, Turkey, and Iran. The study reviewed the existence of comprehensive national newborn screening programs and reported consanguinity rates. A computer based literature search was conducted using relevant keywords to retrieve studies conducted on PKU. A total of 34 articles were included. Prevalence was categorized based on the type of screening method used for PKU diagnoses. The prevalence of classical PKU diagnosed through a comprehensive national newborn screening program ranged from 0.005% to 0.0167%. The highest prevalence was reported in Turkey at 0.0167%, whereas the lowest prevalence was reported in the UAE, 0.005%. The findings of this review emphasize the need for the establishment of more efficient reporting systems in these countries that would help measure Disability-Adjusted Life Year (DALY) in order to estimate the overall societal burden of PKU.

Metabolic syndrome in children and adolescents with phenylketonuria.

PubMed

Kanufre, Viviane C; Soares, Rosângelis D L; Alves, Michelle Rosa A; Aguiar, Marcos J B; Starling, Ana Lúcia P; Norton, Rocksane C

2015-01-01

This study aimed to identify markers of metabolic syndrome (MS) in patients with phenylketonuria (PKU). This was a cross-sectional study consisting of 58 PKU patients (ages of 4-15 years): 29 patients with excess weight, and 29 with normal weight. The biochemical variables assessed were phenylalanine (phe), total cholesterol, HDL-c, triglycerides, glucose, and basal insulin. The patients had Homeostasis Model Assessment (HOMA) and waist circumference assessed. No inter-group difference was found for phe. Overweight patients had higher levels of triglycerides, basal insulin, and HOMA, but lower concentrations of HDL-cholesterol, when compared to the eutrophic patients. Total cholesterol/HDL-c was significantly higher in the overweight group. A positive correlation between basal insulin level and HOMA with waist circumference was found only in the overweight group. The results of this study suggest that patients with PKU and excess weight are potentially vulnerable to the development of metabolic syndrome. Therefore, it is necessary to conduct clinical and laboratory monitoring, aiming to prevent metabolic changes, as well as excessive weight gain and its consequences, particularly cardiovascular risk. Copyright © 2014 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Breast-feeding success among infants with phenylketonuria.

PubMed

Banta-Wright, Sandra A; Shelton, Kathleen C; Lowe, Nancy D; Knafl, Kathleen A; Houck, Gail M

2012-08-01

Breast milk is the nutrition of choice for human infants (American Academy of Pediatrics, 2005; American Association of Family Physicians, 2008; Association of Women's Health Obstetric and Neonatal Nurses, 2005; Canadian Paediatric Society, 2005; U.S. Preventive Services Task Force, 2008; World Health Organization, 2009). In comparison to standard commercial formula, human breast milk has a lower concentration of protein and a lower content of the amino acid phenylalanine (Phe). For infants with phenylketonuria (PKU), these attributes of human breast milk make it ideal as a base source of nutrition. The purpose of this study was to compare the incidence and duration of breast-feeding and corresponding Phe levels of breast-fed and formula-fed infants with PKU in the caseload of a pediatric metabolic clinic at an urban tertiary-care medical center. Charts were reviewed for infants diagnosed with PKU beginning with 2005 and ending with 1980, the year no further breast-feeding cases were identified in the PKU population. During the first year of life, most of the infants, whether breast-fed or formula-fed, had similar mean Phe levels. However, the frequency distributions revealed that more breast-fed infants with PKU had Phe levels within the normal range (120-360 μmol/L) and were less likely to have low Phe levels (<120 μmol/L) than formula-fed infants with PKU. Further research is needed to understand how mothers manage breast-feeding in the context of PKU. Copyright © 2012 Elsevier Inc. All rights reserved.

[Phenylketonuria diagnosed during the neonatal period and breast feeding].

PubMed

Cornejo, Verónica; Manríquez, Viviana; Colombo, Marta; Mabe, Paulina; Jiménez, Mónica; De la Parra, Alicia; Valiente, Alf; Raimann, Erna

2003-11-01

Phenylketonuria (PKU) is due to of a defect in the phenylalanine hydroxylase gene (12q22-24.1) leading to hyperphenylalaninemia. Treatment consists in a low phenylalanine (Phe) diet. To evaluate the evolution of early diagnosed PKU children, receiving direct breast feeding, and a special formula without Phe, during their first six months of life. Nineteen PKU children diagnosed in the neonatal period (19.29 +/- 13.8 days of age), treated with breast feeding and formula without Phe since diagnosis, were studied. Intake of calories, proteins and dietary Phe were quantified. Blood Phe, nutritional status and psychomotor development were also measured. The diet that these children received during the 6 months period of study, had a mean of 127 +/- 19.9 Kcal/kg/day, 1.95 +/- 0.3 g protein/kg/day and 35.3 +/- 9.5 mg Phe/kg/day. Fifteen children maintained the blood level of Phe under 8 mg/dl, considered an excellent metabolic control. Only 4 cases had intermittently high levels, between 10-12 mg/dl. At 6 months of age, 74% of the children maintained breast feeding as the only source of Phe. Sixty three percent had a normal nutritional status, 5.2% were at nutritional risk and 31.6% were overweight. Eighty one percent had a normal mental development. The use of direct breast feeding allows a good metabolic control and improves growth and development of early diagnosed PKU children.

Establishing core outcome sets for phenylketonuria (PKU) and medium-chain Acyl-CoA dehydrogenase (MCAD) deficiency in children: study protocol for systematic reviews and Delphi surveys.

PubMed

Potter, Beth K; Hutton, Brian; Clifford, Tammy J; Pallone, Nicole; Smith, Maureen; Stockler, Sylvia; Chakraborty, Pranesh; Barbeau, Pauline; Garritty, Chantelle M; Pugliese, Michael; Rahman, Alvi; Skidmore, Becky; Tessier, Laure; Tingley, Kylie; Coyle, Doug; Greenberg, Cheryl R; Korngut, Lawrence; MacKenzie, Alex; Mitchell, John J; Nicholls, Stuart; Offringa, Martin; Schulze, Andreas; Taljaard, Monica

2017-12-19

Inherited metabolic diseases (IMD) are a large group of rare single-gene disorders that are typically diagnosed early in life. There are important evidence gaps related to the comparative effectiveness of therapies for IMD, which are in part due to challenges in conducting randomized controlled trials (RCTs) for rare diseases. Registry-based RCTs present a unique opportunity to address these challenges provided the registries implement standardized collection of outcomes that are important to patients and their caregivers and to clinical providers and healthcare systems. Currently there is no core outcome set (COS) for studies evaluating interventions for paediatric IMD. This protocol outlines a study that will establish COS for each of two relatively common IMD in children, phenylketonuria (PKU) and medium-chain acyl-CoA dehydrogenase (MCAD) deficiency. This two-part study is registered with the Core Outcome Measures in Effectiveness Trials (COMET) initiative. Part 1 includes a rapid review and development of an evidence map to identify a comprehensive listing of outcomes reported in past studies of PKU and MCAD deficiency. The review follows established methods for knowledge synthesis, including a comprehensive search strategy, two stages of screening citations against inclusion/exclusion criteria by two reviewers working independently, and extraction of important data elements from eligible studies, including details of the outcomes collected and outcome measurement instruments. The review findings will inform part 2 of our study, a set of Delphi surveys to establish consensus on the highest priority outcomes for each condition. Healthcare providers, families of children with PKU or MCAD deficiency, and health system decision-makers will be invited to participate in two to three rounds of Delphi surveys. The design of the surveys will involve parents of children with IMD who are part of a family advisory forum. This protocol is a crucial step in developing the

Fifty years of phenylketonuria newborn screening - A great success for many, but what about the rest?

PubMed

Groselj, Urh; Tansek, Mojca Zerjav; Battelino, Tadej

2014-01-01

Guthrie's landmark discovery and the subsequent implementation of the first newborn screening programs for phenylketonuria (PKU) and other inherited errors of metabolism (IEM) could be - in a 50 year retrospective - easily considered among the greatest advances in medicine. They have not just improved the quality of hundreds of thousands of lives, but also transformed our understanding and approach to PKU and IEM in general. However, according to the available albeit very scarce data, many countries and regions seem not to share the benefits of the last 50 years of development. Many of them have not yet introduced the newborn screening for PKU or face significant problems in its implementation. In addition, the issue seems to be underrated by the relevant professional forums. Action to improve the current situation should urgently be taken. Copyright © 2014 Elsevier Inc. All rights reserved.

PHENYLKETONURIA, DETECTION IN THE NEWBORN INFANT AS A ROUTINE HOSPITAL PROCEDURE.

ERIC Educational Resources Information Center

GUTHRIE, ROBERT; WHITNEY, STEWART

A FIELD TRIAL OF AN INHIBITION ASSAY METHOD FOR SCREENING FOR PHENYLKETONURIA (PKU) TESTED MORE THAN 400,000 NEWBORN INFANTS PRIOR TO DISCHARGE FROM THE HOSPTIAL. IN ALL, 39 CASES WERE FOUND, A HIGHER INCIDENCE THAN HAD PREVIOUSLY BEEN EXPECTED. THE PRACTICALITY OF THE INHIBITION ASSAY METHOD WAS ALSO DEMONSTRATED. THE REPORT DETAILS THE TRIAL'S…

Psychosocial factors in maternal phenylketonuria: prevention of unplanned pregnancies.

PubMed Central

Waisbren, S E; Shiloh, S; St James, P; Levy, H L

1991-01-01

BACKGROUND. Women with phenylketonuria (PKU) not treated prior to conception can have a pregnancy that results in serious fetal damage. In this report, factors associated with preventing unplanned (and hence late treated) pregnancies are described. METHODS. Subjects included 60 phenylketonuric women and two comparison groups composed of female acquaintances and diabetic women. All were interviewed and administered tests of intelligence, general well-being, knowledge, and personality. RESULTS. Thirty-five percent of the sexually active women with PKU used contraception only sporadically. The variables that best predicted reported frequency of birth control use were the extent to which women felt social support to use contraception (r = .64) along with positive attitudes about birth control (r = .66) and knowledge of family planning (r = .43). For the comparison groups, a different pattern of variables predicted contraceptive use, with locus of control figuring most prominently for the diabetics (r = .39) and social support for birth control being most important for the acquaintances (r = .46). CONCLUSIONS. As more girls with PKU enter childbearing ages, there will be an increased need for specific programs that address psychosocial factors in maternal PKU. PMID:1994738

Qualitative analysis of factors affecting adherence to the phenylketonuria diet in adolescents.

PubMed

Sharman, Rachael; Mulgrew, Kate; Katsikitis, Mary

2013-01-01

Phenylketonuria (PKU) is an inborn error of metabolism that is primarily treated with a severely restricted, low-protein diet to prevent permanent neurological damage. Despite the recognition of the importance of strict dietary adherence in the prevention of intellectual impairment in individuals with PKU, apathy and attrition from diet, especially during adolescence, remain a threat to normal development in this population. This study's aim was to examine adolescents' perception of factors that encourage or inhibit their dietary adherence. This was a qualitative study, with the authors using thematic analysis to interpret the findings. The study was conducted as part of a Metabolic Disorders Association conference. Eight adolescents with PKU were recruited through convenience sampling. A focus group was conducted with the adolescents to gather information about factors that encourage and discourage dietary adherence. Thematic analysis revealed that the adolescents encountered problems explaining the nature and food requirements of their condition to other people. Friends, family, and wanting to maintain "normal" cognitive abilities were identified as factors that encouraged dietary adherence. Adolescents with PKU appear to share several barriers and incentives for maintaining the strict dietary regimen. Considering such perceptions may aid future interventions aiming to reduce diet attrition rates among adolescents.

Communicative and psycholinguistic abilities in children with phenylketonuria and congenital hypothyroidism

PubMed Central

GEJÃO, Mariana Germano; FERREIRA, Amanda Tragueta; SILVA, Greyce Kelly; ANASTÁCIO-PESSAN, Fernanda da Luz; LAMÔNICA, Dionísia Aparecida Cusin

2009-01-01

ABSTRACT The Neonatal Screening for Inborn Errors of Metabolism of the Association of Parents and Friends of Special Needs Individuals (APAE) - Bauru, Brazil, was implanted and accredited by the Brazilian Ministry of Health in 1998. It covers about 286 cities of the Bauru region and 420 collection spots. Their activities include screening, diagnosis, treatment and assistance to congenital hypothyroidism (CH) and phenylketonuria (PKU), among others. In 2005, a partnership was established with the Department of Speech-Language Pathology and Audiology, Bauru School of Dentistry, University of São Paulo, Bauru, seeking to characterize and to follow, by means of research studies, the development of the communicative abilities of children with CH and PKU. Objective: The aim of this study was to describe communicative and psycholinguistic abilities in children with CH and PKU. Materials and Methods: Sixty-eight children (25 children aged 1 to 120 months with PKU and 43 children aged 1 to 60 months with CH) participated in the study. The handbooks were analyzed and different instruments were applied (Observation of Communication Behavior, Early Language Milestone Scale, Peabody Picture Vocabulary Test, Gesell & Amatruda's Behavioral Development Scale, Portage Operation Inventory, Language Development Evaluation Scale, Denver Developmental Screening Test, ABFW Child Language Test-phonology and Illinois Test of Psycholinguistic Abilities), according to the children's age group and developmental level. Results: It was observed that the children with PKU and CH at risk for alterations in their developmental abilities (motor, cognitive, linguistic, adaptive and personal-social), mainly in the first years of life. Alterations in the psycholinguistic abilities were also found, mainly after the preschool age. Attention deficits, language and cognitive alterations were more often observed in children with CH, while attention deficits with hyperactivity and alterations in the

Adherence to tetrahydrobiopterin therapy in patients with phenylketonuria.

PubMed

Rohr, Frances; Wessel, Ann; Brown, Matthew; Charette, Kalin; Levy, Harvey L

2015-01-01

Phenylketonuria (PKU) is an inborn error in phenylalanine metabolism due to deficiency of the enzyme, phenylalanine hydroxylase (PAH). Treatment includes restriction of dietary phenylalanine, and in some individuals, supplementation with the PAH cofactor, tetrahydrobiopterin (sapropterin dihydrochloride). A survey was conducted among patients with PKU who had been prescribed sapropterin to assess reasons for continuing or discontinuing the drug. The primary reason that sapropterin responders discontinued the drug was because of side effects, followed by insufficient reduction of blood phenylalanine and insurance issues. Conversely, those who remained on therapy cited increased tolerance for dietary protein as the main reason for continuation, along with lower blood phenylalanine concentrations and feeling better. This study suggests that adherence to sapropterin therapy is mainly dependent upon the increase in dietary protein allowed when on the drug. Copyright © 2014 Elsevier Inc. All rights reserved.

Learning and behavioural difficulties but not microcephaly in three brothers resulting from undiagnosed maternal phenylketonuria.

PubMed

Shaw-Smith, C; Hogg, S L; Reading, R; Calvin, J; Trump, D

2004-09-01

Universal screening introduced in the 1960s has reduced the incidence of learning disability resulting from phenylketonuria (PKU), which is a treatable condition. Nonetheless, PKU may still be having an impact on the paediatric-age population. We report a woman with previously undiagnosed PKU who was born before the onset of universal screening. She is of normal intelligence, and so the diagnosis was not suspected until after the birth of her three children. Her serum phenylalanine concentration was found to be in excess of 1 mmol/L, well into the toxic range. She has had three sons, all of whom have a significant degree of learning disability resulting from intrauterine exposure to toxic levels of phenylalanine. None of the sons had microcephaly, a physical sign that, if present, might have helped to point towards the correct diagnosis. We suggest that maternal PKU should be suspected where there is sibling recurrence of cognitive impairment, particularly where the mother was born before the initiation of the neonatal screening programme for PKU.

Mutation Analysis in Classical Phenylketonuria Patients Followed by Detecting Haplotypes Linked to Some PAH Mutations.

PubMed

Dehghanian, Fatemeh; Silawi, Mohammad; Tabei, Seyed M B

2017-02-01

Deficiency of phenylalanine hydroxylase (PAH) enzyme and elevation of phenylalanine in body fluids cause phenylketonuria (PKU). The gold standard for confirming PKU and PAH deficiency is detecting causal mutations by direct sequencing of the coding exons and splicing involved sequences of the PAH gene. Furthermore, haplotype analysis could be considered as an auxiliary approach for detecting PKU causative mutations before direct sequencing of the PAH gene by making comparisons between prior detected mutation linked-haplotypes and new PKU case haplotypes with undetermined mutations. In this study, 13 unrelated classical PKU patients took part in the study detecting causative mutations. Mutations were identified by polymerase chain reaction (PCR) and direct sequencing in all patients. After that, haplotype analysis was performed by studying VNTR and PAHSTR markers (linked genetic markers of the PAH gene) through application of PCR and capillary electrophoresis (CE). Mutation analysis was performed successfully and the detected mutations were as follows: c.782G>A, c.754C>T, c.842C>G, c.113-115delTCT, c.688G>A, and c.696A>G. Additionally, PAHSTR/VNTR haplotypes were detected to discover haplotypes linked to each mutation. Mutation detection is the best approach for confirming PAH enzyme deficiency in PKU patients. Due to the relatively large size of the PAH gene and high cost of the direct sequencing in developing countries, haplotype analysis could be used before DNA sequencing and mutation detection for a faster and cheaper way via identifying probable mutated exons.

Parenting a Child with Phenylketonuria: An Investigation into the Factors That Contribute to Parental Distress.

PubMed

Ambler, Olivia; Medford, Emma; Hare, Dougal J

2018-04-20

Phenylketonuria (PKU) is an inherited metabolic condition that can lead to the onset of intellectual disabilities if not strictly managed through a low-protein diet. Parents are responsible for supervising their child's treatment for PKU, which may impact on their experience of distress. This cross-sectional study aimed to identify the factors that contribute to distress in parents who care for a child with PKU, distinct from parents in the general population. Thirty-eight parents of children and adolescents with PKU and 32 parents in the general population completed the questionnaires measuring parental psychological resilience, child behaviour problems, perceived social support and distress. Parents of children with PKU also completed measures of their child's care dependency and behaviour related to developmental and intellectual disabilities. The findings revealed no statistically significant differences in distress between the groups, but parents of children with PKU reported more child behaviour problems. Multiple regression analysis identified that parental psychological resilience and child anxious behaviour explained 35% of the variance in distress for parents of children with PKU. By comparison, parental psychological resilience and generic child behaviour only accounted for 19% of the variance in distress for parents in the general population. This has implications for developing interventions in clinical settings that aim to reduce parents' distress by enhancing their psychological resilience and supporting them to manage child behaviour difficulties, particularly anxious behaviour. Future research should include larger, more diverse samples and use longitudinal study designs.

Fatty acid profile in patients with phenylketonuria and its relationship with bone mineral density.

PubMed

Lage, Sergio; Bueno, María; Andrade, Fernando; Prieto, José Angel; Delgado, Carmen; Legarda, María; Sanjurjo, Pablo; Aldámiz-Echevarría, Luis Jose

2010-12-01

Patients with phenylketonuria (PKU) undergo a restrictive vegan-like diet, with almost total absence of n-3 fatty acids, which have been proposed as potential contributors to bone formation in the healthy population. The PKU diet might lead these patients to bone mass loss and, consequently, to the development of osteopenia/osteoporosis. Therefore, we proposed to analyze their plasma fatty acid profile status and its relationship with bone health. We recruited 47 PKU patients for this cross-sectional study and divided the cohort into three age groups (6-10 years, 11-18 years, 19-42 years). We measured their plasma fatty acid profile and bone mineral density (BMD) (both at the femoral neck and the lumbar spine). Seventy-seven healthy controls also participated as reference values of plasma fatty acids. Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) and total n-3 fatty acids were significantly diminished in PKU patients compared with healthy controls. DHA, EPA, and total n-3 fatty acids were also positively associated with bone mineral density (r = 0.83, p = 0.010; r = 0.57, p = 0.006; r = 0.73, p = 0.040, respectively). There was no association between phenylalanine (Phe), Index of Dietary Control (IDC), calcium, 25-hydroxivitamin D concentrations, daily calcium intake, and BMD. Our results suggest a possible influence of essential fatty acids over BMD in PKU patients. The lack of essential n-3 fatty acids intake in the PKU diet might affect bone mineralization. Further clinical trials are needed to confirm the effect of the n-3 essential fatty acids on bone accrual in a cohort of PKU patients.

Access to treatment for phenylketonuria by judicial means in Rio Grande do Sul, Brazil.

PubMed

Trevisan, Luciano Mangueira; Nalin, Tatiele; Tonon, Tassia; Veiga, Lauren Monteiro; Vargas, Paula; Krug, Bárbara Corrêa; Leivas, Paulo Gilberto Cogo; Schwartz, Ida Vanessa Doederlein

2015-05-01

Treatment of phenylketonuria (PKU) includes the use of a metabolic formula which should be provided free of charge by the Unified Health System (SUS). This retrospective, observational study sought to characterize judicial channels to obtain PKU treatment in Rio Grande do Sul (RS), Brazil. Lawsuits filed between 2001- 2010 and having as beneficiaries PKU patients requesting treatment for the disease were included. Of 20 lawsuits filed, corresponding to 16.8% of RS patients with PKU, 19 were retrieved for analysis. Of these, only two sought to obtain therapies other than metabolic formula. In all the other 17 cases, prior treatment requests had been granted by the State Department of Health. Defendants included the State (n = 19), the Union (n = 1), and municipalities (n = 4). In 18/19 cases, the courts ruled in favor of the plaintiffs. Violation of the right to health and discontinuation of State-provided treatment were the main reasons for judicial recourse. Unlike other genetic diseases, patients with PKU seek legal remedy to obtain a product already covered by the national pharmaceutical assistance policy, suggesting that management failures are a driving factor for judicialization in Brazil.

Food Products Made With Glycomacropeptide, a Low Phenylalanine Whey Protein, Provide a New Alternative to Amino Acid-Based Medical Foods for Nutrition Management of Phenylketonuria

PubMed Central

Van Calcar, Sandra C.; Ney, Denise M.

2012-01-01

Phenylketonuria (PKU), an inborn error in phenylalanine (phe) metabolism, requires lifelong nutrition management with a low-phe diet, which includes a phe-free amino acid-based medical formula to provide the majority of an individual’s protein needs. Compliance with this diet is often difficult for older children, adolescents and adults with PKU. The whey protein glycomacropeptide (GMP) is ideally suited for the PKU diet since it is naturally low in phe. Nutritionally complete, acceptable medical foods and beverages can be made with GMP to increase the variety of protein sources for the PKU diet. As an intact protein, GMP improves protein utilization and increases satiety compared with amino acids. Thus, GMP provides a new, more physiologic source of low-phe dietary protein for those with PKU. PMID:22818728

Generation of urine-derived induced pluripotent stem cells from a patient with phenylketonuria

PubMed Central

Qi, Zijuan; Cui, Yazhou; Shi, Liang; Luan, Jing; Zhou, Xiaoyan; Han, Jinxiang

2018-01-01

Summary The aim of the study was to establish an induced pluripotent stem cell line from urine-derived cells (UiPSCs) from a patient with phenylketonuria (PKU) in order to provide a useful research tool with which to examine the pathology of this rare genetic metabolic disease. Urine-derived epithelial cells (UCs) from a 15-year-old male patient with PKU were isolated and reprogrammed with integration-free episomal vectors carrying an OCT4, SOX2, KLF4, and miR-302-367 cluster. PKU-UiPSCs were verified as correct using alkaline phosphatase staining. Pluripotency markers were detected with real-time PCR and flow cytometry. Promoter methylation in two pluripotent genes, NANOG and OCT4, was analyzed using bisulphite sequencing. An embryoid body (EB) formation assay was also performed. An induced pluripotent stem cell line (iPSC) was generated from epithelial cells in urine from a patient with PKU. This cell line had increased expression of stem cell biomarkers, it efficiently formed EBs, it stained positive for alkaline phosphatase (ALP), and it had a marked decrease in promoter methylation in the NANOG and OCT4 genes. The PKU-UiPSCs created here had typical characteristics and are suitable for further differentiation.

An Investigation of the Neurological and Neuropsychiatric Disturbances in Adults with Undiagnosed and/or Untreated Phenylketonuria in Poland

ERIC Educational Resources Information Center

Mazur, Artur; Jarochowicz, Sabina; Oltarzewski, Mariusz; Sykut-Cegielska, Jolanta; Gradowska, Wanda; Januszek-Trzciakowska, Aleksandra; O'Malley, Grace; Kwolek, Andrzej

2011-01-01

Background: The aim of the study was to determine neurological and neuropsychiatric manifestations in a group of patients with previously undiagnosed or untreated phenylketonuria (PKU) in the south-eastern part of Poland. Methods: The study was conducted among 400 adults with severe intellectual disability who were born prior to neonatal screening…

Evaluation of quality of life and description of the sociodemographic state in adolescent and young adult patients with phenylketonuria (PKU).

PubMed

Simon, Eva; Schwarz, Martin; Roos, Judith; Dragano, Nico; Geraedts, Max; Siegrist, Johannes; Kamp, Gudrun; Wendel, Udo

2008-03-26

Normal intellectual and personal development can be expected in early-diagnosed and treated PKU patients. Aim of the study was to analyse quality of life and social status, which are important parameters for an overall estimation of success of treatment apart from intellectual outcome in adult PKU patients. 67 patients completed a questionnaire on quality of life and social status. Data was compared to the German census on an age matched control collective. Quality of life measured with the Profile of Quality of Life in the Chronically Ill (PLC) revealed mean values for capacity of performance in the patient group in the same range as in the control collective. The analysis of the social state of PKU patients revealed a tendency towards lower or delayed autonomy, and a low rate of forming normal adult relationships in which to have children. Schooling and professional career corresponded approximately to the control collective. Though every chronic disorder must be regarded as restraining, it shows that PKU does not preclude healthy emotional adjustment when the disease is diagnosed early and treated well.

Unbalance between Excitation and Inhibition in Phenylketonuria, a Genetic Metabolic Disease Associated with Autism

PubMed Central

De Jaco, Antonella; Mango, Dalila; De Angelis, Federica; Favaloro, Flores Lietta; Andolina, Diego; Nisticò, Robert; Fiori, Elena; Colamartino, Marco; Pascucci, Tiziana

2017-01-01

Phenylketonuria (PKU) is the most common genetic metabolic disease with a well-documented association with autism spectrum disorders. It is characterized by the deficiency of the phenylalanine hydroxylase activity, causing plasmatic hyperphenylalaninemia and variable neurological and cognitive impairments. Among the potential pathophysiological mechanisms implicated in autism spectrum disorders is the excitation/inhibition (E/I) imbalance which might result from alterations in excitatory/inhibitory synapse development, synaptic transmission and plasticity, downstream signalling pathways, and intrinsic neuronal excitability. Here, we investigated functional and molecular alterations in the prefrontal cortex (pFC) of BTBR-Pahenu2 (ENU2) mice, the animal model of PKU. Our data show higher frequency of inhibitory transmissions and significant reduced frequency of excitatory transmissions in the PKU-affected mice in comparison to wild type. Moreover, in the pFC of ENU2 mice, we reported higher levels of the post-synaptic cell-adhesion proteins neuroligin1 and 2. Altogether, our data point toward an imbalance in the E/I neurotransmission favouring inhibition in the pFC of ENU2 mice, along with alterations of the molecular components involved in the organization of cortical synapse. In addition to being the first evidence of E/I imbalance within cortical areas of a mouse model of PKU, our study provides further evidence of E/I imbalance in animal models of pathology associated with autism spectrum disorders. PMID:28468253

Phenylketonuria and Gut Microbiota: A Controlled Study Based on Next-Generation Sequencing

PubMed Central

Pinheiro de Oliveira, Felipe; Mendes, Roberta Hack; Dobbler, Priscila Thiago; Mai, Volker; Pylro, Victor Salter; Waugh, Sheldon G; Vairo, Filippo; Refosco, Lilia Farret; Schwartz, Ida Vanessa Doederlein

2016-01-01

Phenylketonuria (PKU) is an inborn error of metabolism associated with high blood levels of phenylalanine (Phe). A Phe-restricted diet supplemented with L-amino acids is the main treatment strategy for this disease; if started early, most neurological abnormalities can be prevented. The healthy human gut contains trillions of commensal bacteria, often referred to as the gut microbiota. The composition of the gut microbiota is known to be modulated by environmental factors, including diet. In this study, we compared the gut microbiota of 8 PKU patients on Phe-restricted dietary treatment with that of 10 healthy individuals. The microbiota were characterized by 16S rRNA sequencing using the Ion Torrent™ platform. The most dominant phyla detected in both groups were Bacteroidetes and Firmicutes. PKU patients showed reduced abundance of the Clostridiaceae, Erysipelotrichaceae, and Lachnospiraceae families, Clostridiales class, Coprococcus, Dorea, Lachnospira, Odoribacter, Ruminococcus and Veillonella genera, and enrichment of Prevotella, Akkermansia, and Peptostreptococcaceae. Microbial function prediction suggested significant differences in starch/glucose and amino acid metabolism between PKU patients and controls. Together, our results suggest the presence of distinct taxonomic groups within the gut microbiome of PKU patients, which may be modulated by their plasma Phe concentration. Whether our findings represent an effect of the disease itself, or a consequence of the modified diet is unclear. PMID:27336782

Phenylketonuria and Gut Microbiota: A Controlled Study Based on Next-Generation Sequencing.

PubMed

Pinheiro de Oliveira, Felipe; Mendes, Roberta Hack; Dobbler, Priscila Thiago; Mai, Volker; Pylro, Victor Salter; Waugh, Sheldon G; Vairo, Filippo; Refosco, Lilia Farret; Roesch, Luiz Fernando Würdig; Schwartz, Ida Vanessa Doederlein

2016-01-01

Phenylketonuria (PKU) is an inborn error of metabolism associated with high blood levels of phenylalanine (Phe). A Phe-restricted diet supplemented with L-amino acids is the main treatment strategy for this disease; if started early, most neurological abnormalities can be prevented. The healthy human gut contains trillions of commensal bacteria, often referred to as the gut microbiota. The composition of the gut microbiota is known to be modulated by environmental factors, including diet. In this study, we compared the gut microbiota of 8 PKU patients on Phe-restricted dietary treatment with that of 10 healthy individuals. The microbiota were characterized by 16S rRNA sequencing using the Ion Torrent™ platform. The most dominant phyla detected in both groups were Bacteroidetes and Firmicutes. PKU patients showed reduced abundance of the Clostridiaceae, Erysipelotrichaceae, and Lachnospiraceae families, Clostridiales class, Coprococcus, Dorea, Lachnospira, Odoribacter, Ruminococcus and Veillonella genera, and enrichment of Prevotella, Akkermansia, and Peptostreptococcaceae. Microbial function prediction suggested significant differences in starch/glucose and amino acid metabolism between PKU patients and controls. Together, our results suggest the presence of distinct taxonomic groups within the gut microbiome of PKU patients, which may be modulated by their plasma Phe concentration. Whether our findings represent an effect of the disease itself, or a consequence of the modified diet is unclear.

Phenylalanine ammonia lyase, enzyme substitution therapy for phenylketonuria, where are we now?

PubMed

Sarkissian, Christineh N; Gámez, Alejandra

2005-12-01

Phenylketonuria (PKU) is an autosomal recessive genetic disorder in which mutations in the phenylalanine-4-hydroxylase (PAH) gene result in an inactive enzyme (PAH, EC 1.14.16.1). The effect is an inability to metabolize phenylalanine (Phe), translating into elevated levels of Phe in the bloodstream (hyperphenylalaninemia). If therapy is not implemented at birth, mental retardation can occur. PKU patients respond to treatment with a low-phenylalanine diet, but compliance with the diet is difficult, therefore the development of alternative treatments is desirable. Enzyme substitution therapy with a recombinant phenylalanine ammonia lyase (PAL) is currently being explored. This enzyme converts Phe to the harmless metabolites, trans-cinnamic acid and trace ammonia. Taken orally and when non-absorbable and protected, PAL lowers plasma Phe in mutant hyperphenylalaninemic mouse models. Subcutaneous administration of PAL results in more substantial lowering of plasma and significant reduction in brain Phe levels, however the metabolic effect is not sustained following repeated injections due to an immune response. We have chemically modified PAL by pegylation to produce a protected form of PAL that possesses better specific activity, prolonged half-life, and reduced immunogenicity in vivo. Subcutaneous administration of pegylated molecules to PKU mice has the desired metabolic response (prolonged reduction in blood Phe levels) with greatly attenuated immunogenicity.

PAH mutation spectrum and correlation with PKU manifestation in north Jiangsu province population.

PubMed

Wang, Zhen-Wen; Jiang, Shi-Wen; Zhou, Bao-Cheng

2018-02-01

Phenylketonuria (PKU) is a common autosomal recessive disorder of phenylalanine metabolism and mainly results a deficiency of phenylalanine hydroxylase gene (PAH). The incidence of various PAH mutations have race and ethnicity differences. We report a spectrum of PAH mutations complied from 35 PKU children who are all Chinese Han population from north Jiangsu in this study. All 13 exons and their flanking intron sequences of PAH were determined by Ion Torrent PGM™ sequencing. The relationship of genotype and phenotype was analyzed based on the sum of the arbitrary value (AV) values of the two alleles. We identified 61 mutations, with a frequency of 87.14%, among 70 alleles of 35 patients. The most prevalent mutations were R243Q (26.23%), R241C (9.84%) and V399V (8.20%). Furthermore, the consistency between prediction of the biochemical phenotype and the observed phenotype was 81.25%, with the highest consistency observed in classic PKU (87.50%). A significant correlation was found between pretreatment levels of phenylalanine and AV sum (r = -0.87, P < 0.05). Finally, our study constructs PAH mutation spectrum by next generation sequencing (NGS), and reveals that the PAH genotypes and biochemical phenotypes were significantly correlated. These offers facilitate the provision of appropriate genetic counseling for PKU patients. Copyright © 2017. Published by Elsevier Taiwan.

A different approach to treatment of phenylketonuria: Phenylalanine degradation with recombinant phenylalanine ammonia lyase

PubMed Central

Sarkissian, Christineh N.; Shao, Zhongqi; Blain, Françoise; Peevers, Rosalie; Su, Hongsheng; Heft, Robert; Chang, Thomas M. S.; Scriver, Charles R.

1999-01-01

Phenylketonuria (PKU), with its associated hyperphenylalaninemia (HPA) and mental retardation, is a classic genetic disease and the first to have an identified chemical cause of impaired cognitive development. Treatment from birth with a low phenylalanine diet largely prevents the deviant cognitive phenotype by ameliorating HPA and is recognized as one of the first effective treatments of a genetic disease. However, compliance with dietary treatment is difficult and when it is for life, as now recommended by an internationally used set of guidelines, is probably unrealistic. Herein we describe experiments on a mouse model using another modality for treatment of PKU compatible with better compliance using ancillary phenylalanine ammonia lyase (PAL, EC 4.3.1.5) to degrade phenylalanine, the harmful nutrient in PKU; in this treatment, PAL acts as a substitute for the enzyme phenylalanine monooxygenase (EC 1.14.16.1), which is deficient in PKU. PAL, a robust enzyme without need for a cofactor, converts phenylalanine to trans-cinnamic acid, a harmless metabolite. We describe (i) an efficient recombinant approach to produce PAL enzyme, (ii) testing of PAL in orthologous N-ethyl-N′-nitrosourea (ENU) mutant mouse strains with HPA, and (iii) proofs of principle (PAL reduces HPA)—both pharmacologic (with a clear dose–response effect vs. HPA after PAL injection) and physiologic (protected enteral PAL is significantly effective vs. HPA). These findings open another way to facilitate treatment of this classic genetic disease. PMID:10051643

Deficiency of long-chain polyunsaturated fatty acids in phenylketonuria: a cross-sectional study.

PubMed

Drzymała-Czyż, Sławomira; Kałużny, Łukasz; Krzyżanowska-Jankowska, Patrycja; Walkowiak, Dariusz; Mozrzymas, Renata; Walkowiak, Jarosław

2018-01-01

The etiology of altered blood fatty acid (FA) profile in phenylketonuria (PKU) is understood only partially. We aimed to determine whether FAs deficiency is dependent on the diet or metabolic disturbances. The study comprised 40 PKU patients (20 female, 20 male; aged 11 to 35 years; 12 children and 28 adults) and 40 healthy subjects (HS; 20 female, 20 male, aged 18 to 33 years). We assessed the profile of FAs (gas chromatography/mass spectrometry) and analyzed the 72-hour dietary recalls. The amount of C14:0, C16:0 and C16:1n-7, C18:1n-9 did not differ between the analyzed groups. The percentage of C18:0 was higher, while C20:3n-9, C18:2n-6, C20:2n-6, C20:4n-6, C22:4n-6, C22:5n-6 and C22:6n-3 was lower in PKU than in HS. However, C18:3n-6, C18:3n-3 and n-6/n-3 ratio were higher in PKU patients. The C20:4n-6/C20:3n-6 ratio (reaction catalyzed by Δ5-desaturase), the C22:5n-6/C22:4n-6 and the C22:6n-3/C22:5n-3 ratio (both reactions catalyzed by Δ6 desaturase) were significantly lower in PKU patients. Therefore, the deficiency of long-chain polyunsaturated fatty acids in PKU patients may result not only from inadequate supply but also from metabolic disturbances.

Validation of amino-acids measurement in dried blood spot by FIA-MS/MS for PKU management.

PubMed

Bruno, C; Dufour-Rainfray, D; Patin, F; Vourc'h, P; Guilloteau, D; Maillot, F; Labarthe, F; Tardieu, M; Andres, C R; Emond, P; Blasco, H

2016-09-01

Phenylketonuria (PKU) is a metabolic disorder leading to high concentrations of phenylalanine (Phe) and low concentrations of tyrosine (Tyr) in blood and brain that may be neurotoxic. This disease requires a regular monitoring of plasma Phe and Tyr as well as branched-chain amino-acids concentrations to adapt the Phe-restricted diet and other therapy that may be prescribed in PKU. We validated a Flow Injection Analysis tandem Mass Spectrometry (FIA-MS/MS) to replace the enzymatic method routinely used for neonatal screening in order to monitor in parallel to Phe, Tyr and branched-chain amino-acids not detected by the enzymatic method. We ascertained the performances of the method: linearity, detection and quantification limits, contamination index, accuracy. We cross validated the FIA-MS/MS and enzymatic methods and we evaluated our own reference ranges to monitor Phe, Tyr, Leu, Val on 59 dried blood spots of normal controls. We also evaluated Tyr, Leu and Val concentrations in PKU patients to detect some potential abnormalities, not evaluated by the enzymatic method. We developed a rapid method with excellent performances including precision and accuracy <15%. We noted an excellent correlation of Phe concentrations between FIA-MS/MS and enzymatic methods (p<0.0001) based on our database which are similar to references ranges published. We observed that 50% of PKU patients had lower concentrations of Tyr, Leu and/or Val that could not be detected by the enzymatic method. Based on laboratory accreditation recommendations, we validated a robust, rapid and reliable FIA-MS/MS method to monitor plasma Phe concentrations but also Tyr, Leu and Val concentrations, suitable for PKU management. We evaluated our own reference ranges of concentration for a routine application of this method. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Long-term beneficial effects of the phenylalanine-restricted diet in late-diagnosed individuals with phenylketonuria.

PubMed

Koch, R; Moseley, K; Ning, J; Romstad, A; Guldberg, P; Guttler, F

1999-06-01

The potential benefits to society of treating late-diagnosed mentally retarded persons with phenylketonuria were investigated. In order to ascertain the effects of late dietary intervention, the charts of 124 adults with PKU seen in the metabolic service at the Childrens Hospital of Los Angeles were reviewed. Fifty-nine were diagnosed later than 3 months of age and were over the age of 18 years. They were followed up with medical, psychological, and nutritional assessments. Genotyping was also performed. Twenty-eight have remained on a phenylalanine-restricted diet during the intervening years. All but 3 of the 28 late-diagnosed PKU persons who remained on a restricted diet showed significant intellectual improvement. Seven are able to attend college, 9 are employed, and 12 are attending workshops and/or day care programs. The result of treatment with the phenylalanine-restricted diet was that these individuals could participate in society and were able to arrest the neurodegenerative course characteristic of persons with mutations classified as severe in the phenylalanine hydroxylase gene. We conclude that society could benefit substantially by providing a phenylalanine-restricted diet for late-diagnosed mentally retarded persons with phenylketonuria. Eighteen of 28 such persons who otherwise would have required residential care are living independently. Copyright 1999 Academic Press.

Serum ischemia modified albumin is a possible new marker of oxidative stress in phenylketonuria.

PubMed

Keshavarzi, Fatemeh; Rastegar, Mohsen; Vessal, Mahmood; Rafiei Dehbidi, Gholamreza; Khorsand, Marjan; Ganjkarimi, Amir Hossein; Takhshid, Mohammad Ali

2018-06-01

The role of oxidative stress in the pathogenesis of phenylketonuria (PKU)-associated disorders has been implicated. Ischemia modified albumin (IMA) is a modified form of serum albumin, which is produced under the conditions of oxidative stress. The aim of this study was to measure the serum level of IMA in the PKU patients and to investigate its ability in predicting the status of oxidative stress in these patients. Fifty treated-PKU patients and fifty age- and sex-matched healthy subjects were included in the study. The blood samples were obtained and the serum level of phenylalanine (Phe) was measured using reverse phase HPLC method. The levels of IMA, malondialdehyde (MDA), gamma-glutamyl transferase (GGT) activity, and uric acid (UA) were determined using colorimetric methods. The levels of serum Phe, IMA, and MDA were significantly higher (p < 0.001) and the level of UA (p < 0.05) was lower in the PKU patients compared to control group. Serum IMA level was positively correlated with MDA (r = 0.585, p < 0.001) and UA (r = 0.6, p < 0.001). An inverse relationship was observed between the serum level of IMA and Phe (r = - 0.410, p < 0. 01). Results of the present study suggest that serum IMA level could be used as a novel marker for the evaluation of oxidative stress in the PKU patients.

Motor development skills of 1- to 4-year-old Iranian children with early treated phenylketonuria.

PubMed

Nazi, Sepideh; Rohani, Farzaneh; Sajedi, Firoozeh; Biglarian, Akbar; Setoodeh, Arya

2014-01-01

Objective : To gauge the gross and fine motor development of early treated phenylketonuria (ETPKU) in children in the age range of 1-4 years. Methods : A cross-sectional analytic study was conducted in PKU clinics (reference clinics for PKU follow-up), Tehran, Iran. Seventy children with ETPKU were selected as the case group for the study. ETPKU children were those with early and continuous treatment with a phenylalanine-restricted diet (the mean of blood phenylalanine level during the recent 6 months was 2-6 mg/dL or 120-360 μmol/L). Also, 100 healthy and normal children matched with the ETPKU group for age were randomly selected from 4 kindergartens in four parts of Tehran as a control group. The measurements consisted of a demographic questionnaire, Peabody Developmental Motor Scale-2 (PDMS-2), and pediatrician assessment. Motor quotients were determined by PDMS-2 and then compared in both groups by two independent samples t-test. Results : The mean ages in case and control group were 28.5 (± 11.6) and 29.7 (± 11.3) months, respectively. Comparison of the mean fine, gross, and total developmental motor quotients (DMQs) showed statistically significant differences between the two groups (p < 0.05). The fine and total DMQs of ETPKU children were also correlated with age. In addition, there was a negative correlation between the phenylalanine level and fine (p < 0.001) and total (p = 0.001) DMQs. Conclusion : It seems that ETPKU Iranian children, regardless of following a phenylalanine-restricted diet or not, have lower motor development. It is recommended to plan programs for early detection and intervention of developmental delays in these children.

Formulation and PEGylation optimization of the therapeutic PEGylated phenylalanine ammonia lyase for the treatment of phenylketonuria.

PubMed

Bell, Sean M; Wendt, Dan J; Zhang, Yanhong; Taylor, Timothy W; Long, Shinong; Tsuruda, Laurie; Zhao, Bin; Laipis, Phillip; Fitzpatrick, Paul A

2017-01-01

Phenylketonuria (PKU) is a genetic metabolic disease in which the decrease or loss of phenylalanine hydroxylase (PAH) activity results in elevated, neurotoxic levels of phenylalanine (Phe). Due to many obstacles, PAH enzyme replacement therapy is not currently an option. Treatment of PKU with an alternative enzyme, phenylalanine ammonia lyase (PAL), was first proposed in the 1970s. However, issues regarding immunogenicity, enzyme production and mode of delivery needed to be overcome. Through the evaluation of PAL enzymes from multiple species, three potential PAL enzymes from yeast and cyanobacteria were chosen for evaluation of their therapeutic potential. The addition of polyethylene glycol (PEG, MW = 20,000), at a particular ratio to modify the protein surface, attenuated immunogenicity in an animal model of PKU. All three PEGylated PAL candidates showed efficacy in a mouse model of PKU (BTBR Pahenu2) upon subcutaneous injection. However, only PEGylated Anabaena variabilis (Av) PAL-treated mice demonstrated sustained low Phe levels with weekly injection and was the only PAL evaluated that maintained full enzymatic activity upon PEGylation. A PEGylated recombinant double mutant version of AvPAL (Cys503Ser/Cys565Ser), rAvPAL-PEG, was selected for drug development based on its positive pharmacodynamic profile and favorable expression titers. PEGylation was shown to be critical for rAvPAL-PEG efficacy as under PEGylated rAvPAL had a lower pharmacodynamic effect. rAvPAL and rAvPAL-PEG had poor stability at 4°C. L-Phe and trans-cinnamate were identified as activity stabilizing excipients. rAvPAL-PEG is currently in Phase 3 clinical trials to assess efficacy in PKU patients.

Therapeutic brain modulation with targeted large neutral amino acid supplements in the Pah-enu2 phenylketonuria mouse model.

PubMed

van Vliet, Danique; Bruinenberg, Vibeke M; Mazzola, Priscila N; van Faassen, Martijn Hjr; de Blaauw, Pim; Pascucci, Tiziana; Puglisi-Allegra, Stefano; Kema, Ido P; Heiner-Fokkema, M Rebecca; van der Zee, Eddy A; van Spronsen, Francjan J

2016-11-01

Phenylketonuria treatment consists mainly of a Phe-restricted diet, which leads to suboptimal neurocognitive and psychosocial outcomes. Supplementation of large neutral amino acids (LNAAs) has been suggested as an alternative dietary treatment strategy to optimize neurocognitive outcome in phenylketonuria and has been shown to influence 3 brain pathobiochemical mechanisms in phenylketonuria, but its optimal composition has not been established. In order to provide additional pathobiochemical insight and develop optimal LNAA treatment, several targeted LNAA supplements were investigated with respect to all 3 biochemical disturbances underlying brain dysfunction in phenylketonuria. Pah-enu2 (PKU) mice received 1 of 5 different LNAA-supplemented diets beginning at postnatal day 45. Control groups included phenylketonuria mice receiving an isonitrogenic and isocaloric high-protein diet or the AIN-93M diet, and wild-type mice receiving the AIN-93M diet. After 6 wk, brain and plasma amino acid profiles and brain monoaminergic neurotransmitter concentrations were measured. Brain Phe concentrations were most effectively reduced by supplementation of LNAAs, such as Leu and Ile, with a strong affinity for the LNAA transporter type 1. Brain non-Phe LNAAs could be restored on supplementation, but unbalanced LNAA supplementation further reduced brain concentrations of those LNAAs that were not (sufficiently) included in the LNAA supplement. To optimally ameliorate brain monoaminergic neurotransmitter concentrations, LNAA supplementation should include Tyr and Trp together with LNAAs that effectively reduce brain Phe concentrations. The requirement for Tyr supplementation is higher than it is for Trp, and the relative effect of brain Phe reduction is higher for serotonin than it is for dopamine and norepinephrine. The study shows that all 3 biochemical disturbances underlying brain dysfunction in phenylketonuria can be targeted by specific LNAA supplements. The study thus

PKU Self-Management Timeline

MedlinePlus

... pku UW PKU Clinic News & Events PKU Self-Management Timeline This timeline is also available as an ... file. Click here to download. The PKU Self- Management timeline is included to provide long-term view ...

Optimal management of phenylketonuria: a centralized expert team is more successful than a decentralized model of care.

PubMed

Camfield, Carol S; Joseph, Marissa; Hurley, Teresa; Campbell, Karen; Sanderson, Susan; Camfield, Peter R

2004-07-01

To compare phenylketonuria (PKU) management by a centralized, expert team in the Province of Nova Scotia (NS) with the decentralized approach in New Brunswick (NB). Retrospective chart review documented frequency of outpatient visits, phenylalanine (Phe) concentration, and medical formula use. Structured telephone interviews with the 8 regional NB dietitians (NB-D) documented their knowledge and support in PKU management. Patients with PKU (n=108; age, birth to 42 years) reside in NB (n=69) and NS (n=39). More were lost to contact in NB than in NS (9/69 vs 1/39) and more were completely off diet in NB than in NS (24/60 vs 1/38, P=.05). All 15 children <2 years old followed by a PKU team in either NS or Saint John, NB had optimal Phe levels. Children 2 to 12 years of age in NS had better Phe control and more medical visits than in NB (P <.01). Older patients had more episodes of elevated Phe levels (P=.01). Formula was dispensed in appropriate yearly amounts to 52% in NB and >95% in NS. Mental handicap or borderline intelligence was common in both NB (44%) and NS (42%). All NB-D wished additional specialized medical, nursing, or social work assistance. PKU management appears to be more effective with an expert, coordinated team approach.

Early-onset behavioral and neurochemical deficits in the genetic mouse model of phenylketonuria

PubMed Central

Fiori, Elena; Oddi, Diego; Ventura, Rossella; Colamartino, Marco; Valzania, Alessandro; D’Amato, Francesca Romana; Bruinenberg, Vibeke; van der Zee, Eddy; Puglisi-Allegra, Stefano

2017-01-01

Phenylketonuria (PKU) is one of the most common human inborn errors of metabolism, caused by phenylalanine hydroxylase deficiency, leading to high phenylalanine and low tyrosine levels in blood and brain causing profound cognitive disability, if untreated. Since 1960, population is screened for hyperphenylalaninemia shortly after birth and submitted to early treatment in order to prevent the major manifestations of the disease. However, the dietetic regimen (phenylalanine free diet) is difficult to maintain, and despite the recommendation to a strict and lifelong compliance, up to 60% of adolescents partially or totally abandons the treatment. The development and the study of new treatments continue to be sought, taking advantage of preclinical models, the most used of which is the PAHenu2 (BTBR ENU2), the genetic murine model of PKU. To date, adult behavioral and neurochemical alterations have been mainly investigated in ENU2 mice, whereas there are no clear indications about the onset of these deficiencies. Here we investigated and report, for the first time, a comprehensive behavioral and neurochemical assay of the developing ENU2 mice. Overall, our findings demonstrate that ENU2 mice are significantly smaller than WT until pnd 24, present a significant delay in the acquisition of tested developmental reflexes, impaired communicative, motor and social skills, and have early reduced biogenic amine levels in several brain areas. Our results extend the understanding of behavioral and cerebral abnormalities in PKU mice, providing instruments to an early preclinical evaluation of the effects of new treatments. PMID:28850618

Protein substitute dosage in PKU: how much do young patients need?

PubMed

MacDonald, A; Chakrapani, A; Hendriksz, C; Daly, A; Davies, P; Asplin, D; Hall, K; Booth, I W

2006-07-01

The optimal dose of protein substitute has not been determined in children with phenylketonuria (PKU). To determine if a lower dose of protein substitute could achieve the same or better degree of blood phenylalanine control when compared to the dosage recommended by the UK MRC.(1) In a six week randomised, crossover study, two doses of protein substitute (Protocol A: 2 g/kg/day of protein equivalent; Protocol B: 1.2 g/kg/day protein equivalent) were compared in 25 children with well controlled PKU aged 2-10 years (median 6 years). Each dose of protein substitute was taken for 14 days, with a 14 day washout period in between. Twice daily blood samples (fasting pre-breakfast and evening, at standard times) for plasma phenylalanine were taken on day 8-14 of each protocol. The median usual dose of protein substitute was 2.2 g/kg/day (range 1.5-3.1 g/kg/day). When compared with control values, median plasma phenylalanine on the low dose of protein substitute increased at pre-breakfast by 301 mumol/l (95% CI 215 to 386) and in the evening by 337 micromol/l (95% CI 248 to 431). On the high dose of protein substitute, plasma phenylalanine concentrations remained unchanged when compared to control values. However, wide variability was seen between subjects. A higher dosage of protein substitute appeared to contribute to lower blood phenylalanine concentrations in PKU, but it did have a variable and individual impact and may have been influenced by the carbohydrate (+/- fat) content of the protein substitute.

Longitudinal modelling of the exposure of young UK patients with PKU to acesulfame K and sucralose.

PubMed

O'Sullivan, Aaron J; Pigat, Sandrine; O'Mahony, Cian; Gibney, Michael J; McKevitt, Aideen I

2017-11-01

Artificial sweeteners are used in protein substitutes intended for the dietary management of inborn errors of metabolism (phenylketonuria, PKU) to improve the variety of medical foods available to patients and ensure dietary adherence to the prescribed course of dietary management. These patients can be exposed to artificial sweeteners from the combination of free and prescribed foods. Young children have a higher risk of exceeding acceptable daily intakes (ADI) for additives than adults, due to higher food intakes per kg body weight. Young patients with PKU aged 1-3 years can be exposed to higher levels of artificial sweeteners from these dual sources than normal healthy children and are at a higher risk of exceeding the ADI. Standard intake assessment methods are not adequate to assess the additive exposure of young patients with PKU. The aim of this study was to estimate the combination effect on the intake of artificial sweeteners and the impact of the introduction of new provisions for an artificial sweetener (sucralose, E955) on exposure of PKU patients using a validated probabilistic model. Food consumption data were derived from the food consumption survey data of healthy young children in the United Kingdom from the National Diet and Nutrition Survey (NDNS, 1992-2012). Specially formulated protein substitutes as foods for special medical purposes (FSMPs) were included in the exposure model to replace restricted foods. Inclusion of these protein substitutes is based on recommendations to ensure adequate protein intake in these patients. Exposure assessment results indicated the availability of sucralose for use in FSMPs for PKU leads to changes in intakes in young patients. These data further support the viability of probabilistic modelling as a means to estimate food additive exposure in patients consuming medical nutrition products.

[Singleton and twin pregnancies of PKU patients - individual variability of phenylalanine tolerance: experience of a single treatment center (Preliminary report)].

PubMed

Żółkowska, Joanna; Hozyasz, Kamil K; Nowacka, Maria

2017-01-01

Phenylketonuria (PKU) is the autosomal recessive deficiency of phenylalanine hydroxylase resulting in the accumulation of phenylalanine (Phe) in blood and in the brain. Phe restriction in a patient's diet is determined depending on the amount of Phe intake which allows for stable blood Phe levels within the therapeutic range of 120-360µmol/L. In clinical practice the empirical determination of Phe tolerance relies on frequent assessment of blood Phe concentrations in relation to Phe intake from food records. Untreated maternal PKU may lead to maternal PKU syndrome in offspring. The objective of the study was to compare Phe tolerance during the course of singleton and multiple pregnancies of PKU patients. Case subjects and methods: The cases reviewed included three sets of classical PKU-affected Polish women on a low-phenylalanine diet during the course of singleton and twin pregnancies and their PKU-unaffected newborns. All the patients were under regular supervision of a metabolic dietitian to stabilize blood Phe levels and determine Phe tolerance. Data on pregnancy weight gain, the gestational age when the diet initiated, the percent of Phe assessments < 120 µmol/L and > 360 µmol/L, as well as offspring birth measurements were analyzed. The total increase in Phe tolerance and its pattern during the course of singleton and twin pregnancies differed remarkably in each patient. Three PKU women (Q383X/R408W, EX3DEL/EX3DEL, R281L/R408W) increased their Phe tolerance in singleton and twin pregnancies by 579%/468%, 674%/261%, and 427%/236%, respectively. During the last 10 weeks of singleton and twin pregnancy Phe tolerance showed an increase by 62%/149%, 33%/64%, and 37%/40%, respectively. The analysis of predictors for Phe tolerance showed that an individual's weight gain and the fetal weight gain as estimated from liveborn birth-weight data had no predictive capacity. Individual Phe tolerance in singleton pregnancies of PKU patients does not predict tolerance in

Protein substitute dosage in PKU: how much do young patients need?

PubMed Central

MacDonald, A; Chakrapani, A; Hendriksz, C; Daly, A; Davies, P; Asplin, D; Hall, K; Booth, I W

2006-01-01

Background The optimal dose of protein substitute has not been determined in children with phenylketonuria (PKU). Aim To determine if a lower dose of protein substitute could achieve the same or better degree of blood phenylalanine control when compared to the dosage recommended by the UK MRC.1 Methods In a six week randomised, crossover study, two doses of protein substitute (Protocol A: 2 g/kg/day of protein equivalent; Protocol B: 1.2 g/kg/day protein equivalent) were compared in 25 children with well controlled PKU aged 2–10 years (median 6 years). Each dose of protein substitute was taken for 14 days, with a 14 day washout period in between. Twice daily blood samples (fasting pre‐breakfast and evening, at standard times) for plasma phenylalanine were taken on day 8–14 of each protocol. The median usual dose of protein substitute was 2.2 g/kg/day (range 1.5–3.1 g/kg/day). Results When compared with control values, median plasma phenylalanine on the low dose of protein substitute increased at pre‐breakfast by 301 μmol/l (95% CI 215 to 386) and in the evening by 337 μmol/l (95% CI 248 to 431). On the high dose of protein substitute, plasma phenylalanine concentrations remained unchanged when compared to control values. However, wide variability was seen between subjects. Conclusions A higher dosage of protein substitute appeared to contribute to lower blood phenylalanine concentrations in PKU, but it did have a variable and individual impact and may have been influenced by the carbohydrate (+/− fat) content of the protein substitute. PMID:16547085

Nutritional status in patients with phenylketonuria using glycomacropeptide as their major protein source.

PubMed

Pinto, A; Almeida, M F; Ramos, P C; Rocha, S; Guimas, A; Ribeiro, R; Martins, E; Bandeira, A; MacDonald, A; Rocha, J C

2017-10-01

Low phenylalanine (PHE), glycomacropeptide-based protein substitute (GMP) is an alternative to traditional L-amino acid supplements (AA) used in the dietary management of phenylketonuria (PKU). In a retrospective, longitudinal study, we report the nutritional status of PKU patients taking AA and GMP. Eleven PKU patients aged 27±10 years (1 HPA, 4 mild and 6 classical PKU) on dietary treatment were evaluated (anthropometry, body composition, blood pressure measurements, biochemical markers including vitamin, mineral, lipids, carbohydrates and protein status/metabolism, and nutritional intake assessment) at two different annual reviews. The mean time taking AA was 13±5 months and GMP 13±7 months. Blood phenylalanine (PHE) and tyrosine (TYR) were analysed before and after GMP introduction. Both GMP and AA protein substitutes provided similar protein equivalent intake (0.85 vs 0.75 g/kg/day, P=0.182). In the GMP group, it contributed 57% (27-100%) of the protein substitute intake (with AA delivering the rest of protein substitute intake), providing an additional 34±12 mg/day PHE. Nutritional intake, anthropometry and body composition measurements were similar in both the groups. Median blood PHE did not change (P=0.594), although values within target range improved (36 vs 46%), but this was not statistically significant. Mean blood TYR increased (52.0±19.2 vs 63.2±25.6 μmol/l, P=0.033), and all biochemical markers remained stable, except for a lower A1C haemoglobin (P=0.011). Partial GMP contribution to total protein substitute intake did not affect nutritional status in patients with PKU. Blood PHE control was not adversely affected. The increased blood TYR after GMP introduction necessitates further study.

Depression and anxiety among parents of phenylketonuria children

PubMed Central

Gunduz, Mehmet; Arslan, Nur; Unal, Ozlem; Cakar, Sevim; Kuyum, Pınar; Bulbul, Selda F.

2015-01-01

Objective: To investigate the existence of depression and/or anxiety with underlying risk factors among parents of children with classical phenylketonuria (PKU). Methods: This cross-sectional study was conducted in the Division of Pediatric Metabolism, Ankara Children’s Hospital, Dokuz Eylul University, Kırıkkale University, and Erzurum Local Research Hospital, Turkey, between January and July 2014. Parents of 61 patients and 36 healthy controls completed the self-report questionnaires. We used Beck Depression Inventory (BDI) to assess the parental depression and State-Trait Anxiety Inventory S-T (STAI S-T) to assess parental anxiety. Results: Depression and anxiety scores were significantly higher in the case group (BDI 12.3±9.1; STAI-S: 38.2±9.6; STAI-T: 43.2±6.9) than controls (BDI: 5.4±4.1 p=0.000; STAI-S: 31.8±7.6 p=0.001; STAI-T: 37.0±7.2 p=0.000). Mothers of the patients had higher scores than the other parental groups (BDI: p=0.000, STAI-S: p=0.001 and STAI-T: p=0.000). Logistic regression analysis showed that low educational level of the parent was the only independent factor for depression (OR 9.96, 95% CI: 1.89-52.35, p=0.007) and state anxiety (OR: 6.99, 95% CI: 1.22-40.48, p=0.030) in the case group. Conclusion: A subset of parents with PKU patients have an anxiety or depressive disorder. Supportive services dealing with the parents of chronically ill children such as PKU are needed in order to reduce the level of anxiety. PMID:26492114

A Specific Nutrient Combination Attenuates the Reduced Expression of PSD-95 in the Proximal Dendrites of Hippocampal Cell Body Layers in a Mouse Model of Phenylketonuria.

PubMed

Bruinenberg, Vibeke M; van Vliet, Danique; Attali, Amos; de Wilde, Martijn C; Kuhn, Mirjam; van Spronsen, Francjan J; van der Zee, Eddy A

2016-03-26

The inherited metabolic disease phenylketonuria (PKU) is characterized by increased concentrations of phenylalanine in the blood and brain, and as a consequence neurotransmitter metabolism, white matter, and synapse functioning are affected. A specific nutrient combination (SNC) has been shown to improve synapse formation, morphology and function. This could become an interesting new nutritional approach for PKU. To assess whether treatment with SNC can affect synapses, we treated PKU mice with SNC or an isocaloric control diet and wild-type (WT) mice with an isocaloric control for 12 weeks, starting at postnatal day 31. Immunostaining for post-synaptic density protein 95 (PSD-95), a post-synaptic density marker, was carried out in the hippocampus, striatum and prefrontal cortex. Compared to WT mice on normal chow without SNC, PKU mice on the isocaloric control showed a significant reduction in PSD-95 expression in the hippocampus, specifically in the granular cell layer of the dentate gyrus, with a similar trend seen in the cornus ammonis 1 (CA1) and cornus ammonis 3 (CA3) pyramidal cell layer. No differences were found in the striatum or prefrontal cortex. PKU mice on a diet supplemented with SNC showed improved expression of PSD-95 in the hippocampus. This study gives the first indication that SNC supplementation has a positive effect on hippocampal synaptic deficits in PKU mice.

Executive function impairment in early-treated PKU subjects with normal mental development.

PubMed

Leuzzi, V; Pansini, M; Sechi, E; Chiarotti, F; Carducci, Cl; Levi, G; Antonozzi, I

2004-01-01

Executive functions were studied in 14 early and continuously treated PKU subjects (age 10.8 years, range 8-13) in comparison with controls matched for IQ, sex, age and socioeconomic status. Brain MRI examination was normal in all PKU patients. Neuropsychological evaluation included Wisconsin Card Sorting Test, Rey-Osterreith Complex Figure Test, Elithorn's Perceptual Maze Test, Weigl's Sorting Test, Tower of London, Visual Search and Motor Motor Learning Test. Whatever the IQ, PKU subjects performed worse than controls in tests exploring executive functions. Subgrouping the PKU subjects according to the quality of dietary control for the entire follow-up period (using 400 micromol/L as cut-off value for blood phenylalanine (Phe) concentration) showed that patients with worse dietary control performed more poorly than both the PKU group with the best dietary control and the control group. However, a mild impairment of executive functions was still found in PKU patients with a good dietary control (Phe <400 micromol/L) compared to controls. Concerning the PKU group as a whole, no linear correlation was found between neuropsychological performance and historical and concurrent biochemical parameters. We conclude that (a) PKU patients, even when treated early, rigorously and continuously, show an impairment of frontal lobe functions; (b) a protracted exposure to moderately high levels of Phe can affect frontal lobe functions independently of the possible effect of the same exposure on IQ; (c) in order to reduce the risk of frontal lobe dysfunction, the target of dietary therapy should be to maintain blood Phe concentration below 400 micromol/L.

The Adolescent Adjustment Profile (AAP) in comparisons of patients with obesity, phenylketonuria or neurobehavioural disorders.

PubMed

Olsson, Gunilla Maria; Mårild, Staffan; Alm, Jan; Brodin, Ulf; Rydelius, Per-Anders; Marcus, Claude

2008-01-01

Psychosocial development in children with chronic disease is a key issue in paediatrics. This study investigated whether psychosocial adjustment could be reliably assessed with the 42-item Adolescent Adjustment Profile (AAP) instrument. The study mainly focused on adjustment-to-obesity measurement, although it compared three patient groups with chronic conditions. All phenylketonuria (PKU) patients in Sweden between ages 9 and 18 and their parents and teachers were invited to participate. Patients with neurobehavioural syndromes and obesity were age- and gender-matched with PKU patients. Healthy children constituted a reference group. Psychosocial adjustment was measured using the AAP, which is a multi-informant questionnaire that contains four domains. Information concerning parents' socio-economic and civil status was requested separately. Respondents to the three questionnaires judged the PKU patients to be normal in all four domains. Patients with neurobehavioural syndromes demonstrated less competence and the most problems compared with the other three groups. According to the self-rating, the parent rating and the teacher rating questionnaires, obese patients had internalizing problems. The parent rating and the teacher rating questionnaire scored obese patients as having a lower work capacity than the reference group. Compared with the reference group, not only families with obese children but also families with children with neurobehavioural syndromes had significantly higher divorce rates. Obese patients were also investigated with the Strength and Difficulties Questionnaire (SDQ), another instrument that enables comparison between two measures of adjustment. The AAP had good psychometric properties; it was judged a useful instrument in research on adolescents with chronic diseases.

Spectrum of PAH gene variants among a population of Han Chinese patients with phenylketonuria from northern China.

PubMed

Liu, Ning; Huang, Qiuying; Li, Qingge; Zhao, Dehua; Li, Xiaole; Cui, Lixia; Bai, Ying; Feng, Yin; Kong, Xiangdong

2017-10-05

Phenylketonuria (PKU), which primarily results from a deficiency of phenylalanine hydroxylase (PAH), is one of the most common inherited inborn errors of metabolism that impairs postnatal cognitive development. The incidence of various PAH variations differs by race and ethnicity. The aim of the present study was to characterize the PAH gene variants of a Han population from Northern China. In total, 655 PKU patients and their families were recruited for this study; each proband was diagnosed both clinically and biochemically with phenylketonuria. Subjects were sequentially screened for single-base variants and exon deletions or duplications within PAH via direct Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA). A spectrum of 174 distinct PAH variants was identified: 152 previously documented variants and 22 novel variants. While single-base variants were distributed throughout the 13 exons, they were particularly concentrated in exons 7 (33.3%), 11 (14.2%), 6 (13.2%), 12 (11.0%), 3 (10.4%), and 5 (4.4%). The predominant variant was p.Arg243Gln (17.7%), followed by Ex6-96A > G (8.3%), p.Val399 = (6.4%), p.Arg53His (4.7%), p.Tyr356* (4.7%), p.Arg241Cys (4.6%), p.Arg413Pro (4.6%), p.Arg111* (4.4%), and c.442-1G > A (3.4%). Notably, two patients were also identified as carrying de novo variants. The composition of PAH gene variants in this Han population from Northern China was distinct from those of other ethnic groups. As such, the construction of a PAH gene variant database for Northern China is necessary to lay a foundation for genetic-based diagnoses, prenatal diagnoses, and population screening.

OMEGA-3 LONG-CHAIN POLYUNSATURATED FATTY ACIDS IN OLDER CHILDREN

USDA-ARS?s Scientific Manuscript database

Phenylketonuria (PKU), the most prevalent inborn error of metabolism, is usually secondary to low hepatic activity of phenylalanine hydroxylase, the enzyme that catalyzes conversion of phenylalanine to tyrosine. Growth and development of infants and children with PKU who are managed by mandatory n...

Descriptive and hedonic analyses of low-Phe food formulations containing corn (Zea mays) seedling roots: toward development of a dietary supplement for individuals with phenylketonuria.

PubMed

Cliff, Margaret A; Law, Jessica R; Lücker, Joost; Scaman, Christine H; Kermode, Allison R

2016-01-15

Seedling roots of anthocyanin-rich corn (Zea mays) cultivars contain high levels of phenylalanine ammonia lyase (PAL) activity. The development of a natural dietary supplement containing corn roots could provide the means to improve the restrictive diet of phenylketonuria (PKU) patients by increasing their tolerance to dietary phenylalanine (Phe). Therefore this research was undertaken to explore the sensory characteristics of roots of four corn cultivars as well as to develop and evaluate food products (cereal bar, beverage, jam-like spread) to which roots had been added. Sensory profiles of corn roots were investigated using ten trained judges. Roots of Japanese Striped corn seedlings were more bitter, pungent and astringent than those of white and yellow cultivars, while roots from the Blue Jade cultivar had a more pronounced earthy/mushroom aroma. Consumer research using 24 untrained panelists provided hedonic (degree-of-liking) assessments for products with and without roots (controls). The former had lower mean scores than the controls; however, the cereal bar had scores above 5 on the nine-point scale for all hedonic assessments compared with the other treated products. By evaluating low-Phe food products containing corn roots, this research ascertained that the root-containing low-Phe cereal bar was an acceptable 'natural' dietary supplement for PKU-affected individuals. © 2015 Her Majesty the Queen in Right of Canada. Journal of the Science of Food and Agriculture © 2015 Society of Chemical Industry.

Molecular epidemiology, genotype-phenotype correlation and BH4 responsiveness in Spanish patients with phenylketonuria.

PubMed

Aldámiz-Echevarría, Luis; Llarena, Marta; Bueno, María A; Dalmau, Jaime; Vitoria, Isidro; Fernández-Marmiesse, Ana; Andrade, Fernando; Blasco, Javier; Alcalde, Carlos; Gil, David; García, María C; González-Lamuño, Domingo; Ruiz, Mónica; Ruiz, María A; Peña-Quintana, Luis; González, David; Sánchez-Valverde, Felix; Desviat, Lourdes R; Pérez, Belen; Couce, María L

2016-08-01

Phenylketonuria (PKU), the most common inborn error of amino acid metabolism, is caused by mutations in the phenylalanine-4-hydroxylase (PAH) gene. This study aimed to assess the genotype-phenotype correlation in the PKU Spanish population and the usefulness in establishing genotype-based predictions of BH4 responsiveness in our population. It involved the molecular characterization of 411 Spanish PKU patients: mild hyperphenylalaninemia non-treated (mild HPA-NT) (34%), mild HPA (8.8%), mild-moderate (20.7%) and classic (36.5%) PKU. BH4 responsiveness was evaluated using a 6R-BH4 loading test. We assessed genotype-phenotype associations and genotype-BH4 responsiveness in our population according to literature and classification of the mutations. The mutational spectrum analysis showed 116 distinct mutations, most missense (70.7%) and located in the catalytic domain (62.9%). The most prevalent mutations were c.1066-11G>A (9.7%), p.Val388Met (6.6%) and p.Arg261Gln (6.3%). Three novel mutations (c.61-13del9, p.Ile283Val and p.Gly148Val) were reported. Although good genotype-phenotype correlation was observed, there was no exact correlation for some genotypes. Among the patients monitored for the 6R-BH4 loading test: 102 were responders (87, carried either one or two BH4-responsive alleles) and 194 non-responders (50, had two non-responsive mutations). More discrepancies were observed in non-responders. Our data reveal a great genetic heterogeneity in our population. Genotype is quite a good predictor of phenotype and BH4 responsiveness, which is relevant for patient management, treatment and follow-up.

[Maternal phenylketonuria].

PubMed

Bókay, János; Kiss, Erika; Simon, Erika; Szőnyi, László

2013-05-05

Elevated maternal phenylalanine levels during pregnancy are teratogenic, and may result in embryo-foetopathy, which could lead to stillbirth, significant psychomotor handicaps and birth defects. This foetal damage is known as maternal phenylketonuria. Women of childbearing age with all forms of phenylketonuria, including mild variants such as hyperphenylalaninaemia, should receive detailed counselling regarding their risks for adverse foetal effects, optimally before contemplating pregnancy. The most assured way to prevent maternal phenylketonuria is to maintain the maternal phenylalanine levels within the optimal range already before conception and throughout the whole pregnancy. Authors review the comprehensive programme for prevention of maternal phenylketonuria at the Metabolic Center of Budapest, they survey the practical approach of the continuous maternal metabolic control and delineate the outcome of pregnancies of mothers with phenylketonuria from the introduction of newborn screening until most recently.

Modification of infant hypothyroidism and phenylketonuria screening program using electronic tools.

PubMed

Taheri, Behjat; Haddadpoor, Asefeh; Mirkhalafzadeh, Mahmood; Mazroei, Fariba; Aghdak, Pezhman; Nasri, Mehran; Bahrami, Gholamreza

2017-01-01

Congenital hypothyroidism and phenylketonuria (PKU) are the most common cause for preventable mental retardation in infants worldwide. Timely diagnosis and treatment of these disorders can have lasting effects on the mental development of newborns. However, there are several problems at different stages of screening programs that along with imposing heavy costs can reduce the precision of the screening, increasing the chance of undiagnosed cases which in turn can have damaging consequences for the society. Therefore, given these problems and the importance of information systems in facilitating the management and improving the quality of health care the aim of this study was to improve the screening process of hypothyroidism and PKU in infants with the help of electronic resources. The current study is a qualitative, action research designed to improve the quality of screening, services, performance, implementation effectiveness, and management of hypothyroidism and PKU screening program in Isfahan province. To this end, web-based software was designed. Programming was carried out using Delphi.net software and used SQL Server 2008 for database management. Given the weaknesses, problems, and limitations of hypothyroidism and PKU screening program, and the importance of these diseases in a national scale, this study resulted in design of hypothyroidism and PKU screening software for infants in Isfahan province. The inputs and outputs of the software were designed in three levels including Health Care Centers in charge of the screening program, provincial reference lab, and health and treatment network of Isfahan province. Immediate registration of sample data at the time and location of sampling, providing the provincial reference Laboratory and Health Centers of different eparchies with the ability to instantly observe, monitor, and follow-up on the samples at any moment, online verification of samples by reference lab, creating a daily schedule for reference lab

A Simple Network to Remove Interference in Surface EMG Signal from Single Gene Affected Phenylketonuria Patients for Proper Diagnosis

NASA Astrophysics Data System (ADS)

Mohanty, Madhusmita; Basu, Mousumi; Pattanayak, Deba Narayan; Mohapatra, Sumant Kumar

2018-04-01

Recently Autosomal Recessive Single Gene (ARSG) diseases are highly effective to the children within the age of 5-10 years. One of the most ARSG disease is a Phenylketonuria (PKU). This single gene disease is associated with mutations in the gene that encodes the enzyme phenylalanine hydroxylase (PAH, Gene 612349). Through this mutation process, PAH of the gene affected patient can not properly manufacture PAH as a result the patients suffer from decreased muscle tone which shows abnormality in EMG signal. Here the extraction of the quality of the PKU affected EMG (PKU-EMG) signal is a keen interest, so it is highly necessary to remove the added ECG signal as well as the biological and instrumental noises. In the Present paper we proposed a method for detection and classification of the PKU affected EMG signal. Here Discrete Wavelet Transformation is implemented for extraction of the features of the PKU affected EMG signal. Adaptive Neuro-Fuzzy Inference System (ANFIS) network is used for the classification of the signal. Modified Particle Swarm Optimization (MPSO) and Modified Genetic Algorithm (MGA) are used to train the ANFIS network. Simulation result shows that the proposed method gives better performance as compared to existing approaches. Also it gives better accuracy of 98.02% for the detection of PKU-EMG signal. The advantages of the proposed model is to use MGA and MPSO to train the parameters of ANFIS network for classification of ECG and EMG signal of PKU affected patients. The proposed method obtained the high SNR (18.13 ± 0.36 dB), SNR (0.52 ± 1.62 dB), RE (0.02 ± 0.32), MSE (0.64 ± 2.01), CC (0.99 ± 0.02), RMSE (0.75 ± 0.35) and MFRE (0.01 ± 0.02), RMSE (0.75 ± 0.35) and MFRE (0.01 ± 0.02). From authors knowledge, this is the first time a composite method is used for diagnosis of PKU affected patients. The accuracy (98.02%), sensitivity (100%) and specificity (98.59%) helps for proper clinical treatment. It can help for readers

Metabolomic Insights into the Nutritional Status of Adults and Adolescents with Phenylketonuria Consuming a Low-Phenylalanine Diet in Combination with Amino Acid and Glycomacropeptide Medical Foods

PubMed Central

Stroup, Bridget M.; Murali, Sangita G.; Rohr, Frances; Gleason, Sally T.; van Calcar, Sandra C.; Levy, Harvey L.

2017-01-01

Background Nutrient status in phenylketonuria (PKU) requires surveillance due to the restrictive low-Phe diet in combination with amino acid medical foods (AA-MF) or glycomacropeptide medical foods (GMP-MF). Micronutrient profiles of medical foods are diverse, and optimal micronutrient supplementation in PKU has not been established. Methods In a crossover design, 30 participants with PKU were randomized to consume AA-MF and Glytactin™ GMP-MF in combination with a low-Phe diet for 3 weeks each. Fasting venipunctures, medical food logs, and 3-day food records were obtained. Metabolomic analyses were completed in plasma and urine by Metabolon, Inc. Results The low-Phe diets in combination with AA-MF and GMP-MF were generally adequate based on Dietary Reference Intakes, clinical measures, and metabolomics. Without micronutrient supplementation of medical foods, >70% of participants would have inadequate intakes for 11 micronutrients. Despite micronutrient supplementation of medical foods, inadequate intakes of potassium in 93% of participants and choline in >40% and excessive intakes of sodium in >63% of participants and folic acid in >27% were observed. Sugar intake was excessive and provided 27% of energy. Conclusions Nutrient status was similar with AA-MF and Glytactin GMP-MF. More research related to micronutrient supplementation of medical foods for the management of PKU is needed. PMID:29464117

Tetrahydrobiopterin responsiveness after extended loading test of 12 Danish PKU patients with the Y414C mutation.

PubMed

Nielsen, Jytte Bieber; Nielsen, Karin E; Güttler, Flemming

2010-02-01

Phenylketonuria (PKU) is an inherited metabolic disease characterized by phenylalanine (Phe) accumulation due to defects in the enzyme phenylalanine hydroxylase (PAH). Phe accumulation can lead to cognitive impairment. Some individuals with PKU respond to tetrahydrobiopterin (BH4) treatment, the natural cofactor of PAH, by a reduction in blood Phe concentrations.We tested 12 patients with PKU, 8-29 years of age, all carrying the common Y414C mutation in the PAH gene. Three were homozygous and nine were compound heterozygous, with the second mutation being a putative null mutation. During the study period, genuine protein was increased to approximately 1 g/kg. The patients were treated with 20, 10, and 5 mg BH4/kg/day for 1 week on each dose, starting with 20 mg/kg. A positive response was defined as a decline in blood Phe>30%. Blood Phe was measured four times a week. Nonresponding children were excluded from the study. Eleven of 12 patients had a positive response with 20 mg/kg, 5/10 responded on 10 mg/kg, and 1/9 on 5 mg/kg. Two were late responders, with a response on 20 mg/kg after >48 h. We could confirm the previously reported inconsistent responsiveness of Y414C in the nine heterozygous patients, whereas the three homozygous patients had early median Phe declines of 73%, 51%, and 27%, respectively, on the three different doses. The varying responses despite uniform trial conditions and genotypes may be due to individual differences in BH4 absorption or metabolism. No side effects were observed.

High phenylalanine levels directly affect mood and sustained attention in adults with phenylketonuria: a randomised, double-blind, placebo-controlled, crossover trial.

PubMed

ten Hoedt, Amber E; de Sonneville, Leo M J; Francois, Baudouin; ter Horst, Nienke M; Janssen, Mirian C H; Rubio-Gozalbo, M Estela; Wijburg, Frits A; Hollak, Carla E M; Bosch, Annet M

2011-02-01

The main debate in the treatment of Phenylketonuria (PKU) is whether adult patients need the strict phenylalanine (Phe)-restricted diet. Physicians and patients lack evidence-based guidelines to help them make well-informed choices. We have carried out the first randomised double-blind placebo-controlled trial into the effects of short-term elevation of Phe levels on neuropsychological functions and mood of adults with PKU. Nine continuously treated adults with PKU underwent two 4-week supplementation periods: one with Phe, mimicking normal dietary intake, and one with placebo in randomly allocated order via a randomisation coding list in a double-blind cross-over design. A set of neuropsychological tests (Amsterdam Neuropsychological Tasks) was administered at the end of each study period. In addition, patients and for each patient a friend or relative, completed weekly Profile of Mood States (POMS) questionnaires, evaluating the patients' mood. Phe levels were measured twice weekly. Mean plasma Phe levels were significantly higher during Phe supplementation compared with placebo (p = 0.008). Neuropsychological tests demonstrated an impairment in sustained attention during Phe supplementation (p = 0.029). Both patients and their friend or relative reported lower scores on the POMS questionnaires during Phe supplementation (p = 0.017 and p = 0.040, respectively). High plasma Phe levels have a direct negative effect on both sustained attention and on mood in adult patients with PKU. A Phe-restricted "diet for life" might be an advisable option for many.

Long-term compliance with a novel vitamin and mineral supplement in older people with PKU.

PubMed

MacDonald, A; Lee, P; Davies, P; Daly, A; Lilburn, M; Gokmen Ozel, H; Preece, M A; Hendriksz, C; Chakrapani, A

2008-12-01

The long-term efficacy of vitamin and mineral preparations in dietary-treated adult patients with phenylketonuria (PKU) is unreported. In an open, intervention trial, the acceptability, safety and impact on biochemical and haematological micronutrient status of a new vitamin and mineral tablet (Phlexy Vits, SHS International) was investigated. Fifteen subjects with PKU (median age 21 years, range 8-33 years) on low-phenylalanine diet from two PKU centres were recruited. No vitamins or minerals were added to their protein substitute and for 12 months they took their full daily requirements of vitamin and minerals from Phlexy Vits (5 tablets/daily). All but two subjects had taken alternative vitamin and mineral supplements before the trial. Fasting bloods were taken at baseline (week -2 and at week 0), 4 and 12 months for a range of biochemical and nutritional measurements. By 4 months, serum vitamin B(12) (p = 0.003), serum manganese (p=0.03) and plasma (p=0.03) and red blood cell (p=0.004) glutathionine peroxidase (GSHPx) all significantly increased but remained within normal reference ranges. By 12 months, serum vitamin B(12) (p<0.05) and plasma GSHPx (p<0.05) remained increased. The Phlexy Vits tablets scored better than conventional vitamin and mineral supplements for overall acceptability (p<0.05), and ease of swallowing (p=0.1) at 4 months, although swallowing score deteriorated by 12 months (p<0.05). There was a small but significant deterioration in compliance with taking the vitamin and mineral supplements between 4 and 12 months (p<0.05). In the long term, these comprehensive vitamin and mineral tablets appeared acceptable and improved biochemical nutritional status, although there were long-term compliance and swallowing issues.

Breakfast with glycomacropeptide compared with amino acids suppresses plasma ghrelin levels in individuals with phenylketonuria

PubMed Central

MacLeod, Erin L.; Clayton, Murray K.; van Calcar, Sandra C.; Ney, Denise M.

2010-01-01

Phenylketonuria (PKU) requires a lifelong low-phenylalanine (phe) diet where protein needs are met by consumption of a phe-free amino acid (AA) formula; complaints of persistent hunger are common. Foods made with glycomacropeptide (GMP), an intact protein that contains minimal phe and may promote satiety, provide an alternative to AA formula. The objective was to assess the ability of a GMP breakfast to promote satiety and affect plasma concentrations of AAs, insulin, and the appetite stimulating hormone ghrelin in those with PKU, when compared to an AA-based breakfast. Eleven PKU subjects (8 adults and 3 boys ages 11–14) served as their own controls in an inpatient metabolic study with two 4-day treatments: an AA-based diet followed by a diet replacing all AA formula with GMP foods. Plasma concentrations of AAs, insulin and ghrelin were obtained before and/or 180 minutes after breakfast. Satiety was assessed using a visual analog scale before, immediately after and 180 minutes after breakfast. Postprandial ghrelin concentration was significantly lower (p=0.03) with GMP compared to an AA-based breakfast, with no difference in fasting ghrelin. Lower postprandial ghrelin concentrations were associated with greater feelings of fullness 180 minutes after breakfast suggesting greater satiety with GMP compared to AAs. Postprandial concentrations of insulin and total plasma AAs were higher after a GMP breakfast compared to an AA-based breakfast consistent with slower absorption of AAs from GMP. These results show sustained ghrelin suppression, and suggest greater satiety with ingestion of a meal containing GMP compared with AAs. PMID:20466571

Co-existence of phenylketonuria either with maple syrup urine disease or Sandhoff disease in two patients from Iran: emphasizing the role of consanguinity.

PubMed

Abiri, Maryam; Talebi, Saeed; Uitto, Jouni; Youssefian, Leila; Vahidnezhad, Hassan; Shirzad, Tina; Salehpour, Shadab; Zeinali, Sirous

2016-10-01

Most inborn errors of metabolism (IEMs) are inherited in an autosomal recessive manner. IEMs are one of the major concerns in Iran due to its extensive consanguineous marriages. Herein, we report two patients with two co-existent IEMs: a girl affected by classic phenylketonuria (PKU) and maple syrup urine disease (MSUD) and a male patient affected with Sandhoff disease and PKU, where Sandhoff disease was suspected due to the presence of a cherry-red spot in the eyes at 6 months which is unrelated to PKU. Sequencing of candidate genes in the first patient revealed one novel and three recurrent compound heterozygous mutations of p.Ser231Pro and p.Ala300Ser in the PAH gene and p.Glu330Lys and p.Arg170Cys mutations in the BCKDHB gene. Genetic testing results in the second patient showed previously reported homozygous mutations of p.Arg261Gln in the PAH and p.Arg533Cys mutation in the HEXB gene. Genetic testing confirmed the clinical diagnosis of both diseases in both patients. To the best of our knowledge; this is the first report of the co-existence of two distinct genetic disorders in two individuals from Iran. Co-existent different IEMs in patients complicated the clinical diagnosis and management of the diseases.

Knowledge, compliance and serum phenylalanine concentrations in adolescents and adults with phenylketonuria and the effect of a patient-focused educational resource.

PubMed

Durham-Shearer, S J; Judd, P A; Whelan, K; Thomas, J E

2008-10-01

There is a lack of dedicated resources for adolescent and adult patients with phenylketonuria (PKU) and few studies have examined dietary practices within this group. One hundred and seventy-seven PKU patients were sent questionnaires to assess dietary compliance and the preferred format for an educational resource. Seventy-one patients responded; 32 following diet were recruited to assess the resource's impact on test variables. The results were compared for the intervention group (n = 22) and control group (n = 10) at baseline, and 1 and 6 months after resource intervention. Most patients were aware of dietary recommendations, although this did not always result in compliance. The preferred resource format was a filofax-style folder with inserts (P < 0.05). There was a significant difference in the extent of change in knowledge score between baseline and 1 month in favour of the intervention group (P < 0.05). The improvement in knowledge was not accompanied by a significant improvement in measures of compliance. These findings add to the knowledge base about this patient group and support the use of patient involvement in resource development. It is likely that the test parameters used were not sensitive enough to pick up subtle and longer-term effects on compliance.

Predictive modelling of the exposure to steviol glycosides in Irish patients aged 1-3 years with phenylketonuria and cow's milk protein allergy.

PubMed

O'Sullivan, Aaron J; Pigat, Sandrine; O'Mahony, Cian; Gibney, Michael J; McKevitt, Aideen I

2018-01-01

Children with Phenylketonuria (PKU) and severe cow's milk protein allergy (CMPA) consume prescribed, specially formulated, foods for special medical purposes (FSMPs) as well as restricted amounts of normal foods. These patients are exposed to artificial sweeteners from the consumption of a combination of free and prescribed foods. Young patients with PKU and CMPA have a higher risk of exceeding acceptable daily intakes (ADI) for additives than age-matched healthy children. A predictive modelling approach has been adapted successfully to assess the additive exposure of young patients with PKU and CMPA to artificial sweeteners. Steviol glycosides (E960) are at various stages of regulatory approval for the various food categories in the EU but are not as yet permitted for use in products intended for young children. The aim of this study was to predict potential steviol glycoside exposure in young children with PKU and CMPA considering the potential for future provisions for the use of this sweetener. The recent introduction of steviol glycosides means that no exposure data are available for children with CMPA and PKU. Food consumption data were derived from the food consumption survey data of healthy young children in Ireland from the National Preschool and Nutrition Survey (NPNS, 2010-11). Specially formulated amino acid-based FSMPs are used to replace whole or milk protein foods and were included in the exposure model to replace restricted foods. The recommendations to ensure adequate protein intake in these patients were used to determine FSMP intake. Exposure assessment results indicated that the maximum permitted level (MPL) for FSMPs would warrant careful consideration to avoid exposures above the ADI. These data can be used to inform recommendations for the medical nutrition industry.

Cardiac Teratogenicity in Mouse Maternal Phenylketonuria: Defining phenotype parameters and genetic background influences

PubMed Central

Seagraves, Nikki J.; McBride, Kim L.

2012-01-01

Maternal phenylketonuria (MPKU) is a syndrome including cardiovascular malformations (CVMs), microcephaly, intellectual impairment, and small for gestational age, caused by in-utero exposure to elevated serum phenylalanine (Phe) due to PKU in the mother. It is becoming a public health concern as more women with PKU reach child bearing age. Although a mouse model of PKU, BTBR Pahenu2, has been available for 20 years, it has not been well utilized for studying MPKU. We used this model to delineate critical parameters in Phe cardiovascular teratogenicity and study the effect of genetic background. Dosing and timing experiments were performed with the BTBR Pahenu2 mouse. A dose response curve was noted, with CVM rates at maternal serum Phe levels <360 μM (control), 360 – 600 μM (low), 600 – 900 μM (mid), and >900μM (high) of 11.86%, 16.67%, 30.86%, and 46.67% respectively. A variety of CVMs were noted on the BTBR background, including double outlet right ventricle (DORV), aortic arch artery (AAA)abnormalities, and ventricular septal defects (VSDs). Timed exposure experiments identified a teratogenic window from embryonic day 8.5-13.5, with higher rates of conotruncal and valve defects occurring in early exposure time and persistent truncus arteriosus (PTA) and aortic arch branching abnormalities occurring with late exposure. Compared to the BTBR strain, N10+ Pahenu2 congenics on the C3H/HeJ background had higher rates of CVMs in general and propensity to left ventricular outflow tract (LVOT) malformations, while the C57B/L6 background had similar CVM rates but predominately AAA abnormalities. We have delineated key parameters of Phe cardiovascular teratogenicity, demonstrated the utility of this MPKU model on different mouse strains, and shown how genetic background profoundly affects the phenotype. PMID:22951387

Economic impact of feeding a phenylalanine-restricted diet to adults with previously untreated phenylketonuria.

PubMed

Brown, M C; Guest, J F

1999-02-01

The aim of the present study was to estimate the direct healthcare cost of managing adults with previously untreated phenylketonuria (PKU) for one year before any dietary restrictions and for the first year after a phenylalanine- (PHE-) restricted diet was introduced. The resource use and corresponding costs were estimated from medical records and interviews with health care professionals experienced in caring for adults with previously untreated PKU. The mean annual cost of caring for a client being fed an unrestricted diet was estimated to be 83 996 pound silver. In the first year after introducing a PHE-restricted diet, the mean annual cost was reduced by 20 647 pound silver to 63 348 pound silver as a result of a reduction in nursing time, hospitalizations, outpatient clinic visits and medications. However, the economic benefit of the diet depended on whether the clients were previously high or low users of nursing care. Nursing time was the key cost-driver, accounting for 79% of the cost of managing high users and 31% of the management cost for low users. In contrast, the acquisition cost of a PHE-restricted diet accounted for up to 6% of the cost for managing high users and 15% of the management cost for low users. Sensitivity analyses showed that introducing a PHE-restricted diet reduces the annual cost of care, provided that annual nursing time was reduced by more than 8% or more than 5% of clients respond to the diet. The clients showed fewer negative behaviours when being fed a PHE-restricted diet, which may account for the observed reduction in nursing time needed to care for these clients. In conclusion, feeding a PHE-restricted diet to adults with previously untreated PKU leads to economic benefits to the UK's National Health Service and society in general.

PKU and Maternal PKU: The Cure and the Problem.

ERIC Educational Resources Information Center

Henderson, Robert A.

1989-01-01

A longitudinal study is evaluating the efficacy of a phenylalanine-restricted diet in reducing disabling conditions associated with maternal hyperphenylalaninemia. Titled the Maternal PKU Collaborative Study, it is studying 162 American and Canadian women and involves diet therapy, prenatal examinations, laboratory tests, nutritional evaluation,…

L-Phenylalanine concentration in blood of phenylketonuria patients: a modified enzyme colorimetric assay compared with amino acid analysis, tandem mass spectrometry, and HPLC methods.

PubMed

De Silva, Veronica; Oldham, Charlie D; May, Sheldon W

2010-09-01

Phenylketonuria (PKU) is an autosomal recessive disorder caused by an impaired conversion of L-phenylalanine (Phe) to L-tyrosine, typically resulting from a deficiency in activity of a hepatic and renal enzyme L-phenylalanine hydroxylase. The disease is characterized by an increased concentration of Phe and its metabolites in body fluids. A modified assay based on an enzymatic-colorimetric methodology was developed for measuring blood Phe levels in PKU patients; this method is designed for use with undeproteinized samples and avoids the use of solvents or amphiphilic agents. Thus, the method could be suitable for incorporation into a simple home-monitoring device. We report here on a comparison of blood Phe concentrations in PKU patients measured in undeproteinized plasma using this enzyme colorimetric assay (ECA), with values determined by amino acid analysis (AAA) of deproteinized samples, and HPLC and tandem mass spectrometry (MS/MS) analyses of dried blood spot (DBS) eluates. Pearson correlation coefficients of 0.951, 0.976 and 0.988 were obtained when AAA-measured Phe concentrations were compared with the ECA-, HPLC- or MS/MS-measured values, respectively. A Bland-Altman analysis revealed that mean Phe concentrations determined using AAA were on average 65 μmol/L lower than values measured by our ECA. These results may be the result of minimizing the manipulations performed on the patient sample compared with AAA, HPLC, and MS/MS methods, which involve plasma deproteinization or DBS elution and derivatization. The results reported here confirm that Phe concentrations determined by our ECA method are comparable to those determined by other widely used methods for a broad range of plasma Phe concentrations.

Biochemical Evaluation of Phenylalanine Ammonia Lyase from Endemic Plant Cyathobasis fruticulosa (Bunge) Aellen. for the Dietary Treatment of Phenylketonuria

PubMed Central

Aydaş, Selcen Babaoğlu; Aslım, Belma

2016-01-01

Summary Enzyme substitution therapy with the phenylalanine ammonia lyase (PAL) is a new approach to the treatment of patients with phenylketonuria (PKU). This enzyme is responsible for the conversion of phenylalanine to trans-cinnamic acid. We assessed the PAL enzyme of the endemic plant Cyathobasis fruticulosa (Bunge) Aellen. for its possible role in the dietary treatment of PKU. The enzyme was found to have a high activity of (64.9±0.1) U/mg, with the optimum pH, temperature and buffer (Tris–HCl and l-phenylalanine) concentration levels of pH=8.8, 37 °C and 100 mM, respectively. Optimum enzyme activity was achieved at pH=4.0 and 7.5, corresponding to pH levels of gastric and intestinal juice, and NaCl concentration of 200 mM. The purification of the enzyme by 1.87-fold yielded an activity of 98.6 U/mg. PAL activities determined by HPLC analyses before and after purification were similar. Two protein bands, one at 70 and the other at 23 kDa, were determined by Western blot analysis of the enzyme. This enzyme is a potential candidate for serial production of dietary food and biotechnological products. PMID:27956861

National PKU News

MedlinePlus

... Enter your email for our monthly newsletter * Need books? Our pocket books are great reference tools for caregivers, relatives, and ... quick reference in your desk at work. Baby Books are provided free to all newborn PKU patients ...

Phenylketonuria

MedlinePlus

... inherited disorder that causes an amino acid called phenylalanine to build up in the body. PKU is ... helps create the enzyme needed to break down phenylalanine. Without the enzyme necessary to process phenylalanine, a ...

Probabilistic modelling to assess exposure to three artificial sweeteners of young Irish patients aged 1-3 years with PKU and CMPA.

PubMed

O'Sullivan, Aaron J; Pigat, Sandrine; O'Mahony, Cian; Gibney, Michael J; McKevitt, Aideen I

2016-11-01

The choice of suitable normal foods is limited for individuals with particular medical conditions, e.g., inborn errors of metabolism (phenylketonuria - PKU) or severe cow's milk protein allergy (CMPA). Patients may have dietary restrictions and exclusive or partial replacement of specific food groups with specially formulated products to meet particular nutrition requirements. Artificial sweeteners are used to improve the appearance and palatability of such food products to avoid food refusal and ensure dietary adherence. Young children have a higher risk of exceeding acceptable daily intakes for additives than adults due to higher food intakes kg -1 body weight. The Budget Method and EFSA's Food Additives Intake Model (FAIM) are not equipped to assess partial dietary replacement with special formulations as they are built on data from dietary surveys of consumers without special medical requirements impacting the diet. The aim of this study was to explore dietary exposure modelling as a means of estimating the intake of artificial sweeteners by young PKU and CMPA patients aged 1-3 years. An adapted validated probabilistic model (FACET) was used to assess patients' exposure to artificial sweeteners. Food consumption data were derived from the food consumption survey data of healthy young children in Ireland from the National Preschool and Nutrition Survey (NPNS, 2010-11). Specially formulated foods for special medical purposes were included in the exposure model to replace restricted foods. Inclusion was based on recommendations for adequate protein intake and dietary adherence data. Exposure assessment results indicated that young children with PKU and CMPA have higher relative average intakes of artificial sweeteners than healthy young children. The reliability and robustness of the model in the estimation of patient additive exposures was further investigated and provides the first exposure estimates for these special populations.

PKU: high plasma phenylalanine concentrations are associated with increased prevalence of mood swings.

PubMed

Anjema, Karen; van Rijn, Margreet; Verkerk, Paul H; Burgerhof, Johannes G M; Heiner-Fokkema, M Rebecca; van Spronsen, Francjan J

2011-11-01

In phenylketonuria, knowledge about the relation between behavior and plasma phenylalanine is scarce. The aim of this study was to determine whether high phenylalanine is associated with disturbed behavior noticed by the patient and or close environment (parents or partners). 48 early treated PKU patients (median age 8.5, range 0-35 years) participated (median phenylalanine concentration in total sample 277 (range 89-1171) μmol/l; and in patients <12 years 238 (range 89-521) μmol/l). After sending blood samples, patients or close environment were interviewed with a standardized questionnaire whether they noticed hyperactivity, annoying behavior, mood swings and introvert or extravert behavior. The interviewer as well as the respondents were blinded with regard to the phenylalanine concentration. Patients reported less deviant behavior compared to close environment. Mood swings were positively associated with phenylalanine concentrations in the total group (P=0.039) and patients <12 years (P=0.042). The relationships between temporary high phenylalanine concentrations and hyperactivity, annoying behavior, introvert and extravert behavior were not statistically significant. there is a positive association between phenylalanine concentrations and mood swings. Copyright © 2011 Elsevier Inc. All rights reserved.

Neonatal Screening Tests.

ERIC Educational Resources Information Center

Vigue, Charles L.

1986-01-01

Describes several laboratory experiments that are adaptations of clinical tests for certain genetic diseases in babies. Information and procedures are provided for tests for phenylketonuria (PKU), galactosemia, tyrosinemia, cystinuria, and mucopolysaccharidosis. Discusses the effects of each disease on the infants' development. (TW)

Adult phenylketonuria outcome and management.

PubMed

Trefz, F; Maillot, F; Motzfeldt, K; Schwarz, M

2011-01-01

The problem to evaluate treatment outcome in adult PKU (phenylketonuric) patients lies in the heterogeneity of the adult PKU population. This heterogeneity is not only based on the different treatment history of every individual patient but also on the different severity of the underlying defect of the enzyme phenylalanine hydroxylase. Recent, partly double blind studies in adult PKU patients further support recommendation for lifelong treatment. However, it has become evident that dietary treatment is suboptimal and continuation to adulthood often not accepted. Late detected PKU patients (up to 4-6 years of age) benefit from strict dietary treatment and are able to catch up in intellectual performance. Untreated, severely retarded patients with behavioral changes may benefit from introduction of dietary treatment. However, individual decision is necessary and based on the personal situation of the patient. In early and well treated patients a number of studies have demonstrated that cognitive and neurosychologic tests are different from controls. In addition there is evidence that patients with higher blood phenylalanine (phe) levels demonstrate more often psychiatric symptoms like depression and anxiety. Medical problems are more often observed: there are certain risks as impaired growth, decreased bone mineral density and nutrional deficits probably caused by dietary treatment with an artificial protein substitute and/or missing compliance with an unpleasant diet. The long term risk of a strict dietary treatment must be balanced with the risk of higher blood phe (mean blood phenylalanine >600-900 μmol/L) on cognitive and neuropsychological functions and psychiatric symptoms. Further studies should consider the role of blood phe exposure for brain development in childhood and for brain function in all ages. Besides mean blood phe, fluctuation of blood phe over time is important. Fluctuation of blood phe is decreased by sapropterin treatment in responsive

Newborn screening 50 years later: access issues faced by adults with PKU

PubMed Central

Berry, Susan A.; Brown, Christine; Grant, Mitzie; Greene, Carol L.; Jurecki, Elaina; Koch, Jean; Moseley, Kathryn; Suter, Ruth; van Calcar, Sandra C.; Wiles, Judy; Cederbaum, Stephen

2013-01-01

Fifty years after the implementation of universal newborn screening programs for phenylketonuria, the first disease identified through newborn screening and considered a success story of newborn screening, a cohort of adults with phenylketonuria treated from birth provides valuable information about effects of long-term treatment for inborn errors of metabolism in general, and phenylketonuria specifically. For phenylketonuria, newborn screening allows early implementation of the phenylalanine-restricted diet, eliminating the severe neurocognitive and neuromotor impairment associated with untreated phenylketonuria. However, executive function impairments and psychiatric problems are frequently reported even for those treated early and continuously with the phenylalanine-restricted diet alone. Moreover, a large percentage of adults with phenylketonuria are reported as lost to follow-up by metabolic clinics. While a group of experts identified by the National Institutes of Health convenes to update treatment guidelines for phenylketonuria, we explore individual patient, social, and economic factors preventing >70% of adult phenylketonuria patients in the United States from accessing treatment. As more conditions are identified through newborn screening, factors affecting access to treatment grow in importance, and we must continue to be vigilant in assessing and addressing factors that affect patient treatment outcomes and not just celebrate amelioration of the most severe manifestations of disease. Genet Med 2013:15(8):591–599 PMID:23470838

Newborn screening 50 years later: access issues faced by adults with PKU.

PubMed

Berry, Susan A; Brown, Christine; Grant, Mitzie; Greene, Carol L; Jurecki, Elaina; Koch, Jean; Moseley, Kathryn; Suter, Ruth; van Calcar, Sandra C; Wiles, Judy; Cederbaum, Stephen

2013-08-01

Fifty years after the implementation of universal newborn screening programs for phenylketonuria, the first disease identified through newborn screening and considered a success story of newborn screening, a cohort of adults with phenylketonuria treated from birth provides valuable information about effects of long-term treatment for inborn errors of metabolism in general, and phenylketonuria specifically. For phenylketonuria, newborn screening allows early implementation of the phenylalanine-restricted diet, eliminating the severe neurocognitive and neuromotor impairment associated with untreated phenylketonuria. However, executive function impairments and psychiatric problems are frequently reported even for those treated early and continuously with the phenylalanine-restricted diet alone. Moreover, a large percentage of adults with phenylketonuria are reported as lost to follow-up by metabolic clinics. While a group of experts identified by the National Institutes of Health convenes to update treatment guidelines for phenylketonuria, we explore individual patient, social, and economic factors preventing >70% of adult phenylketonuria patients in the United States from accessing treatment. As more conditions are identified through newborn screening, factors affecting access to treatment grow in importance, and we must continue to be vigilant in assessing and addressing factors that affect patient treatment outcomes and not just celebrate amelioration of the most severe manifestations of disease.

Learning about Phenylketonuria (PKU)

MedlinePlus

... provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited ...

What Is Phenylketonuria (PKU)?

MedlinePlus

... have it? For more information... Acknowledgments Concept 15 : DNA and proteins are key molecules of the cell nucleus. Learn the basic chemistry of DNA and proteins. Concept 27 : Mutations are changes in ...

[Mutation analysis of the PAH gene in children with phenylketonuria from the Qinghai area of China].

PubMed

He, Jiang; Wang, Hui-Zhen; Xu, Fa-Liang; Yang, Xi; Wang, Rui; Zou, Hong-Yun; Yu, Wu-Zhong

2015-11-01

To study the mutation characteristics of the phenylalanine hydroxylase (PAH) gene in children with phenylketonuria (PKU) from the Qinghai area of China, in order to provide basic information for genetic counseling and prenatal diagnosis. Mutations of the PAH gene were detected in the promoter and exons 1-13 and their flanking intronic sequences of PAH gene by PCR and DNA sequencing in 49 children with PKU and their parents from the Qinghai area of China. A total of 30 different mutations were detected in 80 out of 98 mutant alleles (82%), including 19 missense (63%), 5 nonsense (17%), 3 splice-site (10%) and 3 deletions (10%). Most mutations were detected in exons 3, 6, 7, 11 and intron 4 of PAH gene. The most frequent mutations were p.R243Q (19%), IVS4-1G>A (9%), p.Y356X (7%) and p.EX6-96A>G(5%). Two novel mutations p.N93fsX5 (c.279-282delCATC) and p.G171E (c.512G>A) were found. p.H64fsX9(c.190delC) was documented for the second time in Chinese PAH gene. The mutation spectrum of the gene PAH in the Qinghai population was similar to that in other populations in North China while significantly different from that in the populations from some provinces in southern China, Japan and Europe. The mutations of PAH gene in the Qinghai area of China demonstrate a unique diversity, complexity and specificity.

What Are Common Treatments for Phenylketonuria (PKU)?

MedlinePlus

... Snapshot of Pregnancy & Infant Development Advances Snapshot of Child Development Advances Snapshot of Adult & Family Health Advances NICHD ... a small amount of breast milk or regular infant formula to make sure the child ... for normal development but not enough to cause harm. Older children ...

Breast milk feeding in infants with inherited metabolic disorders other than phenylketonuria - a 10-year single-center experience.

PubMed

Pichler, Karin; Michel, Miriam; Zlamy, Manuela; Scholl-Buergi, Sabine; Ralser, Elisabeth; Jörg-Streller, Monika; Karall, Daniela

2017-04-01

Published data on breast milk feeding in infants suffering from inherited metabolic disorders (IMDs) other than phenylketonuria (PKU) are limited and described outcome is variable. We aimed to evaluate retrospectively whether breastfeeding and/or breast milk feeding are feasible in infants with IMDs including organic acidemias, fatty acid oxidation disorders, urea cycle disorders, aminoacidopathies or disorders of galactose metabolism. Data on breastfeeding and breast milk feeding as well as monitoring and neurological outcome were collected retrospectively from our database of patients with the mentioned IMD, who were followed in our metabolic center within the last 10 years. Twenty patients were included in the study, who were either breast fed on demand or received expressed breast milk. All the infants were evaluated clinically and biochemically at 2-4-week intervals, with weight gain as the leading parameter to determine metabolic control. Good metabolic control and adequate neurological development were achieved in all patients but one, who experienced the only metabolic crisis observed within the study period. Breast milk feeding with close clinical and biochemical monitoring is feasible in most IMD and should be considered as it offers nutritional and immunological benefits.

Amino Acid Medical Foods Provide a High Dietary Acid Load and Increase Urinary Excretion of Renal Net Acid, Calcium, and Magnesium Compared with Glycomacropeptide Medical Foods in Phenylketonuria

PubMed Central

Stroup, Bridget M.; Sawin, Emily A.; Murali, Sangita G.; Binkley, Neil; Hansen, Karen E.

2017-01-01

Background. Skeletal fragility is a complication of phenylketonuria (PKU). A diet containing amino acids compared with glycomacropeptide reduces bone size and strength in mice. Objective. We tested the hypothesis that amino acid medical foods (AA-MF) provide a high dietary acid load, subsequently increasing urinary excretion of renal net acid, calcium, and magnesium, compared to glycomacropeptide medical foods (GMP-MF). Design. In a crossover design, 8 participants with PKU (16–35 y) provided food records and 24-hr urine samples after consuming a low-Phe diet in combination with AA-MF and GMP-MF for 1–3 wks. We calculated potential renal acid load (PRAL) of AA-MF and GMP-MF and determined bone mineral density (BMD) measurements using dual X-ray absorptiometry. Results. AA-MF provided 1.5–2.5-fold higher PRAL and resulted in 3-fold greater renal net acid excretion compared to GMP-MF (p = 0.002). Dietary protein, calcium, and magnesium intake were similar. GMP-MF significantly reduced urinary excretion of calcium by 40% (p = 0.012) and magnesium by 30% (p = 0.029). Two participants had low BMD-for-age and trabecular bone scores, indicating microarchitectural degradation. Urinary calcium with AA-MF negatively correlated with L1–L4 BMD. Conclusion. Compared to GMP-MF, AA-MF increase dietary acid load, subsequently increasing urinary calcium and magnesium excretion, and likely contributing to skeletal fragility in PKU. The trial was registered at clinicaltrials.gov as NCT01428258. PMID:28546877

Barriers to successful dietary control among pregnant women with phenylketonuria.

PubMed

Brown, Amanda Savage; Fernhoff, Paul M; Waisbren, Susan E; Frazier, Dianne M; Singh, Rani; Rohr, Fran; Morris, Jill M; Kenneson, Aileen; MacDonald, Pia; Gwinn, Marta; Honein, Margaret; Rasmussen, Sonja A

2002-01-01

The teratogenic effects of maternal PKU are preventable, yet affected babies continue to be born. This study's purpose was to identify barriers to successful dietary control among pregnant women with PKU. An interview-based study was conducted of women with PKU who were known to metabolic disease clinics in three states and pregnant during 1998 to 2000. Medical records were used to document timing of metabolic control. Of 24 women in the study, only 8 (33%) initiated the diet before pregnancy. Of 22 medical records received, only 12 (55%) indicated control of blood phenylalanine levels before 10 weeks' gestation. Risk factors for late dietary control included young age and belief that treatment costs complicated the diet. Although all of the women expressed confidence in the metabolic clinic staff, few perceived their obstetricians were knowledgeable about the maternal PKU diet. Of 13 women enrolled in state-based assistance programs, 9 (69%) reported proof of pregnancy was required for eligibility. Many women using private insurance reported their insurers were unwilling to pay for medical foods. When the data were stratified according to state of residence, differences were observed in the rate of live-born infants, prepregnancy medical food use, average travel time to the metabolic clinic, and gestational week when metabolic control was achieved. Our study's findings may be used to target educational messages to women with PKU and to direct future research directions. For example, obstetric knowledge of maternal PKU needs further evaluation. Discrepancies should be resolved between maternal PKU medical recommendations and the policies of third party-payers. The disparities in financial assistance and services available to pregnant women with PKU residing in different states should be examined further.

Pegvaliase for the treatment of phenylketonuria: Results of a long-term phase 3 clinical trial program (PRISM).

PubMed

Thomas, Janet; Levy, Harvey; Amato, Stephen; Vockley, Jerry; Zori, Roberto; Dimmock, David; Harding, Cary O; Bilder, Deborah A; Weng, Haoling H; Olbertz, Joy; Merilainen, Markus; Jiang, Joy; Larimore, Kevin; Gupta, Soumi; Gu, Zhonghua; Northrup, Hope

2018-05-01

Phenylketonuria (PKU) is caused by phenylalanine hydroxylase (PAH) deficiency that results in phenylalanine (Phe) accumulation. Pegvaliase, PEGylated recombinant Anabaena variabilis phenylalanine ammonia lyase (PAL), converts Phe to trans-cinnamic acid and ammonia, and is a potential enzyme substitution therapy to lower blood Phe in adults with PKU. Two Phase 3 studies, PRISM-1 and PRISM-2, evaluated the efficacy and safety of pegvaliase treatment using an induction, titration, and maintenance dosing regimen in adults with PKU. In PRISM-1, pegvaliase-naïve participants with blood Phe >600 μmol/L were randomized 1:1 to a maintenance dose of 20 mg/day or 40 mg/day of pegvaliase. Participants in PRISM-1 continued pegvaliase treatment in PRISM-2, a 4-part clinical trial that includes an ongoing, open-label, long-term extension study of pegvaliase doses of 5 mg/day to 60 mg/day. Of 261 participants who received pegvaliase treatment, 72.0% and 32.6% reached ≥12 months and ≥ 24 months of study treatment, respectively, and 65% are still actively receiving treatment. Mean (SD) blood Phe was 1232.7 (386.4) μmol/L at baseline, 564.5 (531.2) μmol/L at 12 months, and 311.4 (427) μmol/L at 24 months, a decrease from baseline of 51.1% and 68.7%, respectively. Within 24 months, 68.4% of participants achieved blood Phe ≤600 μmol/L, 60.7% of participants achieved blood Phe ≤360 μmol/L, below the upper limit recommended in the American College of Medical Genetics and Genomics PKU management guidelines, and 51.2% achieved blood Phe ≤120 μmol/L, below the upper limit of normal in the unaffected population. Improvements in neuropsychiatric outcomes were associated with reductions in blood Phe and were sustained with long-term pegvaliase treatment. Adverse events (AEs) were more frequent in the first 6 months of exposure (early treatment phase) than after 6 months of exposure (late treatment phase); 99% of AEs were mild or moderate in

PKU-PET-II: A novel SiPM-based PET imaging system for small animals

NASA Astrophysics Data System (ADS)

Xie, Zhaoheng; Li, Suying; Zhou, Kun; Vuletic, Ivan; Meng, Xiangxi; Zhu, Sihao; Xu, Huan; Yang, Kun; Xu, Baixuan; Zhang, Jinming; Ren, Qiushi

2018-01-01

The objective of this study was to introduce, describe, and validate the performance of a novel preclinical silicon photomultiplier (SiPM)-based PET system (PKU-PET-II). Briefly, the detector assembly consisted of cerium-doped lutetium-yttrium oxyorthosilicate (LYSO) crystals, with dimensions of 2 ×2 ×15 mm3, that offered a 60 mm transaxial field of view (FOV) and 32 mm axial FOV, respectively. The compact front-end electronics readout and digital controller implemented architecture in the FPGA were noteworthy improvements in PKU-PET-II over its predecessor (PKU-PET-I). Based on the National Electrical Manufacturers Association (NEMA) NU 04-2008 standards, the design of the PKU-PET-II system was validated by a phantom experiment. The results presented spatial resolution (evaluated as full width at half maximum) with a system range from 1.68 ±0.07 to 2.31 ±0.03 mm at the FOV center and from 1.43 ±0.02 to 2.10 ±0.10 mm at the 1/4th axial FOV, respectively. The system's absolute sensitivity at the center position was 1.35% with the coincidence window of 6 ns and energy window of 300-700 keV. In addition, the NEMA image quality phantom and an animal study results validated the system imaging performance in preclinical imaging application. In conclusion, this SiPM-based, small-animal PET system (PKU-PET-II) provided higher-resolution, adequate sensitivity, and excellent image quality and has potential as a useful tool for real-time imaging of disease progression and development in vivo.

PKU (Phenylketonuria) in Your Baby

MedlinePlus

... birth and infant mortality. Solving premature birth Featured articles Accomplishments and lessons learned since the establishment of ... The impact of premature birth on society Featured articles How long should you wait before getting pregnant ...

Seizures

MedlinePlus

... of seizures. Some have mild symptoms without shaking. Considerations It may be hard to tell if someone ... Epilepsy Fever (particularly in young children ) Head injury Heart disease Heat illness ( heat intolerance ) High fever Phenylketonuria ( PKU ), ...

Assessment of the impact of phenylketonuria and its treatment on quality of life of patients and parents from seven European countries.

PubMed

Bosch, Annet M; Burlina, Alberto; Cunningham, Amy; Bettiol, Esther; Moreau-Stucker, Flavie; Koledova, Ekaterina; Benmedjahed, Khadra; Regnault, Antoine

2015-06-18

The strict and demanding dietary treatment and mild cognitive abnormalities seen in PKU treated from a young age can be expected to affect the health-related quality of life (HRQoL) of patients and their families. Our aim was to describe the HRQoL of patients with PKU from a large international study, using generic HRQoL measures and an innovative PKU-specific HRQoL questionnaire (PKU-QOL). Analyses were exploratory, performed post-hoc on data collected primarily to validate the PKU-QOL. A multicentre, prospective, non-interventional, observational study conducted in France, Germany, Italy, The Netherlands, Spain, Turkey and the UK. Patients diagnosed with PKU aged ≥9 years old and treated with a Phe-restricted diet and/or Phe-free amino acid protein supplements and/or pharmacological therapy were included in the study; parents of at least one patient with PKU aged <18 years were also included. HRQoL was assessed by generic measures (Pediatric Quality-of-Life Inventory; Medical Outcome Survey 36 item Short Form; Child Health Questionnaire 28 item Parent Form) and the newly developed PKU-QOL. Mean generic domain scores were interpreted using published reference values from the general population. PKU-QOL domain scores were described overall and in different subgroups of patients defined according to severity of PKU, overall assessment of patient's health status by the investigator and treatment with tetrahydrobiopterin (BH4). Data from 559 subjects were analysed: 306 patients (92 children, 110 adolescents, 104 adults) and 253 parents. Mean domain scores of generic measures in the study were comparable to the general population. The highest PKU-QOL impact scores (indicating greater impact) were for emotional impact of PKU, anxiety about blood Phe levels, guilt regarding poor adherence to dietary restrictions or Phe-free amino acid supplement intake and anxiety regarding blood Phe levels during pregnancy. Patients with mild/moderate PKU and those receiving BH4

Mutation analysis of the PAH gene in phenylketonuria patients from Rio de Janeiro, Southeast Brazil.

PubMed

Vieira Neto, Eduardo; Laranjeira, Francisco; Quelhas, Dulce; Ribeiro, Isaura; Seabra, Alexandre; Mineiro, Nicole; D M Carvalho, Lilian; Lacerda, Lúcia; G Ribeiro, Márcia

2018-05-10

Phenylketonuria (PKU) is an autosomal recessive disease resulting from mutations in the PAH gene. Most of the patients are compound heterozygotes, and genotype is a major factor in determining the phenotypic variability of PKU. More than 1,000 variants have been described in the PAH gene. Rio de Janeiro's population has a predominance of Iberian, followed by African and Amerindian ancestries. It is expected that most PKU variants in this Brazilian state have originated in the Iberian Peninsula. However, rare European, African or pathogenic variants that are characteristic of the admixed population of the state might also be found. A total of 102 patients were included in this study. Genomic DNA was isolated from dried blood spots. Sanger sequencing was used for PAH gene variant identification. Deletions and duplications were also screened using MLPA analysis. Haplotypes were also determined. Nine (8.8%) homozygous and 93 (91.2%) compound heterozygous patients were found. The spectrum included 37 causative mutations. Missense, nonsense, and splicing pathogenic variants corresponded to 63.7%, 2.9%, and 22.6% of the mutant alleles, respectively. Large (1.5%), and small deletions, inframe (5.4%) and with frameshift (3.9%), comprised the remainder. The most frequent pathogenic variants were: p.V388M (12.7%), p.R261Q (11.8%), IVS10-11G>A (10.3%), IVS2+5G>C (6.4%), p.S349P (6.4%), p.R252W (5.4%), p.I65T (4.4%), p.T323del (4.4%), and p.P281L (3.4%). One novel variant was detected: c.934G>T (p.G312C) [rs763115697]. The three most frequent pathogenic variants in our study (34.8% of the alleles) were also the most common in other Brazilian states, Portugal, and Spain (p.V388M, p.R261Q, IVS10-11G>A), corroborating that the Iberian Peninsula is the major source of PAH mutations in Rio de Janeiro. Pathogenic variants that have other geographical origins, such IVS2+5G>C, p.G352Vfs*48, and IVS12+1G>A were also detected. Genetic drift and founder effect may have also played a role

Practical aspects of recruitment and retention in clinical trials of rare genetic diseases: the phenylketonuria (PKU) experience.

PubMed

DeWard, Stephanie J; Wilson, Ashley; Bausell, Heather; Volz, Ashley S; Mooney, Kimberly

2014-02-01

Bringing treatments for rare genetic diseases to patients requires clinical research. Despite increasing activism from patient support and advocacy groups to increase access to clinical research studies, connecting rare disease patients with the clinical research opportunities that may help them has proven challenging. Chief among these challenges are the low incidence of these diseases resulting in a very small pool of known patients with a particular disease, difficulty of diagnosing rare genetic diseases, logistical issues such as long distances to the nearest treatment center, and substantial disease burden leading to loss of independence. Using clinical studies of phenylketonuria as an example, this paper discusses how, based on the authors' collective experience, partnership among clinicians, patients, study coordinators, genetic counselors, dietitians, industry, patient support groups, and families can help overcome the challenges of recruiting and retaining patients in rare disease clinical trials. We discuss specific methods of collaboration, communication, and education as part of a long-term effort to build a community committed to advancing the medical care of patients with rare genetic diseases. By talking to patients and families regularly about research initiatives and taking steps to make study participation as easy as possible, rare disease clinic staff can help ensure adequate study enrollment and successful study completion.

Dietary glycemic index, glycemic load and metabolic profile in children with phenylketonuria.

PubMed

Moretti, F; Pellegrini, N; Salvatici, E; Rovelli, V; Banderali, G; Radaelli, G; Scazzina, F; Giovannini, M; Verduci, E

2017-02-01

No data exist in the current literature on the glycemic index (GI) and glycemic load (GL) of the diet of phenylketonuric (PKU) children. The aims of this study were to examine the dietary GI and GL in PKU children on a low-phenylalanine (Phe)-diet and to evaluate whether an association may exist between the carbohydrate quality and the metabolic profile. Twenty-one PKU children (age 5-11 years) and 21 healthy children, gender and age matched, were enrolled. Dietary (including GI and GL) and blood biochemical assessments were performed. No difference was observed for daily energy intake between PKU and healthy children. Compared to healthy controls, PKU children consumed less protein (p = 0.001) and fat (p = 0.028), and more carbohydrate (% of total energy, p = 0.004) and fiber (p = 0.009). PKU children had higher daily GI than healthy children (mean difference (95% confidence interval), 13.7 (9.3-18.3)) and higher GL (31.7 (10.1-53.2)). PKU children exhibited lower blood total and low density lipoprotein cholesterol (LDL) levels (p < 0.01) and higher triglyceride level (p = 0.014) than healthy children, while glucose and insulin concentrations did not differ. In PKU children the dietary GL was associated with triglyceride glucose index (Spearman's correlation coefficient = 0.515, p = 0.034). In PKU children a relationship of the dietary treatment with GI and GL, blood triglycerides and triglyceride glucose index may exist. Improvement towards an optimal diet for PKU children could include additional attention to the management of dietary carbohydrate quality. Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Recommended Guidelines for PKU Programs.

ERIC Educational Resources Information Center

Children's Bureau (DHEW), Washington, DC.

A discussion of screening tests for phenylketonuria recommends and provides some data on two tests, lists five disadvantages of urine tests, and discusses three new tests. Also considered are the role of the central laboratory facility and seven suggestions for screening different types of infants at different times. Treatment or followup programs…

Psychosocial factors in maternal phenylketonuria: women's adherence to medical recommendations.

PubMed Central

Waisbren, S E; Hamilton, B D; St James, P J; Shiloh, S; Levy, H L

1995-01-01

OBJECTIVES. This study identified factors predicting adherence to medical recommendations in maternal phenylketonuria, which can result in severe fetal damage. METHODS. Sixty-nine women with phenylketonuria, 68 of their acquaintances, and 69 women with diabetes mellitus were interviewed annually for 5 years. A model in which each stage in the maternal phenylketonuria life cycle represented a treatment-related goal provided a means to assess adherence. RESULTS. At the stages of prevention of unplanned pregnancy, treatment initiation, and diet continuation throughout pregnancy, attitudes and social support were associated with adherence to medical recommendations. No specific variables were associated with outcome at reproductive decision making, but women with phenylketonuria were more likely to delay making a decision, resulting in unplanned and, hence, untreated or late-treated pregnancy. CONCLUSIONS. Women with phenylketonuria differed from their acquaintances and diabetic women in many respects, suggesting that special programs are needed. Greater emphasis on reproductive decision making is especially needed. Interventions that focus on improving social support networks and attitudes about treatment may increase adherence to recommendations. PMID:7503337

Genetics Home Reference: phenylketonuria

MedlinePlus

... that increases the levels of a substance called phenylalanine in the blood. Phenylalanine is a building block of proteins ( an amino ... some artificial sweeteners. If PKU is not treated, phenylalanine can build up to harmful levels in the ...

Determination of Phenylalanine and Tyrosine by High Performance Liquid Chromatography-Tandem Mass Spectrometry.

PubMed

Peat, Judy; Garg, Uttam

2016-01-01

Hyperphenylalaninemia/phenylketonuria (PKU) is one of the most common inborn errors of amino acid metabolism affecting about 1:15,000 infants in the United States. PKU is an autosomal recessive disorder that if untreated results in mental retardation. The most common cause of PKU is deficiency of the enzyme phenylalanine hydroxylase that converts phenylalanine to tyrosine. Tyrosine deficiency results in impaired synthesis of catecholamines and thyroxine. Less commonly, it can result from defects in the synthesis or regeneration of tetrahydrobiopterin (BH4), an essential cofactor for the enzyme phenylalanine hydroxylase. Increased phenylalanine and decreased tyrosine in blood are used in the diagnosis and follow-up of patients with PKU. LC/MS/MS method is described for the quantification of phenylalanine and tyrosine.

Familial variables as predictors of psychological maladjustment in Lithuanian children with phenylketonuria.

PubMed

Jusiene, Roma; Kucinskas, Vaidutis

2004-03-01

Children with phenylketonuria of early onset under continuous treatment are considered at higher risk for psychological maladjustment than children without other chronic diseases. The aim of the present study was to evaluate the psychological adjustment of Lithuanian children with treated phenylketonuria and analyze it in the context of the psychological adjustment of their parents. The parents of 37 early-treated children (age 4-14 years old) with phenylketonuria and of 37 matched controls were asked to fill out the Child Behavior Checklist and questionnaire on stress coping strategies. Parents of children with phenylketonuria answered a questionnaire on reactions to the child's disease and its impact on the family. Lithuanian children with treated phenylketonuria have significantly more emotional and behavioral problems than healthy controls. They are more withdrawn, anxious/depressed, have more social and attention problems. The higher rates of internalizing and total problems are related to parental maladjustment (feelings of guilt and anger) together with maladaptive (emotional) everyday stress coping strategies. These last two factors promote overindulging the child, which is also a predictor of psychological maladjustment in children with phenylketonuria. The already existing organic vulnerability may account for the greater susceptibility of children with phenylketonuria to psychological risk factors, as for example parental inability to cope adequately with everyday stress related to the demands of disease and its treatment.

Institutionalizing China's Research University through Academic Mobility: The Case of PKU

ERIC Educational Resources Information Center

Xiaoguang, Shi

2015-01-01

Academic mobility is becoming a tread in academic life and a professional development globally, regionally and nationally. This article makes use of a case university--Peking University (PKU)--as an analytical approach to explore how and why academic mobility can happen in China's research universities. The author first presents an overview of the…

Incidence of Neonatal Hyperphenylalaninemia Based on High-performance Liquid Chromatography Confirmatory Technique in Mazandaran Province, Northern Iran (2007–2015)

PubMed Central

Abbaskhanian, Ali; Zamanfar, Daniel; Afshar, Parvaneh; Asadpoor, Einollah; Rouhanizadeh, Hamed; Jafarnia, Ali; Shokzadeh, Mohammad

2017-01-01

Background: Classic phenylketonuria (PKU) is a metabolic disorder. The purpose of this study was to assess epidemiological factors of PKU phenotypes in a neonatal screening program for Mazandaran, Iran. Methods: In this descriptive-retrospective study from 2007 to 2015, neonates PKU level was conducted by phenylalanine level based on a biochemical technique by ELISA and then by confirmatory methods high performance liquid chromatography. Results: Of the 407,244 screened newborns (48.7% girls and 51.3% boys), 14 girls and 13 boys were diagnosed definitely from 465 suspicious cases of PKU. The incidence of PKU was 0.66 in 10,000, which was noted in different severity (severe PKU - 1:67,874, mild PKU - 1:45,249, and HPA - 1:33,937). In addition, we did not detect any cases of nonclassic PKU. Conclusions: Although the consanguineous marriage pattern is a major cause of hyperphenylalaninemia (HPA) particularly in Iranian, there was no significant difference between groups in this study. Now, screening should be executed for all of the family that they have the familial history of PKU in Iran. According to varies actual of prevalence and incidence rate of PKU reported a real patient and taking PKU with mild PKU and HPA, it is recommended, the will provide the PKU reports based on the severity of the disease. PMID:29184644

Rapid carrier screening using short tandem repeats in the phenylalanine hydroxylase gene.

PubMed

Shawky, R M; el-Aleem, K A; Rifaat, M M; el-Naggar, R L; Marzouk, G M

2002-01-01

Phenylketonuria (PKU) is an autosomal recessive genetic disorder caused by defects in the phenylalanine hydroxylase (PAH) system. Our work aimed to screen the PAH locus for the presence of potentially useful short tandem repeats (STR) as markers for carrier detection in PKU families in Egypt, and to determine the level of PAH heterozygosity within the Egyptian population. The system contains at least eight independent alleles in the Egyptian population, transmitted in a Mendelian fashion. Variations in the number of STR in the 16 families studied gave rise to polymorphisms that proved to be suitable markers for PKU carrier detection and prenatal diagnosis. The most frequent allelic fragment size in PKU patients was 246 bp (35.7%), which together with a fragment of 254 bp accounted for 60.7% of the mutant chromosomes.

SOME FACTS AND FIGURES ABOUT CHILDREN AND YOUTH.

ERIC Educational Resources Information Center

Children's Bureau (DHEW), Washington, DC.

IN QUESTION AND ANSWER FORM, THE PAMPHLET PRESENTS STATISTICAL DATA ON CHILDREN AND YOUTH PRIMARILY IN THE UNITED STATES. INFORMATION CONCERNS POPULATION, RESIDENCE, MOBILITY, POVERTY, WORKING MOTHERS, MARRIAGES, DIVORCES, BIRTHS, LIFE EXPECTANCY, MORTALITY, ILLNESS, HANDICAPS, HOSPITALIZATION, ADOPTIONS, PHENYLKETONURIA (PKU) LAWS, CHILD ABUSE…

Glycomacropeptide in children with phenylketonuria: does its phenylalanine content affect blood phenylalanine control?

PubMed

Daly, A; Evans, S; Chahal, S; Santra, S; MacDonald, A

2017-08-01

In phenylketonuria (PKU), there are no data available for children with respect to evaluating casein glycomacropeptide (CGMP) as an alternative to phenylalanine-free protein substitutes [Phe-free L-amino acid (AA)]. CGMP contains a residual amount of phenylalanine, which may alter blood phenylalanine control. In a prospective 6-month pilot study, we investigated the effect on blood phenylalanine control of CGMP-amino acid (CGMP-AA) protein substitute in 22 PKU subjects (13 boys, nine girls), median age (range) 11 years (6-16 years). Twelve received CGMP-AA and nine received Phe-free L-AA, (1 CGMP-AA withdrawal). Subjects partially or wholly replaced Phe-free L-AA with CGMP-AA. If blood phenylalanine exceeded the target range, the CGMP-AA dose was reduced and replaced with Phe-free L-amino acids. The control group remained on Phe-free L-AAs. Phenylalanine, tyrosine and Phe : Tyr ratio concentrations were compared with the results for the previous year. In the CGMP-AA group, there was a significant increase in blood phenylalanine concentrations (pre-study, 275 μmol L -1 ; CGMP-AA, 317 μmol L -1 ; P = 0.02), a decrease in tyrosine concentrations (pre-study, 50 μmol L -1 ; CGMP-AA, 40 μmol L -1 ; P = 0.03) and an increase in Phe : Tyr ratios (pre-study, Phe : Tyr 4.9:1; CGMP-AA, Phe : Tyr 8:1; P = 0.02). In the control group there was a non-significant fall in phenylalanine concentrations (pre-study 325μmol/L: study 280μmol/L [p = 0.9], and no significant changes for tyrosine or phe/tyr ratios [p = 0.9]. Children taking the CGMP-AA found it more acceptable to L-AA. Blood phenylalanine control declined with CGMP-AA but, by titrating the dose of CGMP-AA, blood phenylalanine control remained within target range. The additional intake of phenylalanine may have contributed to the change in blood phenylalanine concentration. CGMP-AA use requires careful monitoring in children. © 2017 The British Dietetic Association Ltd.

Phenylketonuria as a model for protein misfolding diseases and for the development of next generation orphan drugs for patients with inborn errors of metabolism.

PubMed

Muntau, Ania C; Gersting, Søren W

2010-12-01

The lecture dedicated to Professor Horst Bickel describes the advances, successes, and opportunities concerning the understanding of the biochemical and molecular basis of phenylketonuria and the innovative treatment strategies introduced for these patients during the last 60 years. These concepts were transferred to other inborn errors of metabolism and led to significant reduction in morbidity and to an improvement in quality of life. Important milestones were the successful development of a low-phenylalanine diet for phenylketonuria patients, the recognition of tetrahydrobiopterin as an option to treat these individuals pharmacologically, and finally market approval of this drug. The work related to the discovery of a pharmacological treatment led metabolic researchers and pediatricians to new insights into the molecular processes linked to mutations in the phenylalanine hydroxylase gene at the cellular and structural level. Again, phenylketonuria became a prototype disorder for a previously underestimated but now rapidly expanding group of diseases: protein misfolding disorders with loss of function. Due to potential general biological mechanisms underlying these disorders, the door may soon open to a systematic development of a new class of pharmaceutical products. These pharmacological chaperones are likely to correct misfolding of proteins involved in numerous genetic and nongenetic diseases.

When one disease is not enough: succinyl-CoA: 3-oxoacid coenzyme A transferase (SCOT) deficiency due to a novel mutation in OXCT1 in an infant with known phenylketonuria.

PubMed

Schwade, Jan-Niclas; Endmann, Matthias; Hofmann, Thomas; Rust, Stephan; Sass, Jörn Oliver; Rutsch, Frank

2017-10-26

A 9-month-old Turkish girl was admitted several times within 3 months to the hospital in reduced general condition and with extreme tachypnea. The patient had been diagnosed with phenylketonuria (PKU) in newborn screening and has been treated with a low phenylalanine diet and amino acid supplements. Each time an unexplained pronounced metabolic acidosis was noted, and the child was treated with sodium-bicarbonate and glucose-electrolyte infusions. The acidosis with only slightly abnormal glucose, normal lactate levels and pronounced ketonuria suggested a defect in ketone body utilization. Succinyl-CoA: 3-oxoacid CoA transferase (SCOT) enzyme activity was low in patient's fibroblasts. Mutation analysis of the corresponding OXCT1 gene revealed that the patient was a homozygous carrier of the mutation c.1523T>C (p.V508A). We conclude that SCOT deficiency should be considered in the differential diagnosis in patients with recurrent metabolic acidotic episodes, even if they are already known to have a metabolic disease unrelated to this.

Intense beams from gases generated by a permanent magnet ECR ion source at PKU.

PubMed

Ren, H T; Peng, S X; Lu, P N; Yan, S; Zhou, Q F; Zhao, J; Yuan, Z X; Guo, Z Y; Chen, J E

2012-02-01

An electron cyclotron resonance (ECR) ion source is designed for the production of high-current ion beams of various gaseous elements. At the Peking University (PKU), the primary study is focused on developing suitable permanent magnet ECR ion sources (PMECRs) for separated function radio frequency quadrupole (SFRFQ) accelerator and for Peking University Neutron Imaging Facility. Recently, other kinds of high-intensity ion beams are required for new acceleration structure demonstration, simulation of fusion reactor material irradiation, aviation bearing modification, and other applications. So we expanded the ion beam category from O(+), H(+), and D(+) to N(+), Ar(+), and He(+). Up to now, about 120 mA of H(+), 83 mA of D(+), 50 mA of O(+), 63 mA of N(+), 70 mA of Ar(+), and 65 mA of He(+) extracted at 50 kV through a φ 6 mm aperture were produced by the PMECRs at PKU. Their rms emittances are less than 0.2 π mm mrad. Tungsten samples were irradiated by H(+) or He(+) beam extracted from this ion source and H∕He holes and bubbles have been observed on the samples. A method to produce a high intensity H∕He mixed beam to study synergistic effect is developed for nuclear material irradiation. To design a He(+) beam injector for coupled radio frequency quadruple and SFRFQ cavity, He(+) beam transmission experiments were carried out on PKU low energy beam transport test bench and the transmission was less than 50%. It indicated that some electrode modifications must be done to decrease the divergence of He(+) beam.

Glycomacropeptide for nutritional management of phenylketonuria: a randomized, controlled, crossover trial.

PubMed

Ney, Denise M; Stroup, Bridget M; Clayton, Murray K; Murali, Sangita G; Rice, Gregory M; Rohr, Frances; Levy, Harvey L

2016-08-01

To prevent cognitive impairment, phenylketonuria requires lifelong management of blood phenylalanine (Phe) concentration with a low-Phe diet. The diet restricts intake of Phe from natural proteins in combination with traditional amino acid medical foods (AA-MFs) or glycomacropeptide medical foods (GMP-MFs) that contain primarily intact protein and a small amount of Phe. We investigated the efficacy and safety of a low-Phe diet combined with GMP-MFs or AA-MFs providing the same quantity of protein equivalents in free-living subjects with phenylketonuria. This 2-stage, randomized crossover trial included 30 early-treated phenylketonuria subjects (aged 15-49 y), 20 with classical and 10 with variant phenylketonuria. Subjects consumed, in random order for 3 wk each, their usual low-Phe diet combined with AA-MFs or GMP-MFs. The treatments were separated by a 3-wk washout with AA-MFs. Fasting plasma amino acid profiles, blood Phe concentrations, food records, and neuropsychological tests were obtained. The frequency of medical food intake was higher with GMP-MFs than with AA-MFs. Subjects rated GMP-MFs as more acceptable than AA-MFs and noted improved gastrointestinal symptoms and less hunger with GMP-MFs. ANCOVA indicated no significant mean ± SE increase in plasma Phe (62 ± 40 μmol/L, P = 0.136), despite a significant increase in Phe intake from GMP-MFs (88 ± 6 mg Phe/d, P = 0.026). AA-MFs decreased plasma Phe (-85 ± 40 μmol/L, P = 0.044) with stable Phe intake. Blood concentrations of Phe across time were not significantly different (AA-MFs = 444 ± 34 μmol/L, GMP-MFs = 497 ± 34 μmol/L), suggesting similar Phe control. Results of the Behavior Rating Inventory of Executive Function were not significantly different. GMP-MFs provide a safe and acceptable option for the nutritional management of phenylketonuria. The greater acceptability and fewer side effects noted with GMP-MFs than with AA-MFs may enhance dietary adherence for individuals with phenylketonuria

Improvements of PKU PMECRIS for continuous hundred hours CW proton beam operation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peng, S. X., E-mail: sxpeng@pku.edu.cn; Ren, H. T.; Zhang, T.

2016-02-15

In order to improve the source stability, a long term continuous wave (CW) proton beam experiment has been carried out with Peking University compact permanent magnet 2.45 GHz ECR ion source (PKU PMECRIS). Before such an experiment a lot of improvements and modifications were completed on the source body, the Faraday cup and the PKU ion source test bench. At the beginning of 2015, a continuous operation of PKU PMECRIS for 306 h with more than 50 mA CW beam was carried out after success of many short term tests. No plasma generator failure or high voltage breakdown was observedmore » during that running period and the proton source reliability is near 100%. Total beam availability, which is defined as 35-keV beam-on time divided by elapsed time, was higher than 99% [S. X. Peng et al., Chin. Phys. B 24(7), 075203 (2015)]. A re-inspection was performed after another additional 100 h operation (counting time) and no obvious sign of component failure was observed. Counting the previous source testing time together, this PMECRs longevity is now demonstrated to be greater than 460 h. This paper is mainly concentrated on the improvements for this long term experiment.« less

Pegvaliase for the treatment of phenylketonuria: A pivotal, double-blind randomized discontinuation Phase 3 clinical trial.

PubMed

Harding, Cary O; Amato, R Stephen; Stuy, Mary; Longo, Nicola; Burton, Barbara K; Posner, John; Weng, Haoling H; Merilainen, Markus; Gu, Zhonghua; Jiang, Joy; Vockley, Jerry

2018-05-01

Pegvaliase is a recombinant Anabaena variabilis phenylalanine ammonia lyase (PAL) enzyme under investigation for treatment of adult phenylketonuria (PKU). This manuscript describes results of a randomized discontinuation trial (RDT) designed to evaluate the effects of pegvaliase treatment on blood phenylalanine (Phe) and neuropsychiatric outcomes in adults with PKU. PRISM-2 is a 4-part, Phase 3 study that enrolled adults with PKU receiving pegvaliase treatment (initiated in a prior Phase 2 or Phase 3 study). The RDT, Part 2 of PRISM-2, was an 8-week trial that evaluated change in blood Phe concentrations, neuropsychiatric and neurocognitive measures, and safety outcomes in PRISM-2 participants who had achieved at least a 20% blood Phe reduction from pre-treatment baseline with pegvaliase treatment. Participants were randomized 2:1 to either continue pegvaliase (20 mg/day or 40 mg/day) or switch to matching placebo. The pooled pegvaliase group enrolled 66 participants and each placebo group enrolled 14 participants. The primary endpoint of change in blood Phe concentration from RDT entry to RDT Week 8 was met with clinically meaningful and statistically significant differences between the pegvaliase and placebo groups. Mean (SD) blood Phe at the beginning of the RDT when all participants were receiving pegvaliase was 563.9 μM (504.6) in the group assigned to the 20 mg/day placebo group (n = 14), 508.2 μM (363.7) in those assigned to the 40 mg/day placebo group (n = 14), and 503.9 μM (520.3) in those assigned to continue pegvaliase treatment (n = 58). At Week 8 of the RDT, the least squares mean change (95% confidence interval) in blood Phe was 949.8 μM (760.4 to 1139.1) for the 20 mg/day placebo group and 664.8 μM (465.5 to 864.1) for the 40 mg/day placebo group in comparison to 26.5 μM (-68.3 to 121.3) for the pooled (20 mg/day and 40 mg/day) pegvaliase group (P < 0.0001 for pooled pegvaliase group vs each placebo

Glycomacropeptide for nutritional management of phenylketonuria: a randomized, controlled, crossover trial12

PubMed Central

Stroup, Bridget M; Clayton, Murray K; Murali, Sangita G; Rice, Gregory M; Rohr, Frances; Levy, Harvey L

2016-01-01

Background: To prevent cognitive impairment, phenylketonuria requires lifelong management of blood phenylalanine (Phe) concentration with a low-Phe diet. The diet restricts intake of Phe from natural proteins in combination with traditional amino acid medical foods (AA-MFs) or glycomacropeptide medical foods (GMP-MFs) that contain primarily intact protein and a small amount of Phe. Objective: We investigated the efficacy and safety of a low-Phe diet combined with GMP-MFs or AA-MFs providing the same quantity of protein equivalents in free-living subjects with phenylketonuria. Design: This 2-stage, randomized crossover trial included 30 early-treated phenylketonuria subjects (aged 15–49 y), 20 with classical and 10 with variant phenylketonuria. Subjects consumed, in random order for 3 wk each, their usual low-Phe diet combined with AA-MFs or GMP-MFs. The treatments were separated by a 3-wk washout with AA-MFs. Fasting plasma amino acid profiles, blood Phe concentrations, food records, and neuropsychological tests were obtained. Results: The frequency of medical food intake was higher with GMP-MFs than with AA-MFs. Subjects rated GMP-MFs as more acceptable than AA-MFs and noted improved gastrointestinal symptoms and less hunger with GMP-MFs. ANCOVA indicated no significant mean ± SE increase in plasma Phe (62 ± 40 μmol/L, P = 0.136), despite a significant increase in Phe intake from GMP-MFs (88 ± 6 mg Phe/d, P = 0.026). AA-MFs decreased plasma Phe (−85 ± 40 μmol/L, P = 0.044) with stable Phe intake. Blood concentrations of Phe across time were not significantly different (AA-MFs = 444 ± 34 μmol/L, GMP-MFs = 497 ± 34 μmol/L), suggesting similar Phe control. Results of the Behavior Rating Inventory of Executive Function were not significantly different. Conclusions: GMP-MFs provide a safe and acceptable option for the nutritional management of phenylketonuria. The greater acceptability and fewer side effects noted with GMP-MFs than with AA-MFs may enhance

Phenylketonuria: dietary and therapeutic challenges.

PubMed

Giovannini, M; Verduci, E; Salvatici, E; Fiori, L; Riva, E

2007-04-01

PKU subjects need special attention in the definition of optimal supplementation of nutrients, which may be insufficient in relation to the type of diet and may otherwise manifest symptoms of deficit. In particular, it is necessary to pay great attention to the long-chain polyunsaturated fatty acid (LC-PUFA) levels in relation to correct development of the central nervous system. On the basis of numerous beneficial effects currently known, a permanent supplementation with LC-PUFAs, in particular with docosahexaenoic acid, should be considered. Moreover, new formulas, Phe-free peptides, and 'modulated' amino acid preparations might help in preventing nutritional deficiencies and imbalances, with the ultimate aim of improving growth. New strategies--such as supply of tetrahydrobiopterin--need to be optimized in terms of targets, patients and expected outcomes.

A maximum likelihood map of chromosome 1.

PubMed Central

Rao, D C; Keats, B J; Lalouel, J M; Morton, N E; Yee, S

1979-01-01

Thirteen loci are mapped on chromosome 1 from genetic evidence. The maximum likelihood map presented permits confirmation that Scianna (SC) and a fourteenth locus, phenylketonuria (PKU), are on chromosome 1, although the location of the latter on the PGM1-AMY segment is uncertain. Eight other controversial genetic assignments are rejected, providing a practical demonstration of the resolution which maximum likelihood theory brings to mapping. PMID:293128

[The mutation analysis of PAH gene and prenatal diagnosis in classical phenylketonuria family].

PubMed

Yan, Yousheng; Hao, Shengju; Yao, Fengxia; Sun, Qingmei; Zheng, Lei; Zhang, Qinghua; Zhang, Chuan; Yang, Tao; Huang, Shangzhi

2014-12-01

To characterize the mutation spectrum of phenylalanine hydroxylase (PAH) gene and perform prenatal diagnosis for families with classical phenylketonuria. By stratified sequencing, mutations were detected in the exons and flaking introns of PAH gene of 44 families with classical phenylketonuria. 47 fetuses were diagnosed by combined sequencing with linkage analysis of three common short tandem repeats (STR) (PAH-STR, PAH-26 and PAH-32) in the PAH gene. Thirty-one types of mutations were identified. A total of 84 mutations were identified in 88 alleles (95.45%), in which the most common mutation have been R243Q (21.59%), EX6-96A>G (6.82%), IVS4-1G>A (5.86%) and IVS7+2T>A (5.86%). Most mutations were found in exons 3, 5, 6, 7, 11 and 12. The polymorphism information content (PIC) of these three STR markers was 0.71 (PAH-STR), 0.48 (PAH-26) and 0.40 (PAH-32), respectively. Prenatal diagnosis was performed successfully with the combined method in 47 fetuses of 44 classical phenylketonuria families. Among them, 11 (23.4%) were diagnosed as affected, 24 (51.1%) as carriers, and 12 (25.5%) as unaffected. Prenatal diagnosis can be achieved efficiently and accurately by stratified sequencing of PAH gene and linkage analysis of STR for classical phenylketonuria families.

Acceptable low-phenylalanine foods and beverages can be made with glycomacropeptide from cheese whey for individuals with PKU

PubMed Central

Lim, Kyungwha; van Calcar, Sandra C.; Nelson, Kathryn L.; Gleason, Sally T.; Ney, Denise M.

2007-01-01

Glycomacropeptide (GMP) is a whey protein that contains no aromatic amino acids including phenylalanine (phe). The objective of this study was to make a variety of palatable, low-phe foods and beverages with GMP and to assess their acceptability by conducting consumer sensory studies in individuals with PKU. Results demonstrate acceptability of products made with GMP. GMP supplemented with limiting indispensable amino acids could provide an alternative protein source for individuals with PKU. PMID:17644019

Cognitive deficits in a genetic mouse model of the most common biochemical cause of human mental retardation.

PubMed

Zagreda, L; Goodman, J; Druin, D P; McDonald, D; Diamond, A

1999-07-15

Phenylalanine hydroxylase (Pah)-deficient "PKU mice" have a mutation in the Pah gene that causes phenylketonuria (PKU) in humans. PKU produces cognitive deficits in humans if it is untreated. We report here the first evidence that the genetic mouse model of PKU (Pah(enu2)) also produces cognitive impairments. PKU mice were impaired on both odor discrimination reversal and latent learning compared with heterozygote littermates and with wild-type mice of the same BTBR strain. A small container of cinnamon-scented sand was presented on the right or left, and nutmeg-scented sand was presented on the other side; left-right location varied over trials. Digging in sand of the correct scent was rewarded by finding phenylalanine-free chocolate. To prevent scent cuing, new containers were used on every trial, and both containers always contained chocolate. Digging in the incorrect choice was stopped before the chocolate was uncovered. Once criterion was reached, the other scent was rewarded. PKU mice were impaired on reversals 2, 3, and 4. They were also impaired in latent learning. On day 1, half the mice were allowed to explore a maze and discover the location of water. On day 2, all mice were water-deprived and were placed in the maze. Whereas pre-exposed wild-type and heterozygous mice showed evidence that they remembered the location of the water and hence could find the water faster on day 2, pre-exposed PKU mice showed no significant benefit from their pre-exposure on day 1.

Prefrontal Cortex Cognitive Deficits in Children Treated Early and Continuously for PKU.

ERIC Educational Resources Information Center

Diamond, Adele; Prevor, Meredith B.; Druin, Donald P.; Callender, Glenda

1997-01-01

Hypothesized that elevated ratio of phenylalanine to tyrosine in blood of children with phenylketonuria uniquely affects cognitive functions dependent on prefrontal cortex because of the special sensitivity of prefrontally projecting dopamine neurons to small decreases in tyrosine. Found that children whose phenylalanine levels were three to five…

PHENYLKETONURIA, AN INHERITED METABOLIC DISORDER ASSOCIATED WITH MENTAL RETARDATION.

ERIC Educational Resources Information Center

CENTERWALL, WILLARD R.; CENTERWALL, SIEGRIED A.

ADDRESSED TO PUBLIC HEALTH WORKERS AND PHYSICIANS IN GENERAL PRACTICE, THE PAMPHLET INTRODUCES METHODS OF DETECTING AND MANAGING PHENYLKETONURIA, AN INHERITED METABOLIC DISORDER ASSOCIATED WITH MENTAL RETARDATION. INFORMATION, UPDATED FROM THE 1961 EDITION, IS INCLUDED ON THE INCIDENCE AND GENETICS, BIOCHEMISTRY, AND CLINICAL COURSE OF THE…

Mapping the functional landscape of frequent phenylalanine hydroxylase (PAH) genotypes promotes personalised medicine in phenylketonuria.

PubMed

Danecka, Marta K; Woidy, Mathias; Zschocke, Johannes; Feillet, François; Muntau, Ania C; Gersting, Søren W

2015-03-01

In phenylketonuria, genetic heterogeneity, frequent compound heterozygosity, and the lack of functional data for phenylalanine hydroxylase genotypes hamper reliable phenotype prediction and individualised treatment. A literature search revealed 690 different phenylalanine hydroxylase genotypes in 3066 phenylketonuria patients from Europe and the Middle East. We determined phenylalanine hydroxylase function of 30 frequent homozygous and compound heterozygous genotypes covering 55% of the study population, generated activity landscapes, and assessed the phenylalanine hydroxylase working range in the metabolic (phenylalanine) and therapeutic (tetrahydrobiopterin) space. Shared patterns in genotype-specific functional landscapes were linked to biochemical and pharmacological phenotypes, where (1) residual activity below 3.5% was associated with classical phenylketonuria unresponsive to pharmacological treatment; (2) lack of defined peak activity induced loss of response to tetrahydrobiopterin; (3) a higher cofactor need was linked to inconsistent clinical phenotypes and low rates of tetrahydrobiopterin response; and (4) residual activity above 5%, a defined peak of activity, and a normal cofactor need were associated with pharmacologically treatable mild phenotypes. In addition, we provide a web application for retrieving country-specific information on genotypes and genotype-specific phenylalanine hydroxylase function that warrants continuous extension, updates, and research on demand. The combination of genotype-specific functional analyses with biochemical, clinical, and therapeutic data of individual patients may serve as a powerful tool to enable phenotype prediction and to establish personalised medicine strategies for dietary regimens and pharmacological treatment in phenylketonuria. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Dietary amino acid intakes associated with a low-phenylalanine diet combined with amino acid medical foods and glycomacropeptide medical foods and neuropsychological outcomes in subjects with phenylketonuria.

PubMed

Stroup, Bridget M; Murali, Sangita G; Nair, Nivedita; Sawin, Emily A; Rohr, Fran; Levy, Harvey L; Ney, Denise M

2017-08-01

This article provides original data on median dietary intake of 18 amino acids from amino acid medical foods, glycomacropeptide medical foods, and natural foods based on 3-day food records obtained from subjects with phenylketonuria who consumed low-phenylalanine diets in combination with amino acid medical foods and glycomacropeptide medical foods for 3 weeks each in a crossover design. The sample size of 30 subjects included 20 subjects with classical phenylketonuria and 10 with a milder or variant form of phenylketonuria. Results are presented for the Delis-Kaplan Executive Function System and the Cambridge Neuropsychological Test Automated Battery; the tests were administered at the end of each 3-week dietary treatment with amino acid medical foods and glycomacropeptide medical foods. The data are supplemental to our clinical trial, entitled "Glycomacropetide for nutritional management of phenylketonuria: a randomized, controlled, crossover trial, 2016 (1) and "Metabolomic changes demonstrate reduced bioavailability of tyrosine and altered metabolism of tryptophan via the kynurenine pathway with ingestion of medical foods in phenylketonuria, 2017 (2). This data has been made public and has utility to clinicians and researchers due to the following: 1) This provides the first comprehensive report of typical intakes of 18 amino acids from natural foods, as well as amino acid and glycomacropeptide medical foods in adolescents and adults with phenylketonuria; and 2) This is the first evidence of similar standardized neuropsychological testing data in adolescents and adults with early-treated phenylketonuria who consumed amino acid and glycomacropeptide medical foods.

Genotype-phenotype associations in French patients with phenylketonuria and importance of genotype for full assessment of tetrahydrobiopterin responsiveness.

PubMed

Jeannesson-Thivisol, Elise; Feillet, François; Chéry, Céline; Perrin, Pascal; Battaglia-Hsu, Shyue-Fang; Herbeth, Bernard; Cano, Aline; Barth, Magalie; Fouilhoux, Alain; Mention, Karine; Labarthe, François; Arnoux, Jean-Baptiste; Maillot, François; Lenaerts, Catherine; Dumesnil, Cécile; Wagner, Kathy; Terral, Daniel; Broué, Pierre; de Parscau, Loïc; Gay, Claire; Kuster, Alice; Bédu, Antoine; Besson, Gérard; Lamireau, Delphine; Odent, Sylvie; Masurel, Alice; Guéant, Jean-Louis; Namour, Fares

2015-12-15

Mutations in Phenylalanine Hydroxylase (PAH) gene cause phenylketonuria. Sapropterin (BH4), the enzyme cofactor, is an important therapeutical strategy in phenylketonuria. However, PAH is a highly polymorphic gene and it is difficult to identify BH4-responsive genotypes. We seek here to improve prediction of BH4-responsiveness through comparison of genotypes, BH4-loading test, predictions of responsiveness according to the literature and types and locations of mutations. A total of 364 French patients among which, 9 % had mild hyperphenylalaninemia, 17.7 % mild phenylketonuria and 73.1 % classical phenylketonuria, benefited from a 24-hour BH4-loading test and had the PAH gene sequenced and analyzed by Multiplex Ligation Probe Amplification. Overall, 31.6 % of patients were BH4-responsive. The number of different mutations found was 127, including 26 new mutations. The mutations c.434A > T, c.500A > T, c.529G > C, c.1045 T > G and c.1196 T > C were newly classified as being BH4-responsive. We identified 261 genotypes, among which 46 were newly recognized as being BH4-responsive. Even though patients carry 2 responsive alleles, BH4-responsiveness cannot be predicted with certainty unless they present mild hyperphenylalaninemia. BH4-responsiveness cannot be predicted in patients carrying one responsive mutation only. In general, the milder the phenotype is, the stronger the BH4-response is. Almost exclusively missense mutations, particularly in exons 12, 11 and 8, are associated with BH4-responsiveness and any other type of mutation predicts a negative response. This study is the first of its kind, in a French population, to identify the phenotype associated with several combinations of PAH mutations. As others, it highlights the necessity of performing simultaneously BH4 loading test and molecular analysis in monitoring phenylketonuria patients.

Therapeutic implication of L-phenylalanine aggregation mechanism and its modulation by D-phenylalanine in phenylketonuria.

PubMed

Singh, Virender; Rai, Ratan Kumar; Arora, Ashish; Sinha, Neeraj; Thakur, Ashwani Kumar

2014-01-27

Self-assembly of phenylalanine is linked to amyloid formation toxicity in phenylketonuria disease. We are demonstrating that L-phenylalanine self-assembles to amyloid fibrils at varying experimental conditions and transforms to a gel state at saturated concentration. Biophysical methods including nuclear magnetic resonance, resistance by alpha-phenylglycine to fibril formation and preference of protected phenylalanine to self-assemble show that this behaviour of L-phenylalanine is governed mainly by hydrophobic interactions. Interestingly, D-phenylalanine arrests the fibre formation by L-phenylalanine and gives rise to flakes. These flakes do not propagate further and prevent fibre formation by L-phenylalanine. This suggests the use of D-phenylalanine as modulator of L-phenylalanine amyloid formation and may qualify as a therapeutic molecule in phenylketonuria.

Therapeutic implication of L-phenylalanine aggregation mechanism and its modulation by D-phenylalanine in phenylketonuria

PubMed Central

Singh, Virender; Rai, Ratan Kumar; Arora, Ashish; Sinha, Neeraj; Thakur, Ashwani Kumar

2014-01-01

Self-assembly of phenylalanine is linked to amyloid formation toxicity in phenylketonuria disease. We are demonstrating that L-phenylalanine self-assembles to amyloid fibrils at varying experimental conditions and transforms to a gel state at saturated concentration. Biophysical methods including nuclear magnetic resonance, resistance by alpha-phenylglycine to fibril formation and preference of protected phenylalanine to self-assemble show that this behaviour of L-phenylalanine is governed mainly by hydrophobic interactions. Interestingly, D-phenylalanine arrests the fibre formation by L-phenylalanine and gives rise to flakes. These flakes do not propagate further and prevent fibre formation by L-phenylalanine. This suggests the use of D-phenylalanine as modulator of L-phenylalanine amyloid formation and may qualify as a therapeutic molecule in phenylketonuria. PMID:24464217

Post-Translational Incorporation of L-Phenylalanine into the C-Terminus of α-Tubulin as a Possible Cause of Neuronal Dysfunction

PubMed Central

Ditamo, Yanina; Dentesano, Yanela M.; Purro, Silvia A.; Arce, Carlos A.; Bisig, C. Gastón

2016-01-01

α-Tubulin C-terminus undergoes post-translational, cyclic tyrosination/detyrosination, and L-Phenylalanine (Phe) can be incorporated in place of tyrosine. Using cultured mouse brain-derived cells and an antibody specific to Phe-tubulin, we showed that: (i) Phe incorporation into tubulin is reversible; (ii) such incorporation is not due to de novo synthesis; (iii) the proportion of modified tubulin is significant; (iv) Phe incorporation reduces cell proliferation without affecting cell viability; (v) the rate of neurite retraction declines as level of C-terminal Phe incorporation increases; (vi) this inhibitory effect of Phe on neurite retraction is blocked by the co-presence of tyrosine; (vii) microtubule dynamics is reduced when Phe-tubulin level in cells is high as a result of exogenous Phe addition and returns to normal values when Phe is removed; moreover, microtubule dynamics is also reduced when Phe-tubulin is expressed (plasmid transfection). It is known that Phe levels are greatly elevated in blood of phenylketonuria (PKU) patients. The molecular mechanism underlying the brain dysfunction characteristic of PKU is unknown. Beyond the differences between human and mouse cells, it is conceivable the possibility that Phe incorporation into tubulin is the first event (or among the initial events) in the molecular pathways leading to brain dysfunctions that characterize PKU. PMID:27905536

Post-Translational Incorporation of L-Phenylalanine into the C-Terminus of α-Tubulin as a Possible Cause of Neuronal Dysfunction.

PubMed

Ditamo, Yanina; Dentesano, Yanela M; Purro, Silvia A; Arce, Carlos A; Bisig, C Gastón

2016-12-01

α-Tubulin C-terminus undergoes post-translational, cyclic tyrosination/detyrosination, and L-Phenylalanine (Phe) can be incorporated in place of tyrosine. Using cultured mouse brain-derived cells and an antibody specific to Phe-tubulin, we showed that: (i) Phe incorporation into tubulin is reversible; (ii) such incorporation is not due to de novo synthesis; (iii) the proportion of modified tubulin is significant; (iv) Phe incorporation reduces cell proliferation without affecting cell viability; (v) the rate of neurite retraction declines as level of C-terminal Phe incorporation increases; (vi) this inhibitory effect of Phe on neurite retraction is blocked by the co-presence of tyrosine; (vii) microtubule dynamics is reduced when Phe-tubulin level in cells is high as a result of exogenous Phe addition and returns to normal values when Phe is removed; moreover, microtubule dynamics is also reduced when Phe-tubulin is expressed (plasmid transfection). It is known that Phe levels are greatly elevated in blood of phenylketonuria (PKU) patients. The molecular mechanism underlying the brain dysfunction characteristic of PKU is unknown. Beyond the differences between human and mouse cells, it is conceivable the possibility that Phe incorporation into tubulin is the first event (or among the initial events) in the molecular pathways leading to brain dysfunctions that characterize PKU.

A New Model for Allosteric Regulation of Phenylalanine Hydroxylase: Implications for Disease and Therapeutics

PubMed Central

Stith, Linda; Lawrence, Sarah H.; Andrake, Mark; Dunbrack, Roland L.

2013-01-01

The structural basis for allosteric regulation of phenylalanine hydroxylase (PAH), whose dysfunction causes phenylketonuria (PKU), is poorly understood. A new morpheein model for PAH allostery is proposed to consist of a dissociative equilibrium between two architecturally different tetramers whose interconversion requires a ~90° rotation between the PAH catalytic and regulatory domains, the latter of which contains an ACT domain. This unprecedented model is supported by in vitro data on purified full length rat and human PAH. The conformational change is both predicted to and shown to render the tetramers chromatographically separable using ion exchange methods. One novel aspect of the activated tetramer model is an allosteric phenylalanine binding site at the inter-subunit interface of ACT domains. Amino acid ligand-stabilized ACT domain dimerization follows the multimerization and ligand binding behavior of ACT domains present in other proteins in the PDB. Spectroscopic, chromatographic, and electrophoretic methods demonstrate a PAH equilibrium consisting of two architecturally distinct tetramers as well as dimers. We postulate that PKU-associated mutations may shift the PAH quaternary structure equilibrium in favor of the low activity assemblies. Pharmacological chaperones that stabilize the ACT:ACT interface can potentially provide PKU patients with a novel small molecule therapeutic. PMID:23296088

Duty factor variation possibility from 1% to 100% with PKU microwave driven Cs-free volume H{sup −} sources

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peng, S. X., E-mail: sxpeng@pku.edu.cn; Zhang, T.; Ren, H. T.

Microwave driven cesium-free volume H{sup −} sources, that have the ability to deliver tens of mA H{sup −} at 35 keV both in CW and 10% duty factor (100 Hz/1 ms), were developed at Peking University (PKU) [S. X. Peng et al., in Proceeding of IPAC 2015, WEPWA027, Richmond, Virginia, USA, 3–8 May 2015]. Recently, special efforts were paid on the investigation of duty factor variation possibility from 1% to 100% with them. Most of the experiments were carried out with a pulsed length (τ) of 1 ms and different intervals of 99 ms, 49 ms, 39 ms, 29 ms,more » 19 ms, 9 ms, 4 ms, 2 ms, 1 ms, 0.5 ms, and 0 ms, respectively. Other experiments were focused on CW operation and fixed duty factor of 1%. Experimental results prove that PKU H{sup −} sources can deliver tens of mA H{sup −} at duty factor from 1% to 100%. The RF power efficiency increases steadily with the increasing of duty factor from 1% to CW at a fixed pulsed length. Under a given duty factor and pulsed length, RF power efficiency keeps constant and the H{sup −} current increases with RF power linearly. Details will be presented in the paper.« less

Efficacy and safety of BH4 before the age of 4 years in patients with mild phenylketonuria.

PubMed

Leuret, Oriane; Barth, Magalie; Kuster, Alice; Eyer, Didier; de Parscau, Loïc; Odent, Sylvie; Gilbert-Dussardier, Brigitte; Feillet, François; Labarthe, François

2012-11-01

Sapropterin dihydrochloride, an EMEA-approved synthetic formulation of BH4, has been available in Europe since 2009 for PKU patients older than 4 years, but its use with younger children is allowed in France based on an expert recommendation. We report the cases of 15 patients treated under the age of 4 years and demonstrate the safety and efficacy of this treatment for patients in this age group. We report the use of BH4 in 15 PKU patients treated before the age of 4 years. Fifteen patients were enrolled in this retrospective study. Mean phenylalaninemia at diagnosis was 542 ± 164 μM and all patients had mild PKU (maximal phenylalaninemia: 600-1200 μM). BH4 responsiveness was assessed using a 24-hour BH4 loading test (20 mg/kg), performed during the neonatal period (n = 11) or before 18 months of age (n = 4). During the test, these patients exhibited an 80 ± 12% decrease in phenylalaninemia. Long-term BH4 therapy was initiated during the neonatal period (n = 7) or at the age of 13 ± 12 months (n = 8). The median duration of treatment was 23 months [min 7; max 80]. BH4 therapy drastically improved dietary phenylalanine tolerance (456 ± 181 vs 1683 ± 627 mg/day, p < 0.0001) and allowed a phenylalanine-free amino acid mixture to be discontinued or not introduced in 14 patients. Additionally, in the eight patients treated after a few months of diet therapy, BH4 treatment significantly decreased mean phenylalaninemia (352 ± 85 vs 254 ± 64 μM, p < 0.05), raised the percentage of phenylalaninemia tests within therapeutic targets [120-300 μM] (35 ± 25 vs 64 ± 16%, p < 0.05), and reduced phenylalaninemia variance (130 ± 21 vs 93 ± 27 μM, p < 0.05). No side effects were reported. BH4-therapy is efficient and safe before the age of 4 years in mild PKU, BH4-responsive patients.

Phenethylamines in brain and liver of rats with experimentally induced phenylketonuria-like characteristics

PubMed Central

Edwards, David J.; Blau, Karl

1973-01-01

1. Phenethylamines were extracted from brain and liver of rats with phenylketonuria-like characteristics produced in vivo by inhibition of phenylalanine hydroxylase (EC 1.14.3.1) with p-chlorophenylalanine, with or without phenylalanine administration. To protect amines against oxidation by monoamine oxidase, pargyline was also administered. 2. β-Phenethylamine was the major compound found in brain and liver. β-Phenethanolamine and octopamine were also present, in lesser amounts, and the concentrations of these three amines paralleled blood phenylalanine concentrations. By comparison, tissues from control animals had only very low concentrations of these amines. 3. Small amounts of normetadrenaline, m-tyramine and 3-methoxytyramine were also found. 4. The inhibitors used, p-chlorophenylalanine and pargyline, gave rise to p-chlorophenethylamine and benzylamine respectively, the first via decarboxylation, the second probably by breakdown during extraction. 5. Distribution of phenethylamines in different brain regions and in subcellular fractions of rat brain cells was also investigated. The content of phenethylamine was highest in the striatum. 6. These findings are discussed in the light of changes occurring in human patients with uncontrolled phenylketonuria. PMID:4269184

New PAH gene promoter KLF1 and 3'-region C/EBPalpha motifs influence transcription in vitro.

PubMed

Klaassen, Kristel; Stankovic, Biljana; Kotur, Nikola; Djordjevic, Maja; Zukic, Branka; Nikcevic, Gordana; Ugrin, Milena; Spasovski, Vesna; Srzentic, Sanja; Pavlovic, Sonja; Stojiljkovic, Maja

2017-02-01

Phenylketonuria (PKU) is a metabolic disease caused by mutations in the phenylalanine hydroxylase (PAH) gene. Although the PAH genotype remains the main determinant of PKU phenotype severity, genotype-phenotype inconsistencies have been reported. In this study, we focused on unanalysed sequences in non-coding PAH gene regions to assess their possible influence on the PKU phenotype. We transiently transfected HepG2 cells with various chloramphenicol acetyl transferase (CAT) reporter constructs which included PAH gene non-coding regions. Selected non-coding regions were indicated by in silico prediction to contain transcription factor binding sites. Furthermore, electrophoretic mobility shift assay (EMSA) and supershift assays were performed to identify which transcriptional factors were engaged in the interaction. We found novel KLF1 motif in the PAH promoter, which decreases CAT activity by 50 % in comparison to basal transcription in vitro. The cytosine at the c.-170 promoter position creates an additional binding site for the protein complex involving KLF1 transcription factor. Moreover, we assessed for the first time the role of a multivariant variable number tandem repeat (VNTR) region located in the 3'-region of the PAH gene. We found that the VNTR3, VNTR7 and VNTR8 constructs had approximately 60 % of CAT activity. The regulation is mediated by the C/EBPalpha transcription factor, present in protein complex binding to VNTR3. Our study highlighted two novel promoter KLF1 and 3'-region C/EBPalpha motifs in the PAH gene which decrease transcription in vitro and, thus, could be considered as PAH expression modifiers. New transcription motifs in non-coding regions will contribute to better understanding of the PKU phenotype complexity and may become important for the optimisation of PKU treatment.

Spectrum of Phenylalanine Hydroxylase Gene Mutations in Hamadan and Lorestan Provinces of Iran and Their Associations with Variable Number of Tandem Repeat Alleles.

PubMed

Alibakhshi, Reza; Moradi, Keivan; Biglari, Mostafa; Shafieenia, Samaneh

2018-05-01

Phenylketonuria (PKU) is one of the most common known inherited metabolic diseases. The present study aimed to investigate the status of molecular defects in phenylalanine hydroxylase ( PAH ) gene in western Iranian PKU patients (predominantly from Kermanshah, Hamadan, and Lorestan provinces) during 2014-2016. Additionally, the results were compared with similar studies in Iran. Nucleotide sequence analysis of all 13 exons and their flanking intronic regions of the PAH gene was performed in 18 western Iranian PKU patients. Moreover, a variable number of tandem repeat (VNTR) located in the PAH gene was studied. The results revealed a mutational spectrum encompassing 11 distinct mutations distributed along the PAH gene sequence on 34 of the 36 mutant alleles (diagnostic efficiency of 94.4%). Also, four PAH VNTR alleles (with repeats of 3, 7, 8 and 9) were detected. The three most frequent mutations were IVS9+5G>A, IVS7-5T>C, and p.P281L with the frequency of 27.8%, 11%, and 11%, respectively. The results showed that there is not only a consanguineous relation, but also a difference in PAH characters of mutations between Kermanshah and the other two parts of western Iran (Hamadan and Lorestan). Also, it seems that the spectrum of mutations in western Iran is relatively distinct from other parts of the country, suggesting that this region might be a special PAH gene distribution region. Moreover, our findings can be useful in the identification of genotype to phenotype relationship in patients, and provide future abilities for confirmatory diagnostic testing, prognosis, and predict the severity of PKU patients.

Consequences of Variations in Genes that affect Dopamine in Prefrontal Cortex

PubMed Central

Diamond, Adele

2008-01-01

Patricia Goldman-Rakic played a groundbreaking role in investigating the cognitive functions subserved by dorsolateral prefrontal cortex and the key role of dopamine in that. The work discussed here builds on that including: 1) Studies of children predicted to have lower levels of prefrontal dopamine but otherwise basically normal brains (children treated for phenylketonuria [PKU]). Those studies changed medical guidelines, improving the children’s lives. 2) Studies of visual impairments (in contrast sensitivity and motion perception) in PKU children due to reduced retinal dopamine and due to excessive phenylalanine during the first postnatal weeks. Those studies, too, changed medical guidelines. 3) Studies of working memory and inhibitory control differences in typically developing children due to differences in catechol-O-methyltransferase (COMT) genotype, which selectively affect prefrontal dopamine levels. 4) Studies of gender differences in the effect of COMT genotype on cognitive performance in older adults. 5) A hypothesis about fundamental differences between attention deficit hyperactivity disorder (ADHD) that includes hyperactivity and ADHD of the inattentive type. Those disorders are hypothesized to differ in the affected neural system, underlying genetics, responsiveness to medication, comorbidities, and cognitive and behavioral profiles. These sound quite disparate but they all grew systematically out the base laid down by Patricia Goldman-Rakic. PMID:17725999

Long-term safety and efficacy of sapropterin: the PKUDOS registry experience.

PubMed

Longo, Nicola; Arnold, Georgianne L; Pridjian, Gabriella; Enns, Gregory M; Ficicioglu, Can; Parker, Susan; Cohen-Pfeffer, Jessica L

2015-04-01

The Phenylketonuria (PKU) Demographics, Outcomes and Safety (PKUDOS) registry is designed to provide longitudinal safety and efficacy data on subjects with PKU who are (or have been) treated with sapropterin dihydrochloride. The PKUDOS population consists of 1189 subjects with PKU: N = 504 who were continuously exposed to sapropterin from date of registry enrollment, N = 211 who had intermittent exposure to the drug, and N = 474 with some other duration of exposure. Subjects continuously exposed to sapropterin showed an average 34% decrease in blood phenylalanine (Phe)--from 591 ± 382 μmol/L at baseline to 392 ± 239 μmol/L (p = 0.0009) after 5 years. This drop in blood Phe was associated with an increase in dietary Phe tolerance [from 1000 ± 959 mg/day (pre-sapropterin baseline) to 1539 ± 840 mg/day after 6 years]. Drug-related adverse events (AEs) were reported in 6% of subjects, were mostly considered non-serious, and were identified in the gastrointestinal, respiratory, and nervous systems. Serious drug-related AEs were reported in ≤ 1% of subjects. Similar safety and efficacy data were observed for children<4 years. Long-term data from the PKUDOS registry suggest that sapropterin has a tolerable safety profile and that continuous use is associated with a significant and persistent decrease in blood Phe and improvements in dietary Phe tolerance. Copyright © 2015. Published by Elsevier Inc.

Turbulence experiments on the PKU Plasma Test (PPT) device

NASA Astrophysics Data System (ADS)

Xu, Tianchao; Xiao, Chijie; Yang, Xiaoyi; Chen, Yihang; Yu, Yi; Xu, Min; Wang, Long; Lin, Chen; Wang, Xiaogang

2017-10-01

The PKU Plasma Test (PPT) device is a linear plasma device in Peking University, China. It has a vacuum chamber with 1000mm length and 500mm diameter. A pair of Helmholtz coils can generate toroidal magnetic field up to 2000 Gauss, and plasma was generated by a helicon source. Probes and fast camera were used to diagnose the parameters and got the turbulence spectrums, coherent structure, etc. The dynamics of turbulence, coherent structure and parameter profiles have been analyzed, and it has been found that the turbulence states are related to the equilibrium profiles; Some coherent structures exist and show strongly interactions with the background turbulences; The spatial and temporal evolutions of these coherent structures are related to the amplitude of the density gradient and electric field. These results will help on further studies of plasma transport. This work was supported by the National Natural Science Foundation of China under 11575014 and 11375053, CHINA MOST under 2012YQ030142 and ITER-CHINA program 2015GB120001.

Molecular basis of mild hyperphenylalaninaemia in Poland.

PubMed Central

Zekanowski, C; Nowacka, M; Cabalska, B; Bal, J

1997-01-01

The major cause of the different forms of hyperphenylalaninaemia (HPA) is mutations in the gene encoding phenylalanine hydroxylase (PAH). The aim of this study was to determine the mutations responsible for mild forms of HPA and to relate different clinical phenotypes of HPA patients to their PAH genotypes. Four "mild" mutations, including the most frequent A403V and R297H mutations, occurred exclusively in mild hyperphenylalaninaemia (MHP). Mutations A104D, R243Q, R241H, and Y414C were detected in patients with mild phenylketonuria (mild PKU) only. These results may be useful in establishing a molecular differential diagnosis for PAH deficiency in Poland. PMID:9429153

The use of parenteral nutrition for the management of PKU patient undergoing chemotherapy for lymphoma: a case report.

PubMed

Salvarinova-Zivkovic, R; Hartnett, C; Sinclair, G; Dix, D; Horvath, G; Lillquist, Y; Stockler-Ipsiroglu, S

2012-04-01

The metabolic control of phenylalanine levels is a challenge during illness. We present the metabolic management of a 6 year old boy with classical PKU who was diagnosed with stage III intraabdominal Burkit's lymphoma and underwent surgical resection and chemotherapy. The metabolic control during chemotherapy was achieved by the use of parenteral custom made amino acid solution and pro-active adjustment of intake. From the 94 obtained plasma phenylalanine (Phe) levels, 18.4% were above our clinic's recommended upper limit (360 μmol/L, 6 mg/dL) while 52.7% of Phe levels were below the recommended lower limit (120 μmol/L, 2 mg/dL). Phe levels above recommended range were associated with low caloric/protein intake, while levels below recommended range reflected the difficulty in achieving the full prescribed Phe intake. We recommend early institution of custom made amino acid solution with maximum amino acid content and caloric intake to provide optimal phenylalanine control. Administration of phenylalanine via regular intravenous amino acid solution may assist in avoiding low Phe levels when prescribed intake is compromised due to vomiting and other disease related illnesses. Use of custom made, phenylalanine free amino acid solution proved beneficial in the management of blood phenylalanine levels in a PKU patient during chemotherapy for Burkitt lymphoma. Copyright © 2012 Elsevier Inc. All rights reserved.

Plasma phenylalanine and tyrosine responses to different nutritional conditions (fasting/postprandial) in patients with phenylketonuria: effect of sample timing.

PubMed

van Spronsen, F J; van Rijn, M; van Dijk, T; Smit, G P; Reijngoud, D J; Berger, R; Heymans, H S

1993-10-01

To evaluate the adequacy of dietary treatment in patients with phenylketonuria, the monitoring of plasma phenylalanine and tyrosine concentrations is of great importance. The preferable time of blood sampling in relation to the nutritional condition during the day, however, is not known. It was the aim of this study to define guidelines for the timing of blood sampling with a minimal burden for the patient. Plasma concentrations of phenylalanine and tyrosine were measured in nine patients with phenylketonuria who had no clinical evidence of tyrosine deficiency. These values were measured during the day both after a prolonged overnight fast, and before and after breakfast. Phenylalanine showed a small rise during prolonged fasting, while tyrosine decreased slightly. After an individually tailored breakfast, phenylalanine remained stable, while tyrosine showed large fluctuations. It is concluded that the patient's nutritional condition (fasting/postprandial) is not important in the evaluation of the phenylalanine intake. To detect a possible tyrosine deficiency, however, a single blood sample is not sufficient and a combination of a preprandial and postprandial blood sample on the same day is advocated.

Neuropsychological assessment among children and adolescents with phenylketonuria and hyperphenylalaninemia and its relationship with plasma phenylalanine levels.

PubMed

González García, María B; Conde-Guzon, Pablo; Alcalde Martín, Carlos; Conde-Guzon, María J; Velasco Zúñiga, Roberto

2017-06-01

Although with early treatment phenylketonuria patients may have average intelligence levels, it is important to optimize the nutritional management to maintain adequate phenylalanine levels, so that patients can develop their intellectal potential free of abnormalities in their daily activities due to deficits of cognitive executive functions. This study presents a series of 26 patients, diagnosed and treated early, who underwent a psychometric evaluation together with phenylalanine determinations along their lives, and at the time of doing the tests. A trend is observed towards a reverse relationship between IQ and concurrent phenylalanine concentration, phenylalanine median and phenylalanine/tyrosine ratio. Likewise, a trend towards a negative relationship is observed between executive functions and concurrent phenylalanine values along patients' lives. Sociedad Argentina de Pediatría.

A mutation analysis of the phenylalanine hydroxylase (PAH) gene in the Israeli population.

PubMed

Bercovich, D; Elimelech, A; Yardeni, T; Korem, S; Zlotogora, J; Gal, N; Goldstein, N; Vilensky, B; Segev, R; Avraham, S; Loewenthal, R; Schwartz, G; Anikster, Y

2008-05-01

Hyperphenylalaninemia (HPA) is a group of diseases characterized by a persistent elevation of phenylalanine levels in tissues and biological fluids. The most frequent form is phenylalanine hydroxylase deficiency, causing phenylketonuria (PKU). Among 159 Israeli patients (Jews, Muslim and Christian Arabs and Druze) with HPA, in whom at least one of the mutations was characterized, a total of 43 different mutations were detected, including seven novel ones. PKU was very rare among Ashkenazi Jews and relatively frequent among Jews from Yemen, the Caucasian Mountains, Bukhara and Tunisia. The mutations responsible for the high frequency were: exon3del (Yemenite Jews), L48S (Tunisian Jews) and E178G, P281L and L48S (Jews from the Caucasian Mountains and Bukhara). Among the non-Jewish Israeli citizens, the disease was relatively frequent in the Negev and in the Nazareth vicinity, and in many localities a unique mutation was detected, often in a single family. While marked genetic heterogeneity was observed in the Arab and Jewish populations, only one mutation A300S, was frequent in all of the communities. Several of the other frequent mutations were shared by the non-Ashkenazi Jews and Arabs; none were mutual to Ashkenazi Jews and Arabs.

Child and Parent Attributions in Chronic Pediatric Conditions: Phenylketonuria (PKU) as an Exemplar

ERIC Educational Resources Information Center

Antshel, Kevin M.; Brewster, Scott; Waisbren, Susan E.

2004-01-01

Background: Attribution theory, self-regulation, self-handicapping and sick role theories all suggest that children with chronic disease may be held to different standards. This study assesses child and parent attributions in pediatric chronic health conditions and addresses how attributional style may be related to treatment adherence. Methods:…

Elevated phenylalanine on newborn screening: follow-up testing may reveal undiagnosed galactosaemia.

PubMed

Shakespeare, Lynette; Downing, Melanie; Allen, Joyce; Casbolt, Ann-Marie; Ellin, Sheila; Maloney, Martin; Race, Gillian; Bonham, Jim

2010-11-01

Introduction Newborn screening for phenylketonuria (PKU) can reveal other conditions which lead to an increased blood spot phenylalanine (Phe) concentration. We have investigated the proportion of blood spot samples that gave a positive screen due to clinically significant conditions other than PKU, compared the positive predictive value (PPV) of our referral Phe cut-off with that recommended by the UK Newborn Screening Programme Centre (UKNSPC) (>210 and >240 μmol/L, respectively) and evaluated the effectiveness of reflex testing for galactosaemia using a lower blood spot Phe cut-off concentration of 130 μmol/L. All blood spot samples that screened positive, for an increased Phe concentration, between April 2001 and March 2008, were identified from the records of the Sheffield Newborn Screening Laboratory and the diagnoses noted. In addition, all cases of galactosaemia detected in or notified to our screening laboratory within this time were also examined and the screened Phe concentrations compared. Out of 438,674 babies who were screened, 67 had Phe concentration >210 μmol/L (15 per 100,000). Of these, 40 had PKU or persistent hyperphenylalaninaemia with a Phe concentration identified by screening between 270 and 2350 μmol/L. A further 11 were diagnosed with another clinically significant disorder: galactosaemia (n = 8), biopterin defects (n = 2), tyrosinaemia Type 1 (n = 1). In addition, 16 had transient elevations in Phe. In total, nine cases of galactosaemia were identified, of whom, three had Phe concentrations <240 μmol/L with one asymptomatic individual having a concentration <210 μmol/L. Adoption of the UKNSPC recommended cut-off (>240 μmol/L) will not affect the detection rate of classical PKU, but will improve the PPV from 76% to 80%. The use of a lower cut-off (130 μmol/L) for reflex galactosaemia testing enables the timely identification of asymptomatic cases that benefit particularly from early treatment, without prompting any unnecessary

Use of an Amino Acid Mixture in Treatment of Phenylketonuria

PubMed Central

Bentovim, A.; Clayton, Barbara E.; Francis, Dorothy E. M.; Shepherd, Jean; Wolff, O. H.

1970-01-01

Twelve children with phenylketonuria diagnosed and treated from the first few weeks of life were grouped into pairs. Before the trial all of them were receiving a commercial preparation containing a protein hydrolysate low in phenylalanine (Cymogran, Allen and Hanburys Ltd.) as a substitute for natural protein. One of each pair was given an amino acid mixture instead of Cymogran for about 6 months. Use of the mixture involved considerable modification of the diet, and in particular the inclusion of greater amounts of phenylalanine-free foods. All six accepted the new mixture without difficulty, food problems were greatly reduced, parents welcomed the new preparation, and the quality of family life improved. Normal growth was maintained and with a mixture of l amino acids the plasma and urinary amino acid levels were normal. Further studies are needed before the mixture can be recommended for children under 20 months of age. PMID:5477678

Screening Out Controversy: Human Genetics, Emerging Techniques of Diagnosis, and the Origins of the Social Issues Committee of the American Society of Human Genetics, 1964-1973.

PubMed

Mitchell, M X

2017-05-01

In the years following World War II, and increasingly during the 1960s and 1970s, professional scientific societies developed internal sub-committees to address the social implications of their scientific expertise (Moore, Disrupting Science: Social Movements, American Scientists, and the Politics of the Military, 1945-1975. Princeton: Princeton University Press, 2008). This article explores the early years of one such committee, the American Society of Human Genetics' "Social Issues Committee," founded in 1967. Although the committee's name might suggest it was founded to increase the ASHG's public and policy engagement, exploration of the committee's early years reveals a more complicated reality. Affronted by legislators' recent unwillingness to seek the expert advice of human geneticists before adopting widespread neonatal screening programs for phenylketonuria (PKU), and feeling pressed to establish their relevance in an increasingly resource-scarce funding environment, committee members sought to increase the discipline's expert authority. Painfully aware of controversy over abortion rights and haunted by the taint of the discipline's eugenic past, however, the committee proceeded with great caution. Seeking to harness interest in and assert professional control over emerging techniques of genetic diagnosis, the committee strove to protect the society's image by relegating ethical and policy questions about their use to the individual consciences of member scientists. It was not until 1973, after the committee's modest success in organizing support for a retrospective public health study of PKU screening and following the legalization of abortion on demand, that the committee decided to take a more publicly engaged stance.

Sapropterin: a review of its use in the treatment of primary hyperphenylalaninaemia.

PubMed

Sanford, Mark; Keating, Gillian M

2009-01-01

Sapropterin dihydrochloride (Kuvan), hereafter referred to as sapropterin, is a synthetic formulation of the active 6R-isomer of tetrahydrobiopterin, a naturally occurring cofactor for phenylalanine hydroxylase. In the EU, sapropterin is approved for the treatment of hyperphenylalaninaemia in patients >or=4 years of age with tetrahydrobiopterin-responsive phenylketonuria (PKU) and in adults and children with tetrahydrobiopterin deficiency who have been shown to be responsive to such treatment. In the US, it is approved to reduce blood phenylalanine levels in patients with hyperphenylalaninaemia due to tetrahydrobiopterin-responsive PKU. Oral sapropterin effectively lowers blood phenylalanine levels in a proportion of patients with PKU; to date, there are no published efficacy trials of the specific sapropterin formulation under review in patients with tetrahydrobiopterin deficiency. Sapropterin was well tolerated in patients with PKU, although longer-term tolerability data are required. Sapropterin is the first non-dietary treatment for patients with PKU that has been shown in randomized, double-blind trials to be effective in lowering blood phenylalanine levels. Thus, sapropterin provides a promising treatment option for patients with PKU who are tetrahydrobiopterin-responsive. PHARMACOLOGICAL PROPERTIES: The mechanism of action of sapropterin in lowering blood phenylalanine levels in patients with PKU has not been fully elucidated, but appears to be related, in part, to its effect in augmenting and stabilizing mutant phenylalanine hydroxylases, resulting in increased clearance of phenylalanine from the body. In tetrahydrobiopterin deficiency, its mechanism of action is presumed to be secondary to replacement of endogenous tetrahydrobiopterin. In healthy adults, orally-administered sapropterin is absorbed into the bloodstream, reaching maximum concentrations in 3-4 hours. It has a mean elimination half-life of approximately 4 hours in healthy adults and, based on

How Darwinian reductionism refutes genetic determinism.

PubMed

Rosoff, Philip M; Rosenberg, Alex

2006-03-01

Genetic determinism labels the morally problematical claim that some socially significant traits, traits we care about, such as sexual orientation, gender roles, violence, alcoholism, mental illness, intelligence, are largely the results of the operation of genes and not much alterable by environment, learning or other human intervention. Genetic determinism does not require that genes literally fix these socially significant traits, but rather that they constrain them within narrow channels beyond human intervention. In this essay we analyze genetic determinism in light of what is now known about the inborn error of metabolism phenylketonuria (PKU), which has for so long been the poster child 'simple' argument in favor of some form of genetic determinism. We demonstrate that this case proves the exact opposite of what it has been proposed to support and provides a strong refutation of genetic determinism in all its guises.

An Economic Evaluation of Neonatal Screening for Inborn Errors of Metabolism Using Tandem Mass Spectrometry in Thailand.

PubMed

Thiboonboon, Kittiphong; Leelahavarong, Pattara; Wattanasirichaigoon, Duangrurdee; Vatanavicharn, Nithiwat; Wasant, Pornswan; Shotelersuk, Vorasuk; Pangkanon, Suthipong; Kuptanon, Chulaluck; Chaisomchit, Sumonta; Teerawattananon, Yot

2015-01-01

Inborn errors of metabolism (IEM) are a rare group of genetic diseases which can lead to several serious long-term complications in newborns. In order to address these issues as early as possible, a process called tandem mass spectrometry (MS/MS) can be used as it allows for rapid and simultaneous detection of the diseases. This analysis was performed to determine whether newborn screening by MS/MS is cost-effective in Thailand. A cost-utility analysis comprising a decision-tree and Markov model was used to estimate the cost in Thai baht (THB) and health outcomes in life-years (LYs) and quality-adjusted life year (QALYs) presented as an incremental cost-effectiveness ratio (ICER). The results were also adjusted to international dollars (I$) using purchasing power parities (PPP) (1 I$ = 17.79 THB for the year 2013). The comparisons were between 1) an expanded neonatal screening programme using MS/MS screening for six prioritised diseases: phenylketonuria (PKU); isovaleric acidemia (IVA); methylmalonic acidemia (MMA); propionic acidemia (PA); maple syrup urine disease (MSUD); and multiple carboxylase deficiency (MCD); and 2) the current practice that is existing PKU screening. A comparison of the outcome and cost of treatment before and after clinical presentations were also analysed to illustrate the potential benefit of early treatment for affected children. A budget impact analysis was conducted to illustrate the cost of implementing the programme for 10 years. The ICER of neonatal screening using MS/MS amounted to 1,043,331 THB per QALY gained (58,647 I$ per QALY gained). The potential benefits of early detection compared with late detection yielded significant results for PKU, IVA, MSUD, and MCD patients. The budget impact analysis indicated that the implementation cost of the programme was expected at approximately 2,700 million THB (152 million I$) over 10 years. At the current ceiling threshold, neonatal screening using MS/MS in the Thai context is not cost

An Economic Evaluation of Neonatal Screening for Inborn Errors of Metabolism Using Tandem Mass Spectrometry in Thailand

PubMed Central

Thiboonboon, Kittiphong; Leelahavarong, Pattara; Wattanasirichaigoon, Duangrurdee; Vatanavicharn, Nithiwat; Wasant, Pornswan; Shotelersuk, Vorasuk; Pangkanon, Suthipong; Kuptanon, Chulaluck; Chaisomchit, Sumonta; Teerawattananon, Yot

2015-01-01

Background Inborn errors of metabolism (IEM) are a rare group of genetic diseases which can lead to several serious long-term complications in newborns. In order to address these issues as early as possible, a process called tandem mass spectrometry (MS/MS) can be used as it allows for rapid and simultaneous detection of the diseases. This analysis was performed to determine whether newborn screening by MS/MS is cost-effective in Thailand. Method A cost-utility analysis comprising a decision-tree and Markov model was used to estimate the cost in Thai baht (THB) and health outcomes in life-years (LYs) and quality-adjusted life year (QALYs) presented as an incremental cost-effectiveness ratio (ICER). The results were also adjusted to international dollars (I$) using purchasing power parities (PPP) (1 I$ = 17.79 THB for the year 2013). The comparisons were between 1) an expanded neonatal screening programme using MS/MS screening for six prioritised diseases: phenylketonuria (PKU); isovaleric acidemia (IVA); methylmalonic acidemia (MMA); propionic acidemia (PA); maple syrup urine disease (MSUD); and multiple carboxylase deficiency (MCD); and 2) the current practice that is existing PKU screening. A comparison of the outcome and cost of treatment before and after clinical presentations were also analysed to illustrate the potential benefit of early treatment for affected children. A budget impact analysis was conducted to illustrate the cost of implementing the programme for 10 years. Results The ICER of neonatal screening using MS/MS amounted to 1,043,331 THB per QALY gained (58,647 I$ per QALY gained). The potential benefits of early detection compared with late detection yielded significant results for PKU, IVA, MSUD, and MCD patients. The budget impact analysis indicated that the implementation cost of the programme was expected at approximately 2,700 million THB (152 million I$) over 10 years. Conclusion At the current ceiling threshold, neonatal screening using MS

Relationships between phenylalanine levels, intelligence and socioeconomic status of patients with phenylketonuria.

PubMed

Castro, Isabel Pimenta Spínola; Borges, Juliana Martins; Chagas, Heloísa Alves; Tibúrcio, Jacqueline; Starling, Ana Lúcia Pimenta; Aguiar, Marcos José Burle de

2012-07-01

To assess intelligence and its relationship with blood phenylalanine concentrations and socioeconomic status in patients with phenylketonuria after 6 to 12 years of treatment. Sixty-three children were classified according to phenylalanine levels and socioeconomic status and assessed using the Wechsler Intelligence Scale for Children. The Statistical Package for the Social Sciences (SPSS) was used to analyze phenylalanine; ANOVA was used to analyze intelligence quotients (IQ) and phenylalanine levels; and ordinal logistic regression was used to analyze the likelihood of higher IQ. The overall IQ scores of 90.5% of the children were within a range from borderline intellectual deficiency to very high intelligence; for verbal IQ this proportion was 96.8% and 92.1% had performance IQ scores within this band. The categories from low to upper-medium socioeconomic status contained 98.4% of patients' families. The likelihood of having medium to high IQ was 4.29 times greater for children with good phenylalanine control and 4.03 greater for those from higher socioeconomic strata. Treatment prevented mental retardation in 90.5% of the patients. Control of phenylalanine levels and higher socioeconomic status were associated with higher IQ scores.

A framework for assessing outcomes from newborn screening: on the road to measuring its promise

PubMed Central

Hinton, Cynthia F.; Homer, Charles J.; Thompson, Alexis A.; Williams, Andrea; Hassell, Kathryn L.; Feuchtbaum, Lisa; Berry, Susan A.; Comeau, Anne Marie; Therrell, Bradford L.; Brower, Amy; Harris, Katharine B.; Brown, Christine; Monaco, Jana; Ostrander, Robert J.; Zuckerman, Alan E.; Kaye, Celia; Dougherty, Denise; Greene, Carol; Green, Nancy S.

2016-01-01

Newborn screening (NBS) is intended to identify congenital conditions prior to the onset of symptoms in order to provide early intervention that leads to improved outcomes. NBS is a public health success, providing reduction in mortality and improved developmental outcomes for screened conditions.. However, it is less clear to what extent newborn screening achieves the long-term goals relating to improved health, growth, development and function. We propose a framework for assessing outcomes for the health and well-being of children identified through NBS programs. The framework proposed here, and this manuscript, were approved for publication by the Secretary of Health and Human Services’ Advisory Committee on Heritable Disorders in Newborns and Children (ACHDNC). This framework can be applied to each screened condition within the Recommended Uniform Screening Panel (RUSP), recognizing that the data elements and measures will vary by condition. As an example, we applied the framework to sickle cell disease and phenylketonuria (PKU), two diverse conditions with different outcome measures and potential sources of data. Widespread and consistent application of this framework across state NBS and child health systems is envisioned as useful to standardize approaches to assessment of outcomes and for continuous improvement of the NBS and child health systems. PMID:27268406

Nano-Calorimetry based point of care biosensor for metabolic disease management.

PubMed

Kazura, Evan; Lubbers, Brad R; Dawson, Elliott; Phillips, John A; Baudenbacher, Franz

2017-09-01

Point of care (POC) diagnostics represents one of the fastest growing health care technology segments. Developments in microfabrication have led to the development of highly-sensitive nanocalorimeters ideal for directly measuring heat generated in POC biosensors. Here we present a novel nano-calorimeter-based biosensor design with differential sensing to eliminate common mode noise and capillary microfluidic channels for sample delivery to the thermoelectric sensor. The calorimeter has a resolution of 1.4 ± 0.2 nJ/(Hz) 1/2 utilizing a 27 junction bismuth/titanium thermopile, with a total Seebeck coefficient of 2160 μV/K. Sample is wicked to the calorimeter through a capillary channel making it suitable for monitoring blood obtained through a finger prick (<1 μL sample required). We demonstrate device performance in a model assay using catalase, achieving a threshold for hydrogen peroxide quantification of 50 μM. The potential for our device as a POC blood test for metabolic diseases is shown through the quantification of phenylalanine (Phe) in serum, an unmet necessary service in the management of Phenylketonuria (PKU). Pegylated phenylalanine ammonia-lyase (PEG-PAL) was utilized to react with Phe, but reliable detection was limited to <5 mM due to low enzymatic activity. The POC biosensor concept can be multiplexed and adapted to a large number of metabolic diseases utilizing different immobilized enzymes.

Web-based newborn screening system for metabolic diseases: machine learning versus clinicians.

PubMed

Chen, Wei-Hsin; Hsieh, Sheau-Ling; Hsu, Kai-Ping; Chen, Han-Ping; Su, Xing-Yu; Tseng, Yi-Ju; Chien, Yin-Hsiu; Hwu, Wuh-Liang; Lai, Feipei

2013-05-23

A hospital information system (HIS) that integrates screening data and interpretation of the data is routinely requested by hospitals and parents. However, the accuracy of disease classification may be low because of the disease characteristics and the analytes used for classification. The objective of this study is to describe a system that enhanced the neonatal screening system of the Newborn Screening Center at the National Taiwan University Hospital. The system was designed and deployed according to a service-oriented architecture (SOA) framework under the Web services .NET environment. The system consists of sample collection, testing, diagnosis, evaluation, treatment, and follow-up services among collaborating hospitals. To improve the accuracy of newborn screening, machine learning and optimal feature selection mechanisms were investigated for screening newborns for inborn errors of metabolism. The framework of the Newborn Screening Hospital Information System (NSHIS) used the embedded Health Level Seven (HL7) standards for data exchanges among heterogeneous platforms integrated by Web services in the C# language. In this study, machine learning classification was used to predict phenylketonuria (PKU), hypermethioninemia, and 3-methylcrotonyl-CoA-carboxylase (3-MCC) deficiency. The classification methods used 347,312 newborn dried blood samples collected at the Center between 2006 and 2011. Of these, 220 newborns had values over the diagnostic cutoffs (positive cases) and 1557 had values that were over the screening cutoffs but did not meet the diagnostic cutoffs (suspected cases). The original 35 analytes and the manifested features were ranked based on F score, then combinations of the top 20 ranked features were selected as input features to support vector machine (SVM) classifiers to obtain optimal feature sets. These feature sets were tested using 5-fold cross-validation and optimal models were generated. The datasets collected in year 2011 were used as

Web-Based Newborn Screening System for Metabolic Diseases: Machine Learning Versus Clinicians

PubMed Central

Chen, Wei-Hsin; Hsu, Kai-Ping; Chen, Han-Ping; Su, Xing-Yu; Tseng, Yi-Ju; Chien, Yin-Hsiu; Hwu, Wuh-Liang; Lai, Feipei

2013-01-01

Background A hospital information system (HIS) that integrates screening data and interpretation of the data is routinely requested by hospitals and parents. However, the accuracy of disease classification may be low because of the disease characteristics and the analytes used for classification. Objective The objective of this study is to describe a system that enhanced the neonatal screening system of the Newborn Screening Center at the National Taiwan University Hospital. The system was designed and deployed according to a service-oriented architecture (SOA) framework under the Web services .NET environment. The system consists of sample collection, testing, diagnosis, evaluation, treatment, and follow-up services among collaborating hospitals. To improve the accuracy of newborn screening, machine learning and optimal feature selection mechanisms were investigated for screening newborns for inborn errors of metabolism. Methods The framework of the Newborn Screening Hospital Information System (NSHIS) used the embedded Health Level Seven (HL7) standards for data exchanges among heterogeneous platforms integrated by Web services in the C# language. In this study, machine learning classification was used to predict phenylketonuria (PKU), hypermethioninemia, and 3-methylcrotonyl-CoA-carboxylase (3-MCC) deficiency. The classification methods used 347,312 newborn dried blood samples collected at the Center between 2006 and 2011. Of these, 220 newborns had values over the diagnostic cutoffs (positive cases) and 1557 had values that were over the screening cutoffs but did not meet the diagnostic cutoffs (suspected cases). The original 35 analytes and the manifested features were ranked based on F score, then combinations of the top 20 ranked features were selected as input features to support vector machine (SVM) classifiers to obtain optimal feature sets. These feature sets were tested using 5-fold cross-validation and optimal models were generated. The datasets

[Evaluation of the usefulness for neonatal mass screening in light of 35 years personal experience].

PubMed

Bozkowa, K; Cabalska, B; Radomyska, B; Ołtarzewski, M; Lenartowska, I

1999-01-01

The results and the significance of neonatal mass-screening programmes for inborn errors of metabolism, conducted by the National Research Institute of Mother and Child (NRIMC), are discussed. As the first in Poland, in 1964, mass-screening for phenylketonuria (PKU) was introduced. The BIA-Guthrie test was used. Other Guthrie tests (GBIA) were applied in homocystinuria, tyrosinemia, histidinemia and leucinosis (Maple Syrup Urine Disease-MSUD). In the middle of the 60. the Beutler and Baluda test was introduced for galactosaemia, as well as the Efron urine test in infant screening for different inborn errors of metabolism. In the middle of the 70., neonatal mass-screening for cystic fibrosis (CF, mucoviscidosis) was started. Meconium tests and the sweat test with ion selective chloride electrode were used. Apart from inborn errors of metabolism, we also introduced a screening programme for neuroblastoma in which vaniline mandelic acid (VMA) in urine was estimated and for congenital hypothyroidism were TSH level was assessed. The results of screening are shown in the tables and in the figures. In our opinion the best clinical results are obtained with screening for congenital hypothyroidism and for PKU, since very early detection and treatment in these diseases prevents severe mental retardation. We therefore consider that both these screening programmes should be treated as obligatory examinations in all neonates. Taking into consideration the fact that there are different types of hyperhenylalaninemias, the principles of differential diagnosis are discussed. Molecular genetic investigations, carried out in the NRIMC Department of Genetics proved to be a very important procedure in the verification of diagnosis of different mutations. The authors also discuss the problem of dietary treatment duration in PKU. In our opinion the hypophenyloalanine diet regimen in girls, should not be discontinued during adolescence, since there is the problem of maternal PKU and the

Beyond Hydrophobicity: Aqueous Interfaces, Interactions, and Reactions

NASA Astrophysics Data System (ADS)

Perkins, Russell James

Many important chemical reactions from all branches of chemistry occur with water as a solvent. Furthermore, in environmental chemistry, biochemistry, and synthetic chemistry, key reactions occur in heterogeneous aqueous systems, where interfacial effects are particularly important. Despite the importance of aqueous environments and the tremendous amount of work done to study them, there are aspects that require further explanation and remain controversial. I have performed experimental studies to help elucidate the fundamental characteristics of aqueous systems, while examining specific phenomena across several fields. The genetic disorder phenylketonuria (PKU) can result in increased levels of the aromatic amino acid phenylalanine in human serum. Much of my work has focused on the driving forces behind partitioning of aromatic small molecules, including phenylalanine, into air-water or membrane-water interfacial regions, and the consequences of partitioning on interfacial properties. Drastically different behaviors for structurally similar aromatic molecules are observed, differences that cannot be explained by hydrophobic effects. These observations can be explained, however, through the development of a more detailed picture of interactions and partitioning, including the formation of interfacial aggregates. For phenylalanine, this partitioning appears to result in drastic changes in membrane morphology and permeability. This is a likely molecular-level cause for the damage associated with the disease state of PKU. Aqueous systems are further complicated by the reactivity of water. It often serves not only the role of a solvent, but also a reactant, a product, and/or a catalyst. I explore this reactivity using an organic molecule with relevance to environmental chemistry, zymonic acid. Zymonic acid forms spontaneously from pyruvic acid, an important atmospheric species. While zymonic acid exists as a single species in solid form when dissolved in DMSO, once in

Investigation of Fibril Forming Mechanisms of l-Phenylalanine and l-Tyrosine: Microscopic Insight toward Phenylketonuria and Tyrosinemia Type II.

PubMed

Banik, Debasis; Kundu, Sangita; Banerjee, Pavel; Dutta, Rupam; Sarkar, Nilmoni

2017-02-23

Phenylketonuria and tyrosinemia type II, the two metabolic disorders, are originated due to the complications in metabolism of phenylalanine (Phe) and tyrosine (Tyr), respectively. Several neurological injuries, involving microcephaly, mental retardation, epilepsy, motor disease, and skin problems etc., are the symptoms of these two diseases. It has been reported that toxic amyloid fibrils are formed at high concentrations of Phe and Tyr. Our study indicates that the fibril forming mechanisms of Phe and Tyr are completely different. In the case of Phe, -NH 3 + and -COO - groups of neighboring molecules interact via hydrogen bonding and polar interactions. On the other hand, there is no role of - NH 3 + group in the fibril forming mechanism of Tyr. In Tyr fibril, the two hydrogen bonding partners are -OH and -COO - groups. In addition, we have also investigated the effect of three lanthanide cations on the fibrillar assemblies of Phe. It has been observed that the efficiencies of three lanthanides to inhibit the fibrillar assemblies of Phe follow the order Tb 3+ < Sm 3+ < Eu 3+ .

Phenylalanine tolerance can already reliably be assessed at the age of 2 years in patients with PKU.

PubMed

van Spronsen, F J; van Rijn, M; Dorgelo, B; Hoeksma, M; Bosch, A M; Mulder, M F; de Klerk, J B C; de Koning, T; Rubio-Gozalbo, M Estela; de Vries, M; Verkerk, P H

2009-02-01

The clinical severity of phenylalanine hydroxylase deficiency is usually defined by either pre-treatment phenylalanine (Phe) concentration or Phe tolerance at 5 years of age. So far, little is known about the course of Phe tolerance or the ability of both pre-treatment Phe and Phe tolerance at early age to predict Phe tolerance at later age. This study was conducted to investigate the course of the individual Phe tolerance and to assess the predictive value of both the pre-treatment Phe concentration and Phe tolerance at 1 and 6 months and 1, 2, 3 and 5 years for Phe tolerance at 10 years of age. Data on blood Phe concentration, prescribed Phe intake and weight of 213 early and continuously treated Dutch PKU patients up to 10 years of age were collected. Data acquired under good metabolic control were used in the study. Tolerance was expressed in mg/day and mg/kg per day. Data at 1 and 6 months and at 1, 2, 3 and 5 years of 61, 58, 59, 57, 56 and 59 patients were included for comparison with the Phe tolerance at 10 years. Phe tolerances (mg/kg per day) at 2, 3 and 5 years showed a clear correlation with the tolerance at 10 years of age (r = 0.608, r = 0.725 and r = 0.661). Results for tolerance expressed as mg/day were comparable. Pre-treatment Phe concentrations did not correlate significantly with the tolerance. Pre-treatment Phe is unreliable but Phe tolerance is a reliable predictor of the tolerance at 10 years of age, starting at 2 years of age.

6R-tetrahydrobiopterin treated PKU patients below 4 years of age: Physical outcomes, nutrition and genotype.

PubMed

Aldámiz-Echevarría, Luis; Bueno, María A; Couce, María L; Lage, Sergio; Dalmau, Jaime; Vitoria, Isidro; Llarena, Marta; Andrade, Fernando; Blasco, Javier; Alcalde, Carlos; Gil, David; García, María C; González-Lamuño, Domingo; Ruiz, Mónica; Ruiz, María A; Peña-Quintana, Luis; González, David; Sánchez-Valverde, Felix

2015-05-01

Phenylalanine-restricted diets have proven effective in treating phenylketonuria. However, such diets have occasionally been reported to hinder normal development. Our study aimed to assess whether treating 0-4-year-old phenylketonuric patients with 6R-tetrahydrobiopterin might prevent growth retardation later in life. We conducted a longitudinal retrospective study which examined anthropometric characteristics of phenylketonuric patients on 6R-tetrahydrobiopterin therapy (22 subjects), and compared them with a group of phenylketonuric patients on protein-restricted diets (44 subjects). Nutritional issues were also considered. We further explored possible relationships between mutations in the PAH gene, BH4 responsiveness and growth outcome. No significant growth improvements were observed in either the group on 6R-tetrahydrobiopterin treatment (height Z-score: initial= -0.57 ± 1.54; final=-0.52 ± 1.29; BMI Z-score: initial=0.17 ± 1.05; final=0.18 ± 1.00) or the diet-only group (height Z-score: initial=-0.92 ± 0.96; final= -0.78 ± 1.08; BMI Z-score: initial=0.17 ± 0.97; final=-0.07 ± 1.03) over the 1-year observation period. Furthermore, we found no significant differences (p>0.05) between the two groups at any of the time points considered (0, 6 and 12 months). Patients on 6R-tetrahydrobiopterin increased their phenylalanine intake (from 49.1 [25.6-60.3] to 56.5 [39.8-68.3] mgkg(-1)day(-1)) and natural protein intake (from 1.0 [0.8-1.7] to 1.5 [1.0-1.8] g kg(-1)day(-1)), and some patients managed to adopt normal diets. Higher phenylalanine and natural protein intakes were positively correlated with better physical outcomes in the diet-only group (p<0.05). No correlation was found between patient genotype and physical outcomes, results being similar regardless of the nutritional approach used. We did not detect any side effects due to 6R-tetrahydrobiopterin administration. Our study indicates that treating 0-4-year-old phenylketonuric patients with 6R

Showing Value in Newborn Screening: Challenges in Quantifying the Effectiveness and Cost-Effectiveness of Early Detection of Phenylketonuria and Cystic Fibrosis

PubMed Central

Grosse, Scott D.

2015-01-01

Decision makers sometimes request information on the cost savings, cost-effectiveness, or cost-benefit of public health programs. In practice, quantifying the health and economic benefits of population-level screening programs such as newborn screening (NBS) is challenging. It requires that one specify the frequencies of health outcomes and events, such as hospitalizations, for a cohort of children with a given condition under two different scenarios—with or without NBS. Such analyses also assume that everything else, including treatments, is the same between groups. Lack of comparable data for representative screened and unscreened cohorts that are exposed to the same treatments following diagnosis can result in either under- or over-statement of differences. Accordingly, the benefits of early detection may be understated or overstated. This paper illustrates these common problems through a review of past economic evaluations of screening for two historically significant conditions, phenylketonuria and cystic fibrosis. In both examples qualitative judgments about the value of prompt identification and early treatment to an affected child were more influential than specific numerical estimates of lives or costs saved. PMID:26702401

Simultaneous determination of creatinine, creatine, and UV-absorbing amino acids using dual-mode gradient low-capacity cation-exchange chromatography.

PubMed

Yokoyama, Yukio; Tsuji, Sachiyo; Sato, Hisakuni

2005-08-26

A simple and versatile cation-exchange chromatography technique for the simultaneous determination of urinary creatinine (Cre), creatine (Crn), methionine (Met), tyrosine (Tyr), phenylalanine (Phe), histidine (His), and tryptophan (Trp) was developed. A novel low-capacity cation-exchange column packed with a newly developed sulfoacylated hypercross-linked macroreticular polystyrene-divinylbenzene resin, referred to as TMR-A/75 (capacity: 75 microequiv/column), was successfully used with a binary dual-mode gradient eluting system. Two solvents, (A) 25 mM phosphoric acid-methanol (30:70, v/v) and (B) 25 mM disodium hydrogenphosphate-methanol (30:70, v/v) were pumped through the column by programming solvent delivery ratios as 0 to 5 min: A-B (55:45, pH 3.6); 5-21 min: A-B (49:51, pH 5.3); and 21-35 min: A-B (55:45, pH 3.6). The flow rate was simultaneously time-programmed to be 0.6 mL/min from 0 to 19 min and to be 1.0 mL/min from 19 to 35 min. This eluting system could permit the use of the UV detection at 210 nm. The analytes, Crn, Met, Tyr, His, Cre, Phe, and Trp, were well separated in this order in 27 min with minimum resolution of approximately 2, and the cycle time was about 35 min. Retention time of each analyte was very reproducible with relative standard deviations (RSDs) between 0.05 and 0.38% (n = 5). The peak area responses were also reproducible with RSDs between 0.74 and 2.24% (n = 5). Calibration lines based on area data were linear from 1 to 1000 microM with r2 values of 0.9998 (Crn), 0.9998 (Met), 0.9999 (Tyr), 0.9999 (His), 1.0000 (Cre), 1.0000 (Phe), and 0.9999 (Trp). The method was applicable to the screening and/or chemical diagnosis of inherited metabolic disorders such as phenylketonuria (PKU), tyrosinemia, and Lowe syndrome. The creatinine ratios of diagnostic markers (microM/microM Cre) were easily determined. The Phe/Cre ratios for five urines from patients with PKU ranged from 0.162 to 0.521, and the Tyr/Cre ratio for tyrosinemia was 0

Nutritional Treatment for Inborn Errors of Metabolism: Indications, Regulations, and Availability of Medical Foods and Dietary Supplements Using Phenylketonuria as an Example

PubMed Central

Camp, Kathryn M.; Lloyd-Puryear, Michele A.; Huntington, Kathleen L.

2012-01-01

Medical foods and dietary supplements are used to treat rare inborn errors of metabolism (IEM) identified through state-based universal newborn screening. These products are regulated under Food and Drug Administration (FDA) food and dietary supplement statutes. The lack of harmony in terminology used to refer to medical foods and dietary supplements and the misuse of words that imply that FDA regulates these products as drugs have led to confusion. These products are expensive and, although they are used for medical treatment of IEM, third-party payer coverage of these products is inconsistent across the United States. Clinicians and families report termination of coverage in late adolescence, failure to cover treatment during pregnancy, coverage for select conditions only, or no coverage. We describe the indications for specific nutritional treatment products for IEM and their regulation, availability, and categorization. We conclude with a discussion of the problems that have contributed to the paradox of identifying individuals with IEM through newborn screening but not guaranteeing that they receive optimal treatment. Throughout the paper, we use the nutritional treatment of phenylketonuria as an example of IEM treatment. PMID:22854513

Genetic study of the PAH locus in the Iranian population: familial gene mutations and minihaplotypes.

PubMed

Razipour, Masoumeh; Alavinejad, Elaheh; Sajedi, Seyede Zahra; Talebi, Saeed; Entezam, Mona; Mohajer, Neda; Kazemi-Sefat, Golnaz-Ensieh; Gharesouran, Jalal; Setoodeh, Aria; Mohaddes Ardebili, Seyyed Mojtaba; Keramatipour, Mohammad

2017-10-01

Phenylketonuria (PKU), one of the most common inborn errors of amino acid metabolism, is caused by mutations in the phenylalanine hydroxylase (PAH) gene (PAH). PKU has wide allelic heterogeneity, and over 600 different disease-causing mutations in PAH have been detected to date. Up to now, there have been no reports on the minihaplotype (VNTR/STR) analysis of PAH locus in the Iranian population. The aims of the present study were to determine PAH mutations and minihaplotypes in Iranian families with PAH deficiency and to investigate the correlation between them. A total of 81 Iranian families with PAH deficiency were examined using PCR-sequencing of all 13 PAH exons and their flanking intron regions to identify sequence variations. Fragment analysis of the PAH minihaplotypes was performed by capillary electrophoresis for 59 families. In our study, 33 different mutations were found accounting for 95% of the total mutant alleles. The majority of these mutations (72%) were distributed across exons 7, 11, 2 and their flanking intronic regions. Mutation c.1066-11G > A was the most common with a frequency of 20.37%. The less frequent mutations, p.Arg261Gln (8%), p.Arg243Ter (7.4%), p.Leu48Ser (7.4%), p.Lys363Asnfs*37 (6.79%), c.969 + 5G > A (6.17%), p.Pro281Leu (5.56), c.168 + 5G > C (5.56), and p.Arg261Ter (4.94) together comprised about 52% of all mutant alleles. In this study, a total of seventeen PAH gene minihaplotypes were detected, six of which associated exclusively with particular mutations. Our findings indicate a broad PAH mutation spectrum in the Iranian population, which is consistent with previous studies reporting a wide range of PAH mutations, most likely due to ethnic heterogeneity. High prevalence of c.1066-11G > A mutation linked to minihaplotype 7/250 among both Iranian and Mediterranean populations is indicative of historical and geographical links between them. Also, strong association between particular mutations and minihaplotypes

Simple and rapid analytical method for detection of amino acids in blood using blood spot on filter paper, fast-GC/MS and isotope dilution technique.

PubMed

Kawana, Shuichi; Nakagawa, Katsuhiro; Hasegawa, Yuki; Yamaguchi, Seiji

2010-11-15

A simple and rapid method for quantitative analysis of amino acids, including valine (Val), leucine (Leu), isoleucine (Ile), methionine (Met) and phenylalanine (Phe), in whole blood has been developed using GC/MS. In this method, whole blood was collected using a filter paper technique, and a 1/8 in. blood spot punch was used for sample preparation. Amino acids were extracted from the sample, and the extracts were purified using cation-exchange resins. The isotope dilution method using ²H₈-Val, ²H₃-Leu, ²H₃-Met and ²H₅-Phe as internal standards was applied. Following propyl chloroformate derivatization, the derivatives were analyzed using fast-GC/MS. The extraction recoveries using these techniques ranged from 69.8% to 87.9%, and analysis time for each sample was approximately 26 min. Calibration curves at concentrations from 0.0 to 1666.7 μmol/l for Val, Leu, Ile and Phe and from 0.0 to 333.3 μmol/l for Met showed good linearity with regression coefficients=1. The method detection limits for Val, Leu, Ile, Met and Phe were 24.2, 16.7, 8.7, 1.5 and 12.9 μmol/l, respectively. This method was applied to blood spot samples obtained from patients with phenylketonuria (PKU), maple syrup urine disease (MSUD), hypermethionine and neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), and the analysis results showed that the concentrations of amino acids that characterize these diseases were increased. These results indicate that this method provides a simple and rapid procedure for precise determination of amino acids in whole blood. Copyright © 2010 Elsevier B.V. All rights reserved.

Serum phenylalanine screening

MedlinePlus

... phenylalanine. If PKU is not detected early, increasing phenylalanine levels in the baby will cause intellectual disability. When discovered early, changes in the diet can help prevent the severe side effects of PKU.

Three novel variants (p.Glu178Lys, p.Val245Met, p.Ser250Phe) of the phenylalanine hydroxylase (PAH) gene impair protein expression and function in vitro.

PubMed

Zong, Yanan; Liu, Ning; Ma, Shanshan; Bai, Ying; Guan, Fangxia; Kong, Xiangdong

2018-08-20

Phenylketonuria (PKU) is the most common inherited metabolic disease, an autosomal recessive disorder affecting >10,000 newborns each year globally. It can be caused by over 1000 different naturally occurring mutations in the phenylalanine hydroxylase (PAH) gene. We analyzed three novel naturally occurring PAH gene variants: p.Glu178Lys (c.532G>A), p.Val245Met (c.733G>A) and p.Ser250Phe (c.749C>T). The mutant effect on the PAH enzyme structure and function was predicted by bioinformatics software. Vectors expressing the corresponding PAH variants were generated for expression in E. coli and in HEK293T cells. The RNA expression of the three PAH variants was measured by quantitative reverse transcription polymerase chain reaction (RT-qPCR). The mutant PAH protein levels were determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), western blot and enzyme-linked immunosorbent assay (ELISA). All three variants were predicted to be pathogenic by bioinformatics analysis. The transcription of the three PAH variants was similar to the wild type PAH gene in HEK293T cells. In contrast, the levels of mutant PAH proteins decreased significantly compared to the wild type control, in both E. coli and HEK293T cells. Our results indicate that the three novel PAH gene variants (p.Glu178Lys, p.Val245Met, p.Ser250Phe) impair PAH protein expression and function in prokaryotic and eukaryotic cells. Copyright © 2018. Published by Elsevier B.V.

Recent Astronomical Development in Asia Pacific Rim

NASA Astrophysics Data System (ADS)

Leung, K.-C.

2009-08-01

For over two decades The Pacific Rim Conference on Stellar Astrophysics series has been held exclusively at the Asian Rim. The primary reason is that the majority of nations in Asia are less developed in Astronomy than many countries on the American Rim. At time same time, many nations in Asia are less able to afford the costs of long distance travel for astronomical conferences. As a result Asia has had a hold on the Pacific Rim Conferences. Over the last few years new research institutes have been coming on board. The ones that have most visibly emerged are; National Astronomical Research Institute of Thailand, NARIT, The Astrophysical Research Center for the Structure and Evolution of the Cosmos, ARCSEC, and Kavli Institute of Astronomy and Astrophysics at Peking University, KIAA-PKU. It is interesting to note the development and structure of each is very different. So far they all appear to be working well. Hopefully they will provide a variety of models for astronomical institutes in developing nations of the region and perhaps beyond.

What Conditions or Disorders are Commonly Associated with Down Syndrome?

MedlinePlus

... Society Hib Vaccine PKU and Newborn Screening Congenital Hypothyroidism Annual NICHD Research Advances Snapshot of Early Development ... do infants without Down syndrome, for example. 2 Hypothyroidism . The thyroid is a gland that makes hormones ...

Biallelic Mutations in DNAJC12 Cause Hyperphenylalaninemia, Dystonia, and Intellectual Disability.

PubMed

Anikster, Yair; Haack, Tobias B; Vilboux, Thierry; Pode-Shakked, Ben; Thöny, Beat; Shen, Nan; Guarani, Virginia; Meissner, Thomas; Mayatepek, Ertan; Trefz, Friedrich K; Marek-Yagel, Dina; Martinez, Aurora; Huttlin, Edward L; Paulo, Joao A; Berutti, Riccardo; Benoist, Jean-François; Imbard, Apolline; Dorboz, Imen; Heimer, Gali; Landau, Yuval; Ziv-Strasser, Limor; Malicdan, May Christine V; Gemperle-Britschgi, Corinne; Cremer, Kirsten; Engels, Hartmut; Meili, David; Keller, Irene; Bruggmann, Rémy; Strom, Tim M; Meitinger, Thomas; Mullikin, James C; Schwartz, Gerard; Ben-Zeev, Bruria; Gahl, William A; Harper, J Wade; Blau, Nenad; Hoffmann, Georg F; Prokisch, Holger; Opladen, Thomas; Schiff, Manuel

2017-02-02

Phenylketonuria (PKU, phenylalanine hydroxylase deficiency), an inborn error of metabolism, can be detected through newborn screening for hyperphenylalaninemia (HPA). Most individuals with HPA harbor mutations in the gene encoding phenylalanine hydroxylase (PAH), and a small proportion (2%) exhibit tetrahydrobiopterin (BH 4 ) deficiency with additional neurotransmitter (dopamine and serotonin) deficiency. Here we report six individuals from four unrelated families with HPA who exhibited progressive neurodevelopmental delay, dystonia, and a unique profile of neurotransmitter deficiencies without mutations in PAH or BH 4 metabolism disorder-related genes. In these six affected individuals, whole-exome sequencing (WES) identified biallelic mutations in DNAJC12, which encodes a heat shock co-chaperone family member that interacts with phenylalanine, tyrosine, and tryptophan hydroxylases catalyzing the BH 4 -activated conversion of phenylalanine into tyrosine, tyrosine into L-dopa (the precursor of dopamine), and tryptophan into 5-hydroxytryptophan (the precursor of serotonin), respectively. DNAJC12 was undetectable in fibroblasts from the individuals with null mutations. PAH enzyme activity was reduced in the presence of DNAJC12 mutations. Early treatment with BH 4 and/or neurotransmitter precursors had dramatic beneficial effects and resulted in the prevention of neurodevelopmental delay in the one individual treated before symptom onset. Thus, DNAJC12 deficiency is a preventable and treatable cause of intellectual disability that should be considered in the early differential diagnosis when screening results are positive for HPA. Sequencing of DNAJC12 may resolve any uncertainty and should be considered in all children with unresolved HPA. Copyright © 2017 American Society of Human Genetics. All rights reserved.

Aspartame intolerance.

PubMed

Garriga, M M; Metcalfe, D D

1988-12-01

Aspartame is a food additive marketed under the brand name Nutrasweet. Aspartame is a white, odorless, crystalline powder and consists of two amino acids, L-aspartic acid and L-phenylalanine. It is 180 times as sweet as sugar. The Food and Drug Administration (FDA) first allowed its use in dry foods in July 1981 and then approved its use in carbonated beverages in July 1983. It has subsequently been approved for use in a number of materials including multivitamins, fruit juices, stick-type confections, breath mints, and iced tea. The FDA requires the statement "phenylketonurics: contains phenylalanine" on labels of food products containing aspartame because individuals with phenylketonuria (PKU) must restrict their intake of phenylalanine. Aspartame is judged to be free of long-term cancer risks. Aspartame is not stable under certain conditions including baking and cooking, and prolonged exposure to acid conditions. In such situations it loses its sweetness. Products formed from aspartame include its component amino acids (phenylalanine and aspartic acid), methanol, and diketopiperazine (DKP). Animal studies show DKP to be nontoxic. Methanol occurs in small amounts and does not exceed that formed during consumption of many foods including fresh fruits and vegetables. FDA's Center for Food Safety and Applied Nutrition (CFSAN) monitors aspartame's safety in part through reports of adverse reactions. After aspartame was approved for use in carbonated beverages, the FDA received an increased number of reports concerning adverse reactions related to aspartame. The Centers for Disease Control (CDC) reviewed these reports, which included complaints of neurologic, gastrointestinal, andallergic reactions.(ABSTRACT TRUNCATED AT 250 WORDS)

Determination of branched chain amino acids, methionine, phenylalanine, tyrosine and alpha-keto acids in plasma and dried blood samples using HPLC with fluorescence detection.

PubMed

Kand'ár, Roman; Záková, Pavla; Jirosová, Jana; Sladká, Michaela

2009-01-01

The determination of branched chain amino acids [BCAA; valine (Val), leucine (Leu), isoleucine (Ile)], alpha-keto acids derived from BCAA [BCKA; alpha-ketoisovaleric acid (KIV), alpha-ketoisocaproic acid (KIC), alpha-ketomethylvaleric acid (KMV)], methionine (Met), phenylalanine (Phe) and tyrosine (Tyr) is currently the most reliable approach for the diagnosis of maple syrup urine disease (MSUD), hypermethioninemia, phenylketonuria (PKU) and tyrosinemia. The aim of this study was to develop rapid and simple HPLC methods for measurement of BCAA, Met, Phe, Tyr and BCKA in plasma and dried blood samples. Samples of peripheral venous blood with EDTA as anticoagulant were obtained from a group of healthy blood donors (n=70, 35 females, 27-41 years of age and 35 males, 28-43 years of age). Blood-spot samples from a group of newborns (n=80, 40 girls and 40 boys 3-5 days of age) were collected onto #903 Specimen Collection Paper and allowed to dry for at least 24 h before analysis. Prior to separation, the amino acids (AA) were derivatized with o-phthaldialdehyde (OPA) and BCKA with o-phenylenediamine (OPD). Reverse phase column chromatography (LiChroCart 125-4 Purospher RP-18e, 5 microm) was used for separation and fluorescence detection used to monitoring of effluent. For AA analysis, 25 mmol/L sodium hydrogenphosphate-methanol (90:10, v/v), pH 6.5+/-0.1 was used as mobile phase A and 100% methanol was used as mobile phase B. Measurement of BCKA used a mixture of methanol and deionized water (55:45, v/v) as mobile phase A and mobile phase B consisted of 100% methanol. Analytical performance of these methods was satisfactory for the determination of all AA and BCKA. The intra-assay and inter-assay coefficients of variation were below 10% and recovery ranged from 90%-110%. We have developed simple, rapid and selective HPLC methods with fluorescence detection for the determination of BCAA, Met, Phe, Tyr and BCKA in plasma and dried blood samples.

PKU-RBRC Workshop on Transverse Spin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Avakian,H.; Bunce, G.; Yuan, F.

2008-06-30

Understanding the structure of the nucleon is a fundamental question in subatomic physics, and it has been under intensive investigation for the last several years. Modern research focuses in particular on the spin structure of the nucleon. Experimental and theoretical investigations worldwide over the last few decades have established that, contrary to nave quark model expectations, quarks carry only about 30% of the totd spin of the proton. The origin of the remaining spin is the key question in current hadronic physics and also the major driving forces for the current and future experiments, such as RHIC and CEBAF inmore » US, JPARC in Japan, COMPASS at CERN in Europe, FAIR at GSI in Germany. Among these studies, the transverse-spin physics develops actively and rapidly in the last few years. Recent studies reveal that transverse-spin physics is closely related to many fundamental properties of the QCD dynamics such as the factorization, the non-trivial universality of the parton distribution and fragmentation functions. It was very timely to bring together the theorists and experimentalists in this field at this workshop to review and discuss the latest developments and future perspective in hadronic spin physics. This workshop was very success iu many aspects. First of all, it attracted almost every expert working in this field. We had more than eighty participants in total, among them 27 came from the US institutes, 13 from Europe, 3 from Korea, and 2 from Japan. The rest participants came from local institutes in China. Second, we arranged plenty physics presentations, and the program covers all recent progresses made in the last few years. In total, we had 47 physics presentations, and two round table discussions. The discussion sessions were especially very useful and very much appreciated by all participants. In addition, we also scheduled plenty time for discussion in each presentation, and the living discussions impressed and benefited all

Effect of dietary aspartame on plasma concentrations of phenylalanine and tyrosine in normal and homozygous phenylketonuric patients.

PubMed

Mackey, S A; Berlin, C M

1992-07-01

Six normal subjects each ingested a single 12-oz can of a diet cola (Diet Coke) providing 184 mg aspartame (APM), of which 104 mg is phenylalanine (Phe), and, on another occasion, a single 12-oz can of regular cola (Coke Classic). Neither cola significantly affected plasma concentrations of Phe or tyrosine over the three-hour postingestion study period. Each of five homozygous phenylketonuric (PKU) subjects (ages 11, 16, 17, 21, and 23 years) ingested a single 12-oz can of the same diet cola. In these five subjects (three with classic PKU and two with hyperphenylalinemia), the increase in plasma Phe concentrations varied from 0.26 mg/dL to 1.77 mg/dL two or three hours after ingestion (baseline levels, 5.04 to 17.2 mg/dL). Tyrosine concentrations did not differ significantly from baseline levels. The data indicate that ingestion of dietary Phe, as supplied in a single can of diet cola, is readily handled in both normal and PKU subjects. The small increases in plasma Phe concentrations in the homozygous PKU patients are not considered clinically significant.

[The development of molecular human genetics and its significance for perspectives of modern medicine].

PubMed

Coutelle, C; Speer, A; Grade, K; Rosenthal, A; Hunger, H D

1989-01-01

The introduction of molecular human genetics has become a paradigma for the application of genetic engineering in medicine. The main principles of this technology are the isolation of molecular probes, their application in hybridization reactions, specific gene-amplification by the polymerase chain reaction, and DNA sequencing reactions. These methods are used for the analysis of monogenic diseases by linkage studies and the elucidation of the molecular defect causing these conditions, respectively. They are also the basis for genomic diagnosis of monogenic diseases, introduced into the health care system of the GDR by a national project on Duchenne/Becker muscular dystrophy, Cystic Fibrosis and Phenylketonuria. The rapid development of basic research on the molecular analysis of the human genome and genomic diagnosis indicates, that human molecular genetics is becoming a decisive basic discipline of modern medicine.

[A Comprehensive Care System for Children with Anorexia Nervosa in Pediatric Practice].

PubMed

Watanabe, Hisako

2015-01-01

Against the backdrop of rapid industrialization and westernization after the World War II, there has been an ever increasing number of children with anorexia nervosa (AN) in pediatric practice, making it one of the most common diseases in children. With a severe lack of AN specialists in Japan, pediatricians need to face the daunting task of treating AN on their own. Malnutrition overlooked during periods of growth and development yields a risk of death, growth disturbance and an intractable conditions with secondary disorders of brain atrophy, osteoporosis, infertility, maltreatment and childrearing failures, mental disorders and others, which can last for life. Prevention is the best and a must for AN, and an early detection and treatment need to be in place to mitigate its progress and aggravation. It is crucial that an effective care is provided in early, treatable stage to assist the patient back to a healthy developmental trajectory. In 1993, the Department of Pediatrics, School of Medicine, Keio University (hereafter PKU) appointed a child psychiatrist as its fulltime staff and has included inpatient treatment of AN as a compulsory item of its postgraduate training program. Over the past twenty years, PKU has developed a comprehensive treatment system of AN (Scientific Report of Ministry of Welfare and Labor 2006). In the primary care of AN, a screening tool using simple physical measurement of weight on growth chart combined with pulse proves effective. When a weight on growth chart reveals an unhealthy weight loss and is combined with bradycardia, it detects AN at sensitivity of 83% and specificity of 93%. In the secondary care of AN, 40 pediatric institutions affiliated with PKU implemented early treatment of AN with the support of the Mental Health Division of PKU. In the tertiary care for severely emaciated AN patients, an around-the-clock intensive treatment program, called Anorexia Nervosa Intensive Care Unit (ANICU) was instituted. The gist of ANICU

Phenylketonuria

MedlinePlus

Kliegman RM, Stanton BF, St. Geme JW, Schor NF. Defects in metabolism of amino acids. In: Kliegman RM, Stanton BF, St. Geme JW, Schor NF, eds. Nelson Textbook of Pediatrics . 20th ed. Philadelphia, ...

Efficient production of triacylglycerols rich in docosahexaenoic acid (DHA) by osmo-heterotrophic marine protists.

PubMed

Liu, Ying; Tang, Jie; Li, Jingjing; Daroch, Maurycy; Cheng, Jay J

2014-12-01

Thraustochytrids have recently emerged as a promising source for docosahexaenoic acid (DHA) production due to their high growth rate and oil content. In this study, two thraustochytrid isolates, Aurantiochytrium sp. PKU#SW7 and Thraustochytriidae sp. PKU#Mn16 were used for DHA production. Following growth parameters were optimized to maximize DHA production: temperature, pH, salinity, and glucose concentration. Both isolates achieved the highest DHA yield at the cultivation temperature of 28 °C, pH 6, 100 % seawater, and 2 % glucose. A DHA yield of 1.395 g/l and 1.426 g/l was achieved under the optimized culture conditions. Further investigation revealed that both isolates possess simple fatty acids profiles with palmitic acid and DHA as their dominant constituents, accounting for ∼79 % of total fatty acids. To date, very few studies have focused on the DHA distribution in various lipid fractions which is an important factor for identifying strains with a potential for industrial DHA production. In the present study, the lipids profiles of each strain both revealed that the majority of DHA was distributed in neutral lipids (NLs), and the DHA distribution in NLs of PKU#SW7 was exclusively in the form of triacylglycerols (TAGs) which suggest that PKU#SW7 could be utilized as an alternative source of DHA for dietary supplements. The fermentation process established for both strains also indicating that Aurantiochytrium sp. PKU#SW7 was more suitable for cultivation in fermenter. In addition, the high percentage of saturated fatty acids produced by the two thraustochytrids indicates their potential application in biodiesel production. Overall, our findings suggest that two thraustochytrid isolates are suitable candidates for biotechnological applications.

Selective screening for inborn errors of metabolism and secondary methylmalonic aciduria in pregnancy at high risk district of neural tube defects: a human metabolome study by GC-MS in China.

PubMed

Song, Yuan-Zong; Li, Bing-Xiao; Hao, Hu; Xin, Ruo-Lei; Zhang, Ting; Zhang, Chun-Hua; Kobayashi, Keiko; Wang, Zi-Neng; Zheng, Xiao-Ying

2008-05-01

Urease pretreatment-gas chromatography-mass spectrometry (UP-GC-MS) has become a valuable tool in the field of metabolome research, including analysis of inborn errors of metabolism (IEMs) and acquired metabolic disturbances secondary to nutrition or drugs. This research aims to screen IEMs in Chinese patients and to explore the cause of neural tube defects (NTDs), a congenital malformation very common in North China. Urine samples from 618 patients at high risk of IEMs in China were collected, and UP-GC-MS was performed in the selective screening. Urinary methylmalonate (MMA) levels in pregnancy with and without NTDs fetus, respectively, at Luliang district, a countryside region with NTDs incidence 227/10,000, Shanxi Province, North China, were analyzed by GC-MS-selective ion monitoring, and compared with that from control region. Among the 618 patients, 22 kinds and 59 cases of IEM were found. Methylmalonic aciduria (MMAuria) is on top of the list, followed by neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), phenylketonuria (PKU), multiple carboxylase deficiency (MCD), etc. Satisfactory therapeutic effects have been achieved in patients such as NICCD, MCD, and galactosemia. At Luliang district, urinary MMA levels in pregnancy, no matter NTDs-affected or unaffected, are both significantly (P<0.01) higher than that in normal control, while serum B(12) levels in NTDs-affected pregnancy are significantly lower than that both in NTDs-unaffected group (P<0.01) and in normal control (P<0.01). Furthermore, B(12) <52.5 pmol/L is associated with a 7.78-fold increased NTDs risk (P<0.01) at Luliang district. Selective screening for IEMs by UP-GC-MS provides valuable evidences for the diagnosis of IEMs. MMAuria secondary to B(12) deficiency is quite common at Luliang district, suggesting B(12) deficiency is involved in the development of NTDs in the specific population. This metabolome research by UP-GC-MS provides valuable epidemiological information

Essentials of PKU for Young Adults with PKU and Their Significant Others

MedlinePlus

... 2* and measured amounts of fruits, vegetables, bread, pasta and cereals. Many foods must be eliminated from ... of the diet is low protein breads and pastas. They are nearly free of phenylalanine, allow greater ...

How Is PKU Monitored?

MedlinePlus

... important components of the clinic visit at the University of Washington. Food records are usually a 3 day diary of all foods and beverages eaten and the amounts consumed. These diaries should ...

Neonatal hypothyroid screening in monitoring of iodine deficiency and iodine supplementation in Poland.

PubMed

Ołtarzewski, M; Szymborski, J

2003-01-01

Neonatal hypothyroid screening in Poland is standardised and all newborns screening data are registered in central data base in the National Institute of Mother and Child. About 400,000 newborns are screened per year for hypothyroidism (TSH) and phenylketonuria (PKU). Unfortunately, obstetric clinics still use antiseptics that contain iodine. According to our data 71% of clinics used iodine in 1998 (58% iodine tincture and 13% povidone iodine) and 58.2% (35.4 iodine tincture and 13% povidone iodine) in the year 2000. Presence of iodine resulted in over 3 times increase of a percentage of TSH levels over cut off, increasing the number of false positives in the hypothyroid screening. Analysis of TSH distribution for iodine containing and iodine free hospitals gave totally different estimation of iodine deficiency according to WHO criteria. In the group of iodine free hospitals 24 regions were classified as not deficient, 9 regions were borderline with a fraction of TSH levels over 5 mlU/l of 3-5%. 10 regions could not be analysed because all hospitals declared use of iodine. In the second group all regions were iodine deficient. TSH distribution since 1994 shows significant decrease of percentage of TSH levels over cut off from 2.23% in 1994 to 0.16 in 1997 and to 0.12 in 2000. These changes are most probably connected with successive introduction of iodine supplementation which became obligatory in 1997 and suggest that iodine supplementation covers iodine requirements during pregnancy. Iodine deficiency and iodine supplementation in Poland can be studied using TSH blood spot newborn screening results in correlation with data on interfering factors and in reference to modified criteria for the analytical test and the population. To reduce false positive rate in neonatal hypothyroid screening iodine containing antiseptics, particularly iodine tincture, should be withdrawn from all obstetrics clinics in Poland.

Coverage of the Victorian newborn screening programme in 2003: a retrospective population study.

PubMed

Jaques, Alice M; Collins, Veronica R; Pitt, James; Halliday, Jane L

2008-09-01

To assess the coverage of the newborn screening (NBS) program in Victoria, Australia, and identify potential predictors of not being screened. Victoria, Australia, 2003. The Victorian NBS program screens for phenylketonuria (PKU), cystic fibrosis, congenital hypothyroidism and more than 20 metabolic conditions, such as medium chain acyl-coenzyme A dehydrogenase (MCAD) deficiency. Victorian birth records (n = 63,018) were linked to Victorian NBS records (n = 62,876) using probabilistic record linkage. Binary logistic regression was used to identify potential predictors of not being screened. Uptake of NBS was 99.4% (62,643/63,018), resulting in 0.6% (375) of livebirths not matched to a NBS test. Neonatal death was the most significant factor associated with not being screened (relative risk (RR) = 407, 95%Cl = 314 to 526). After adjustment, surviving livebirths had an increased likelihood of not being matched to a NBS record if they: were transferred between hospitals (odds ratio (OR) = 2.4, 95% confidence interval (Cl) 1.5 to 3.9); were born at home (OR = 12.1, 95%Cl 6.3 to 23.3); resided in rural Victoria (OR = 2.6, 95%Cl 1.5 to 4.3); stayed in hospital for one day or less (OR = 4.6, 95%Cl 2.8 to 7.6); or whose mothers were primiparous (OR = 1.5, 95%Cl 1.1 to 2.1). NBS uptake is extremely high in Victoria with over 99% of livebirths screened. Particular risk factors for not having NBS have now been identified, which could lead to changes around monitoring neonates who are not born in a hospital, or leave/transfer hospital, before the NBS period (48-72 hours). Future studies could determine whether those not screened had opted-out or were not offered NBS.

Rapid determination of amino acids in neonatal blood samples based on derivatization with isobutyl chloroformate followed by solid-phase microextraction and gas chromatography/mass spectrometry.

PubMed

Deng, Chunhui; Li, Ning; Zhang, Xiangmin

2004-01-01

The purpose of this study was to develop a simple, rapid and sensitive analytical method for determination of amino acids in neonatal blood samples. The developed method involves the employment of derivatization and a solid-phase microextraction (SPME) technique together with gas chromatography/mass spectrometry (GC/MS). Amino acids in blood samples were derivatized by a mixture of isobutyl chloroformate, methanol and pyridine, and the N(O,S)-alkoxycarbonyl alkyl esters thus formed were headspace extracted by a SPME fiber. Finally, the extracted analytes on the fiber were desorbed and detected by GC/MS in electron impact (EI) mode. L-Valine, L-leucine, L-isoleucine, L-phenylanaline and L-tyrosine in blood samples were quantitatively analyzed by measurement of the corresponding N(O,S)-alkoxycarbonyl alkyl esters using an external standard method. SPME conditions were optimized, and the method was validated. The method was applied to diagnosis of neonatal phenylkenuria (PKU) and maple syrup urine disease (MSUD) by the analyses of five amino acids in blood samples. The results showed that the proposed method is a potentially powerful tool for simultaneous screening for neonatal PKU and MSUD. Copyright (c) 2004 John Wiley & Sons, Ltd.

A screening method for biotinidase deficiency in newborns.

PubMed

Heard, G S; Secor McVoy, J R; Wolf, B

1984-01-01

We describe a method for neonatal screening for biotinidase (EC 3.5.1.12) deficiency. Biotinidase activity is assessed colorimetrically from dried samples of whole blood spotted on the same filter papers as used in the neonatal screening for phenylketonuria. After the reaction, samples from normal infants are characteristically purple, whereas those from affected individuals are straw-colored. To confirm the deficiency, the enzyme is quantitatively assayed in additional blood spots or serum. A pilot study has been initiated with samples obtained by the Commonwealth of Virginia for phenylketonuria testing.

What Is a Pediatric Geneticist?

MedlinePlus

... or achondroplasia) Conditions that can cause disabilities (fetal alcohol syndrome, or fragile X syndrome) Inborn errors of metabolism (cystic fibrosis, phenylketonuria, or sickle cell disease) Familial ...

Designing medical foods for inherited metabolic disorders: why intact protein is superior to amino acids.

PubMed

Ney, Denise Marie; Etzel, Mark Raymond

2017-04-01

Phenylketonuria and tyrosinemia are inherited metabolic disorders characterized by high blood levels of phenylalanine (Phe) or tyrosine (Tyr), due to mutations in genes affecting Phe and Tyr metabolism, respectively. The primary management is a lifelong diet restricted in protein from natural foods in combination with medical foods comprised mixtures of synthetic amino acids. Compliance is often poor after childhood leading to neuropsychological sequela. Glycomacropeptide, an intact 64 amino acid glycophosphopeptide isolated from cheese whey, provides a new paradigm for the management of phenylketonuria and tyrosinemia because glycomacropeptide contains no Phe and Tyr in its pure form, and is also a prebiotic. Medical foods made from glycomacropeptide have been used successfully for the management of phenylketonuria and tyrosinemia. Preclinical and clinical studies demonstrate that intact protein from glycomacropeptide provides a more acceptable and physiologic source of defined protein compared to amino acids in medical foods. For example, harmful gut bacteria were reduced, beneficial short chain fatty acids increased, renal workload decreased, protein utilization increased, and bone fragility decreased using intact protein versus amino acids. Advances in biotechnology will propel the transition from synthetic amino acids to intact proteins for the management of inherited metabolic disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

21 CFR 862.1560 - Urinary phenylketones (nonquantitative) test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... and treatment of congenital phenylketonuria which, if untreated, may cause mental retardation. (b) Classification. Class I (general controls). The device is exempt from the premarket notification procedures in...

Newborn screening tests

MedlinePlus

... adrenal hyperplasia Congenital hypothyroidism Cystic fibrosis Fatty acid metabolism disorders Galactosemia Glucose-6-phosphate dehydrogenase deficiency (G6PD) Human immunodeficiency disease (HIV) Organic acid metabolism disorders Phenylketonuria ( ...

What Is the Diet for PKU?

MedlinePlus

... and carefully measured amounts of fruits, vegetables, bread, pasta, and cereals. Many people who follow a low ... food pattern eat special low protein breads and pastas. They are nearly free of phe, allow greater ...

Phenylketonuria Genetic Screening Simulation

ERIC Educational Resources Information Center

Erickson, Patti

2012-01-01

After agreeing to host over 200 students on a daylong genetics field trip, the author needed an easy-to-prepare genetics experiment to accompany the DNA-necklace and gel-electrophoresis activities already planned. One of the student's mothers is a pediatric physician at the local hospital, and she suggested exploring genetic-disease screening…

Nutrition Update, 1978.

ERIC Educational Resources Information Center

Weininger, Jean; Briggs, George M.

1978-01-01

Reviews current nutrition research areas with important practical applications. Topics include hypertension, preventable birth defects, phenylketonuria and genetic diseases, new molecular genetics techniques, and saccharin and sweetners. Entries are brief and a 65-reference list is given. (MA)

Screening of Pesticides with the Potential of Inducing DSB and Successive Recombinational Repair

PubMed Central

2017-01-01

A study was realized to ascertain whether eight selected pesticides would induce double strand breaks (DSB) in lymphocyte cultures and whether this damage would induce greater levels of proteins Rad51 participating in homologous recombination or of p-Ku80 participating in nonhomologous end joining. Only five pesticides were found to induce DSB of which only glyphosate and paraoxon induced a significant increase of p-Ku80 protein, indicating that nonhomologous end joining recombinational DNA repair system would be activated. The type of gamma-H2AX foci observed was comparable to that induced by etoposide at similar concentrations. These results are of importance since these effects occurred at low concentrations in the micromolar range, in acute treatments to the cells. Effects over longer exposures in actual environmental settings are expected to produce cumulative damage if repeated events of recombination take place over time. PMID:29129974

Newborn Screening Tests

MedlinePlus

... and adolescence and sometimes into adult life. This diet cuts out all high-protein foods, so people with PKU often need to ... appetite and are very irritable. A carefully controlled diet that cuts out certain high-protein foods containing the three amino acids can prevent ...

A New High-Resolution N2O Emission Inventory for China in 2008

NASA Astrophysics Data System (ADS)

Shang, Z.; Zhou, F.; Ciais, P.; Tao, S.; Piao, S.; Raymond, P. A.; He, C.; Li, B.; Wang, R.; Wang, X.; Peng, S.; Zeng, Z.; Chen, H.; Ying, N.; Hou, X.; Xu, P.

2014-12-01

The amount and geographic distribution of N2O emissions over China remain largely uncertain. Most of existing emission inventories use uniform emission factors (EFs) and the associated parameters and apply spatial proxies to downscale national or provincial data, resulting in the introduction of spatial bias. In this study, county-level and 0.1° × 0.1° gridded anthropogenic N2O emission inventories for China (PKU-N2O) in 2008 are developed based on high-resolution activity data and regional EFs and parameters. These new estimates are compared with estimates from EDGAR v4.2, GAINS-China, National Development and Reform Commission of China (NDRC), and with two sensitivity tests: one that uses high-resolution activity data but the default IPCC methodology (S1) and the other that uses regional EFs and parameters but starts from coarser-resolution activity data. The total N2O emissions are 2150 GgN2O/yr (interquartile range from 1174 to 2787 GgN2O/yr). Agriculture contributes 64% of the total, followed by energy (17%), indirect emissions (12%), wastes (5%), industry (2.8%), and wildfires (0.2%). Our national emission total is 17% greater than that of the EDGAR v4.2 global product sampled over China and is also greater than the GAINS-China, NDRC, and S1 estimates by 10%, 50%, and 17%, respectively. We also found that using uniform EFs and parameters or starting from national/provincial data causes systematic spatial biases compared to PKU-N2O. In addition, the considerable differences between the relative contributions of the six sectors across the six Agro-Climate Zones primarily reflect the different distributions of industrial activities and land use. Eastern China (8.7% area of China) is the largest contributor of N2O emissions and accounts for nearly 25% of the total. Spatial analysis also shows nonlinear relationships between N2O emission intensities and urbanization. Per-capita and per-GDP N2O emissions increase gradually with an increase in the urban

Nutritional Considerations for Severely Handicapped Children.

ERIC Educational Resources Information Center

Sobsey, Dick

Children and adults with severe disabilities may have nutritional problems due to the effects of the primary disability (including such syndromes as phenylketonuria, galactosemia, and Hurler's Disease), effects related to medications (including anticonvulsants, tranquilizers, and laxatives), effects of food preferences (restrictive food…

Nuclear Data Online Services at Peking University

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fan, T.S.; Guo, Z.Y.; Ye, W.G.

2005-05-24

The Institute of Heavy Ion Physics at Peking University has developed a new nuclear data online services software package. Through the web site (http://ndos.nst.pku.edu.cn), it offers online access to main relational nuclear databases: five evaluated neutron libraries (BROND, CENDL, ENDF, JEF, JENDL), the ENSDF library, the EXFOR library, the IAEA photonuclear library and the charged particle data of the FENDL library. This software allows the comparison and graphic representations of the different data sets. The computer programs of this package are based on the Linux implementation of PHP and the MySQL software.

Nuclear Data Online Services at Peking University

NASA Astrophysics Data System (ADS)

Fan, T. S.; Guo, Z. Y.; Ye, W. G.; Liu, W. L.; Liu, T. J.; Liu, C. X.; Chen, J. X.; Tang, G. Y.; Shi, Z. M.; Huang, X. L.; Chen, J. E.

2005-05-01

The Institute of Heavy Ion Physics at Peking University has developed a new nuclear data online services software package. Through the web site (http://ndos.nst.pku.edu.cn), it offers online access to main relational nuclear databases: five evaluated neutron libraries (BROND, CENDL, ENDF, JEF, JENDL), the ENSDF library, the EXFOR library, the IAEA photonuclear library and the charged particle data of the FENDL library. This software allows the comparison and graphic representations of the different data sets. The computer programs of this package are based on the Linux implementation of PHP and the MySQL software.

Newborn Screening To Prevent Mental Retardation. The Arc Q & A.

ERIC Educational Resources Information Center

Arc, Arlington, TX.

This information fact sheet on screening newborns to prevent mental retardation defines newborn screening and outlines how screening is performed. It discusses the six most common disorders resulting in mental retardation for which states most commonly screen. These include phenylketonuria, congenital hypothyroidism, galactosemia, maple syrup…

Newborn Screening: National Library of Medicine Literature Search, January 1980 through March 1987. No. 87-2.

ERIC Educational Resources Information Center

Patrias, Karen

This bibliography, prepared by the National Library of Medicine through a literature search of its online databases, covers all aspects of newborn screening. It includes references to screening for: inborn errors of metabolism, such as phenylketonuria and galactosemia; hemoglobinopathies, particularly sickle cell disease; congenital hypothyroidism…

Dicarboxylic acids, ketocarboxylic acids, α-dicarbonyls, fatty acids, and benzoic acid in urban aerosols collected during the 2006 Campaign of Air Quality Research in Beijing (CAREBeijing-2006)

NASA Astrophysics Data System (ADS)

Ho, K. F.; Lee, S. C.; Ho, Steven Sai Hang; Kawamura, Kimitaka; Tachibana, Eri; Cheng, Y.; Zhu, Tong

2010-10-01

Ground-based studies of PM2.5 were conducted for determination of 30 water-soluble organic species, including dicarboxylic acids, ketocarboxylic acids and dicarbonyls, nine fatty acids, and benzoic acid, during the Campaign of Air Quality Research in Beijing 2006 (CAREBeijing-2006; 21 August to 4 September 2006) at urban (Peking University, PKU) and suburban (Yufa) sites of Beijing. Molecular distributions of dicarboxylic acids demonstrated that oxalic acid (C2) was the most abundant species, followed by phthalic acid (Ph) and succinic acid (C4) at both sites. The sum of three dicarboxylic acids accounted for 71% and 74% of total quantified water-soluble organics (327-1552 and 329-1124 ng m-3) in PKU and Yufa, respectively. Positive correlation was found between total quantified water-soluble species and water-soluble organic compounds (WSOC). On a carbon basis, total quantified dicarboxylic acids and ketocarboxylic acids and dicarbonyls account for up to 14.2% and 30.4% of the WSOC in PKU and Yufa, respectively, suggesting that they are the major WSOC fractions in Beijing. The distributions of fatty acids are characterized by a strong even carbon number predominance with maximum at hexadecanoic acid (C16:0). The ratio of octadecanoic acid (C18:0) to hexadecanoic acid (C16:0) (0.39-0.85, with an average of 0.36) suggests that in addition to vehicular emissions, an input from cooking emissions is important, as is biogenic emission. Benzoic acid that has been proposed as a primary pollutant from vehicular exhaust and a secondary product from photochemical reactions was found to be abundant: 72.2 ± 58.1 ng m-3 in PKU and 78.0 ± 47.3 ng m-3 in Yufa. According to the 72 hour back trajectory analysis, when the air mass passed over the southern or southeastern part of Beijing (24-25 August and 1-2 September), the highest concentrations of organic compounds were observed. On the contrary, when the clean air masses came straight from the north during 3-4 September, the

Parenteral nutrition in patients with inborn errors of metabolism - a therapeutic problem.

PubMed

Kaluzny, L; Szczepanik, M; Siwinska-Mrozek, Z; Borkowska-Klos, M; Cichy, W; Walkowiak, J

2014-06-01

Parenteral nutrition is now a standard part of supportive treatment in pediatric departments. We describe four cases in which parenteral nutrition was extremely difficult due to coincidence with inborn errors of metabolism. The first two cases was fatty acid beta-oxidation disorders associated with necrotizing enterocolitis and congenital heart disease. Thus, limitations of intravenous lipid intake made it difficult to maintain a good nutritional status. The third case was phenylketonuria associated with a facial region tumour (rhabdomyosarcoma), in which parenteral nutrition was complicated because of a high phenylalanine content in the amino acid formulas for parenteral nutrition. The fourth patient was a child with late-diagnosed tyrosinemia type 1, complicated with encephalopathy - during intensive care treatment the patient needed nutritional support, including parenteral nutrition - we observed amino acid formula problems similar to those in the phenylketonuria patient. Parenteral nutrition in children with inborn errors of metabolism is a rare, but very important therapeutic problem. Total parenteral nutrition formulas are not prepared for this group of diseases.

Seeking a Roadmap to Becoming World Class: Strategic Planning at Peking University. Research & Occasional Paper Series: CSHE.11.13

ERIC Educational Resources Information Center

Guangkuan, Xie

2013-01-01

Strategic planning plays an important but sometimes controversial role in higher education. This paper examines how strategic planning works in Chinese universities, using Peking University as a case study. This essay discusses the rationale for why Peking University (PKU) decided to pursue status as a world-class university along with objectives…

Genome-scale fluxes predicted under the guidance of enzyme abundance using a novel hyper-cube shrink algorithm.

PubMed

Xie, Zhengwei; Zhang, Tianyu; Ouyang, Qi

2018-02-01

One of the long-expected goals of genome-scale metabolic modelling is to evaluate the influence of the perturbed enzymes on flux distribution. Both ordinary differential equation (ODE) models and constraint-based models, like Flux balance analysis (FBA), lack the capacity to perform metabolic control analysis (MCA) for large-scale networks. In this study, we developed a hyper-cube shrink algorithm (HCSA) to incorporate the enzymatic properties into the FBA model by introducing a pseudo reaction V constrained by enzymatic parameters. Our algorithm uses the enzymatic information quantitatively rather than qualitatively. We first demonstrate the concept by applying HCSA to a simple three-node network, whereby we obtained a good correlation between flux and enzyme abundance. We then validate its prediction by comparison with ODE and with a synthetic network producing voilacein and analogues in Saccharomyces cerevisiae. We show that HCSA can mimic the state-state results of ODE. Finally, we show its capability of predicting the flux distribution in genome-scale networks by applying it to sporulation in yeast. We show the ability of HCSA to operate without biomass flux and perform MCA to determine rate-limiting reactions. Algorithm was implemented by Matlab and C ++. The code is available at https://github.com/kekegg/HCSA. xiezhengwei@hsc.pku.edu.cn or qi@pku.edu.cn. Supplementary data are available at Bioinformatics online. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

First structure of full-length mammalian phenylalanine hydroxylase reveals the architecture of an autoinhibited tetramer

PubMed Central

Arturo, Emilia C.; Gupta, Kushol; Héroux, Annie; Stith, Linda; Cross, Penelope J.; Parker, Emily J.; Loll, Patrick J.; Jaffe, Eileen K.

2016-01-01

Improved understanding of the relationship among structure, dynamics, and function for the enzyme phenylalanine hydroxylase (PAH) can lead to needed new therapies for phenylketonuria, the most common inborn error of amino acid metabolism. PAH is a multidomain homo-multimeric protein whose conformation and multimerization properties respond to allosteric activation by the substrate phenylalanine (Phe); the allosteric regulation is necessary to maintain Phe below neurotoxic levels. A recently introduced model for allosteric regulation of PAH involves major domain motions and architecturally distinct PAH tetramers [Jaffe EK, Stith L, Lawrence SH, Andrake M, Dunbrack RL, Jr (2013) Arch Biochem Biophys 530(2):73–82]. Herein, we present, to our knowledge, the first X-ray crystal structure for a full-length mammalian (rat) PAH in an autoinhibited conformation. Chromatographic isolation of a monodisperse tetrameric PAH, in the absence of Phe, facilitated determination of the 2.9 Å crystal structure. The structure of full-length PAH supersedes a composite homology model that had been used extensively to rationalize phenylketonuria genotype–phenotype relationships. Small-angle X-ray scattering (SAXS) confirms that this tetramer, which dominates in the absence of Phe, is different from a Phe-stabilized allosterically activated PAH tetramer. The lack of structural detail for activated PAH remains a barrier to complete understanding of phenylketonuria genotype–phenotype relationships. Nevertheless, the use of SAXS and X-ray crystallography together to inspect PAH structure provides, to our knowledge, the first complete view of the enzyme in a tetrameric form that was not possible with prior partial crystal structures, and facilitates interpretation of a wealth of biochemical and structural data that was hitherto impossible to evaluate. PMID:26884182

Enhanced saturated fatty acids accumulation in cultures of newly-isolated strains of Schizochytrium sp. and Thraustochytriidae sp. for large-scale biodiesel production.

PubMed

Wang, Qiuzhen; Sen, Biswarup; Liu, Xianhua; He, Yaodong; Xie, Yunxuan; Wang, Guangyi

2018-08-01

Heterotrophic marine protists (Thraustochytrids) have received increasingly global attention as a renewable, sustainable and alternative source of biodiesel because of their high ability of saturated fatty acids (SFAs) accumulation. Yet, the influence of extrinsic factors (nutrients and environmental conditions) on thraustochytrid culture and optimal conditions for high SFAs production are poorly described. In the present study, two different thraustochytrid strains, Schizochytrium sp. PKU#Mn4 and Thraustochytriidae sp. PKU#Mn16 were studied for their growth and SFAs production profiles under various conditions (carbon, nitrogen, temperature, pH, KH 2 PO 4 , salinity, and agitation speed). Of the culture conditions, substrates (C and N) source and conc., temperature, and agitation speed significantly influenced the cell growth and SFAs production of both strains. Although both the strains were capable of growth and SFAs production in the broad range of culture conditions, their physiological responses to KH 2 PO 4 , pH, and salinity were dissimilar. Under their optimal batch culture conditions, peak SFAs productions of 3.3g/L and 2.2g/L with 62% and 49% SFAs contents (relative to total fatty acids) were achieved, respectively. The results of 5-L fed-batch fermentation under optimal conditions showed a nearly 4.5-fold increase in SFAs production (i.e., 7.5g/L) by both strains compared to unoptimized conditions. Of the two strains, the quality of biodiesel produced from the fatty acids of PKU#Mn4 met the biodiesel standard defined by ASTM6751. This study, to the knowledge of the authors, is the first comprehensive report of optimal fermentation conditions demonstrating enhanced SFAs production by strains belonging to two different thraustochytrid genera and provides the basis for large-scale biodiesel production. Copyright © 2018. Published by Elsevier B.V.

VizieR Online Data Catalog: LAMOST candidate members of star clusters (Xiang+, 2015)

NASA Astrophysics Data System (ADS)

Xiang, M. S.; Liu, X. W.; Yuan, H. B.; Huang, Y.; Huo, Z. Y.; Zhang, H. W.; Chen, B. Q.; Zhang, H. H.; Sun, N. C.; Wang, C.; Zhao, Y. H.; Shi, J. R.; Luo, A. L.; Li, G. P.; Wu, Y.; Bai, Z. R.; Zhang, Y.; Hou, Y. H.; Yuan, H. L.; Li, G. W.; Wei, Z.

2015-08-01

In this work, we describe the algorithms and implementation of LSP3, the LAMOST Stellar Parameter Pipeline at Peking University, a pipeline developed to determine the stellar parameters (radial velocity Vr, effective temperature Teff, surface gravity logg and metallicity [Fe/H]) from LAMOST spectra based on a template-matching technique. Following the data policy of LAMOST surveys, the data as well as the LSP3 pipeline will be public released as value-added products of the first data release of LAMOST (LAMOST DR1; Bai et al., 2015, A&A submitted), currently scheduled in 2014 December and can be accessed via http://lamost973.pku.edu.cn/site/node/4, along with a description file. (1 data file).

Chiral Topological Orders in an Optical Raman Lattice (Open Source)

DTIC Science & Technology

2016-03-01

towhomany correspondence should be addressed. E-mail: xiongjunliu@pku.edu.cn Keywords: optical lattice, gaugefields, Chern insulator , topological order...onlymeasuring the Bloch states in the two symmetricmomentumpoints of the first Brillouin zone. Further, we also show that heating in the present optical Raman...spontaneous decay of excited states. Realization of a gapped insulating topological state typically necessitates an optical lattice and synthetic

Anthropometric characteristics and nutrition in a cohort of PAH-deficient patients.

PubMed

Aldámiz-Echevarría, Luis; Bueno, María A; Couce, María L; Lage, Sergio; Dalmau, Jaime; Vitoria, Isidro; Andrade, Fernando; Blasco, Javier; Alcalde, Carlos; Gil, David; García, María C; González-Lamuño, Domingo; Ruiz, Mónica; Peña-Quintana, Luis; Ruiz, María A; González, David; Sánchez-Valverde, Felix

2014-08-01

Treating phenylketonuria based upon strict vegetarian diets has occasionally been found to hamper physical development, some patients presenting with growth retardation and malnutrition. In addition, some researchers have reported an association between higher protein intakes and attaining better developmental outcomes, although it remains unclear which protein fraction (natural or synthetic) has the greatest influence on growth. The present study aimed to evaluate anthropometric characteristics and nutrition in a cohort of patients with phenylketonuria and mild-hyperphenylalaninaemia from birth to adulthood. We conducted a retrospective longitudinal study comparing anthropometric characteristics (weight, height, body mass index, and growth rate) in our patients and healthy subjects, with the measurements expressed as z-scores. Nutritional issues were also considered. Data were collected every 6 months from birth to 18 years of age. Growth impairment was observed in phenylketonuric patients. Specifically, there were two well-differentiated periods throughout which height fell well below z-score = 0: from birth to two years of age, and on reaching adulthood. We also found height and weight to be positively correlated with phenylalanine intake. No growth retardation was seen in the patients with mild-hyperphenylalaninaemia. Phenylketonuric patients showed growth impairment in the early stages, with higher phenylalanine intakes being associated with attaining better developmental outcomes in this period. Therefore, prescribing very stringent diets in the early years might predispose phenylketonuric patients to retarded growth later in life, with growth outcomes in adulthood being well below the 50th percentile for healthy subjects. Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

PlantTFDB 4.0: toward a central hub for transcription factors and regulatory interactions in plants.

PubMed

Jin, Jinpu; Tian, Feng; Yang, De-Chang; Meng, Yu-Qi; Kong, Lei; Luo, Jingchu; Gao, Ge

2017-01-04

With the goal of providing a comprehensive, high-quality resource for both plant transcription factors (TFs) and their regulatory interactions with target genes, we upgraded plant TF database PlantTFDB to version 4.0 (http://planttfdb.cbi.pku.edu.cn/). In the new version, we identified 320 370 TFs from 165 species, presenting a more comprehensive genomic TF repertoires of green plants. Besides updating the pre-existing abundant functional and evolutionary annotation for identified TFs, we generated three new types of annotation which provide more directly clues to investigate functional mechanisms underlying: (i) a set of high-quality, non-redundant TF binding motifs derived from experiments; (ii) multiple types of regulatory elements identified from high-throughput sequencing data; (iii) regulatory interactions curated from literature and inferred by combining TF binding motifs and regulatory elements. In addition, we upgraded previous TF prediction server, and set up four novel tools for regulation prediction and functional enrichment analyses. Finally, we set up a novel companion portal PlantRegMap (http://plantregmap.cbi.pku.edu.cn) for users to access the regulation resource and analysis tools conveniently. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Evaluation of an adsorbent based on agricultural waste (corn cobs) for removal of tyrosine and phenylalanine from aqueous solutions.

PubMed

Alves, Cibele C O; Franca, Adriana S; Oliveira, Leandro S

2013-01-01

Adsorption of phenolic amino acids, such as phenylalanine and tyrosine, is quite relevant for the production of protein hydrolysates used as dietary formulations for patients suffering from congenital disorders of amino acid metabolism, such as phenylketonuria. In this study, an adsorbent prepared from corn cobs was evaluated for the removal of tyrosine (Tyr) from both a single component solution and a binary aqueous solution with phenylalanine (Phe). The adsorption behavior of tyrosine was similar to that of phenylalanine in single component solutions, however, with a much lower adsorption capacity (14 mg g(-1) for Tyr compared to 109 mg g(-1) for Phe). Tyr adsorption kinetics was satisfactorily described by a pseudosecond-order model as it was for Phe. In adsorption equilibrium studies for binary mixtures, the presence of Tyr in Phe solutions favored Phe faster adsorption whereas the opposite behavior was observed for the presence of Phe in Tyr solutions. Such results indicate that, in binary systems, Phe will be adsorbed preferably to Tyr, and this is a welcome feature when employing the prepared adsorbent for the removal of Phe from protein hydrolysates to be used in dietary formulations for phenylketonuria treatment.

Application of laser therapy in treating inherited forms of psychoverbal retardation in children

NASA Astrophysics Data System (ADS)

Ulas, V. Y.; Voinova, V. M.; Il'in, L. B.; Troitskaya, L. A.; Dobrynina, E. V.; Kazantseva, L. Z.

2001-04-01

An investigation was made of applying combined laser therapy in the treatment of 619 children (422 children constituted the experimental group and 197 children composed the control group) affected by inherited forms of psychoverbal retardation. It was found that low-intensity He-Ne laser radiation with the wavelength of 632.8 nm and the output power of 2 mW made it possible to improve the children's mental development. Moreover, it effectively increased their mental activities, such as speech, communication, arbitrary behavior regulation, and locomotory functions. Laser therapy applied in treating children affected by the arrested mental development aggravated by obesity additionally decreased their body weight, increased their field of vision, and eliminated dyslipidemia. It was also found that contraindications to He-Ne laser acupuncture included phenylketonuria-related noncorrected metabolic defects, convulsive syndromes, epileptic activities, convulsive readiness, and cerebrolysine intramuscular injections.

Newborn screening: a review of history, recent advancements, and future perspectives in the era of next generation sequencing.

PubMed

Almannai, Mohammed; Marom, Ronit; Sutton, V Reid

2016-12-01

The purpose of this review is to summarize the development and recent advancements of newborn screening. Early initiation of medical care has modified the outcome for many disorders that were previously associated with high morbidity (such as cystic fibrosis, primary immune deficiencies, and inborn errors of metabolism) or with significant neurodevelopmental disabilities (such as phenylketonuria and congenital hypothyroidism). The new era of mass spectrometry and next generation sequencing enables the expansion of the newborn screen panel, and will help to address technical issues such as turnaround time, and decreasing false-positive and false-negative rates for the testing. The newborn screening program is a successful public health initiative that facilitates early diagnosis of treatable disorders to reduce long-term morbidity and mortality.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, A. L.; Chen, J. E.; State Key Laboratory of Nuclear Physics and Technology, Institute of Heavy Ion Physics, School of Physics, Peking University, Beijing 100871

Negative hydrogen ion beam can be compensated by the trapping of ions into the beam potential. When the beam propagates through a neutral gas, these ions arise due to gas ionization by the beam ions. However, the high neutral gas pressure may cause serious negative hydrogen ion beam loss, while low neutral gas pressure may lead to ion-ion instability and decompensation. To better understand the space charge compensation processes within a negative hydrogen beam, experimental study and numerical simulation were carried out at Peking University (PKU). The simulation code for negative hydrogen ion beam is improved from a 2D particle-in-cell-Montemore » Carlo collision code which has been successfully applied to H{sup +} beam compensated with Ar gas. Impacts among ions, electrons, and neutral gases in negative hydrogen beam compensation processes are carefully treated. The results of the beam simulations were compared with current and emittance measurements of an H{sup −} beam from a 2.45 GHz microwave driven H{sup −} ion source in PKU. Compensation gas was injected directly into the beam transport region to modify the space charge compensation degree. The experimental results were in good agreement with the simulation results.« less

[Model project for updating neonatal screening in Bavaria: concept and initial results].

PubMed

Liebl, B; Fingerhut, R; Röschinger, W; Muntau, A; Knerr, I; Olgemöller, B; Zapf, A; Roscher, A A

2000-04-01

The newborn screening programme in Bavaria was confronted with several problems. Number of disorders and process quality no longer complied with screening guidelines. Mixed financing, distributed between the state (PKU, galactosaemia) and health insurances (hypothyroidism) had promoted an increasing dissipation of the system. Notified participation rates had dropped to < 80%. Increasing need for a second screening due to early discharge was an additional challenge. To overcome these problems, and considering the availability of improved screening methodology (tandem mass spectrometry) the programme was reorganised. The project, which started on Jan 1, 1999, is based on a cooperation model between laboratory (logistics, analysis), universities (treatment, scientific evaluation), and public health services (coordination, tracking). Time of blood sampling was predated to the third day of life. Screening was extended to biotinidase deficiency, congenital adrenal hyperplasia (CAH) and by introduction of tandem mass spectrometry for screening of many other disorders (besides PKU). Insurances now finance complete laboratory analysis which was transferred to the private sector. To enable all newborn to participate, the names of screened children are matched against birth lists by public health services on a regional basis. Recalls and conspicuous results are consistently followed up until disorders are either excluded or confirmed. Two clinical hotlines were established in the children's hospitals of the universities in Munich (Southern Bavaria) and in Erlangen (Northern Bavaria). Written consent is required for participation in the programme. Participation in the new programme could be continually increased; coverage is > 95% since April. In several cases screening was made up for not tested children by contacting their parents. Omitted screening was mostly due to misunderstandings regarding testing responsibility or lost samples. Altogether 52 cases of disorder were

Arabidopsis Hormone Database: a comprehensive genetic and phenotypic information database for plant hormone research in Arabidopsis

PubMed Central

Peng, Zhi-yu; Zhou, Xin; Li, Linchuan; Yu, Xiangchun; Li, Hongjiang; Jiang, Zhiqiang; Cao, Guangyu; Bai, Mingyi; Wang, Xingchun; Jiang, Caifu; Lu, Haibin; Hou, Xianhui; Qu, Lijia; Wang, Zhiyong; Zuo, Jianru; Fu, Xiangdong; Su, Zhen; Li, Songgang; Guo, Hongwei

2009-01-01

Plant hormones are small organic molecules that influence almost every aspect of plant growth and development. Genetic and molecular studies have revealed a large number of genes that are involved in responses to numerous plant hormones, including auxin, gibberellin, cytokinin, abscisic acid, ethylene, jasmonic acid, salicylic acid, and brassinosteroid. Here, we develop an Arabidopsis hormone database, which aims to provide a systematic and comprehensive view of genes participating in plant hormonal regulation, as well as morphological phenotypes controlled by plant hormones. Based on data from mutant studies, transgenic analysis and gene ontology (GO) annotation, we have identified a total of 1026 genes in the Arabidopsis genome that participate in plant hormone functions. Meanwhile, a phenotype ontology is developed to precisely describe myriad hormone-regulated morphological processes with standardized vocabularies. A web interface (http://ahd.cbi.pku.edu.cn) would allow users to quickly get access to information about these hormone-related genes, including sequences, functional category, mutant information, phenotypic description, microarray data and linked publications. Several applications of this database in studying plant hormonal regulation and hormone cross-talk will be presented and discussed. PMID:19015126

Arabidopsis Hormone Database: a comprehensive genetic and phenotypic information database for plant hormone research in Arabidopsis.

PubMed

Peng, Zhi-yu; Zhou, Xin; Li, Linchuan; Yu, Xiangchun; Li, Hongjiang; Jiang, Zhiqiang; Cao, Guangyu; Bai, Mingyi; Wang, Xingchun; Jiang, Caifu; Lu, Haibin; Hou, Xianhui; Qu, Lijia; Wang, Zhiyong; Zuo, Jianru; Fu, Xiangdong; Su, Zhen; Li, Songgang; Guo, Hongwei

2009-01-01

Plant hormones are small organic molecules that influence almost every aspect of plant growth and development. Genetic and molecular studies have revealed a large number of genes that are involved in responses to numerous plant hormones, including auxin, gibberellin, cytokinin, abscisic acid, ethylene, jasmonic acid, salicylic acid, and brassinosteroid. Here, we develop an Arabidopsis hormone database, which aims to provide a systematic and comprehensive view of genes participating in plant hormonal regulation, as well as morphological phenotypes controlled by plant hormones. Based on data from mutant studies, transgenic analysis and gene ontology (GO) annotation, we have identified a total of 1026 genes in the Arabidopsis genome that participate in plant hormone functions. Meanwhile, a phenotype ontology is developed to precisely describe myriad hormone-regulated morphological processes with standardized vocabularies. A web interface (http://ahd.cbi.pku.edu.cn) would allow users to quickly get access to information about these hormone-related genes, including sequences, functional category, mutant information, phenotypic description, microarray data and linked publications. Several applications of this database in studying plant hormonal regulation and hormone cross-talk will be presented and discussed.

PlantTFDB: a comprehensive plant transcription factor database

PubMed Central

Guo, An-Yuan; Chen, Xin; Gao, Ge; Zhang, He; Zhu, Qi-Hui; Liu, Xiao-Chuan; Zhong, Ying-Fu; Gu, Xiaocheng; He, Kun; Luo, Jingchu

2008-01-01

Transcription factors (TFs) play key roles in controlling gene expression. Systematic identification and annotation of TFs, followed by construction of TF databases may serve as useful resources for studying the function and evolution of transcription factors. We developed a comprehensive plant transcription factor database PlantTFDB (http://planttfdb.cbi.pku.edu.cn), which contains 26 402 TFs predicted from 22 species, including five model organisms with available whole genome sequence and 17 plants with available EST sequences. To provide comprehensive information for those putative TFs, we made extensive annotation at both family and gene levels. A brief introduction and key references were presented for each family. Functional domain information and cross-references to various well-known public databases were available for each identified TF. In addition, we predicted putative orthologs of those TFs among the 22 species. PlantTFDB has a simple interface to allow users to search the database by IDs or free texts, to make sequence similarity search against TFs of all or individual species, and to download TF sequences for local analysis. PMID:17933783

Selected environmental risk factors and congenital heart defects.

PubMed

Kuciene, Renata; Dulskiene, Virginija

2008-01-01

The aim of the article is to review the published scientific literature and epidemiological studies about the effect of selected environmental risk factors on congenital heart defects in infants. According to recent reports, the prevalence of congenital heart defects is around 1% of live births. Congenital heart malformations are the leading cause of infant mortality. Unfortunately, the majority of the causes of heart defects remain unknown. These malformations are caused by interaction of genetic and environmental factors. The article reviews selected environmental risk factors: maternal illnesses and conditions associated with metabolic disorder (maternal diabetes, obesity, phenylketonuria), maternal lifestyle factors (alcohol use, smoking), which may increase the risk of congenital heart defects.

Spatial and Temporal Trends in Global Emissions of Nitrogen Oxides from 1960 to 2014.

PubMed

Huang, Tianbo; Zhu, Xi; Zhong, Qirui; Yun, Xiao; Meng, Wenjun; Li, Bengang; Ma, Jianmin; Zeng, Eddy Y; Tao, Shu

2017-07-18

The quantification of nitrogen oxide (NO x ) emissions is critical for air quality modeling. Based on updated fuel consumption and emission factor databases, a global emission inventory was compiled with high spatial (0.1° × 0.1°), temporal (monthly), and source (87 sources) resolutions for the period 1960 to 2014. The monthly emission data have been uploaded online ( http://inventory.pku.edu.cn ), along with a number of other air pollutant and greenhouse gas data for free download. Differences in source profiles, not global total quantities, between our results and those reported previously were found. There were significant differences in total and per capita emissions and emission intensities among countries, especially between the developing and developed countries. Globally, the total annual NO x emissions finally stopped increasing in 2013 after continuously increasing over several decades, largely due to strict control measures taken in China in recent years. Nevertheless, the peak year of NO x emissions was later than for many other major air pollutants. Per capita emissions, either among countries or over years, follow typical inverted U-shaped environmental Kuznets curves, indicating that the emissions increased during the early stage of development and were restrained when socioeconomic development reached certain points. Although the trends are similar among countries, the turning points of developing countries appeared sooner than those of developed countries in terms of development status, confirming late-move advantages.

A sialic acid assay in isolation and purification of bovine k-casein glycomacropeptide: a review.

PubMed

Nakano, Takuo; Ozimek, Lech

2014-01-01

Sialic acid is a carbohydrate moiety of k-casein glycomacropeptide (GMP), which is a 64 amino acid residue C-terminal sialylated phosphorylated glycopeptide released from k-casein by the action of chymosin during cheese making. GMP lacks aromatic amino acids including phenylalanine, tyrosine, and tryptophan. Because of its unique amino acid composition and various biological activities, GMP is thought to be a potential ingredient for dietetic foods (e.g., a food for PKU patients) and pharmaceuticals. Thus, increased attention has been given to the development of techniques to purify GMP. In this review, techniques of GMP purification described in patents and scientific research papers were introduced. A sialic acid assay is the important method to track GMP isolation and purification processes, for which the thiobarbituric acid reaction with 1-propanol as a chromophore extracting solvent is an inexpensive, practical and specific technique. Sephacryl S-200 gel filtration chromatography, cellulose acetate electrophoresis, and sodium dodecyl sulfate polyacrylamide gel electrophoresis are the major techniques to identify sialic acid specific to GMP. Sephacryl S-200 chromatography and cellulose acetate electrophoresis are also used to detect GMP sialic acid in whey pearmeate and whey added commercial margarine samples. Future research includes development of an economical industrial scale method to produce high purity GMP.

Mutation Spectrum and Birth Prevalence of Inborn Errors of Metabolism among Emiratis

PubMed Central

Al-Shamsi, Aisha; Hertecant, Jozef L.; Al-Hamad, Sania; Souid, Abdul-Kader; Al-Jasmi, Fatma

2014-01-01

Objectives: This study aimed to determine the mutation spectrum and prevalence of inborn errors of metabolism (IEM) among Emiratis. Methods: The reported mutation spectrum included all patients who were diagnosed with IEM (excluding those with lysosomal storage diseases [LSD]) at Tawam Hospital Metabolic Center in Abu Dhabi, United Arab Emirates, between January 1995 and May 2013. Disease prevalence (per 100,000 live births) was estimated from data available for 1995–2011. Results: In 189 patients, 57 distinct IEM were diagnosed, of which 20 (35%) entities were previously reported LSD (65 patients with 39 mutations), with a birth prevalence of 26.87/100,000. This study investigated the remaining 37 (65%) patients with other IEM (124 patients with 62 mutations). Mutation analysis was performed on 108 (87%) of the 124 patients. Five patients with biotinidase deficiency had compound heterozygous mutations, and two siblings with lysinuric protein intolerance had two homozygous mutations. The remaining 103 (95%) patients had homozygous mutations. As of this study, 29 (47%) of the mutations have been reported only in Emiratis. Two mutations were found in three tribes (biotinidase deficiency [BTD, c.1330G>C] and phenylketonuria [PAH, c.168+5G>C]). Two mutations were found in two tribes (isovaleric aciduria [IVD, c.1184G>A] and propionic aciduria [PCCB, c.990dupT]). The remaining 58 (94%) mutations were each found in individual tribes. The prevalence was 48.37/100,000. The most prevalent diseases (2.2–4.9/100,000) were biotinidase deficiency; tyrosinemia type 1; phenylketonuria; propionic aciduria; glutaric aciduria type 1; glycogen storage disease type Ia, and mitochondrial deoxyribonucleic acid depletion. Conclusion: The IEM birth prevalence (LSD and non-LSD) was 75.24/100,000. These results justify implementing prevention programmes that incorporate genetic counselling and screening. PMID:24516753

Reptilian behavioural patterns in childhood autism.

PubMed

Thong, Y H

1984-04-01

Childhood autism may be caused by damage to three phylogenetically distinct regions of the brain, or their major pathways and connections. Injury to the neocortex results in loss of language and cognitive function, while injury to the limbic cortex results in autistic withdrawal and abolition of play behaviour. Injury to the more primitive striatal complex, mammalian counterpart of the brain of reptiles, results in a bizarre and truncated form of stereotyped and ritualistic behaviour. The causes of brain injury in childhood autism could be those common in the perinatal period including cerebral anoxia, haemorrhage, phenylketonuria, neurolipidoses , meningitis, toxoplasmosis, and congenital rubella. All these conditions have previously been shown to be associated with childhood autism.

Carrier screening for single gene disorders.

PubMed

Rose, Nancy C; Wick, Myra

2018-04-01

Screening for genetic disorders began in 1963 with the initiation of newborn screening for phenylketonuria. Advances in molecular technology have made both newborn screening for newborns affected with serious disorders, and carrier screening of individuals at risk for offspring with genetic disorders, more complex and more widely available. Carrier screening today can be performed secondary to family history-based screening, ethnic-based screening, and expanded carrier screening (ECS). ECS is panel-based screening, which analyzes carrier status for hundreds of genetic disorders irrespective of patient race or ethnicity. In this article, we review the historical and current aspects of carrier screening for single gene disorders, including future research directions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Direct amino acid analyses of mozzarella cheese.

PubMed

Hoskins, M N

1985-12-01

The amino acid content of mozzarella (low moisture, part skim milk) and asadero cheeses was determined by the column chromatographic method. Data from the direct analyses of the mozzarella cheeses were compared with the calculated amino acid composition reported in tables in Agriculture Handbook No. 8-1. Phenylalanine and tyrosine contents were found to be higher in the direct analyses than in the calculated data in Handbook No. 8-1 (1.390 gm and 1.127 gm for phenylalanine, and 1.493 gm and 1.249 gm for tyrosine per 100 gm edible portion, respectively). That is of particular concern in the dietary management of phenylketonuria, in which accuracy in computing levels of phenylalanine and tyrosine is essential.

Therapeutic uses of microencapsulated genetically engineered cells.

PubMed

Chang, T M; Prakash, S

1998-05-01

Microencapsulated genetically engineered cells have the potential to treat a wide range of diseases. For example, in experimental animals, implanted microencapsulated cells have been used to secrete growth hormone to treat dwarfism, neurotrophic factors for amyotrophic lateral sclerosis, beta-endorphin to decrease pain, factor XI for hemophilia B, and nerve growth factors to protect axotomized neurons. For some applications, microencapsulated cells can even be given orally. They can be engineered to remove unwanted molecules from the body as they travel through the intestine, and are finally excreted in the stool without being retained in the body. This application has enormous potential for the removal of urea in kidney failure, ammonia in liver failure and amino acids such as phenylalanine in phenylketonuria and other inborn errors of metabolism.

A resolution designating December 3, 2012, as "National Phenylketonuria Awareness Day".

THOMAS, 112th Congress

Sen. Isakson, Johnny [R-GA

2012-09-19

Senate - 09/19/2012 Submitted in the Senate, considered, and agreed to without amendment and with a preamble by Unanimous Consent. (All Actions) Tracker: This bill has the status Agreed to in SenateHere are the steps for Status of Legislation:

A resolution designating December 3, 2014, as "National Phenylketonuria Awareness Day".

THOMAS, 113th Congress

Sen. Isakson, Johnny [R-GA

2014-11-20

Senate - 12/03/2014 Resolution agreed to in Senate without amendment and with a preamble by Unanimous Consent. (All Actions) Tracker: This bill has the status Agreed to in SenateHere are the steps for Status of Legislation:

Deuteron injector for Peking University Neutron Imaging Facility projecta)

NASA Astrophysics Data System (ADS)

Ren, H. T.; Peng, S. X.; Lu, P. N.; Zhou, Q. F.; Yuan, Z. X.; Zhao, J.; Zhang, M.; Song, Z. Z.; Yu, J. X.; Guo, Z. Y.; Chen, J. E.

2012-02-01

The deuteron injector developed for the PKUNIFTY (Peking University Neutron Imaging Facility) has been installed and commissioned at Peking University (PKU). The injector system must transfer 50 keV 50 mA of D+ ion beam to the entrance of the 2 MeV radio frequency quadrupole (RFQ) with 10% duty factor (1 ms, 100 Hz). A compact 2.45 GHz permanent magnet electron cyclotron resonance (PMECR) ion source and a 1.36 m long low energy beam transport (LEBT) line using two solenoids was developed as the deuteron injector. A ϕ5 mm four-quadrant diaphragm was used to simulate the entrance of RFQ electrodes. The beam parameters are measured after this core with an emittance measurement unit (EMU) and a bending magnet for ion fraction analysis at the end of injector. During the commissioning, 77 mA of total deuteron beam was extracted from PMECR and 56 mA of pure D+ beam that passed through the ϕ5 mm four-quadrant diaphragm was obtained at the position of RFQ entrance with the measured normalized rms emittance 0.12-0.16π mm mrad. Ion species analysis results show that the deuteron fraction is as high as 99.5%. All of the parameters satisfy PKUNIFTY's requirements. In this paper, we will describe the deuteron injector design and report the commissioning results as well as the initial operation.

iSeq: Web-Based RNA-seq Data Analysis and Visualization.

PubMed

Zhang, Chao; Fan, Caoqi; Gan, Jingbo; Zhu, Ping; Kong, Lei; Li, Cheng

2018-01-01

Transcriptome sequencing (RNA-seq) is becoming a standard experimental methodology for genome-wide characterization and quantification of transcripts at single base-pair resolution. However, downstream analysis of massive amount of sequencing data can be prohibitively technical for wet-lab researchers. A functionally integrated and user-friendly platform is required to meet this demand. Here, we present iSeq, an R-based Web server, for RNA-seq data analysis and visualization. iSeq is a streamlined Web-based R application under the Shiny framework, featuring a simple user interface and multiple data analysis modules. Users without programming and statistical skills can analyze their RNA-seq data and construct publication-level graphs through a standardized yet customizable analytical pipeline. iSeq is accessible via Web browsers on any operating system at http://iseq.cbi.pku.edu.cn .

Affinity chromatography matrices for depletion and purification of casein glycomacropeptide from bovine whey.

PubMed

Baieli, María F; Urtasun, Nicolás; Martinez, María J; Hirsch, Daniela B; Pilosof, Ana M R; Miranda, María V; Cascone, Osvaldo; Wolman, Federico J

2017-01-01

Casein glycomacropeptide (CMP) is a 64- amino acid peptide found in cheese whey, which is released after κ-casein specific cleavage by chymosin. CMP lacks aromatic amino acids, a characteristic that makes it usable as a nutritional supplement for people with phenylketonuria. CMP consists of two nonglycosylated isoforms (aCMP A and aCMP B) and its different glycosylated forms (gCMP A and gCMP B). The most predominant carbohydrate of gCMP is N-acetylneuraminic acid (sialic acid). Here, we developed a CMP purification process based on the affinity of sialic acid for wheat germ agglutinin (WGA). After formation of chitosan beads and adsorption of WGA, the agglutinin was covalently attached with glutaraldehyde. Two matrices with different WGA density were assayed for CMP adsorption. Maximum adsorption capacities were calculated according to the Langmuir model from adsorption isotherms developed at pH 7.0, being 137.0 mg/g for the matrix with the best performance. In CMP reduction from whey, maximum removal percentage was 79% (specifically 33.7% of gCMP A and B, 75.8% of aCMP A, and 93.9% of aCMP B). The CMP was recovered as an aggregate with an overall yield of 64%. Therefore, the matrices developed are promising for CMP purification from cheese whey. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 33:171-180, 2017. © 2016 American Institute of Chemical Engineers.

The significant role of amino acids during pregnancy: nutritional support.

PubMed

Manta-Vogli, Penelope D; Schulpis, Kleopatra H; Dotsikas, Yannis; Loukas, Yannis L

2018-06-18

Pregnancy is characterized by a complexity of metabolic processes that may impact fetal development and infant health outcome. Normal fetal growth and development depend on a continuous supply of nutrients via the placenta. The placenta transports, utilizes, produces and interconverts amino acids (AAs). Concentrations of both nonessential and essential AAs in maternal plasma decrease in early pregnancy and persist at low concentrations throughout. The decline is greatest for the glucogenic AAs and AAs of the urea cycle. Additionally there is a large placental utilization of the branched-chain AAs, some of which are transaminated to alpha ketoacids and contribute to placental ammonia production. Both nonessential and essential AAs regulate key metabolic pathways to improve health, survival, growth, development, lactation, and reproduction of organisms. Some of the nonessential AAs (eg glutamine, glutamate and arginine) play also important roles in regulating gene expression, cell signaling, antioxidant responses, immunity, and neurological function. Nutritional support during pregnancy is of great interest focusing not only to common pregnancies but also to those with low socioeconomic status, vegan-vegetarian groups and pregnant women with metabolic disorders, the most known maternal phenylketonuria. The latter is of great interest because phenylalanine must be within the recommended range throughout pregnancy in addition to other nutrients such as vitamin B12, folate, etc. Loss of the adherence to this specific diet results in congenital malformations of the fetus. In addition to the routine laboratory test, quantitation of plasma AAs may be necessary throughout pregnancy.

[Prevalence of diseases diagnosed by the Program of Neonatal Screening in Maringá, Paraná, Brazil: 2001-2006].

PubMed

Luz, Geisa dos Santos; Carvalho, Maria Dalva de Barros; Pelloso, Sandra Marisa; Higarashi, Ieda Harumi

2008-09-01

Irreversible sequels of some genetic diseases can be prevented by neonatal screening. The aim of this paper was to verify the prevalence of diseases diagnosed by the National Program of Neonatal Screening (PNTN) in Maringá, Paraná, Brazil, between 2001 and 2006. This cross-sectional descriptive study included 20,529 newborn infants screened by that program. Out of those, 859 were re-examined, and 21 had the disease confirmed. Considering all screened newborn infants and the number of diagnostics per disease, the following disease prevalence was determine: phenylketonuria--1:20,529; congenital hypothyrodism--1:2,281; hemoglobinopahies--1:3,421; cystic fibrosis--1:10,264; and biotinidase deficiency--1:6,843. Understanding disease status and prevalence of newborns in a population allows the establishment and the improvement of public policies aimed at the children.

Global atmospheric emissions and transport of polycyclic aromatic hydrocarbons: Evaluation of modeling and transboundary pollution

NASA Astrophysics Data System (ADS)

Shen, Huizhong; Tao, Shu

2014-05-01

Global atmospheric emissions of 16 polycyclic aromatic hydrocarbons (PAHs) from 69 major sources were estimated for a period from 1960 to 2030. Regression models and a technology split method were used to estimated country and time specific emission factors, resulting in a new estimate of PAH emission factor variation among different countries and over time. PAH emissions in 2007 were spatially resolved to 0.1° × 0.1° grids based on a newly developed global high-resolution fuel combustion inventory (PKU-FUEL-2007). MOZART-4 (The Model for Ozone and Related Chemical Tracers, version 4) was applied to simulate the global tropospheric transport of Benzo(a)pyrene, one of the high molecular weight carcinogenic PAHs, at a horizontal resolution of 1.875° (longitude) × 1.8947° (latitude). The reaction with OH radical, gas/particle partitioning, wet deposition, dry deposition, and dynamic soil/ocean-air exchange of PAHs were considered. The simulation was validated by observations at both background and non-background sites, including Alert site in Canadian High Arctic, EMEP sites in Europe, and other 254 urban/rural sites reported from literatures. Key factors effecting long-range transport of BaP were addressed, and transboundary pollution was discussed.

Genes and (Common) Pathways Underlying Drug Addiction

PubMed Central

Li, Chuan-Yun; Mao, Xizeng; Wei, Liping

2008-01-01

Drug addiction is a serious worldwide problem with strong genetic and environmental influences. Different technologies have revealed a variety of genes and pathways underlying addiction; however, each individual technology can be biased and incomplete. We integrated 2,343 items of evidence from peer-reviewed publications between 1976 and 2006 linking genes and chromosome regions to addiction by single-gene strategies, microrray, proteomics, or genetic studies. We identified 1,500 human addiction-related genes and developed KARG (http://karg.cbi.pku.edu.cn), the first molecular database for addiction-related genes with extensive annotations and a friendly Web interface. We then performed a meta-analysis of 396 genes that were supported by two or more independent items of evidence to identify 18 molecular pathways that were statistically significantly enriched, covering both upstream signaling events and downstream effects. Five molecular pathways significantly enriched for all four different types of addictive drugs were identified as common pathways which may underlie shared rewarding and addictive actions, including two new ones, GnRH signaling pathway and gap junction. We connected the common pathways into a hypothetical common molecular network for addiction. We observed that fast and slow positive feedback loops were interlinked through CAMKII, which may provide clues to explain some of the irreversible features of addiction. PMID:18179280

LocExpress: a web server for efficiently estimating expression of novel transcripts.

PubMed

Hou, Mei; Tian, Feng; Jiang, Shuai; Kong, Lei; Yang, Dechang; Gao, Ge

2016-12-22

The temporal and spatial-specific expression pattern of a transcript in multiple tissues and cell types can indicate key clues about its function. While several gene atlas available online as pre-computed databases for known gene models, it's still challenging to get expression profile for previously uncharacterized (i.e. novel) transcripts efficiently. Here we developed LocExpress, a web server for efficiently estimating expression of novel transcripts across multiple tissues and cell types in human (20 normal tissues/cells types and 14 cell lines) as well as in mouse (24 normal tissues/cell types and nine cell lines). As a wrapper to RNA-Seq quantification algorithm, LocExpress efficiently reduces the time cost by making abundance estimation calls increasingly within the minimum spanning bundle region of input transcripts. For a given novel gene model, such local context-oriented strategy allows LocExpress to estimate its FPKMs in hundreds of samples within minutes on a standard Linux box, making an online web server possible. To the best of our knowledge, LocExpress is the only web server to provide nearly real-time expression estimation for novel transcripts in common tissues and cell types. The server is publicly available at http://loc-express.cbi.pku.edu.cn .

[Generalized neonatal screening based on laboratory tests].

PubMed

Ardaillou, Raymond; Le Gall, Jean-Yves

2006-11-01

Implementation of a generalized screening program for neonatal diseases must obey precise rules. The disease must be severe, recognizable at an early stage, amenable to an effective treatment, detectable with a non expensive and widely applicable test; it must also be a significant public health problem. Subjects with positive results must be offered immediate treatment or prevention. All screening programs must be regularly evaluated. In France, since 1978, a national screening program has been organized by a private association ("Association française pour le dépistage et la prévention des handicaps de l'enfant") and supervised by the "Caisse nationale d'assurance maladie" and "Direction Générale de la Sante". Five diseases are now included in the screening program: phenylketonuria, hypothyroidism, congenital adrenal hyperplasia, cystic fibrosis and sickle cell disease (the latter only in at-risk newborns). Toxoplasmosis is a particular problem because only the children of mothers who were not tested during the pregnancy or who seroconverted are screened. Neonatal screening for phenylketonuria and hypothyrodism is unanimously recommended. Screening for congenital adrenal hyperplasia is approved in most countries. Cases of sickle cell disease and cystic fibrosis are more complex because--not all children who carry the mutations develop severe forms;--there is no curative treatment;--parents may become anxious, even though the phenotype is sometimes mild or even asymptomatic. Supporters of screening stress the benefits of early diagnosis (which extends the life expectancy of these children, particularly in the case of sickle cell disease), the fact that it opens up the possibility of prenatal screening of future pregnancies, and the utility of informing heterozygous carriers identified by familial screening. Neonatal screening for other diseases is under discussion. Indeed, technical advances such as tandem mass spectrometry make it possible to detect about 50

Biochemical, metabolic, and behavioral characteristics of immature chronic hyperphenylalanemic rats

PubMed Central

Dienel, Gerald A.; Cruz, Nancy F.

2015-01-01

Phenylketonuria and hyperphenylalanemia are inborn errors in metabolism of phenylalanine arising from defects in steps to convert phenylalanine to tyrosine. Phe accumulation causes severe mental retardation that can be prevented by timely identification of affected individuals and their placement on a Phe-restricted diet. In spite of many studies in patients and animal models, the basis for acquisition of mental retardation during the critical period of brain development is not adequately understood. All animal models for human disease have advantages and limitations, and characteristics common to different models are most likely to correspond to the disorder. This study established similar levels of Phe exposure in developing rats between 3 and 16 days of age using three models to produce chronic hyperphenylalanemia, and identified changes in brain amino acid levels common to all models that persist for ~16h of each day. In a representative model, local rates of glucose utilization (CMRglc) were determined at 25–27 days of age, and only selective changes that appeared to depend on Phe exposure were observed. CMRglc was reduced in frontal cortex and thalamus and increased in hippocampus and globus pallidus. Behavioral testing to evaluate neuromuscular competence revealed poor performance in chronically-hyperphenylalanemic rats that persisted for at least three weeks after cessation of Phe injections and did not occur with mild or acute hyperphenylalanemia. Thus, the abnormal amino acid environment, including hyperglycinemia, in developing rat brain is associated with selective regional changes in glucose utilization and behavioral abnormalities that are not readily reversed after they are acquired. PMID:26224289

Image retrieval by information fusion based on scalable vocabulary tree and robust Hausdorff distance

NASA Astrophysics Data System (ADS)

Che, Chang; Yu, Xiaoyang; Sun, Xiaoming; Yu, Boyang

2017-12-01

In recent years, Scalable Vocabulary Tree (SVT) has been shown to be effective in image retrieval. However, for general images where the foreground is the object to be recognized while the background is cluttered, the performance of the current SVT framework is restricted. In this paper, a new image retrieval framework that incorporates a robust distance metric and information fusion is proposed, which improves the retrieval performance relative to the baseline SVT approach. First, the visual words that represent the background are diminished by using a robust Hausdorff distance between different images. Second, image matching results based on three image signature representations are fused, which enhances the retrieval precision. We conducted intensive experiments on small-scale to large-scale image datasets: Corel-9, Corel-48, and PKU-198, where the proposed Hausdorff metric and information fusion outperforms the state-of-the-art methods by about 13, 15, and 15%, respectively.

Plasma studies of the permanent magnet electron cyclotron resonance ion source at Peking University.

PubMed

Ren, H T; Peng, S X; Xu, Y; Zhao, J; Lu, P N; Chen, J; Zhang, A L; Zhang, T; Guo, Z Y; Chen, J E

2014-02-01

At Peking University (PKU) we have developed several 2.45 GHz Permanent Magnet Electron Cyclotron Resonance ion sources for PKUNIFTY, SFRFQ, Coupled RFQ&SFRFQ, and Dielectric-Wall Accelerator (DWA) projects (respectively, 50 mA of D(+), 10 mA of O(+), 10 mA of He(+), and 50 mA of H(+)). In order to improve performance of these ion sources, it is necessary to better understand the principal factors that influence the plasma density and the atomic ion fraction. Theoretical analysis about microwave transmission and cut-off inside the discharge chamber were carried out to study the influence of the discharge chamber diameters. As a consequence, experimental studies on plasma density and ion fraction with different discharge chamber sizes have been carried out. Due to the difficulties in measuring plasma density inside the discharge chamber, the output beam current was measured to reflect the plasma density. Experimental results show that the plasma density increases to the maximum and then decreases significantly as the diameter changed from 64 mm to 30 mm, and the atomic ion fraction has the same tendency. The maximum beam intensity was obtained with the diameter of 35 mm, but the maximum atomic ion fraction with a diameter of 40 mm. The experimental results are basically accordant with the theoretical calculation. Details are presented in this paper.

Prediction of Human Cytochrome P450 Inhibition Using a Multitask Deep Autoencoder Neural Network.

PubMed

Li, Xiang; Xu, Youjun; Lai, Luhua; Pei, Jianfeng

2018-05-30

Adverse side effects of drug-drug interactions induced by human cytochrome P450 (CYP450) inhibition is an important consideration in drug discovery. It is highly desirable to develop computational models that can predict the inhibitive effect of a compound against a specific CYP450 isoform. In this study, we developed a multitask model for concurrent inhibition prediction of five major CYP450 isoforms, namely, 1A2, 2C9, 2C19, 2D6, and 3A4. The model was built by training a multitask autoencoder deep neural network (DNN) on a large dataset containing more than 13 000 compounds, extracted from the PubChem BioAssay Database. We demonstrate that the multitask model gave better prediction results than that of single-task models, previous reported classifiers, and traditional machine learning methods on an average of five prediction tasks. Our multitask DNN model gave average prediction accuracies of 86.4% for the 10-fold cross-validation and 88.7% for the external test datasets. In addition, we built linear regression models to quantify how the other tasks contributed to the prediction difference of a given task between single-task and multitask models, and we explained under what conditions the multitask model will outperform the single-task model, which suggested how to use multitask DNN models more effectively. We applied sensitivity analysis to extract useful knowledge about CYP450 inhibition, which may shed light on the structural features of these isoforms and give hints about how to avoid side effects during drug development. Our models are freely available at http://repharma.pku.edu.cn/deepcyp/home.php or http://www.pkumdl.cn/deepcyp/home.php .

COMMITTEES: SQM2008-International Conference on Strangeness in Quark Matter SQM2008-International Conference on Strangeness in Quark Matter

NASA Astrophysics Data System (ADS)

2008-04-01

Local Organising Committee Xiangzhou Cai (SINPA) Weiqin Chao (CCAST) Liewen Chen (SJTU) Jianping Cheng (Tsinghua University) Jinghua Fu (CCNU) Yuanning Gao (Tsinghua University) Xiaomei Li (CIAE) Zuotang Liang (Shandong University) Feng Liu (CCNU), Co-chair Yuxin Liu (PKU) Qing Wang (Tsinghua University) Qun Wang (USTC) Hushan Xu (IMP) Daicui Zhou (CCNU) Pengfei Zhuang (Tsinghua University), Co-chair Bingsong Zou (IHEP) International Advisory Committee Jörg Aichelin, Nantes Federico Antinori, Padova Tamás Biró, Budapest Peter Braun-Munzinger, GSI Jean Cleymans, Cape Town László Csernai, Bergen Timothy Hallman, BNL Huan Zhong Huang, UCLA Takeshi Kodama, Rio de Janeiro Carlos Lourenço, CERN Yu-Gang Ma, Shanghai Jes Masden, Aarhus Yasuo Miake, Tsukuba Berndt Müller, Duke Grazyna Odyniec, LBNL Helmut Oeschler, Darmstadt Johann Rafelski, Arizona Hans Georg Ritter, LBNL Karel Šafařík, CERN Jack Sandweiss, Yale George S F Stephans, MIT Horst Stöcker, Frankfurt Thomas Ullrich, BNL Nu Xu, LBNL William A Zajc, Columbia

PepPat, a pattern-based oligopeptide homology search method and the identification of a novel tachykinin-like peptide.

PubMed

Jiang, Ying; Gao, Ge; Fang, Gang; Gustafson, Eric L; Laverty, Maureen; Yin, Yanbin; Zhang, Yong; Luo, Jingchu; Greene, Jonathan R; Bayne, Marvin L; Hedrick, Joseph A; Murgolo, Nicholas J

2003-05-01

PepPat, a hybrid method that combines pattern matching with similarity scoring, is described. We also report PepPat's application in the identification of a novel tachykinin-like peptide. PepPat takes as input a query peptide and a user-specified regular expression pattern within the peptide. It first performs a database pattern match and then ranks candidates on the basis of their similarity to the query peptide. PepPat calculates similarity over the pattern spanning region, enhancing PepPat's sensitivity for short query peptides. PepPat can also search for a user-specified number of occurrences of a repeated pattern within the target sequence. We illustrate PepPat's application in short peptide ligand mining. As a validation example, we report the identification of a novel tachykinin-like peptide, C14TKL-1, and show it is an NK1 (neuokinin receptor 1) agonist whose message is widely expressed in human periphery. PepPat is offered online at: http://peppat.cbi.pku.edu.cn.

PlantTFDB 3.0: a portal for the functional and evolutionary study of plant transcription factors

PubMed Central

Jin, Jinpu; Zhang, He; Kong, Lei; Gao, Ge; Luo, Jingchu

2014-01-01

With the aim to provide a resource for functional and evolutionary study of plant transcription factors (TFs), we updated the plant TF database PlantTFDB to version 3.0 (http://planttfdb.cbi.pku.edu.cn). After refining the TF classification pipeline, we systematically identified 129 288 TFs from 83 species, of which 67 species have genome sequences, covering main lineages of green plants. Besides the abundant annotation provided in the previous version, we generated more annotations for identified TFs, including expression, regulation, interaction, conserved elements, phenotype information, expert-curated descriptions derived from UniProt, TAIR and NCBI GeneRIF, as well as references to provide clues for functional studies of TFs. To help identify evolutionary relationship among identified TFs, we assigned 69 450 TFs into 3924 orthologous groups, and constructed 9217 phylogenetic trees for TFs within the same families or same orthologous groups, respectively. In addition, we set up a TF prediction server in this version for users to identify TFs from their own sequences. PMID:24174544

Variants of uncertain significance in newborn screening disorders: implications for large-scale genomic sequencing.

PubMed

Narravula, Alekhya; Garber, Kathryn B; Askree, S Hussain; Hegde, Madhuri; Hall, Patricia L

2017-01-01

As exome and genome sequencing using high-throughput sequencing technologies move rapidly into the diagnostic process, laboratories and clinicians need to develop a strategy for dealing with uncertain findings. A commitment must be made to minimize these findings, and all parties may need to make adjustments to their processes. The information required to reclassify these variants is often available but not communicated to all relevant parties. To illustrate these issues, we focused on three well-characterized monogenic, metabolic disorders included in newborn screens: classic galactosemia, caused by GALT variants; phenylketonuria, caused by PAH variants; and medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, caused by ACADM variants. In 10 years of clinical molecular testing, we have observed 134 unique GALT variants, 46 of which were variants of uncertain significance (VUS). In PAH, we observed 132 variants, including 17 VUS, and for ACADM, we observed 64 unique variants, of which 33 were uncertain. After this review, 17 VUS (37%; 7 in ACADM, 9 in GALT, and 1 in PAH) were reclassified from uncertain (6 to benign or likely benign and 11 to pathogenic or likely pathogenic). We identified common types of missing information that would have helped make a definitive classification and categorized this information by ease and cost to obtain.Genet Med 19 1, 77-82.

A Whole-Cell Surface Plasmon Resonance Sensor Based on a Leucine Auxotroph of Escherichia coli Displaying a Gold-Binding Protein: Usefulness for Diagnosis of Maple Syrup Urine Disease.

PubMed

Woo, Min-Ah; Park, Jung Hun; Cho, Daeyeon; Sim, Sang Jun; Kim, Moon Il; Park, Hyun Gyu

2016-03-01

We developed a whole-cell surface plasmon resonance (SPR) sensor based on a leucine auxotroph of Escherichia coli displaying a gold-binding protein (GBP) in response to cell growth and applied this sensor to the diagnosis of maple syrup urine disease, which is represented by the elevated leucine level in blood. The leucine auxotroph was genetically engineered to grow displaying GBP in a proportion to the concentration of target amino acid leucine. The GBP expressed on the surface of the auxotrophs directly bound to the golden surface of an SPR chip without the need for any additional treatment or reagents, which consequently produced SPR signals used to determine leucine levels in a test sample. Gold nanoparticles (GNPs) were further applied to the SPR system, which significantly enhanced the signal intensity up to 10-fold by specifically binding to GBP expressed on the cell surface. Finally, the diagnostic utility of our system was demonstrated by its employment in reliably determining different statuses of maple syrup urine disease based on a known cutoff level of leucine. This new approach based on an amino acid-auxotrophic E. coli strain expressing a GBP that binds to an SPR sensor holds great promise for detection of other metabolic diseases of newborn babies including homocystinuria and phenylketonuria, which are also associated with abnormal levels of amino acids.

Utilization of a hospital information system for outpatient prescription screening process at the PKU Muhammadiyah Yogyakarta Hospital

NASA Astrophysics Data System (ADS)

Ismail, R.; Perwitasari, D. A.; Supadmi, W.; Risdiana, I.

2017-11-01

Prescription screening includes administrative and clinical precision of the drug, dosage, frequency and route of administration, therapeutic duplication, allergic or sensitive reactions, and actual or potential interactions. The study was aimed to identify the obstacles and compliance level of users, as well as the design of a prescription screening information system and its users’ perceptions. This study used qualitative and quantitative research design with action research studies involving pharmacists, pharmacy technicians, a programmer and clinical practice student pharmacists. The obstacle of pharmacists in doing prescription screening was the long duration in the process of manual prescription review. The compliance of pharmacists in manual prescription review was under 50%. The prescription information system was created by the programmer on the proposal of pharmacists in the form of front view, pharmacy display, sales display, prescription display, prescription display per period and display of recapped prescriptions. Perception of the usefulness was very high with a value of 4.5±0.577 and perception of ease of use was very high with a value of 4.214±0.534 from 28 respondents. The prescription information system was created by a programmer upon the recommendations of pharmacists. Perception of the usefulness and ease of use was very high.

Newborn bloodspot screening in the UK--past, present and future.

PubMed

Downing, Melanie; Pollitt, Rodney

2008-01-01

Screening newborn babies for inherited metabolic disease began in the UK in the late 1950s with the 'nappy test' for phenylketonuria. In 1969 the Department of Health recommended changing to bloodspot screening using the techniques developed in the USA by Robert Guthrie and his associates. Bloodspot screening for various other disorders (galactosaemia, maple syrup urine disease, homocystinuria, cystic fibrosis and others) was introduced on a patchy local basis but, until 2000, the only additional disorder officially recommended was congenital hypothyroidism. Screening for haemoglobinopathies received official support in 2000 and for cystic fibrosis in 2001 though implementation was slow, particularly for the latter. Both these screens have raised difficult issues relating to genetic privacy and the detection of carrier status in children. During the last decade screening has become increasingly subject to central control. Though a more consistent and systematic approach was clearly needed, this has undoubtedly slowed the rate of innovation. In particular the UK has lagged behind many other European countries in the application of tandem mass spectrometry (MS-MS) though, following a major pilot study, screening for medium-chain acyl-CoA dehydrogenase deficiency is now in the process of introduction. Attempts to codify clinical and laboratory procedures have also proved controversial, highlighting marked differences in practice in various parts of the country and the difficulty of rationalizing these within a practicable and scientifically justified framework. Notwithstanding this, there are many positive developments and newborn screening remains a stimulating and rewarding field in which to work.

A simple method for the analysis by MS/MS of underivatized amino acids on dry blood spots from newborn screening.

PubMed

Wang, Chunyan; Zhang, Wenyan; Song, Fengrui; Liu, Zhiqiang; Liu, Shuying

2012-05-01

The analysis by electrospray-ionization tandem mass spectrometry of amino acids with butyl esterification and isotopically labeled internal standard is routine in newborn screening laboratories worldwide. In the present study, we established a direct analysis method of higher accuracy that uses a non-deuterated internal standard. The automatic sampler and the pump of an LC apparatus were used to inject sample and mobile phase to MS, but no LC column was needed. The dry blood spot (DBS) material was prepared at levels of low, medium and high concentration; the running time was 1 min. In parallel to the new procedure, we applied the established method to analyze nine amino acids on DBS of healthy newborns and phenylketonuria newborns. The newly proposed method of product ion confirmation scan along with multiple reaction monitoring resulted in a very accurate identification of each amino acid. Our innovative protocol had high sensitivity and specificity in the analysis of cases of suspected metabolic diseases.

Interaction of L-Phenylalanine with a Phospholipid Monolayer at the Water-Air Interface.

PubMed

Griffith, Elizabeth C; Perkins, Russell J; Telesford, Dana-Marie; Adams, Ellen M; Cwiklik, Lukasz; Allen, Heather C; Roeselová, Martina; Vaida, Veronica

2015-07-23

The interaction of L-phenylalanine with a 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) monolayer at the air-water interface was explored using a combination of experimental techniques and molecular dynamics (MD) simulations. By means of Langmuir trough methods and Brewster angle microscopy, L-phenylalanine was shown to significantly alter the interfacial tension and the surface domain morphology of the DPPC film. In addition, confocal microscopy was used to explore the aggregation state of L-phenylalanine in the bulk aqueous phase. Finally, MD simulations were performed to gain molecular-level information on the interactions of L-phenylalanine and DPPC at the interface. Taken together, these results show that L-phenylalanine intercalates into a DPPC film at the air-water interface, thereby affecting the surface tension, phase morphology, and ordering of the DPPC film. The results are discussed in the context of biological systems and the mechanism of diseases such as phenylketonuria.

Global atmospheric emissions of polycyclic aromatic hydrocarbons from 1960 to 2008 and future predictions.

PubMed

Shen, Huizhong; Huang, Ye; Wang, Rong; Zhu, Dan; Li, Wei; Shen, Guofeng; Wang, Bin; Zhang, Yanyan; Chen, Yuanchen; Lu, Yan; Chen, Han; Li, Tongchao; Sun, Kang; Li, Bengang; Liu, Wenxin; Liu, Junfeng; Tao, Shu

2013-06-18

Global atmospheric emissions of 16 polycyclic aromatic hydrocarbons (PAHs) from 69 major sources were estimated for a period from 1960 to 2030. Regression models and a technology split method were used to estimate country and time specific emission factors, resulting in a new estimate of PAH emission factor variation among different countries and over time. PAH emissions in 2007 were spatially resolved to 0.1° × 0.1° grids based on a newly developed global high-resolution fuel combustion inventory (PKU-FUEL-2007). The global total annual atmospheric emission of 16 PAHs in 2007 was 504 Gg (331-818 Gg, as interquartile range), with residential/commercial biomass burning (60.5%), open-field biomass burning (agricultural waste burning, deforestation, and wildfire, 13.6%), and petroleum consumption by on-road motor vehicles (12.8%) as the major sources. South (87 Gg), East (111 Gg), and Southeast Asia (52 Gg) were the regions with the highest PAH emission densities, contributing half of the global total PAH emissions. Among the global total PAH emissions, 6.19% of the emissions were in the form of high molecular weight carcinogenic compounds and the percentage of the carcinogenic PAHs was higher in developing countries (6.22%) than in developed countries (5.73%), due to the differences in energy structures and the disparities of technology. The potential health impact of the PAH emissions was greatest in the parts of the world with high anthropogenic PAH emissions, because of the overlap of the high emissions and high population densities. Global total PAH emissions peaked at 592 Gg in 1995 and declined gradually to 499 Gg in 2008. Total PAH emissions from developed countries peaked at 122 Gg in the early 1970s and decreased to 38 Gg in 2008. Simulation of PAH emissions from 2009 to 2030 revealed that PAH emissions in developed and developing countries would decrease by 46-71% and 48-64%, respectively, based on the six IPCC SRES scenarios.

Global atmospheric emissions of polycyclic aromatic hydrocarbons from 1960 to 2008 and future predictions

PubMed Central

Shen, Huizhong; Huang, Ye; Wang, Rong; Zhu, Dan; Li, Wei; Shen, Guofeng; Wang, Bin; Zhang, Yanyan; Chen, Yuanchen; Lu, Yan; Chen, Han; Li, Tongchao; Sun, Kang; Li, Bengang; Liu, Wenxin; Liu, Junfeng; Tao, Shu

2013-01-01

Global atmospheric emissions of 16 polycyclic aromatic hydrocarbons (PAHs) from 69 major sources were estimated for a period from 1960 to 2030. Regression models and a technology split method were used to estimate country and time specific emission factors, resulting in a new estimate of PAH emission factor variation among different countries and over time. PAH emissions in 2007 were spatially resolved to 0.1°× 0.1° grids based on a newly developed global high-resolution fuel combustion inventory (PKU-FUEL-2007). The global total annual atmospheric emission of 16 PAHs in 2007 was 504 Gg (331-818 Gg, as interquartile range), with residential/commercial biomass burning (60.5%), open-field biomass burning (agricultural waste burning, deforestation, and wildfire, 13.6%), and petroleum consumption by on-road motor vehicles (12.8%) as the major sources. South (87 Gg), East (111 Gg), and Southeast Asia (52 Gg) were the regions with the highest PAH emission densities, contributing half of the global total PAH emissions. Among the global total PAH emissions, 6.19% of the emissions were in the form of high molecular weight carcinogenic compounds and the percentage of the carcinogenic PAHs was higher in developing countries (6.22%) than in developed countries (5.73%), due to the differences in energy structures and the disparities of technology. The potential health impact of the PAH emissions was greatest in the parts of the world with high anthropogenic PAH emissions, because of the overlap of the high emissions and high population densities. Global total PAH emissions peaked at 592 Gg in 1995 and declined gradually to 499 Gg in 2008. Total PAH emissions from developed countries peaked at 122 Gg in the early 1970s and decreased to 38 Gg in 2008. Simulation of PAH emissions from 2009 to 2030 revealed that PAH emissions in developed and developing countries would decrease by 46-71% and 48-64%, respectively, based on the six IPCC SRES scenarios. PMID:23659377

[Mass neonatal screening using biological testing].

PubMed

Ardaillou, R; Le Gall, J-Y

2007-04-01

Implementation of a generalized screening program for neonatal diseases obeys precise guidelines. The disease must be severe, recognizable at an early stage, accessible to an effective treatment, detected with a non expansive and widely applicable test and it must represent an important health problem. In case of positive results, treatment or prevention shall be offered immediately and any screening program has to be regularly evaluated. There is in France since 1978 a national screening program that depends on a private association ("Association française pour le dépistage et la prévention des handicaps de l'enfant") and is supervised by the "Caisse nationale d'assurance maladie" and the "Direction Générale de la Sante". Presently, five diseases are included in the screening program: phenylketonuria, hypothyroidism, congenital adrenal hyperplasia, cystic fibrosis and sickle cell disease, the latter only in at risk newborns. Toxoplasmosis represents a particular problem because screening takes place only in children of mothers that have not been controlled during their pregnancy or in case of seroconversion. Neonatal screening of phenylketonuria and hypothyrodism is unanimously recommended. That of congenital adrenal hyperplasia is approved in most countries. The cases of sickle cell disease and cystic fibrosis are more complex because: 1) all the children that carry the mutations are not affected with a severe disease; 2) there is no curative treatment; 3) parents given information are made anxious, sometimes wrongly if the disease is mild or asymptomatic. The supporters of the screening insist on the interest of an early diagnosis which makes longer the life time of these children, the possibility for the parents to utilize prenatal screening in case of a future pregnancy, and the information given to the heterozygous carriers following a familial screening. The question is raised of the extension of neonatal screening to other diseases. This is now

Phenylalanine hydroxylase deficiency in Mexico: genotype-phenotype correlations, BH4 responsiveness and evidence of a founder effect.

PubMed

Vela-Amieva, M; Abreu-González, M; González-del Angel, A; Ibarra-González, I; Fernández-Lainez, C; Barrientos-Ríos, R; Monroy-Santoyo, S; Guillén-López, S; Alcántara-Ortigoza, M A

2015-07-01

The mutational spectrum of the phenylalanine hydroxylase gene (PAH) in Mexico is unknown, although it has been suggested that PKU variants could have a differential geographical distribution. Genotype-phenotype correlations and genotype-based predictions of responsiveness to tetrahydrobiopterin (BH4 ) have never been performed. We sequenced the PAH gene and determined the geographic origin of each allele, mini-haplotype associated, genotype-phenotype correlations and genotype-based prediction of BH4 responsiveness in 48 Mexican patients. The mutational spectrum included 34 variants with c.60+5G>T being the most frequent (20.8%) and linked to haplotype 4.3 possibly because of a founder effect and/or genetic drift. Two new variants were found c.1A>T and c.969+6T>C. The genotype-phenotype correlation was concordant in 70.8%. The genotype-based prediction to BH4 -responsiveness was 41.7%, this information could be useful for the rational selection of candidates for BH4 testing and therapy. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[A new strategy of gene therapy for hyperphenylalaninemia rats].

PubMed

Jia, X; Liu, J; Xiang, H

2000-06-01

To construct a recombinant vector which expresses active phenylalanine-amonia-lyase (PAL) in Lactococcus lactis (L. L.), and to convert phe into cinnamic acid in small intestine by the engineering L. L. to decrease the phe level in the peripheral blood, and to cure hyperphenylalaninemia rats. PAL cDNA from Petroselinum crispum was subcloned into expression vector pMG36e and transformed L. L. The pMG36ePAL/L.L. was screened and characterized by using PCR and HPLC, and prepared as enteric-coated microcapsules and oral liquid type preparation that were given orally to hyperphenylalaninemia-rats. Engineering L. L. expressing PAL activity was obtained. The phe levels plasma of in the rats receiving preparations made from the engineering L. L. were significantly reduced compared with non-treated hyperphenylalaninemia rats. And the effects of different preparations were different from each other. The engineering L. L. expressing PAL activity can reduce the blood phe level of the hyperphenylalaninemia rats. This may be a potential way for PKU gene therapeutics.

Reduction of L-phenylalanine in protein hydrolysates using L-phenylalanine ammonia-lyase from Rhodosporidium toruloides.

PubMed

Castañeda, María Teresita; Adachi, Osao; Hours, Roque Alberto

2015-10-01

L-Phenylalanine ammonia-lyase (PAL, EC 4.3.1.25) from Rhodosporidium toruloides was utilized to remove L-phenylalanine (L-Phe) from different commercial protein hydrolysates. A casein acid hydrolysate (CAH, L-Phe ~2.28 %) was employed as a model substrate. t-Cinnamic acid resulting from deamination of L-Phe was extracted, analyzed at λ = 290 nm, and used for PAL activity determination. Optimum reaction conditions, optimized using successive Doehlert design, were 35 mg mL(-1) of CAH and 800 mU mL(-1) of PAL, while temperature and pH were 42 °C and 8.7, respectively. Reaction kinetics of PAL with CAH was determined under optimized conditions. Then, removal of L-Phe from CAH was tested. Results showed that more than 92 % of initial L-Phe was eliminated. Similar results were obtained with other protein hydrolysates. These findings demonstrate that PAL is a useful biocatalyst for L-Phe removal from protein hydrolysates, which can be evaluated as potential ingredients in foodstuffs for PKU patients.

Recent progress of the Laser-driven Ion-beam Trace Probe

NASA Astrophysics Data System (ADS)

Yang, Xiaoyi; Xiao, Chijie; Chen, Yihang; Xu, Tianchao; Yu, Yi; Xu, Min; Wang, Long; Lin, Chen; Wang, Xiaogang

2017-10-01

The Laser-driven Ion-beam Trace Probe (LITP) is a new method to diagnose the poloidal magnetic field and radial electric field in tokamaks. Recently significant progresses have been made as follows. 1) The experimental system has been set up on the PKU Plasma Test (PPT) linear device and begun to validate the principle of LITP, including the ion source, the ion detector and the poloidal magnetic field cable. Preliminary experimental results matched the theoretical prediction well. 2) The reconstruction principle has been improved including the nonlinear effect. 3) Tomography methods have been applied in the reconstruction codes. Now the laser-driven ion-beam accelerator has been setup on the PPT device, and further test of LITP will start soon. After that a prototype of LITP system will be designed and setup on the HL-2A tokamak device. This work was supported by the CHINA MOST under 2012YQ030142, ITER-CHINA program 2015GB120001 and National Natural Science Foundation of China under 11575014 and 11375053.

[A rare case of infant poisoning due to accidental administration of 1,2,3-triketohydrinden hydrate (ninhydrin)].

PubMed

Polak, Piotr; Sołtyszewski, Ireneusz; Niemcunowicz-Janica, Anna; Siwińska-Ziółkowska, Agnieszka; Widecka-Deptuch, Emilia; Lukasik, Marcin; Janica, Jerzy

2007-01-01

The paper presents a case of medical malpractice during the test for phenylketonuria. The authors analyzed all documents collected in the course of the investigation of infant poisoning due to accidental administration of ninhydrin. The medical assessment was based on an extensive review of the case history, as well as on spectroscopy (FT-IR), chromatography and chemical analysis findings that allowed for confirming the presence of the toxic substance in the evidence material collected during the initial investigation. The obtained results confirmed the presence of ninhydrin in the tea cup and in the teaspoon, which were used to prepare the diagnostic medium. No ninhydrin was found in other investigated materials. The employment of routine research methods, including GC-MS, FT-IR and UV-VIS, allowed for detection and identification of the pure chemical form of ninhydrin, as well as its color complex with amino acids. The detailed case analysis, as well as the variability of extensive evidence material collected during the investigation allowed for determining the identity of persons responsible for accidental administration of the poisoning substance to the infant.

Inhibition of Fibrillar Assemblies of l-Phenylalanine by Crown Ethers: A Potential Approach toward Phenylketonuria.

PubMed

Banik, Debasis; Dutta, Rupam; Banerjee, Pavel; Kundu, Sangita; Sarkar, Nilmoni

2016-08-11

In this article, our aim is to investigate the interaction of l-phenylalanine (l-Phe) fibrils with crown ethers (CEs). For this purpose, two different CEs (15-Crown-5 (15C5) and 18-Crown-6 (18C6)) were used. Interestingly, we have observed that both CEs have the ability to arrest fibril formation. However, 18C6 was found to be a better candidate compared to 15C5. Field emission scanning electron microscopy and fluorescence lifetime imaging microscopy were used to monitor the fibril-arresting kinetics of CEs. The arresting process was further confirmed by fluorescence correlation spectroscopy and nuclear magnetic resonance studies.

Identifying micro-inversions using high-throughput sequencing reads.

PubMed

He, Feifei; Li, Yang; Tang, Yu-Hang; Ma, Jian; Zhu, Huaiqiu

2016-01-11

The identification of inversions of DNA segments shorter than read length (e.g., 100 bp), defined as micro-inversions (MIs), remains challenging for next-generation sequencing reads. It is acknowledged that MIs are important genomic variation and may play roles in causing genetic disease. However, current alignment methods are generally insensitive to detect MIs. Here we develop a novel tool, MID (Micro-Inversion Detector), to identify MIs in human genomes using next-generation sequencing reads. The algorithm of MID is designed based on a dynamic programming path-finding approach. What makes MID different from other variant detection tools is that MID can handle small MIs and multiple breakpoints within an unmapped read. Moreover, MID improves reliability in low coverage data by integrating multiple samples. Our evaluation demonstrated that MID outperforms Gustaf, which can currently detect inversions from 30 bp to 500 bp. To our knowledge, MID is the first method that can efficiently and reliably identify MIs from unmapped short next-generation sequencing reads. MID is reliable on low coverage data, which is suitable for large-scale projects such as the 1000 Genomes Project (1KGP). MID identified previously unknown MIs from the 1KGP that overlap with genes and regulatory elements in the human genome. We also identified MIs in cancer cell lines from Cancer Cell Line Encyclopedia (CCLE). Therefore our tool is expected to be useful to improve the study of MIs as a type of genetic variant in the human genome. The source code can be downloaded from: http://cqb.pku.edu.cn/ZhuLab/MID .

Estimated tetrachloroethylene (C2Cl4) emissions for 1992 2014 in China and a high resolution gridded emission in 2010

NASA Astrophysics Data System (ADS)

Bie, P.; Li, Z.; Hu, J.

2016-12-01

Estimated tetrachloroethylene (C2Cl4) emissions for 1992 2014 in China and a high resolution gridded emission in 2010 Pengju Bie1, Zhifang Li1, Jianxin Hu1,*1Collaborative Innovation Center for Regional Environmental Quality, College of Environmental Sciences and Engineering, Peking University, Beijing 100871, China *Corresponding author E-mail: jianxin@pku.edu.cnTel: 86-10-62756593 Fax: 86-10-62760755 Evaluating the contribution from tetrachloroethylene (C2Cl4, PCE) to stratospheric halogen loading requires the knowledge of the spatial and temporal variability of emissions, and thus the tropospheric degradation and removal. And the short atmospheric lifetime (90 days) leads to a large regional variability. This study estimated the emissions of China from 1992 to 2014, based on emission functions and aggregated information given reasonable uncertainties. Results show that the emissions increased from 5.3(3.8 7.0) Gg to 176.9(131.2 232.1) Gg with a moderate growth rate of 17.3%/yr during 1992 2014. More than 97.3% of emissions stemmed from solvents sector. Considering the GDP data availability and the comparable estimate to that of top-down method in 2010, we developed a gridded emission inventory on a 0.5°×0.5° latitude-longitude grid of this year. Due to the more advanced social-economic conditions and more intensive industrial establishment, greater PCE emissions were observed to originate from East China, especially for Jiangsu and Zhejiang provinces, and Beijing-Tianjin-Hebei region and Pearl River Delta (PRD) region.

Validation of behaviour measurement instrument of patients with diabetes mellitus and hypertension

NASA Astrophysics Data System (ADS)

Saputri, G. Z.; Akrom; Dini, S. M.

2017-11-01

Non-adherence to the treatment of chronic diseases such as hypertension and Diabetes Mellitus (DM) is a major obstacle in achieving patient therapy targets and quality of life of patients. A comprehensive approach involving pharmacists counselling has shown influences on changes in health behaviour and patient compliance. Behaviour changes in patients are one of the parameters to assess the effectiveness of counselling and education by pharmacists. Therefore, it is necessary to develop questionnaires of behaviour change measurement in DM-hypertension patients. This study aims to develop a measurement instrument in the form of questionnaires in assessing the behaviour change of DM-hypertension patients. Preparation of question items from the questionnaire research instrument refers to some guidelines and previous research references. Test of questionnaire instrument valid was done with expert validation, followed by pilot testing on 10 healthy respondents, and 10 DM-hypertension patients included in the inclusion criteria. Furthermore, field validation test was conducted on 37 patients who had undergone outpatient care at the PKU Muhammadiyah Yogyakarta City Hospital and The Gading Clinic in Yogyakarta. The inclusion criteria were male and female patients, aged 18-65, diagnosed with type 2 diabetes with hypertension who received oral antidiabetic drugs and antihypertensives, and who were not illiterate and co-operative. The data were collected by questionnaire interviews by a standardized pharmacist. The result of validation test using Person correlation shows the value of 0.33. The results of the questionnaire validation test on 37 patients showed 5 items of invalid questions with the value of r <0.33, e: questions 2, 3, 6, 10 and 11, while the other 10 questions show the value of Pearson correlation > 0.33. The reliability value is shown from the Cronbach's alpha value of 0.722 (> 0.6), implying that the questionnaire is reliable for DM-hypertension patients. This

CavityPlus: a web server for protein cavity detection with pharmacophore modelling, allosteric site identification and covalent ligand binding ability prediction.

PubMed

Xu, Youjun; Wang, Shiwei; Hu, Qiwan; Gao, Shuaishi; Ma, Xiaomin; Zhang, Weilin; Shen, Yihang; Chen, Fangjin; Lai, Luhua; Pei, Jianfeng

2018-05-10

CavityPlus is a web server that offers protein cavity detection and various functional analyses. Using protein three-dimensional structural information as the input, CavityPlus applies CAVITY to detect potential binding sites on the surface of a given protein structure and rank them based on ligandability and druggability scores. These potential binding sites can be further analysed using three submodules, CavPharmer, CorrSite, and CovCys. CavPharmer uses a receptor-based pharmacophore modelling program, Pocket, to automatically extract pharmacophore features within cavities. CorrSite identifies potential allosteric ligand-binding sites based on motion correlation analyses between cavities. CovCys automatically detects druggable cysteine residues, which is especially useful to identify novel binding sites for designing covalent allosteric ligands. Overall, CavityPlus provides an integrated platform for analysing comprehensive properties of protein binding cavities. Such analyses are useful for many aspects of drug design and discovery, including target selection and identification, virtual screening, de novo drug design, and allosteric and covalent-binding drug design. The CavityPlus web server is freely available at http://repharma.pku.edu.cn/cavityplus or http://www.pkumdl.cn/cavityplus.

Genetic epidemiology of single gene defects in Chile.

PubMed Central

Cruz-Coke, R; Moreno, R S

1994-01-01

We have studied the correlation between the ethnic structure and the prevalence of single gene defects in Chile. At present the Chilean population is approximately 64% white and 35% Amerindian with traces of other admixture. Fewer than 4% of the Chilean population are foreign born. Investigations indicate that all severe diseases and many others without impaired reproduction have mutation rates within the range of the white population. Classical ethnic diseases are very rare. Autosomal recessive disorders have a wide range of variability: cystic fibrosis has a low incidence and PKU has a similar incidence to English rates. Only 30% of the inborn errors of metabolism have been described in Chilean medical publications. In addition, no Chilean haemoglobin or haptoglobin variants have been described. Some rare inherited diseases in Chilean human isolates have been described, including achromatopsia, chondrocalcinosis, and Creutzfeldt-Jakob disease. The prevalence of intrahepatic cholestasis of pregnancy and supernumerary nipples is the highest in the world and they are associated with aboriginal origin. Single gene defects in Chile are probably shaped by factors related to its ethnic population structure. These local rare single gene defects may be good markers of population admixture for genetic epidemiological studies. PMID:7815439

Potentials and limitations of microorganisms as renal failure biotherapeutics

PubMed Central

Jain, Poonam; Shah, Sapna; Coussa, Razek; Prakash, Satya

2009-01-01

Renal insufficiency leads to uremia, a complicated syndrome. It thus becomes vital to reduce waste metabolites and regulate water and electrolytes in kidney failure. The most common treatment of this disease is either dialysis or transplantation. Although these treatments are very effective, they are extremely costly. Recently artificial cells, microencapsulated live bacterial cells, and other cells have been studied to manage renal failure metabolic wastes. The procedure for microencapsulation of biologically active material is well documented and offers many biomedical applications. Microencapsulated bacteria have been documented to efficiently remove urea and several uremic markers such as ammonia, creatinine, uric acid, phosphate, potassium, magnesium, sodium, and chloride. These bacteria also have further potential as biotherapeutic agents because they can be engineered to remove selected unwanted waste. This application has enormous potential for removal of waste metabolites and electrolytes in renal failure as well as other diseases such as liver failure, phenylketonuria, and Crohn’s disease, to name a few. This paper discusses the various options available to date to manage renal failure metabolites and focuses on the potential of using encapsulated live cells as biotherapeutic agents to control renal failure waste metabolites and electrolytes. PMID:19707412

Performance evaluation for screening laboratories of the Asia-Pacific region.

PubMed

Hannon, W Harry

2003-01-01

The Centers for Disease Control and Prevention (CDC) has a long history of involvement in quality assurance (QA) activities for support of newborn screening laboratories. Since 1978, CDC's Newborn Screening Quality Assurance Program (NSQAP), has distributed dried-blood spot (DBS) materials for external QA and has maintained related projects to serve newborn screening laboratories. The first DBS materials were distributed for congenital hypothyroidism screening in 1978 and by 2001, NSQAP had expanded to over 30 disorders and performance monitoring for all filter paper production lots from approved commercial sources. In 2001, there were 250 active NSQAP participants, 167 laboratories from 45 countries and 83 laboratories in the United States. Of these laboratories, 31 are from the Asia Pacific Region representing nine countries primarily for two disorders. In 1999, US laboratories had more errors for Performance Evaluation (PE) specimens than other laboratories; but in 2000, US laboratories had fewer errors. International laboratories reported 0.3% false-negative PE clinical assessments for congenital hypothyroidism and 0.5% for phenylketonuria (0.5%) in 2000. Paperless PE data-reporting operation using an Internet website has recently been implemented.

The cystic fibrosis gene: Medical and social implications for heterozygote detection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wilfond, B.S.; Fost, N.

1990-05-23

The primary goal of mass screening programs for cystic fibrosis carriers should be to allow people to make more informed reproductive decisions. However, previous experience with genetic screening programs, including those for phenylketonuria and sickle cell disease, have revealed complex problems including error, confusion, and stigmatization. These problems could be greater with cystic fibrosis, since more than 8 million Americans may be carriers and entrepreneurial interests can be expected to promote screening in what could become a billion-dollar industry. The present frequency of the detectable mutation ({Delta}F{sub 508}), 75%, will complicate the counseling process. The sensitivity of the test tomore » detect at-risk couples would be 56%. The cost of screening could be as much as $2.2 million for each cystic fibrosis birth avoided. Regardless of improvements in the detection rate, implementation of population screening should be delayed until pilot studies that demonstrate its safety and effectiveness are completed. While studies are in progress, preconception testing should be offered to adult relatives of cystic fibrosis patients as part of a comprehensive program following institutional review board approval for compassionate use.« less

Application of liquid chromatography-tandem mass spectrometry in the diagnosis and follow-up of maple syrup urine disease in a Chinese population.

PubMed

Lin, Na; Ye, Jun; Qiu, Wenjuan; Han, Lianshu; Zhang, Huiwen; Gu, Xuefan

2013-01-01

Maple syrup urine disease (MSUD) is an inherited disorder caused by a deficiency of the mitochondrial branched-chain keto acid dehydrogenase complex. We investigated whether liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a more reliable and accurate method than MS/MS in the diagnosis and management of patients with MSUD in a Chinese population. A total of 370 dried blood spots (DBS) from healthy neonates, 44 DBS specimens from phenylketonuria neonates, and 38 DBS samples from 10 MSUD patients were retrospectively tested using the LC-MS/MS method. The results were compared with those obtained by the MS/MS method. The reference intervals of branched-chain amino acids (BCAAs) and alloiosleucine (Allo-Ile) were estimated for both sexes. In classic MSUD patients, Allo-Ile was markedly elevated (average of 136 μmol/L, which was significantly higher than the normal value, <5 μmol/L). The averages of BCAAs were also markedly elevated continually during the treatment. The application of the LC-MS/MS method in the measurement of Allo-Ile and BCAAs in DBS is more useful for diagnosing and managing classic MSUD than the MS/MS method.

Developed-developing country partnerships: Benefits to developed countries?

PubMed Central

2012-01-01

Developing countries can generate effective solutions for today’s global health challenges. This paper reviews relevant literature to construct the case for international cooperation, and in particular, developed-developing country partnerships. Standard database and web-based searches were conducted for publications in English between 1990 and 2010. Studies containing full or partial data relating to international cooperation between developed and developing countries were retained for further analysis. Of 227 articles retained through initial screening, 65 were included in the final analysis. The results were two-fold: some articles pointed to intangible benefits accrued by developed country partners, but the majority of information pointed to developing country innovations that can potentially inform health systems in developed countries. This information spanned all six WHO health system components. Ten key health areas where developed countries have the most to learn from the developing world were identified and include, rural health service delivery; skills substitution; decentralisation of management; creative problem-solving; education in communicable disease control; innovation in mobile phone use; low technology simulation training; local product manufacture; health financing; and social entrepreneurship. While there are no guarantees that innovations from developing country experiences can effectively transfer to developed countries, combined developed-developing country learning processes can potentially generate effective solutions for global health systems. However, the global pool of knowledge in this area is virgin and further work needs to be undertaken to advance understanding of health innovation diffusion. Even more urgently, a standardized method for reporting partnership benefits is needed—this is perhaps the single most immediate need in planning for, and realizing, the full potential of international cooperation between developed and

Developed-developing country partnerships: benefits to developed countries?

PubMed

Syed, Shamsuzzoha B; Dadwal, Viva; Rutter, Paul; Storr, Julie; Hightower, Joyce D; Gooden, Rachel; Carlet, Jean; Bagheri Nejad, Sepideh; Kelley, Edward T; Donaldson, Liam; Pittet, Didier

2012-06-18

Developing countries can generate effective solutions for today's global health challenges. This paper reviews relevant literature to construct the case for international cooperation, and in particular, developed-developing country partnerships. Standard database and web-based searches were conducted for publications in English between 1990 and 2010. Studies containing full or partial data relating to international cooperation between developed and developing countries were retained for further analysis. Of 227 articles retained through initial screening, 65 were included in the final analysis. The results were two-fold: some articles pointed to intangible benefits accrued by developed country partners, but the majority of information pointed to developing country innovations that can potentially inform health systems in developed countries. This information spanned all six WHO health system components. Ten key health areas where developed countries have the most to learn from the developing world were identified and include, rural health service delivery; skills substitution; decentralisation of management; creative problem-solving; education in communicable disease control; innovation in mobile phone use; low technology simulation training; local product manufacture; health financing; and social entrepreneurship. While there are no guarantees that innovations from developing country experiences can effectively transfer to developed countries, combined developed-developing country learning processes can potentially generate effective solutions for global health systems. However, the global pool of knowledge in this area is virgin and further work needs to be undertaken to advance understanding of health innovation diffusion. Even more urgently, a standardized method for reporting partnership benefits is needed--this is perhaps the single most immediate need in planning for, and realizing, the full potential of international cooperation between developed and

MetaComp: comprehensive analysis software for comparative meta-omics including comparative metagenomics.

PubMed

Zhai, Peng; Yang, Longshu; Guo, Xiao; Wang, Zhe; Guo, Jiangtao; Wang, Xiaoqi; Zhu, Huaiqiu

2017-10-02

During the past decade, the development of high throughput nucleic sequencing and mass spectrometry analysis techniques have enabled the characterization of microbial communities through metagenomics, metatranscriptomics, metaproteomics and metabolomics data. To reveal the diversity of microbial communities and interactions between living conditions and microbes, it is necessary to introduce comparative analysis based upon integration of all four types of data mentioned above. Comparative meta-omics, especially comparative metageomics, has been established as a routine process to highlight the significant differences in taxon composition and functional gene abundance among microbiota samples. Meanwhile, biologists are increasingly concerning about the correlations between meta-omics features and environmental factors, which may further decipher the adaptation strategy of a microbial community. We developed a graphical comprehensive analysis software named MetaComp comprising a series of statistical analysis approaches with visualized results for metagenomics and other meta-omics data comparison. This software is capable to read files generated by a variety of upstream programs. After data loading, analyses such as multivariate statistics, hypothesis testing of two-sample, multi-sample as well as two-group sample and a novel function-regression analysis of environmental factors are offered. Here, regression analysis regards meta-omic features as independent variable and environmental factors as dependent variables. Moreover, MetaComp is capable to automatically choose an appropriate two-group sample test based upon the traits of input abundance profiles. We further evaluate the performance of its choice, and exhibit applications for metagenomics, metaproteomics and metabolomics samples. MetaComp, an integrative software capable for applying to all meta-omics data, originally distills the influence of living environment on microbial community by regression analysis

AnnoLnc: a web server for systematically annotating novel human lncRNAs.

PubMed

Hou, Mei; Tang, Xing; Tian, Feng; Shi, Fangyuan; Liu, Fenglin; Gao, Ge

2016-11-16

Long noncoding RNAs (lncRNAs) have been shown to play essential roles in almost every important biological process through multiple mechanisms. Although the repertoire of human lncRNAs has rapidly expanded, their biological function and regulation remain largely elusive, calling for a systematic and integrative annotation tool. Here we present AnnoLnc ( http://annolnc.cbi.pku.edu.cn ), a one-stop portal for systematically annotating novel human lncRNAs. Based on more than 700 data sources and various tool chains, AnnoLnc enables a systematic annotation covering genomic location, secondary structure, expression patterns, transcriptional regulation, miRNA interaction, protein interaction, genetic association and evolution. An intuitive web interface is available for interactive analysis through both desktops and mobile devices, and programmers can further integrate AnnoLnc into their pipeline through standard JSON-based Web Service APIs. To the best of our knowledge, AnnoLnc is the only web server to provide on-the-fly and systematic annotation for newly identified human lncRNAs. Compared with similar tools, the annotation generated by AnnoLnc covers a much wider spectrum with intuitive visualization. Case studies demonstrate the power of AnnoLnc in not only rediscovering known functions of human lncRNAs but also inspiring novel hypotheses.

Analysis the Accuracy of Digital Elevation Model (DEM) for Flood Modelling on Lowland Area

NASA Astrophysics Data System (ADS)

Zainol Abidin, Ku Hasna Zainurin Ku; Razi, Mohd Adib Mohammad; Bukari, Saifullizan Mohd

2018-04-01

Flood is one type of natural disaster that occurs almost every year in Malaysia. Commonly the lowland areas are the worst affected areas. This kind of disaster is controllable by using an accurate data for proposing any kinds of solutions. Elevation data is one of the data used to produce solutions for flooding. Currently, the research about the application of Digital Elevation Model (DEM) in hydrology was increased where this kind of model will identify the elevation for required areas. University of Tun Hussein Onn Malaysia is one of the lowland areas which facing flood problems on 2006. Therefore, this area was chosen in order to produce DEM which focussed on University Health Centre (PKU) and drainage area around Civil and Environment Faculty (FKAAS). Unmanned Aerial Vehicle used to collect aerial photos data then undergoes a process of generating DEM according to three types of accuracy and quality from Agisoft PhotoScan software. The higher the level of accuracy and quality of DEM produced, the longer time taken to generate a DEM. The reading of the errors created while producing the DEM shows almost 0.01 different. Therefore, it has been identified there are some important parameters which influenced the accuracy of DEM.

Plasma arachidonic acid and serum thromboxane B2 concentrations in phenylketonuric children negatively correlate with dietary compliance.

PubMed

Agostoni, C; Marangoni, F; Riva, E; Giovannini, M; Galli, C

1997-03-01

The study addresses the relationship of plasma arachidonic acid and thromboxane production with the dietary compliance in treated phenylketonuric patients, whose vegan-like dietary pattern makes them a useful model to evaluate the effects of the near-total avoidance of animal fats. Thirteen treated phenylketonuric children were compared with twelve healthy controls for arachidonic acid intake, plasma fatty acids and platelet thromboxane B2 production, assessed as accumulation of this eicosanoid in serum. The calculated intake of arachidonic acid was lower in phenylketonurics than in controls and this was associated with lower levels in plasma lipids. Plasma arachidonic acid concentrations and serum thromboxane B2 levels correlated with the last 12 months phenylalanine levels, taken as negative indicator of dietary compliance. A direct relationship between plasma arachidonic acid concentration and thromboxane B2 production was observed only in phenylketonuric patients (r = 0.74, P = 0.01). While well-compliant PKU subjects have low arachidonic acid and thromboxane concentrations in plasma, the low compliance with animal food avoidance, evoking higher phenylalanine levels, results in elevation of both plasma arachidonic acid and serum thromboxane B2. This gives support to the hypothesis that the consumption of animal fats may affect the production of arachidonic acid-derived platelet eicosanoids.

Detection of novel visible-light region absorbance peaks in the urine after alkalization in patients with alkaptonuria.

PubMed

Tokuhara, Yasunori; Shukuya, Kenichi; Tanaka, Masami; Mouri, Mariko; Ohkawa, Ryunosuke; Fujishiro, Midori; Takahashi, Tomoo; Okubo, Shigeo; Yokota, Hiromitsu; Kurano, Makoto; Ikeda, Hitoshi; Yamaguchi, Seiji; Inagaki, Shinobu; Ishige-Wada, Mika; Usui, Hiromi; Yatomi, Yutaka; Shimosawa, Tatsuo

2014-01-01

Alkaptonuria, caused by a deficiency of homogentisate 1,2-dioxygenase, results in the accumulation of homogentisic acid (2,5-dihydroxyphenylacetic acid, HGA) in the urine. Alkaptonuria is suspected when the urine changes color after it is left to stand at room temperature for several hours to days; oxidation of homogentisic acid to benzoquinone acetic acid underlies this color change, which is accelerated by the addition of alkali. In an attempt to develop a facile screening test for alkaptonuria, we added alkali to urine samples obtained from patients with alkaptonuria and measured the absorbance spectra in the visible light region. We evaluated the characteristics of the absorption spectra of urine samples obtained from patients with alkaptonuria (n = 2) and compared them with those of urine specimens obtained from healthy volunteers (n = 5) and patients with phenylketonuria (n = 3), and also of synthetic homogentisic acid solution after alkalization. Alkalization of the urine samples and HGA solution was carried out by the addition of NaOH, KOH or NH4OH. The sample solutions were incubated at room temperature for 1 min, followed by measurement of the absorption spectra. Addition of alkali to alkaptonuric urine yielded characteristic absorption peaks at 406 nm and 430 nm; an identical result was obtained from HGA solution after alkalization. The absorbance values at both 406 nm and 430 nm increased in a time-dependent manner. In addition, the absorbance values at these peaks were greater in strongly alkaline samples (NaOH- KOH-added) as compared with those in weakly alkaline samples (NH4OH-added). In addition, the peaks disappeared following the addition of ascorbic acid to the samples. We found two characteristic peaks at 406 nm and 430 nm in both alkaptonuric urine and HGA solution after alkalization. This new quick and easy method may pave the way for the development of an easy method for the diagnosis of alkaptonuria.

Detection of Novel Visible-Light Region Absorbance Peaks in the Urine after Alkalization in Patients with Alkaptonuria

PubMed Central

Tokuhara, Yasunori; Shukuya, Kenichi; Tanaka, Masami; Mouri, Mariko; Ohkawa, Ryunosuke; Fujishiro, Midori; Takahashi, Tomoo; Okubo, Shigeo; Yokota, Hiromitsu; Kurano, Makoto; Ikeda, Hitoshi; Yamaguchi, Seiji; Inagaki, Shinobu; Ishige-Wada, Mika; Usui, Hiromi; Yatomi, Yutaka; Shimosawa, Tatsuo

2014-01-01

Background Alkaptonuria, caused by a deficiency of homogentisate 1,2-dioxygenase, results in the accumulation of homogentisic acid (2,5-dihydroxyphenylacetic acid, HGA) in the urine. Alkaptonuria is suspected when the urine changes color after it is left to stand at room temperature for several hours to days; oxidation of homogentisic acid to benzoquinone acetic acid underlies this color change, which is accelerated by the addition of alkali. In an attempt to develop a facile screening test for alkaptonuria, we added alkali to urine samples obtained from patients with alkaptonuria and measured the absorbance spectra in the visible light region. Methods We evaluated the characteristics of the absorption spectra of urine samples obtained from patients with alkaptonuria (n = 2) and compared them with those of urine specimens obtained from healthy volunteers (n = 5) and patients with phenylketonuria (n = 3), and also of synthetic homogentisic acid solution after alkalization. Alkalization of the urine samples and HGA solution was carried out by the addition of NaOH, KOH or NH4OH. The sample solutions were incubated at room temperature for 1 min, followed by measurement of the absorption spectra. Results Addition of alkali to alkaptonuric urine yielded characteristic absorption peaks at 406 nm and 430 nm; an identical result was obtained from HGA solution after alkalization. The absorbance values at both 406 nm and 430 nm increased in a time-dependent manner. In addition, the absorbance values at these peaks were greater in strongly alkaline samples (NaOH- KOH-added) as compared with those in weakly alkaline samples (NH4OH-added). In addition, the peaks disappeared following the addition of ascorbic acid to the samples. Conclusions We found two characteristic peaks at 406 nm and 430 nm in both alkaptonuric urine and HGA solution after alkalization. This new quick and easy method may pave the way for the development of an easy method for the diagnosis of

PREFACE: 15th International Workshop on Advanced Computing and Analysis Techniques in Physics Research (ACAT2013)

NASA Astrophysics Data System (ADS)

Wang, Jianxiong

2014-06-01

This volume of Journal of Physics: Conference Series is dedicated to scientific contributions presented at the 15th International Workshop on Advanced Computing and Analysis Techniques in Physics Research (ACAT 2013) which took place on 16-21 May 2013 at the Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, China. The workshop series brings together computer science researchers and practitioners, and researchers from particle physics and related fields to explore and confront the boundaries of computing and of automatic data analysis and theoretical calculation techniques. This year's edition of the workshop brought together over 120 participants from all over the world. 18 invited speakers presented key topics on the universe in computer, Computing in Earth Sciences, multivariate data analysis, automated computation in Quantum Field Theory as well as computing and data analysis challenges in many fields. Over 70 other talks and posters presented state-of-the-art developments in the areas of the workshop's three tracks: Computing Technologies, Data Analysis Algorithms and Tools, and Computational Techniques in Theoretical Physics. The round table discussions on open-source, knowledge sharing and scientific collaboration stimulate us to think over the issue in the respective areas. ACAT 2013 was generously sponsored by the Chinese Academy of Sciences (CAS), National Natural Science Foundation of China (NFSC), Brookhaven National Laboratory in the USA (BNL), Peking University (PKU), Theoretical Physics Cernter for Science facilities of CAS (TPCSF-CAS) and Sugon. We would like to thank all the participants for their scientific contributions and for the en- thusiastic participation in all its activities of the workshop. Further information on ACAT 2013 can be found at http://acat2013.ihep.ac.cn. Professor Jianxiong Wang Institute of High Energy Physics Chinese Academy of Science Details of committees and sponsors are available in the PDF

Children in family foster care have greater health risks and less involvement in Child Health Services.

PubMed

Köhler, M; Emmelin, M; Hjern, A; Rosvall, M

2015-05-01

This study investigated the impact of being in family foster care on selected health determinants and participation in Child Health Services (CHS). Two groups of 100 children, born between 1992 and 2008, were studied using data from Swedish Child Health Services for the preschool period up to the age of six. The first group had been in family foster care, and the controls, matched for age, sex and geographic location, had not. Descriptive statistics were used to describe differences in health determinants and participation in Child Health Services between the two groups. The foster care group had higher health risks, with lower rates of breastfeeding and higher levels of parental smoking. They were less likely to have received immunisations and attended key nurse or physician visits and speech and vision screening. Missing data for the phenylketonuria test were more common in children in family foster care. Children in family foster care were exposed to more health risks than the control children and had lower participation in the universal child health programme during the preschool period. These results call for secure access to high-quality preventive health care for this particularly vulnerable group of children. ©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Emerging trends in nutraceutical applications of whey protein and its derivatives.

PubMed

Patel, Seema

2015-11-01

The looming food insecurity demands the utilization of nutrient-rich residues from food industries as value-added products. Whey, a dairy industry waste has been characterized to be excellent nourishment with an array of bioactive components. Whey protein comprises 20 % of total milk protein and it is rich in branched and essential amino acids, functional peptides, antioxidants and immunoglobulins. It confers benefits against a wide range of metabolic diseases such as cardiovascular complications, hypertension, obesity, diabetes, cancer and phenylketonuria. The protein has been validated to boost recovery from resistance exercise-injuries, stimulate gut physiology and protect skin against detrimental radiations. Apart from health invigoration, whey protein has proved its suitability as fat replacer and emulsifier. Further, its edible and antimicrobial packaging potential renders its highly desirable in food as well as pharmaceutical sectors. Considering the enormous nutraceutical worth of whey protein, this review emphasizes on its established and emerging biological roles. Present and future scopes in food processing and dietary supplement formulation are discussed. Associated hurdles are identified and how technical advancement might augment its applications are explored. This review is expected to provide valuable insight on whey protein-fortified functional foods, associated technical hurdles and scopes of improvement.

Synthesis and degradation of phenylalanine ammonia-lyase of Rhodosporidium toruloides.

PubMed Central

Gilbert, H J; Tully, M

1982-01-01

The regulation of the enzyme phenylalanine ammonia-lyase (PAL), which is of potential use in oral treatment of phenylketonuria, was investigated. Antiserum against PAL was prepared and was shown to be monospecific for the enzyme by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The native enzyme and two inactive mutant forms of the enzyme were purified to homogeneity by immunoaffinity chromatography, using anti-PAL immunoglobulin G-Sepharose 4B. Both mutant enzymes contained intact prosthetic groups. The formation of PAL catalytic activity after phenylalanine was added to yeast cultures was paralleled by the appearance of enzyme antigen. During induction, uptake of [3H]leucine into the enzyme was higher than uptake into total protein. Our results are consistent with de novo synthesis of an enzyme induced by phenylalanine, rather than activation of a proenzyme. The half-lives of PAL and total protein were similar in both exponential and stationary phase cultures. No metabolite tested affected the rate of enzyme degradation. Glucose repressed enzyme synthesis, whereas ammonia reduced phenylalanine uptake and pool size and so may repress enzyme synthesis through inducer exclusion. The synthesis of enzyme antigen by a mutant unable to metabolize phenylalanine indicated that this amino acid is the physiological inducer of the enzyme. PMID:7068528

Synthesis and degradation of phenylalanine ammonia-lyase of Rhodosporidium toruloides.

PubMed

Gilbert, H J; Tully, M

1982-05-01

The regulation of the enzyme phenylalanine ammonia-lyase (PAL), which is of potential use in oral treatment of phenylketonuria, was investigated. Antiserum against PAL was prepared and was shown to be monospecific for the enzyme by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The native enzyme and two inactive mutant forms of the enzyme were purified to homogeneity by immunoaffinity chromatography, using anti-PAL immunoglobulin G-Sepharose 4B. Both mutant enzymes contained intact prosthetic groups. The formation of PAL catalytic activity after phenylalanine was added to yeast cultures was paralleled by the appearance of enzyme antigen. During induction, uptake of [3H]leucine into the enzyme was higher than uptake into total protein. Our results are consistent with de novo synthesis of an enzyme induced by phenylalanine, rather than activation of a proenzyme. The half-lives of PAL and total protein were similar in both exponential and stationary phase cultures. No metabolite tested affected the rate of enzyme degradation. Glucose repressed enzyme synthesis, whereas ammonia reduced phenylalanine uptake and pool size and so may repress enzyme synthesis through inducer exclusion. The synthesis of enzyme antigen by a mutant unable to metabolize phenylalanine indicated that this amino acid is the physiological inducer of the enzyme.

Structural basis for ligand-dependent dimerization of phenylalanine hydroxylase regulatory domain

PubMed Central

Patel, Dipali; Kopec, Jolanta; Fitzpatrick, Fiona; McCorvie, Thomas J.; Yue, Wyatt W.

2016-01-01

The multi-domain enzyme phenylalanine hydroxylase (PAH) catalyzes the hydroxylation of dietary I-phenylalanine (Phe) to I-tyrosine. Inherited mutations that result in PAH enzyme deficiency are the genetic cause of the autosomal recessive disorder phenylketonuria. Phe is the substrate for the PAH active site, but also an allosteric ligand that increases enzyme activity. Phe has been proposed to bind, in addition to the catalytic domain, a site at the PAH N-terminal regulatory domain (PAH-RD), to activate the enzyme via an unclear mechanism. Here we report the crystal structure of human PAH-RD bound with Phe at 1.8 Å resolution, revealing a homodimer of ACT folds with Phe bound at the dimer interface. This work delivers the structural evidence to support previous solution studies that a binding site exists in the RD for Phe, and that Phe binding results in dimerization of PAH-RD. Consistent with our structural observation, a disease-associated PAH mutant impaired in Phe binding disrupts the monomer:dimer equilibrium of PAH-RD. Our data therefore support an emerging model of PAH allosteric regulation, whereby Phe binds to PAH-RD and mediates the dimerization of regulatory modules that would bring about conformational changes to activate the enzyme. PMID:27049649

Comparing Spiritual Development and Cognitive Development.

ERIC Educational Resources Information Center

Love, Patrick G.

2002-01-01

Three spiritual development theories and theorists (i.e., Parks, Fowler, and Helminiak) were compared with traditional cognitive development theory and theorists. The analysis reveals both commonalities between the two sets of theories and unique contributions to an understanding of student development on the part of spiritual development theory.…

App Development Paradigms for Instructional Developers

ERIC Educational Resources Information Center

Luterbach, Kenneth J.; Hubbell, Kenneth R.

2015-01-01

To create instructional apps for desktop, laptop and mobile devices, developers must select a development tool. Tool selection is critical and complicated by the large number and variety of app development tools. One important criterion to consider is the type of development environment, which may primarily be visual or symbolic. Those distinct…

Sustainable Development: The Challenge for Community Development.

ERIC Educational Resources Information Center

Gamble, Dorothy N.; Weil, Marie O.

1997-01-01

Five areas of inquiry shape the sustainable development movement: environmental movement, women's movement, overpopulation concerns, critique of development models, and new indicators of social progress. Community development workers are challenged to prepare local development projects within a sustainable development framework. (SK)

Culturable diversity and biochemical features of thraustochytrids from coastal waters of Southern China.

PubMed

Liu, Ying; Singh, Purnima; Sun, Yuan; Luan, Shengji; Wang, Guangyi

2014-04-01

Thraustochytrids are ubiquitous marine osmo-heterotrophic fungi-like microorganisms with only about 40 identified species till now. In this study, a total of 60 thraustochytrid strains were isolated from marine coastal habitats. Analysis of 18S rRNA gene sequences revealed that they belonged to three genera, i.e., Schizochytrium, Aurantiochytrium, and Thraustochytrium. All of the isolates were found to show considerable cellulolytic and lipolytic activities. Strains of Aurantiochytrium sp. and Thraustochytrium sp. were found to produce the highest levels of extracellular polysaccharides (EPS), which reached 345 μg ml(-1) in the growth media. Fourier transform infrared (FTIR) spectra of the EPS samples derived from two thraustochytrids (PKU#Sed1 and #SW1) displayed peaks for carbohydrates, proteins, lipids, uronic acids, and nucleic acids. Fatty acid profiles of four thraustochytrids comprised of palmitic acid (C16:0) and docosahexaenoic acid (DHA) as their major constituents. Schizochytrium sp. demonstrated the highest DHA production at 44 % of total fatty acids (TFA) with biomass and DHA yield of 7.1 and 1.6 g l(-1), respectively, on the fourth day of growth. All the four isolates exhibited considerable production of palmitic acid (16:0) in their fatty acid profiles ranging from 35 to 50 % TFA. This is the first report on extracellular enzymes, EPS, and DHA production from thraustochytrids isolated from the coastal habitats of China.

The use of mass spectrometry to analyze dried blood spots.

PubMed

Wagner, Michel; Tonoli, David; Varesio, Emmanuel; Hopfgartner, Gérard

2016-01-01

Dried blood spots (DBS) typically consist in the deposition of small volumes of capillary blood onto dedicated paper cards. Comparatively to whole blood or plasma samples, their benefits rely in the fact that sample collection is easier and that logistic aspects related to sample storage and shipment can be relatively limited, respectively, without the need of a refrigerator or dry ice. Originally, this approach has been developed in the sixties to support the analysis of phenylalanine for the detection of phenylketonuria in newborns using bacterial inhibition test. In the nineties tandem mass spectrometry was established as the detection technique for phenylalanine and tyrosine. DBS became rapidly recognized for their clinical value: they were widely implemented in pediatric settings with mass spectrometric detection, and were closely associated to the debut of newborn screening (NBS) programs, as a part of public health policies. Since then, sample collection on paper cards has been explored with various analytical techniques in other areas more or less successfully regarding large-scale applications. Moreover, in the last 5 years a regain of interest for DBS was observed and originated from the bioanalytical community to support drug development (e.g., PK studies) or therapeutic drug monitoring mainly. Those recent applications were essentially driven by improved sensitivity of triple quadrupole mass spectrometers. This review presents an overall view of all instrumental and methodological developments for DBS analysis with mass spectrometric detection, with and without separation techniques. A general introduction to DBS will describe their advantages and historical aspects of their emergence. A second section will focus on blood collection, with a strong emphasis on specific parameters that can impact quantitative analysis, including chromatographic effects, hematocrit effects, blood effects, and analyte stability. A third part of the review is dedicated to

Entrepreneurial Intentions in Developing and Developed Countries

ERIC Educational Resources Information Center

Iakovleva, Tatiana; Kolvereid, Lars; Stephan, Ute

2011-01-01

Purpose: This study proposes to use the Theory of Planned Behaviour to predict entrepreneurial intentions among students in five developing and nine developed countries. The purpose is to investigate whether entrepreneurial intention and its antecedents differ between developing and developed countries, and to test the theory in the two groups of…

World Development Report 1985. International Capital and Economic Development. World Development Indicators.

ERIC Educational Resources Information Center

International Bank for Reconstruction and Development, Washington, DC.

Focusing on the contribution that international capital makes to economic development, this report shows how countries at different stages of development have used external finance productively; how the institutional and policy environment affects the volume and composition of financial flows to developing countries; and how the international…

Developing the Developers: Supporting and Researching the Learning of Professional Development Facilitators

ERIC Educational Resources Information Center

Perry, Emily; Boylan, Mark

2018-01-01

Research on teacher professional development is extensive but there are fewer studies about the practitioners who facilitate professional development. Here we report on a pilot programme for professional development facilitators rooted in a cycle of action research. Informed by a categorisation of professional knowledge and skills of facilitators,…

Childbirth experience according to a group of Brazilian primiparas.

PubMed

Nakano, Ana Márcia Spanó; Homsi Jorge Ferreira, Cristine; de Almeida, Ana Maria; Gomes, Flávia Azevedo

2012-12-01

to understand the meaning of the childbirth experience for Brazilian primiparas in the postpartum period. a qualitative approach using semi-structured interviews. Content analysis was used to derive the two themes that emerged from the discourses. participants were recruited at four primary-level health-care units in Ribeirão Preto, Brazil. After providing written informed consent, an appointment was made for an interview at the participants' homes. 20 primiparas in the postpartum period, aged 15-26 years old, who attended the health-care units to vaccinate their infants and test for phenylketonuria. two thematic categories emerged from the interviews: the meaning attributed to childbirth (with four subcategories) and perceptions of care. Among the participants, the childbirth experience was marked by the 'fear of death' and 'losing the child'. The pain of giving birth was expected, and the moment of childbirth was associated with pain of high intensity. childbirth is considered synonymous with physical and emotional suffering, pain, fear and risk of death. this research indicates the need to break the current mechanistic model of care on which health professionals' actions are based. Care during childbirth must be guided by the foundation that women are the subjects of childbirth actions, in an attempt to emphasise actions that grant them with the autonomy and empowerment needed to experience the situation. Copyright © 2011 Elsevier Ltd. All rights reserved.

Inherited metabolic disorders in Thailand.

PubMed

Wasant, Pornswan; Svasti, Jisnuson; Srisomsap, Chantragan; Liammongkolkul, Somporn

2002-08-01

The study of inborn errors of metabolism (IEM) in Thailand is in its infancy. The majority are clinically diagnosed since there are only a handful of clinicians and scientists with expertise in inherited metabolic disorders, shortage of well-equipped laboratory facilities and lack of governmental financial support. Genetic metabolic disorders are usually not considered a priority due to prevalence of infectious diseases and congenital infections. From a retrospective study at the Medical Genetics Unit, Department of Pediatrics, Siriraj Hospital; estimated pediatrics patients with suspected IEM were approximately 2-3 per cent of the total pediatric admissions of over 5,000 annually. After more than 10 years of research and accumulated clinical experiences, a genetic metabolic center is being established in collaboration with expert laboratories both in Bangkok (Chulabhorn Research Institute) and abroad (Japan and the United States). Numerous inherited metabolic disorders were identified--carbohydrate, amino acids, organic acids, mitochondrial fatty acid oxidation, peroxisomal, mucopolysaccharidoses etc. This report includes the establishment of genetic metabolic center in Thailand, research and pilot studies in newborn screening in Thailand and a multicenter study from 5 institutions (Children's National Center, King Chulalongkorn Memorial Hospital, Pramongkutklao Hospital, Ramathibodi and Siriraj Hospitals). Inherited metabolic disorders reported are fructose-1,6-bisphosphatase deficiency, phenylketonuria, homocystinuria, nonketotic hyperglycinemia, urea cycle defect (arginino succinate lyase deficiency, argininosuccinate synthetase deficiency), Menkes disease, propionic acidemia and mucopolysaccharidoses (Hurler, Hurler-Scheie).

How Well Do Customers of Direct-to-Consumer Personal Genomic Testing Services Comprehend Genetic Test Results? Findings from the Impact of Personal Genomics Study.

PubMed

Ostergren, Jenny E; Gornick, Michele C; Carere, Deanna Alexis; Kalia, Sarah S; Uhlmann, Wendy R; Ruffin, Mack T; Mountain, Joanna L; Green, Robert C; Roberts, J Scott

2015-01-01

To assess customer comprehension of health-related personal genomic testing (PGT) results. We presented sample reports of genetic results and examined responses to comprehension questions in 1,030 PGT customers (mean age: 46.7 years; 59.9% female; 79.0% college graduates; 14.9% non-White; 4.7% of Hispanic/Latino ethnicity). Sample reports presented a genetic risk for Alzheimer's disease and type 2 diabetes, carrier screening summary results for >30 conditions, results for phenylketonuria and cystic fibrosis, and drug response results for a statin drug. Logistic regression was used to identify correlates of participant comprehension. Participants exhibited high overall comprehension (mean score: 79.1% correct). The highest comprehension (range: 81.1-97.4% correct) was observed in the statin drug response and carrier screening summary results, and lower comprehension (range: 63.6-74.8% correct) on specific carrier screening results. Higher levels of numeracy, genetic knowledge, and education were significantly associated with greater comprehension. Older age (≥ 60 years) was associated with lower comprehension scores. Most customers accurately interpreted the health implications of PGT results; however, comprehension varied by demographic characteristics, numeracy and genetic knowledge, and types and format of the genetic information presented. Results suggest a need to tailor the presentation of PGT results by test type and customer characteristics. © 2015 S. Karger AG, Basel.

Autosomal recessive disorders among Arabs: an overview from Kuwait.

PubMed Central

Teebi, A S

1994-01-01

Kuwait has a cosmopolitan population of 1.7 million, mostly Arabs. This population is a mosaic of large and small minorities representing most Arab communities. In general, Kuwait's population is characterized by a rapid rate of growth, large family size, high rates of consanguineous marriages within the Arab communities with low frequency of intermarriage between them, and the presence of genetic isolates and semi-isolates in some extended families and Bedouin tribes. Genetic services have been available in Kuwait for over a decade. During this time it has become clear that Arabs have a high frequency of genetic disorders, and in particular autosomal recessive traits. Their pattern is unique and some disorders are relatively common. Examples are Bardet-Biedl and Meckel syndromes, phenylketonuria, and familial Mediterranean fever. A relatively large number of new syndromes and variants have been delineated in Kuwait's population, many being the result of homozygosity for autosomal recessive genes that occurred because of inbreeding. Some of these syndromes have subsequently been found in other parts of the world, negating the concept of the private syndrome. This paper provides an overview of autosomal recessive disorders among the Arabs in Kuwait from a personal perspective and published studies, and highlights the need for genetic services in Arab countries with the goal of prevention and treatment of genetic disorders. PMID:8014972

How Well Do Customers of Direct-to-Consumer Personal Genomic Testing Services Comprehend Genetic Test Results? Findings from the Impact of Personal Genomics Study

PubMed Central

Ostergren, Jenny E.; Gornick, Michele C.; Carere, Deanna Alexis; Kalia, Sarah S.; Uhlmann, Wendy R.; Ruffin, Mack T.; Mountain, Joanna L.; Green, Robert C.; Roberts, J. Scott

2016-01-01

Aim To assess customer comprehension of health-related personal genomic testing (PGT) results. Methods We presented sample reports of genetic results and examined responses to comprehension questions in 1,030 PGT customers (mean age: 46.7 years; 59.9% female; 79.0% college graduates; 14.9% non-White; 4.7% of Hispanic/Latino ethnicity). Sample reports presented a genetic risk for Alzheimer’s disease and type 2 diabetes, carrier screening summary results for >30 conditions, results for phenylketonuria and cystic fibrosis, and drug response results for a statin drug. Logistic regression was used to identify correlates of participant comprehension. Results Participants exhibited high overall comprehension (mean score: 79.1% correct). The highest comprehension (range: 81.1–97.4% correct) was observed in the statin drug response and carrier screening summary results, and lower comprehension (range: 63.6–74.8% correct) on specific carrier screening results. Higher levels of numeracy, genetic knowledge, and education were significantly associated with greater comprehension. Older age (≥ 60 years) was associated with lower comprehension scores. Conclusions Most customers accurately interpreted the health implications of PGT results; however, comprehension varied by demographic characteristics, numeracy and genetic knowledge, and types and format of the genetic information presented. Results suggest a need to tailor the presentation of PGT results by test type and customer characteristics. PMID:26087778

Experience of the Manitoba Perinatal Screening Program, 1965-85.

PubMed Central

Fox, J G

1987-01-01

The Manitoba Perinatal Screening Program is guided by a committee of medical specialists with skills in the diagnosis and management of disorders of metabolism in the newborn. The program is voluntary and is centralized at Cadham Provincial Laboratory, in Winnipeg. A filter card blood specimen is collected from newborns on discharge from hospital, and a filter card urine sample is collected and mailed to the laboratory by the mother when the infant is about 2 weeks of age. The overall compliance rates for the blood and urine specimens are approximately 100% and 84% respectively. The blood specimen is screened for phenylalanine and other amino acids, thyroxine, galactose, galactose-1-phosphate and biotinidase. The urine specimen is screened for amino acids, including cystine, as well as methylmalonic acid and homocystine. Between 1965 and 1985, 83 cases of metabolic disorders were detected, including 23 cases of primary hypothyroidism, 14 of classic phenylketonuria, 5 of galactosemia variants, 3 of galactosemia, 2 of maple syrup urine disease and 1 of hereditary tyrosinemia. The direct cost per infant screened is $5.50, and the cost:benefit ratio is approximately 7.5:1. Maternal serum alpha-fetoprotein screening is being made available as the necessary supporting clinical facilities become available. On the basis of this experience, the author outlines the components that are important for an effective screening program. PMID:3676929

A modern view of phenylalanine ammonia lyase.

PubMed

MacDonald, M Jason; D'Cunha, Godwin B

2007-06-01

Phenylalanine ammonia lyase (PAL; E.C.4.3.1.5), which catalyses the biotransformation of L-phenylalanine to trans-cinnamic acid and ammonia, was first described in 1961 by Koukol and Conn. Since its discovery, much knowledge has been gathered with reference to the enzyme's catabolic role in microorganisms and its importance in the phenyl propanoid pathway of plants. The 3-dimensional structure of the enzyme has been characterized using X-ray crystallography. This has led to a greater understanding of the mechanism of PAL-catalyzed reactions, including the discovery of a recently described cofactor, 3,5-dihydro-5-methyldiene-4H-imidazol-4-one. In the past 3 decades, PAL has gained considerable significance in several clinical, industrial, and biotechnological applications. The reversal of the normal physiological reaction can be effectively employed in the production of optically pure L-phenylalanine, which is a precursor of the noncalorific sweetener aspartame (L-phenylalanyl-L-aspartyl methyl ester). The enzyme's natural ability to break down L-phenylalanine makes PAL a reliable treatment for the genetic condition phenylketonuria. In this mini-review, we discuss prominent details relating to the physiological role of PAL, the mechanism of catalysis, methods of determination and purification, enzyme kinetics, and enzyme activity in nonaqueous media. Two topics of current study on PAL, molecular biology and crystal structure, are also discussed.

Expression and Properties of the Highly Alkalophilic Phenylalanine Ammonia-Lyase of Thermophilic Rubrobacter xylanophilus

PubMed Central

Kovács, Klaudia; Bánóczi, Gergely; Varga, Andrea; Szabó, Izabella; Holczinger, András; Hornyánszky, Gábor; Zagyva, Imre

2014-01-01

The sequence of a phenylalanine ammonia-lyase (PAL; EC: 4.3.1.24) of the thermophilic and radiotolerant bacterium Rubrobacter xylanophilus (RxPAL) was identified by screening the genomes of bacteria for members of the phenylalanine ammonia-lyase family. A synthetic gene encoding the RxPAL protein was cloned and overexpressed in Escherichia coli TOP 10 in a soluble form with an N-terminal His6-tag and the recombinant RxPAL protein was purified by Ni-NTA affinity chromatography. The activity assay of RxPAL with l-phenylalanine at various pH values exhibited a local maximum at pH 8.5 and a global maximum at pH 11.5. Circular dichroism (CD) studies showed that RxPAL is associated with an extensive α-helical character (far UV CD) and two distinctive near-UV CD peaks. These structural characteristics were well preserved up to pH 11.0. The extremely high pH optimum of RxPAL can be rationalized by a three-dimensional homology model indicating possible disulfide bridges, extensive salt-bridge formation and an excess of negative electrostatic potential on the surface. Due to these properties, RxPAL may be a candidate as biocatalyst in synthetic biotransformations leading to unnatural l- or d-amino acids or as therapeutic enzyme in treatment of phenylketonuria or leukemia. PMID:24475062

Newborn screening by matrix-assisted laser desorption/ionization mass spectrometry based on parylene-matrix chip.

PubMed

Kim, Jo-Il; Noh, Joo-Yoon; Kim, Mira; Park, Jong-Min; Song, Hyun-Woo; Kang, Min-Jung; Pyun, Jae-Chul

2017-08-01

Newborn screening for diagnosis of phenylketonuria, homocystinuria, and maple syrup urine disease have been conducted by analyzing the concentration of target amino acids using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-ToF MS) based on parylene-matrix chip. Parylene-matrix chip was applied to MALDI-ToF MS analysis reducing the matrix peaks significantly at low mass-to-charge ratio range (m/z < 500). Reproducibility of inter-spot and intra-spot analyses of amino acids was less than 10%. Methanol extraction was adopted for simple and rapid sample preparation of serum before mass spectrometric analysis showing 13.3 to 45% of extraction efficiency. Calibration curves for diagnosis of neonatal metabolic disorders were obtained by analyzing methanol-extracted serum spiked with target amino acids using MALDI-ToF MS. They showed good linearity (R 2  > 0.98) and the LODs were ranging from 9.0 to 22.9 μg/mL. Effect of proteins in serum was estimated by comparing MALDI-ToF mass spectra of amino acids-spiked serum before and after the methanol extraction. Interference of other amino acids on analysis of target analyte was determined to be insignificant. From these results, MALDI-ToF MS based on parylene-matrix chip could be applicable to medical diagnosis of neonatal metabolic disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

Balancing economic development with environmental protection in developing and lesser developed countries

DOE Office of Scientific and Technical Information (OSTI.GOV)

El-Ashry, M.T.

1993-01-01

Recent experience suggests that poverty and environmental degradation go hand in hand. Economic development, on the other hand, provides the financial and technical resources needed for the protection of human health and natural ecosystems. Balancing economic development and environmental protection in developing countries requires a refocusing of economic activity -- not towards producing less, but producing differently. Strategies for the integration of economic development and environmental protection are outlined here, as is the proposed role that will need to be played by the World Bank. 4 refs., 3 figs.

Development.

ERIC Educational Resources Information Center

Boydell, Tom

1982-01-01

Explores the theories and models of self-actualization and human development. Twelve tables illustrate developmental stages, ways of knowing, moral and ethical development, management style, goals of learning, organizational development, and other dimensions. Availability: M.E.A.D. Subscriptions, C.S.M.L., University of Lancaster, Lancaster LA1…

The Social Development Summit and the developing countries.

PubMed

Barnabas, A P; Kulkarni, P D; Nanavatty, M C; Singh, R R

1996-01-01

This article discusses some concerns of the 1996 UN Summit on Social Development. Conference organizers identified the three key conference issues as poverty alleviation, social integration of the marginalized and disadvantaged, and expansion of productive employment. The goal of a "society for all" means dealing with the increasing differences between rich and poor countries, the survival of weaker economies in a competitive market system, wide variations in consumption patterns between countries, attainment of political stability while respecting ethnic identity, the rise in social problems among countries with a high human development index, and increasing joblessness. The Human Development Report for 1994 emphasizes human security. Social development is not the equivalent of human resource development nor a side issue of economic growth. The integration of ethnic groups poses social and political problems. There remains a question about what political system and culture would be best for social integration. Developed countries define poverty as the inability of people and government to provide resources and necessary services for people's productive activity. Poverty in developing countries is blamed on colonialism. Globally, developed countries control 71% of world trade. Sharing resources to meet basic needs throughout the world is not an operational ideal. The highest 20% of income earners receive 83% of the world income. The culture of poverty is the strategy used by the poor to survive. Welfare is not an end in itself but does enable the poor to improve their conditions. Development that focuses on productive employment is uncertain. Developed and developing countries do not share similar perceptions of human rights. There is a question as to who should set the priorities for social development. Sustainable social development is related to preservation of natural resources, control of population growth, and promotion of social security.

Developing New Academic Developers: Doing before Being?

ERIC Educational Resources Information Center

Kensington-Miller, Barbara; Brailsford, Ian; Gossman, Peter

2012-01-01

A small group of new academic developers reflected on their induction into the profession and wondered if things could have been done differently. The researchers decided to question the directors of three tertiary academic development units about how they recruited new developers, what skills and competences they looked for and how they inducted…

PISA for Development and the Sustainable Development Goals. PISA for Development Brief 17

ERIC Educational Resources Information Center

OECD Publishing, 2017

2017-01-01

The PISA for Development brief series is a set of concise monthly education policy-oriented notes published by the OECD which are designed to describe a specific PISA for Development topic. In this brief, PISA's role in monitoring the fourth United Nations Sustainable Development Goal--to "ensure inclusive and equitable quality education and…

Child Development in Developing Countries: Introduction and Methods

PubMed Central

Bornstein, Marc H.; Britto, Pia Rebello; Nonoyama-Tarumi, Yuko; Ota, Yumiko; Petrovic, Oliver; Putnick, Diane L.

2011-01-01

The Multiple Indicator Cluster Survey (MICS) is a nationally representative, internationally comparable household survey implemented to examine protective and risk factors of child development in developing countries around the world. This Introduction describes the conceptual framework, nature of the MICS3, and general analytic plan of articles in this Special Section. The articles that follow describe the situations of children with successive foci on nutrition, parenting, discipline and violence, and the home environment addressing two common questions: How do developing and underresearched countries in the world vary with respect to these central indicators of children's development? and How do key indicators of national development relate to child development in each of these substantive areas? The Special Section concludes with policy implications from the international findings. PMID:22277004

Training and Development in Developing Countries.

ERIC Educational Resources Information Center

Savage, Ernest; Samuel, Errol

Differences in training in developing countries can be traced to the experiences of colonization, industrialization, and advancing technology. Since decolonization after World War II, developing countries have had to cope with depleted primary resources and unprecedented and unexpectedly rapid industrialization. Industrialization has taken the…

Developing New Models for Collection Development.

ERIC Educational Resources Information Center

Stoffle, Carla J.; Fore, Janet; Allen, Barbara

1999-01-01

Discusses the need to develop new models for collection development in academic libraries, based on experiences at the University of Arizona. Highlights include changes in the organizational chart; focusing on users' information goals and needs; integrative services; shared resources; interlibrary loans; digital technology; and funding. (LRW)

Development of the talent development environment questionnaire for sport.

PubMed

Martindale, Russell J J; Collins, Dave; Wang, John C K; McNeill, Michael; Lee, Kok Sonk; Sproule, John; Westbury, Tony

2010-09-01

As sporting challenge at the elite level becomes ever harder, maximizing effectiveness of the talent development pathway is crucial. Reflecting this need, this paper describes the development of the Talent Development Environment Questionnaire, which has been designed to facilitate the development of sporting potential to world-class standard. The questionnaire measures the experiences of developing athletes in relation to empirically identified "key features" of effective talent development environments. The first phase involved the generation of questionnaire items with clear content and face validity. The second phase explored the factor structure and reliability. This was carried out with 590 developing athletes through application of exploratory factor analysis with oblique rotation, principal axis factoring extraction and cronbach alpha tests. This yielded a 59-item, seven-factor structure with good internal consistency (0.616-0.978). The Talent Development Environment Questionnaire appears to be a promising psychometric instrument that can potentially be useful for education and formative review in applied settings, and as a measurement tool in talent development research.

Organization Development

ERIC Educational Resources Information Center

Huse, Edgar F.

1978-01-01

Organization Development (OD) is the application of behavioral-science knowledge to enhance an organization's effectiveness and efficiency. This article discusses the evolution of organization development, the basic components of an OD program, typologies of OD interventions, problems with organization development, and organization development in…

Career Development.

ERIC Educational Resources Information Center

Wyly, Jeanie Rountree

Career development has become very pertinent for adult educators inasmuch as career development programs have been shown to increase effectiveness and efficiency in the field of adult education. Career development programs can vary widely in their content, approach, and philosophy. Various theories have been proposed to explain career development.…

SIRU development. Volume 1: System development

NASA Technical Reports Server (NTRS)

Gilmore, J. P.; Cooper, R. J.

1973-01-01

A complete description of the development and initial evaluation of the Strapdown Inertial Reference Unit (SIRU) system is reported. System development documents the system mechanization with the analytic formulation for fault detection and isolation processing structure; the hardware redundancy design and the individual modularity features; the computational structure and facilities; and the initial subsystem evaluation results.

CCLasso: correlation inference for compositional data through Lasso.

PubMed

Fang, Huaying; Huang, Chengcheng; Zhao, Hongyu; Deng, Minghua

2015-10-01

Direct analysis of microbial communities in the environment and human body has become more convenient and reliable owing to the advancements of high-throughput sequencing techniques for 16S rRNA gene profiling. Inferring the correlation relationship among members of microbial communities is of fundamental importance for genomic survey study. Traditional Pearson correlation analysis treating the observed data as absolute abundances of the microbes may lead to spurious results because the data only represent relative abundances. Special care and appropriate methods are required prior to correlation analysis for these compositional data. In this article, we first discuss the correlation definition of latent variables for compositional data. We then propose a novel method called CCLasso based on least squares with [Formula: see text] penalty to infer the correlation network for latent variables of compositional data from metagenomic data. An effective alternating direction algorithm from augmented Lagrangian method is used to solve the optimization problem. The simulation results show that CCLasso outperforms existing methods, e.g. SparCC, in edge recovery for compositional data. It also compares well with SparCC in estimating correlation network of microbe species from the Human Microbiome Project. CCLasso is open source and freely available from https://github.com/huayingfang/CCLasso under GNU LGPL v3. dengmh@pku.edu.cn Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Consumerism & Development.

ERIC Educational Resources Information Center

Ockenden, Sandy

1991-01-01

This material asks social studies students in Canada to recognize the implications of the lifestyles of citizens in developed countries, and the power that consumers have to create change for a better world, to be agents of positive development. Development is seen as a four faceted process. This model implies that development is an approach to…

Literacy Education and Sustainable Development in Developing Societies

ERIC Educational Resources Information Center

Oghenekohwo, Jonathan E.; Frank-Oputu, Ekima A.

2017-01-01

The development of a literate society is a pre-requisite for the emergence of a knowledge economy. The thesis advanced in this paper is that, without massive investment and promotion of literacy education, development that is targeted at the 17-point sustainable development goals (SDGs) will be bereft of citizen's empowerment, engagement,…

Popular Participation in Development: Emerging Trends in Community Development.

ERIC Educational Resources Information Center

United Nations, New York, NY. Dept. of Economic and Social Affairs.

A first attempt is made to place in perspective the accumulated experience of nearly 20 years of community development activity in both developed and developing countries. The purpose of this study is to stimulate further inquiry into community development practice, process, and theory in order for it to become a more effective instrument in the…

Child Development

MedlinePlus

... ARTICLES Scientific articles. RESEARCH Legacy for Children™ study. Child Development: What's New Article: Differences in health care, family, ... Disorders, Learning Disorders, and other developmental conditions. ... Development Basics Early Brain Development Developmental Screening Screening for ...

Biotechnology developments in the livestock sector in developing countries.

PubMed

Onteru, Suneel; Ampaire, Agatha; Rothschild, Max

2010-01-01

Global meat and milk consumption is exponentially increasing due to population growth, urbanization and changes in lifestyle in the developing world. This is an excellent opportunity for developing countries to improve the livestock sector by using technological advances. Biotechnology is one of the avenues for improved production in the "Livestock revolution". Biotechnology developments applied to livestock health, nutrition, breeding and reproduction are improving with a reasonable pace in developing countries. Simple bio-techniques such as artificial insemination have been well implemented in many parts of the developing world. However, advanced technologies including transgenic plant vaccines, marker assisted selection, solid state fermentation for the production of fibrolytic enzymes, transgenic fodders, embryo transfer and animal cloning are confined largely to research organizations. Some developing countries such as Taiwan, China and Brazil have considered the commercialization of biotechnology in the livestock sector. Organized livestock production systems, proper record management, capacity building, objective oriented research to improve farmer's income, collaborations with the developed world, knowledge of the sociology of an area and research on new methods to educate farmers and policy makers need to be improved for the creation and implementation of biotechnology advances in the livestock sector in the developing world.

Developer Network

DOE Office of Scientific and Technical Information (OSTI.GOV)

2012-08-21

NREL's Developer Network, developer.nrel.gov, provides data that users can access to provide data to their own analyses, mobile and web applications. Developers can retrieve the data through a Web services API (application programming interface). The Developer Network handles overhead of serving up web services such as key management, authentication, analytics, reporting, documentation standards, and throttling in a common architecture, while allowing web services and APIs to be maintained and managed independently.

Cost-effectiveness analysis of universal newborn screening for medium chain acyl-CoA dehydrogenase deficiency in France

PubMed Central

2012-01-01

Background Five diseases are currently screened on dried blood spots in France through the national newborn screening programme. Tandem mass spectrometry (MS/MS) is a technology that is increasingly used to screen newborns for an increasing number of hereditary metabolic diseases. Medium chain acyl-CoA dehydrogenase deficiency (MCADD) is among these diseases. We sought to evaluate the cost-effectiveness of introducing MCADD screening in France. Methods We developed a decision model to evaluate, from a societal perspective and a lifetime horizon, the cost-effectiveness of expanding the French newborn screening programme to include MCADD. Published and, where available, routine data sources were used. Both costs and health consequences were discounted at an annual rate of 4%. The model was applied to a French birth cohort. One-way sensitivity analyses and worst-case scenario simulation were performed. Results We estimate that MCADD newborn screening in France would prevent each year five deaths and the occurrence of neurological sequelae in two children under 5 years, resulting in a gain of 128 life years or 138 quality-adjusted life years (QALY). The incremental cost per year is estimated at €2.5 million, down to €1 million if this expansion is combined with a replacement of the technology currently used for phenylketonuria screening by MS/MS. The resulting incremental cost-effectiveness ratio (ICER) is estimated at €7 580/QALY. Sensitivity analyses indicate that while the results are robust to variations in the parameters, the model is most sensitive to the cost of neurological sequelae, MCADD prevalence, screening effectiveness and screening test cost. The worst-case scenario suggests an ICER of €72 000/QALY gained. Conclusions Although France has not defined any threshold for judging whether the implementation of a health intervention is an efficient allocation of public resources, we conclude that the expansion of the French newborn screening programme

Cost-effectiveness analysis of universal newborn screening for medium chain acyl-CoA dehydrogenase deficiency in France.

PubMed

Hamers, Françoise F; Rumeau-Pichon, Catherine

2012-06-08

Five diseases are currently screened on dried blood spots in France through the national newborn screening programme. Tandem mass spectrometry (MS/MS) is a technology that is increasingly used to screen newborns for an increasing number of hereditary metabolic diseases. Medium chain acyl-CoA dehydrogenase deficiency (MCADD) is among these diseases. We sought to evaluate the cost-effectiveness of introducing MCADD screening in France. We developed a decision model to evaluate, from a societal perspective and a lifetime horizon, the cost-effectiveness of expanding the French newborn screening programme to include MCADD. Published and, where available, routine data sources were used. Both costs and health consequences were discounted at an annual rate of 4%. The model was applied to a French birth cohort. One-way sensitivity analyses and worst-case scenario simulation were performed. We estimate that MCADD newborn screening in France would prevent each year five deaths and the occurrence of neurological sequelae in two children under 5 years, resulting in a gain of 128 life years or 138 quality-adjusted life years (QALY). The incremental cost per year is estimated at €2.5 million, down to €1 million if this expansion is combined with a replacement of the technology currently used for phenylketonuria screening by MS/MS. The resulting incremental cost-effectiveness ratio (ICER) is estimated at €7 580/QALY. Sensitivity analyses indicate that while the results are robust to variations in the parameters, the model is most sensitive to the cost of neurological sequelae, MCADD prevalence, screening effectiveness and screening test cost. The worst-case scenario suggests an ICER of €72 000/QALY gained. Although France has not defined any threshold for judging whether the implementation of a health intervention is an efficient allocation of public resources, we conclude that the expansion of the French newborn screening programme to MCADD would appear to be cost

Henry Friesen Award Lecture. Work, the clinician-scientist and human biochemical genetics.

PubMed

Scriver, C R

2001-08-01

The pursuit of human biochemical genetics has allowed us to understand better how the person with the (genetic) disease differs from the disease the person has and to develop the concept that genetics belongs in all aspects of health care. It is a perspective that comes quite readily to the clinician-scientist, and the restoration of that "species" in the era of functional genomics is strongly recommended. Garrod, the initial founder of human "biochemical genetics" belonged to the clinician-scientist community. Archibald Edward Garrod introduced a paradigm, new for its day, in medicine: biochemistry is dynamic and different from the static nature of organic chemistry. It led him to think about metabolic pathways and to recognize that variation in Mendelian heredity could explain an "inborn error of metabolism." At the time, Garrod had no idea about the nature of a gene. Genes are now well understood; genomes are being described for one organism after another (including Homo sapiens) and it is understood that genomes "speak biochemistry (not phenotype)." Accordingly, in the era of genomics, biochemistry and physiology become the bases of functional genomics, and it is possible to appreciate why "nothing in biology makes sense without evolution" (and nothing in medicine will make sense without biology). Mendelian, biochemical and molecular genetics together have revealed what lies behind the 4 canonical inborn errors described by Garrod (albinisn, alkaptonuria, cystinuria and pentosuria). Both older and newer ideas in genetics, new tools for applying them (and renewed respect for the clinician-scientist) will enhance our understanding of the human biological variation that accounts for variant states of health and overt disease. A so-called monogenic phenotype (phenylketonuria) is used to illustrate, in some detail, that all disease phenotypes are, in one way or another, likely to be complex in nature. What can be known and what ought to be done, with knowledge about

Curriculum Development: Teacher Involvement in Curriculum Development

ERIC Educational Resources Information Center

Alsubaie, Merfat Ayesh

2016-01-01

In order for curriculum development to be effective and schools to be successful, teachers must be involved in the development process. An effective curriculum should reflect the philosophy, goals, objectives, learning experiences, instructional resources, and assessments that comprise a specific educational program ("Guide to curriculum…

Teacher Development.

ERIC Educational Resources Information Center

1997

Eight conference papers on language teacher development are presented, including: "Mosaics of Teacher Development and Socialization" (Andrew Barfield, Paul A. Beaufait, Sean Conley, Tim Murphey, Katsura Haruko), a panel presentation on aspects of and experiments in teacher development; "Questions About Teaching? Answers from…

Developing Teachers: Improving Professional Development for Teachers

ERIC Educational Resources Information Center

Coe, Robert; Aloisi, Cesare; Higgins, Steve; Major, Lee Elliot

2015-01-01

This document is a summary of the report "What Makes Great Teaching". It argues that improved teacher ­development will positively impact on pupil attainment, particular those from disadvantaged backgrounds. "Developing Teachers" presents five policy recommendations which have been signed by 17 of Britain's leading headteachers…

Computer codes developed and under development at Lewis

NASA Technical Reports Server (NTRS)

Chamis, Christos C.

1992-01-01

The objective of this summary is to provide a brief description of: (1) codes developed or under development at LeRC; and (2) the development status of IPACS with some typical early results. The computer codes that have been developed and/or are under development at LeRC are listed in the accompanying charts. This list includes: (1) the code acronym; (2) select physics descriptors; (3) current enhancements; and (4) present (9/91) code status with respect to its availability and documentation. The computer codes list is grouped by related functions such as: (1) composite mechanics; (2) composite structures; (3) integrated and 3-D analysis; (4) structural tailoring; and (5) probabilistic structural analysis. These codes provide a broad computational simulation infrastructure (technology base-readiness) for assessing the structural integrity/durability/reliability of propulsion systems. These codes serve two other very important functions: they provide an effective means of technology transfer; and they constitute a depository of corporate memory.

Faculty Development.

ERIC Educational Resources Information Center

Gillan, Bob, Ed.; McFerrin, Karen, Ed.

This document contains the following papers on faculty development and technology: "Involving Faculty in Faculty Development" (Kristine Blair and Dan Madigan); "Technology Use in Higher Education: A Faculty Development Model" (Jessica Kahn); "A Faculty of Education as a Community of Learners: Growing to Meet the Demands of…

A Murine Model for Human Sepiapterin-Reductase Deficiency

PubMed Central

Yang, Seungkyoung; Lee, Young Jae; Kim, Jin-Man; Park, Sean; Peris, Joanna; Laipis, Philip; Park, Young Shik; Chung, Jae Hoon; Oh, S. Paul

2006-01-01

Tetrahydrobiopterin (BH4) is an essential cofactor for several enzymes, including all three forms of nitric oxide synthases, the three aromatic hydroxylases, and glyceryl-ether mono-oxygenase. A proper level of BH4 is, therefore, necessary for the metabolism of phenylalanine and the production of nitric oxide, catecholamines, and serotonin. BH4 deficiency has been shown to be closely associated with diverse neurological psychiatric disorders. Sepiapterin reductase (SPR) is an enzyme that catalyzes the final step of BH4 biosynthesis. Whereas the number of cases of neuropsychological disorders resulting from deficiencies of other catalytic enzymes involved in BH4 biosynthesis and metabolism has been increasing, only a handful of cases of SPR deficiency have been reported, and the role of SPR in BH4 biosynthesis in vivo has been poorly understood. Here, we report that mice deficient in the Spr gene (Spr−/−) display disturbed pterin profiles and greatly diminished levels of dopamine, norepinephrine, and serotonin, indicating that SPR is essential for homeostasis of BH4 and for the normal functions of BH4-dependent enzymes. The Spr−/− mice exhibit phenylketonuria, dwarfism, and impaired body movement. Oral supplementation of BH4 and neurotransmitter precursors completely rescued dwarfism and phenylalanine metabolism. The biochemical and behavioral characteristics of Spr−/− mice share striking similarities with the symptoms observed in SPR-deficient patients. This Spr mutant strain of mice will be an invaluable resource to elucidate many important issues regarding SPR and BH4 deficiencies. PMID:16532389

Career Development.

ERIC Educational Resources Information Center

1996

This document consists of four papers presented during a symposium on career development moderated by David Bjorkquist at the 1996 conference of the Academy of Human Resource Development (AHRD). "A Mentoring Model for Career Development" (Mary Finnegan) describes a study that created a model based on the assumption that mentoring is an essential…

Levels of Indicator Development for Education for Sustainable Development

ERIC Educational Resources Information Center

Rode, Horst; Michelsen, Gerd

2008-01-01

The article summarizes some considerations about the development of indicators for education for sustainable development (ESD). It reflects the present state of discussion, especially from a German perspective, and includes present developments in the area of quality criteria and standards for ESD. These discussion threads only denote the…

Developing Key Competencies for Sustainable Development in Higher Education

ERIC Educational Resources Information Center

Barth, Matthias; Godemann, Jasmin; Rieckmann, Marco; Stoltenberg, Ute

2007-01-01

Purpose: To date, little attention has been given to the circumstances in which the process of developing key competencies for sustainable development may take place. The purpose of this paper is to consider, the possibilities both of formal and informal learning and their relationship to competence development within higher education.…

Resume Development.

ERIC Educational Resources Information Center

Lorenzen, Elizabeth A.; And Others

This paper presents a step-by-step guide for developing a resume as part of a job search campaign. The paper presents the following information: purposes of the resume; steps in resume development; resume formats; resume headings; and some "do's and some "don't's." The paper also includes a list of 161 action verbs for use in resume development, a…

[The general concepts of development and the principle of sustainable development].

PubMed

Romanov, Iu A

1995-01-01

A concept of the sustainable development principle proposed by the United Nations/International Committee on Environment and Development (ICED, 1987) and gained acceptance at the United Nations Conference on Environment and Development (Rio-de-Janeiro, 1992) lies not in the notion of a sustained character of the development but in an understanding of the development as a steadily and long existing and maintained process that is in advocating the stability of the development. It is known, that the state instability of open self-organizing and self-developing systems including the social ones is the the source of the development having a probabilistic, bifurcate and not quite predictable character. Such an understanding of the development should be well represented in the action initiated in the frame work of national and international state ecological policies.

Part I: Cognitive Development in Children--Piaget Development and Learning

ERIC Educational Resources Information Center

Piaget, Jean

2003-01-01

In this article, the author gives a general introduction of a few ideas on cognitive development in children. In the first part, he deals with the topic of development, a process which concerns the totality of the structures of knowledge. He reviews the stages of development of operational structures, distinguishes four main stages of development,…

Career Development in the Schools. Issues in Career Development

ERIC Educational Resources Information Center

Eliason, Grafton T., Ed.; Patrick, John, Ed.

2008-01-01

"Career Development in the Schools" describes a dynamic process that continues to evolve in its rationale and practice. In many schools and in a variety of scholarly writings, the status of career development is controversial. Some observers assert that career development should be seen as a by-product of all of the knowledge and activities that…

Minority Business Development and Economic Development Policy in New York. Implications for Black Entrepreneurs and Communities. Report of the Subcommittee on Economic Development. Volume 5, Economic Development.

ERIC Educational Resources Information Center

New York Governor's Advisory Committee for Black Affairs, Albany.

New York State should develop a comprehensive justification for its involvement in minority business development and each State program should be closely associated with that rationale. Minority business development programs are often short-sighted, potentially conflicting, and yield unimpressive results. Development of Economic Development Zones…

User participation in healthcare IT development: a developers' viewpoint in Finland.

PubMed

Martikainen, Susanna; Korpela, Mikko; Tiihonen, Tuija

2014-03-01

Recent research showed that physicians in Finland were highly critical of their information technology (IT) systems. They were also critical of the methods of collaboration with the developers of the health IT systems (HITS) in use at the time of the questionnaire. This study turned the set-up around and asked systems developers the same questions about collaboration. What is developers' view on end user participation in HITS development at the moment? How would developers wish end users to participate in systems development? Do the developers' views differ from the physicians' (end users') views of the current state of collaboration in developing IT systems? A web-based questionnaire study was conducted in one of the major HITS provider companies in Finland among all developers, including software developers and customer support and sales personnel. Both quantitative and free-text questions of a previous study were adapted for the purpose. The responses were analyzed with qualitative and basic quantitative methods. The response rate of the questionnaire was 37% and 136 responses were received. The developers who responded were experienced workers; 81% of the respondents had 6 years or more of work experience in IT systems development and 35% of them had 6 years or more of work experience in the healthcare domain. Almost three-quarters (72%) of the respondents agreed with the statement 'I work with users'. Almost all the developers (90%) thought that they are interested in user feedback and also 81% thought that they take the end users' opinions and experiences into account when developing software. A majority of the developers (57%) considered that corrections and modifications are currently not implemented quickly enough. The most popular means of user participation were that 'users would present their work and needs related to it in their workplace' (76%), followed by user groups (75%). The developers suggested many traditional user-centered and usability design

A phenomenological investigation of science center exhibition developers' expertise development

NASA Astrophysics Data System (ADS)

Young, Denise L.

The purpose of this study was to examine the exhibition developer role in the context of United States (U.S.) science centers, and more specifically, to investigate the way science center exhibition developers build their professional expertise. This research investigated how successfully practicing exhibition developers described their current practices, how they learned to be exhibition developers, and what factors were the most important to the developers in building their professional expertise. Qualitative data was gathered from 10 currently practicing exhibition developers from three science centers: the Exploratorium, San Francisco, California; the Field Museum, Chicago, Illinois; and the Science Museum of Minnesota, St. Paul, Minnesota. In-depth, semistructured interviews were used to collect the data. The study embraced aspects of the phenomenological tradition and sought to derive a holistic understanding of the position and how expertise was built for it. The data were methodically coded and organized into themes prior to analysis. The data analysis found that the position consisted of numerous and varied activities, but the developers' primary roles were advocating for the visitor, storytelling, and mediating information and ideas. They conducted these activities in the context of a team and relied on an established exhibition planning process to guide their work. Developers described a process of learning exhibition development that was experiential in nature. Learning through daily practice was key, though they also consulted with mentors and relied on visitor studies to gauge the effectiveness of their work. They were adept at integrating prior knowledge gained from many aspects of their lives into their practice. The developers described several internal factors that contributed to their expertise development including the desire to help others, a natural curiosity about the world, a commitment to learning, and the ability to accept critique. They

PARENT DEVELOPMENT

PubMed Central

Friedman, David Belais

1957-01-01

Today's parents tend to be overwhelmed with advice from many sources. In his role as family counselor, the pediatrician must understand and consider the emotional development of parents in relation to their child's development; otherwise, his advice and counsel do not “take” and he becomes tired and frustrated and angry. Parents progress through definite stages of development: Stage 1: Learning the cues—the struggle of the parents to interpret the infant's needs. Stage 2: Learning to accept growth and development—the parent learning to accept some loss of control of the toddler. Stage 3: Learning to separate—the parent learning to allow the child to develop independently. Stage 4: Learning to accept rejection, without deserting—the struggle of the parents not to intrude and yet to be there when needed. Stage 5: Learning to build a new life having been thoroughly discredited by one's teenager—the parent learning to live independently while the teenager struggles to develop his own identity. The pediatrician who is accepting, sensitive and a good listener and who keeps in mind that parents as well as children have capacities for growth and development, will be a potent factor in promoting good parent-child relationships and many times more effective in dealing with the child in health and disease. PMID:13383387

Developing a research and development strategy for primary care.

PubMed Central

Harris, A

1993-01-01

General practice research has been a minority activity and underfunded in the past. The creation of the purchaser and provider split, the introduction of medical audit, and the new research and development strategy for the NHS provide an opportunity to focus research on the health needs of the population. FHSAs, with the regional health authority, should develop a local strategy for research and development and appoint a lead officer, who may be the medical adviser. When negotiating contracts FHSAs need to back up their arguments with research evidence. NHS development research should cover quality, distribution, accessibility, outcome, and effectiveness. FHSAs should play a part in disseminating knowledge in the interests of achieving an effective and high quality service. GPs should be encouraged to participate in research by relaxing the regulations of compulsory hours of patient service and by creating a practice development allowance. Images p191-a PMID:8443486

Develop a Skill while Learning about Human Development.

ERIC Educational Resources Information Center

Wiggins, R. Gene

1979-01-01

Described is a student group project involving the development of a slide presentation based on some aspect of human growth and development or educational psychology. Included in the description is a list of project titles and a sample of the project assignment outline. (JMD)

Child Development in Developing Countries: Introduction and Methods

ERIC Educational Resources Information Center

Bornstein, Marc H.; Britto, Pia Rebello; Nonoyama-Tarumi, Yuko; Ota, Yumiko; Petrovic, Oliver; Putnick, Diane L.

2012-01-01

The Multiple Indicator Cluster Survey (MICS) is a nationally representative, internationally comparable household survey implemented to examine protective and risk factors of child development in developing countries around the world. This introduction describes the conceptual framework, nature of the MICS3, and general analytic plan of articles…

EYE DEVELOPMENT

PubMed Central

Baker, Nicholas E.; Li, Ke; Quiquand, Manon; Ruggiero, Robert; Wang, Lan-Hsin

2014-01-01

The eye has been one of the most intensively studied organs in Drosophila. The wealth of knowledge about its development, as well as the reagents that have been developed, and the fact that the eye is dispensable for survival, also make the eye suitable for genetic interaction studies and genetic screens. This chapter provides a brief overview of the methods developed to image and probe eye development at multiple developmental stages, including live imaging, immunostaining of fixed tissues, in situ hybridizations, and scanning electron microscopy and color photography of adult eyes. Also summarized are genetic approaches that can be performed in the eye, including mosaic analysis and conditional mutation, gene misexpression and knockdown, and forward genetic and modifier screens. PMID:24784530

DEVELOPING STATE POLICIES SUPPORTIVE OF BIOENERGY DEVELOPMENT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kathryn Baskin

2004-10-31

Working within the context of the Southern States Biobased Alliance (SSBA) and with officials in each state, the Southern States Energy Board (SSEB) is identifying bioenergy-related policies and programs within each state to determine their impact on the development, deployment or use of bioenergy. In addition, SSEB will determine which policies have impacted industry's efforts to develop, deploy or use biobased technologies or products. As a result, SSEB will work with the Southern States Biobased Alliance to determine how policy changes might address any negative impacts or enhance positive impacts. In addition to analysis of domestic policies and programs, thismore » project will include the development of a U.S.-Brazil Biodiesel Pilot Project. The purpose of this effort is to promote and facilitate the commercialization of biodiesel and bioenergy production and demand in Brazil.« less

Development Dialogue. Towards a Theory of Rural Development.

ERIC Educational Resources Information Center

Haque, Wahidul; And Others

1977-01-01

The study attempts to redefine the objectives of Asian development in terms of rapid social change and the redistribution of political power to the rural masses via collectivism. Part I, "The Perspective", describes the largely "anti" rural development experiences of four Asian countries (India, Bangladesh, Sri Lanka, China) in…

Toddler development

MedlinePlus

Toddlers are children ages 1 to 3. CHILD DEVELOPMENT THEORIES Cognitive (thought) development skills typical for toddlers include: Early use of instruments or tools Following visual (then later, invisible) displacement (moving from ...

The development speed paradox: can increasing development speed reduce R&D productivity?

PubMed

Lendrem, Dennis W; Lendrem, B Clare

2014-03-01

In the 1990s the pharmaceutical industry sought to increase R&D productivity by shifting development tasks into parallel to reduce development cycle times and increase development speed. This paper presents a simple model demonstrating that, when attrition rates are high as in pharmaceutical development, such development speed initiatives can increase the expected time for the first successful molecule to complete development. Increasing the development speed of successful molecules could actually reduce R&D productivity - the development speed paradox. Copyright © 2013 Elsevier Ltd. All rights reserved.

Professional development for primary science teaching in Thailand: Knowledge, orientations, and practices of professional developers and professional development participants

NASA Astrophysics Data System (ADS)

Musikul, Kusalin

The purpose of this study was to examine an entire PD project as a case to understand the dynamic nature of science PD in a holistic manner. I used a pedagogical content knowledge model by Magnusson, Krajcik, and Borko (1999) as my theoretical framework in examining the professional developers' and teacher participants' knowledge, orientation, and practice for professional development and elementary science teaching. The case study is my research tradition; I used grounded theory for data analysis. The primary data sources were interview, card sort activity, and observation field notes collected during the PD and subsequently in teacher participants' classrooms. Secondary data sources were documents and artifacts that I collected from the professional developers and teachers. An analysis of the data led me to interpret the following findings: (a) the professional developers displayed multiple orientations. These orientations included activity-driven, didactic, discovery, and pedagogy-driven orientations. The orientations that were found among the professional developers deviated from the reformed Thai Science Education Standards; (b) the professional developers had limited PCK for PD, which were knowledge of teachers' learning, knowledge of PD strategies, knowledge of PD curriculum, and knowledge of assessment.; (c) the professional developers' knowledge and orientations influenced their decisions in selecting PD activities and teaching approaches; (d) their orientations and PCK as well as the time factor influenced the design and implementation of the professional development; (e) the elementary teachers displayed didactic, activity-driven, and academic rigor orientations. The orientations that the teachers displayed deviated from the reformed Thai Science Education Standards; and (f) the elementary teachers exhibited limited PCK. It is evident that the limitation of one type of knowledge resulted in an ineffective use of other components of PCK. This study

Analysis of Development Environment and Development Trend of Chinese Tourism

NASA Astrophysics Data System (ADS)

Zhao, Liyun; Li, Lingzhi

2018-01-01

Since the reform and opening up of Chinese tourism industry, the scale has been continuously expanded and the income from tourism has been continuously increasing. Chinese tourism industry has become one of the most potential industries in the service industry. By analyzing the development environment and development trend of Chinese tourism industry from 2000 to 2016, we can understand the current situation of Chinese tourism development and provide suggestions for better development of Chinese tourism industry.

Developing Entrepreneurial Resilience: Implications for Human Resource Development

ERIC Educational Resources Information Center

Lee, Jin; Wang, Jia

2017-01-01

Purpose: Leadership development has attracted much research attention within the human resource development (HRD) community. However, little scholarly effort has been made to study a special group of leaders--entrepreneurs. This paper aims to fill in this knowledge gap by taking a close look at entrepreneurial resilience, a key ability of…

High flow rate development: process optimization using megasonic immersion development (MID)

NASA Astrophysics Data System (ADS)

Courboin, Daniel; Choi, Jong Woo; Jung, Sang Hyun; Baek, Seung Hee; Kim, Lee Ju

2004-12-01

In previous study the high impact of development by-products on Critical Dimension (CD) through the microloading effect has been demonstrated for a Novolak resist. In this paper, through further tests involving Chemically Amplified Resist (CAR) and Novolak resist, the microloading effect of development is characterized and tentative mechanism is presented. Megasonic Immersion Development (MID), a high flow rate development technique similar to the Proximity Gap Suction Development (PGSD), was used and compared with spin spray development and puddle development. On TOK IP3600, a Novolak resist, we have explored a wide range of process conditions with MID. Developer temperature was varied from 5°C to 40°C with TMAH developer concentration of 1.9% and 2.38% resulting in an isofocal dose range of 90mJ to 190mJ. Exposure Focus Matrix (EFM) with a specific microloading pattern and resist cross sections were performed. The best conditions are quite far from the standard process advised by the resist supplier. Very nice standing wave profile was obtained at high temperature development. On CAR, JEOL 9000MVII, a 50kV e-beam vector scan tool, and ETEC ALTA 4300, a DUV raster scan tool, were used with different develop process techniques including MID. FujiFilm Arch FEP-171 positive CAR and Sumitomo NEB-22 negative CAR were used on 50kV writing tool. Sumitomo PEK-130 was used on DUV writing tool. FEP-171 and PEK-1300 show microloading effect on high density patterns but not NEB-22. MID shows also improved reproduction of develop features in the chrome and a 20% improvement of CD uniformity. The results of this study seem to indicate that a closer look in their development process is needed for 90nm and 65nm technologies.

Child Development

MedlinePlus

... grow older, they develop in several different ways. Child development includes physical, intellectual, social, and emotional changes. ... same sex. Peer approval becomes very important. Your child may try new behaviors to be part of " ...

Toddler development.

PubMed

Colson, E R; Dworkin, P H

1997-08-01

The toddler years are ones of exciting and challenging changes in cognitive, affective, and physical growth. Physical growth is particularly remarkable for the child's increasing skills and ability to navigate the environment. Affective development is marked by the push for autonomy and independence and the highly visible nature of the child's temperament or behavioral style. The toddler also enters the wonderful years of imagination and pretend play. Perhaps most noteworthy is the child's dramatic increase in ability to communicate with others through speech and language, as evidence of the progression to symbolic thinking. The dynamic changes in children's development during the toddler years have important implications for child health supervision. Familiarity with toddler development will enable the pediatrician to monitor children's development effectively and to address common, stage-related behaviors with families during anticipatory guidance.

Health in the developing world: achieving the Millennium Development Goals.

PubMed Central

Sachs, Jeffrey D.

2004-01-01

The Millennium Development Goals depend critically on scaling up public health investments in developing countries. As a matter of urgency, developing-country governments must present detailed investment plans that are sufficiently ambitious to meet the goals, and the plans must be inserted into existing donor processes. Donor countries must keep the promises they have often reiterated of increased assistance, which they can easily afford, to help improve health in the developing countries and ensure stability for the whole world. PMID:15654410

NASA's Exploration Technology Development Program Energy Storage Project Battery Technology Development

NASA Technical Reports Server (NTRS)

Reid, Concha M.; Miller, Thomas B.; Mercer, Carolyn R.; Jankovsky, Amy L.

2010-01-01

Technical Interchange Meeting was held at Saft America s Research and Development facility in Cockeysville, Maryland on Sept 28th-29th, 2010. The meeting was attended by Saft, contractors who are developing battery component materials under contracts awarded through a NASA Research Announcement (NRA), and NASA. This briefing presents an overview of the components being developed by the contractor attendees for the NASA s High Energy (HE) and Ultra High Energy (UHE) cells. The transition of the advanced lithium-ion cell development project at NASA from the Exploration Technology Development Program Energy Storage Project to the Enabling Technology Development and Demonstration High Efficiency Space Power Systems Project, changes to deliverable hardware and schedule due to a reduced budget, and our roadmap to develop cells and provide periodic off-ramps for cell technology for demonstrations are discussed. This meeting gave the materials and cell developers the opportunity to discuss the intricacies of their materials and determine strategies to address any particulars of the technology.

Agile Software Development

ERIC Educational Resources Information Center

Biju, Soly Mathew

2008-01-01

Many software development firms are now adopting the agile software development method. This method involves the customer at every level of software development, thus reducing the impact of change in the requirement at a later stage. In this article, the principles of the agile method for software development are explored and there is a focus on…

World Development Report 1991: The Challenge of Development.

ERIC Educational Resources Information Center

World Bank, Washington, DC.

This report attempts to show how government and markets can interact most effectively to promote rapid economic development and benefit all people. The world economy is reviewed and an assessment is made of the impact of external factors on development. Alternative scenarios, optimistic and pessimistic, for the 1990s are considered. Four…

Preschooler development

MedlinePlus

... include: Spreading with a knife Drawing a triangle LANGUAGE DEVELOPMENT The 3-year-old uses: Pronouns and prepositions ... why" questions Stuttering may occur in the normal language development of toddlers ages 3 to 4 years. It ...

Speech Development

MedlinePlus

... able to assess your child’s speech production and language development and make appropriate therapy recommendations. It is also ... pathologist should consistently assess your child’s speech and language development, as well as screen for hearing problems (with ...

Sustainable developments

NASA Astrophysics Data System (ADS)

Showstack, Randy

Hundreds of diplomats, along with industry, finance, environment, and labor leaders from around the world met from April 20 to May 1 for the sixth session of the United Nations Commission for Sustainable Development (CSD), an annual follow-up conference to track the Agenda 21 program of action adopted at the 1992 Rio de Janeiro Earth Summit.During the session, which focused on freshwater management concerns and the role of industry in sustainable development, the participants discussed a number of issues about development and parity among northern and southern hemisphere countries.

Some observations on World Development Report 2011: conflict, security and development.

PubMed

Gangolli, Leena V

2011-01-01

The World Development Report 2011 describes the relationship between conflict, security and development and makes a strong argument in favour of strengthening legitimate institutions to reduce the fragility of countries facing protracted cycles of violence, and moving from violence to resilience in order to realise development goals. While highlighting some of the lessons learned from the report (the nature of violence in the 21st century, the global reach of seemingly local conflicts, the universality of conflict as an impediment to development, the role of the international community, and the impact on health), this comment discusses the role of development on conflict and security--particularly the role of imbalanced inequitable development on fuelling conflict and insecurity.

Pro-development soap operas: a novel approach to development communication.

PubMed

Brown, W J; Singhal, A; Rogers, E M

1989-01-01

Soap operas have their roots in 18th century English romance novels. These evolved into serialized radio dramas. In their current form, they were developed primarily to attract large audiences in order to sell consumer products. Hence the name soap which refers to the soap manufacturers who commonly advertise on such programs. In the world of soap operas there are 2 kinds. Those that function primarily to entertain and sell consumer products, and those that primarily entertain, but infuse positive social messages. The former are found everywhere, but are the only kind in America. The latter are found exclusively in developing countries. American soap operas have conveyed pro-social messages in the past, but they differ fundamentally from pro-development soap operas in their theoretical foundations. American soap operas are created by people who want to sell consumer goods. Development soap operas are created by people who want to convey pro-social messages that will aid their country's development. Both must be popular in order to be successful, but the former lack moral coherency, are unrealistic, erode values, and are created through a process of a theoretical development; while the latter have moral coherency, are realistic, promote values, and are created through a process of theoretical development. The 1st pro-development soap opera was Ven Conmigo (Come With Me) and was produced in Mexico between 1975-76. Its primary purpose was to increase adult literacy. During the year it ran, applicants at adult literacy centers rose by 600,000 or 63% compared to 7% the year before, and 2% the year after. The 2nd pro-development soap opera was Acompaname (Accompany Me) and it primary purpose was to promote family planning. It ran from 1977-78 and during that time the number of family planning adopters rose by 560,000 and contraceptive sale sin Mexico rose sharply. The question of what are pro-social messages and who should control them must be answered by each country in

Growth and Development

MedlinePlus

... Tots Understanding Puberty Your Child's Changing Voice Your Child's Development: 1.5 Years (18 Months) Your Child's Growth ... 8 Months Your Baby's Growth: 9 Months Your Child's Development (Birth to 3 Years) Your Child's Development: 15 ...

How we developed a role-based portfolio for teachers' professional development.

PubMed

Pyörälä, Eeva

2014-09-01

Faculty development requires practical tools for supporting teachers' professional development. In a modern medical education context, teachers need to adapt to various educational roles. This article describes how a role-based portfolio with a qualitative self-assessment scale was developed. It strives to encourage and support teachers' growth in different educational roles. The portfolio was developed between 2009 and 2012 at the University of Helsinki in dialogue with teachers involved in faculty development. It is based on the role framework presented by Harden and Crosby. Today, it also involves the educational premises of constructive alignment, reflection and a scholarly approach to teaching. The role-based portfolio has led the teachers to discover new educational roles and set goals in their professional development.

Comparison of Psychomotor Development Screening Test and Clinical Assessment of Psychomotor Development

PubMed

Radmilović, Goranka; Matijević, Valentina; Zavoreo, Iris

2016-12-01

Numerous adverse factors are acting in the prenatal, perinatal and postnatal period of life and may be the cause of later mild or severe deviations from normal psychomotor development. Therefore, it is crucial to identify infants with neurological risk factors and infants that already have a delay from orderly development, in order to immediately initiate the rehabilitation process. The aim of this study was to determine whether there is difference in the assessment of psychomotor development in neurological risk children based on the psychomotor development test (Croatian, Razvoj psihomotorike, RPM test) and clinical evaluation of neuromotor development. RPM test is designed for rough estimate of psychomotor development in children in the first two years of life. The study included 15 full term children (8 male and 7 female) with clinical diagnosis of mild paraparesis and mild deviation from normal psychological and social development, and 15 full term children (8 male and 7 female) without neurological risk factors and deviations from normal psychomotor development, all at the age of 12-24 months. Of the 15 children diagnosed with mild paraparesis, none had delayed psychomotor development, 6.7% had suspect development and 93.3% had normal development on RPM test. All children in the control group had normal development on RPM test. According to the results, the RPM test is not sensitive enough to detect mild neurodevelopmental disorders.

Success rates for product development strategies in new drug development.

PubMed

Dahlin, E; Nelson, G M; Haynes, M; Sargeant, F

2016-04-01

While research has examined the likelihood that drugs progress across phases of clinical trials, no research to date has examined the types of product development strategies that are the most likely to be successful in clinical trials. This research seeks to identify the strategies that are most likely to reach the market-those generated using a novel product development strategy or strategies that combine a company's expertise with both drugs and indications, which we call combined experience strategies. We evaluate the success of product development strategies in the drug development process for a sample of 2562 clinical trials completed by 406 US pharmaceutical companies. To identify product development strategies, we coded each clinical trial according to whether it consisted of an indication or a drug that was new to the firm. Accordingly, a clinical trial that consists of both an indication and a drug that were both new to the firm represents a novel product development strategy; indication experience is a product development strategy that consists of an indication that a firm had tested previously in a clinical trial, but with a drug that was new to the firm; drug experience is a product development strategy that consists of a drug that the firm had prior experience testing in clinical trials, but with an indication that was new to the firm; combined experience consists of both a drug and an indication that the firm had experience testing in clinical trials. Success rates for product development strategies across clinical phases were calculated for the clinical trials in our sample. Combined experience strategies had the highest success rate. More than three and a half percent (0·036) of the trials that combined experience with drugs and indications eventually reached the market. The next most successful strategy is drug experience (0·025) with novel strategies trailing closely (0·024). Indication experience strategies are the least successful (0·008

Science and Development

ERIC Educational Resources Information Center

Auger, Pierre

1973-01-01

The relation between science and socioeconomic development in both developed and developing countries is discussed. The interdependence of pure and applied science, technology and finance, knowledge and tradition, and national, regional, and world-wide efforts in behalf of progress are characterized. (BL)

Management Guidelines for Database Developers' Teams in Software Development Projects

NASA Astrophysics Data System (ADS)

Rusu, Lazar; Lin, Yifeng; Hodosi, Georg

Worldwide job market for database developers (DBDs) is continually increasing in last several years. In some companies, DBDs are organized as a special team (DBDs team) to support other projects and roles. As a new role, the DBDs team is facing a major problem that there are not any management guidelines for them. The team manager does not know which kinds of tasks should be assigned to this team and what practices should be used during DBDs work. Therefore in this paper we have developed a set of management guidelines, which includes 8 fundamental tasks and 17 practices from software development process, by using two methodologies Capability Maturity Model (CMM) and agile software development in particular Scrum in order to improve the DBDs team work. Moreover the management guidelines developed here has been complemented with practices from authors' experience in this area and has been evaluated in the case of a software company. The management guidelines for DBD teams presented in this paper could be very usefully for other companies too that are using a DBDs team and could contribute towards an increase of the efficiency of these teams in their work on software development projects.

Development of anti-inflammatory drugs - the research and development process.

PubMed

Knowles, Richard Graham

2014-01-01

The research and development process for novel drugs to treat inflammatory diseases is described, and several current issues and debates relevant to this are raised: the decline in productivity, attrition, challenges and trends in developing anti-inflammatory drugs, the poor clinical predictivity of experimental models of inflammatory diseases, heterogeneity within inflammatory diseases, 'improving on the Beatles' in treating inflammation, and the relationships between big pharma and biotechs. The pharmaceutical research and development community is responding to these challenges in multiple ways which it is hoped will lead to the discovery and development of a new generation of anti-inflammatory medicines. © 2013 Nordic Pharmacological Society. Published by John Wiley & Sons Ltd.

Numerical Development

ERIC Educational Resources Information Center

Siegler, Robert S.; Braithwaite, David W.

2016-01-01

In this review, we attempt to integrate two crucial aspects of numerical development: learning the magnitudes of individual numbers and learning arithmetic. Numerical magnitude development involves gaining increasingly precise knowledge of increasing ranges and types of numbers: from non-symbolic to small symbolic numbers, from smaller to larger…

Professional Development.

ERIC Educational Resources Information Center

Benson, Chris, Ed.

2000-01-01

This serial issue contains 12 articles on the theme of "Professional Development," specifically about how teachers in the Bread Loaf Rural Teacher Network (BLRTN) are fostering their own and each other's development as teachers. The BLRTN consists of approximately 260 rural teachers in Alaska, Arizona, Colorado, Georgia, Kentucky,…

Educational Developer 2.0: How Educational Development Leaders Will Need to Develop Themselves in the Era of Innovation

ERIC Educational Resources Information Center

Sievers, Julie

2016-01-01

How should educational developers develop their own expertise and skills in the twenty-first century? Today educational developers are drawing on new discoveries in educational research, supporting new pedagogies in many fields, and experimenting with new technologies for teaching and learning. Yet they must do so in a time of uncertain and…

Exploring Faculty Developers' Experiences to Inform Our Understanding of Competence in Faculty Development.

PubMed

Baker, Lindsay; Leslie, Karen; Panisko, Danny; Walsh, Allyn; Wong, Anne; Stubbs, Barbara; Mylopoulos, Maria

2018-02-01

Now a mainstay in medical education, faculty development has created the role of the faculty developer. However, faculty development research tends to overlook faculty developers' roles and experiences. This study aimed to develop an empirical understanding of faculty developer competence by digging deeper into the actions, experiences, and perceptions of faculty developers as they perform their facilitator role. A constructivist grounded theory approach guided observations of faculty development activities, field interviews, and formal interviews with 31 faculty developers across two academic institutions from 2013 to 2014. Analysis occurred alongside and informed data collection. Themes were identified using a constant comparison process. Consistent with the literature, findings highlighted the knowledge and skills of the faculty developer and the importance of context in the design and delivery of faculty development activities. Three novel processes (negotiating, constructing, and attuning) were identified that integrate the individual faculty developer, her context, and the evolution of her competence. These findings suggest that faculty developer competence is best understood as a situated construct. A faculty developer's ability to attune to, construct, and negotiate her environment can both enhance and minimize the impact of contextual variables as needed. Thus, faculty developers do not passively experience context; rather, they actively interact with their environment in ways that maximize their performance. Faculty developers should be trained for the adaptive, situated use of knowledge.

Inspiration from heart development: Biomimetic development of functional human cardiac organoids.

PubMed

Richards, Dylan J; Coyle, Robert C; Tan, Yu; Jia, Jia; Wong, Kerri; Toomer, Katelynn; Menick, Donald R; Mei, Ying

2017-10-01

Recent progress in human organoids has provided 3D tissue systems to model human development, diseases, as well as develop cell delivery systems for regenerative therapies. While direct differentiation of human embryoid bodies holds great promise for cardiac organoid production, intramyocardial cell organization during heart development provides biological foundation to fabricate human cardiac organoids with defined cell types. Inspired by the intramyocardial organization events in coronary vasculogenesis, where a diverse, yet defined, mixture of cardiac cell types self-organizes into functional myocardium in the absence of blood flow, we have developed a defined method to produce scaffold-free human cardiac organoids that structurally and functionally resembled the lumenized vascular network in the developing myocardium, supported hiPSC-CM development and possessed fundamental cardiac tissue-level functions. In particular, this development-driven strategy offers a robust, tunable system to examine the contributions of individual cell types, matrix materials and additional factors for developmental insight, biomimetic matrix composition to advance biomaterial design, tissue/organ-level drug screening, and cell therapy for heart repair. Copyright © 2017 Elsevier Ltd. All rights reserved.

Human Behavior, Learning, and the Developing Brain: Typical Development

ERIC Educational Resources Information Center

Coch, Donna, Ed.; Fischer, Kurt W., Ed.; Dawson, Geraldine, Ed.

2010-01-01

This volume brings together leading authorities from multiple disciplines to examine the relationship between brain development and behavior in typically developing children. Presented are innovative cross-sectional and longitudinal studies that shed light on brain-behavior connections in infancy and toddlerhood through adolescence. Chapters…

Collection Development Project.

ERIC Educational Resources Information Center

Nuby, Mary

Undertaken to provide data on the current status of collection development in selected academic libraries, this study also analyzed the structure of the collection development function at Chicago Academic Library Council (CALC) institutions and outlined a formal collection development policy for Chicago State University's Douglas Library.…

HRD Professional Development.

ERIC Educational Resources Information Center

1998

This document contains four papers from a symposium on professional development of human resource development (HRD) professionals. "Lifelong Learning and Performance: The Role of Key Qualifications in Human Resource Development" (Simone J. van Zolingen, Wim J. Nijhof) argues that, besides being of interest to employers, key…

Advanced Gas Turbine (AGT) Technology Development Project, ceramic component developments

NASA Technical Reports Server (NTRS)

Teneyck, M. O.; Macbeth, J. W.; Sweeting, T. B.

1987-01-01

The ceramic component technology development activity conducted by Standard Oil Engineered Materials Company while performing as a principal subcontractor to the Garrett Auxiliary Power Division for the Advanced Gas Turbine (AGT) Technology Development Project (NASA Contract DEN3-167) is summarized. The report covers the period October 1979 through July 1987, and includes information concerning ceramic technology work categorized as common and unique. The former pertains to ceramic development applicable to two parallel AGT projects established by NASA contracts DEN3-168 (AGT100) and DEN3-167 (AGT101), whereas the unique work solely pertains to Garrett directed activity under the latter contract. The AGT101 Technology Development Project is sponsored by DOE and administered by NASA-Lewis. Standard Oil directed its efforts toward the development of ceramic materials in the silicon-carbide family. Various shape forming and fabrication methods, and nondestructive evaluation techniques were explored to produce the static structural components for the ceramic engine. This permitted engine testing to proceed without program slippage.

Oh, Develop

NASA Technical Reports Server (NTRS)

Post, Todd

2003-01-01

In a mature view of the subject, career development is not simply four years of college or a week at training, culminating in a diploma or a certificate to hang on an office wall. That's why we wanted to take a broad look at career development in this issue of ASK. Take for example, Dr. Gerald Mulenburg s contribution, Fly on the Wall. When Mulenburg and other members of a knowledge-sharing group at Ames were invited to observe an upcoming project review, Mulenburg thought it would be interesting to learn how another project does its reviews. Note that Mulenburg is no fresh out who's never attended a NASA project review. Not only has he been through a fair share of them as the reviewed, he has also been on the other side of the table as a reviewer. This experienced project manager recognizes that at any stage of a career there is room to grow and develop one's repertoire. Too often people associate career development with textbooks and role classroom training, far removed from project life. But classroom training need not be like this, as you'll find in our Special Feature, The Enterprise Project by Wendy Dolci, which sprung out of an APPL Advanced Project Management class in July 2003 at Ames Research Center. In addition to Dolci, some of her classmates contribute to the story. Mike Sander of the Jet Propulsion Laboratory, project manager for the Mars Science Laboratory mission, who provided the assignment on which the story is based, also has a cameo in the story. We think Dolci's story is an inspiring example of what classroom training can be if it's approached imaginatively and made to serve a practical purpose. Another story from Ames, by Frank Larsen, takes a different twist on career development. At the annual Experimental Aircraft Association Fly-in in Oshkosh, Wisconsin, Larsen represented Ames at a NASA booth. While there, Larsen met a colleague from Glenn Research Center. Months later on a project with a quick turnaround, he remembered his colleague from

Staff Development.

ERIC Educational Resources Information Center

Purcell, Larry O.

Staff development programs and activities are common methods of stimulating change in the behavior of educators. These programs may be designed for a number of purposes, including (1) problem-solving within the local school or district; (2) remediation to develop work-related skills; (3) motivation to change and improve staff; and (4) development…

Management Development.

ERIC Educational Resources Information Center

1997

This document contains three papers from a symposium on management development. "LMX (Leader-Member Exchange) Theory, Personality Type, and Management Development" (Janet Z. Burns) reports the results of a study on the similarities and differences in personality type (as outlined in the theories of Carl Jung and Isabel Myers) and its relationship…

Exploring land developer perspectives on conservation subdivision design and environmentally sustainable land development.

PubMed

Göçmen, Z Aslıgül

2014-11-01

Insight into land developers' perspectives on alternative residential developments and the barriers they experience in trying to develop them can be crucial in efforts to change environmentally damaging low-density, large-lot, and automobile-dependent residential patterns. Using a semi-structured interview instrument followed by short surveys, I examined the views of 16 developers in Waukesha County, WI, USA, a county that has experienced significant development pressures and widespread implementation of conservation subdivision design. The land developer investigation focused on conservation subdivision design familiarity and implementation, and identified a number of barriers that developers experienced in implementing the design. While the majority of the developers appeared familiar with the design and had experience developing conservation subdivisions, their motivations for developing them varied, as did their on-site conservation practices. The barriers included the lack of land use regulations supporting the design, economic factors, community opposition, and a lack of knowledge about sustainable residential development practices. Strategies to promote more environmentally sustainable residential land development patterns include providing a more supportive institutional environment, enacting different regulations and guidelines for natural resources protection, and offering education on ecologically sound development and planning practices.

Exploring Land Developer Perspectives on Conservation Subdivision Design and Environmentally Sustainable Land Development

NASA Astrophysics Data System (ADS)

Göçmen, Z. Aslıgül

2014-11-01

Insight into land developers' perspectives on alternative residential developments and the barriers they experience in trying to develop them can be crucial in efforts to change environmentally damaging low-density, large-lot, and automobile-dependent residential patterns. Using a semi-structured interview instrument followed by short surveys, I examined the views of 16 developers in Waukesha County, WI, USA, a county that has experienced significant development pressures and widespread implementation of conservation subdivision design. The land developer investigation focused on conservation subdivision design familiarity and implementation, and identified a number of barriers that developers experienced in implementing the design. While the majority of the developers appeared familiar with the design and had experience developing conservation subdivisions, their motivations for developing them varied, as did their on-site conservation practices. The barriers included the lack of land use regulations supporting the design, economic factors, community opposition, and a lack of knowledge about sustainable residential development practices. Strategies to promote more environmentally sustainable residential land development patterns include providing a more supportive institutional environment, enacting different regulations and guidelines for natural resources protection, and offering education on ecologically sound development and planning practices.

21st Century Science for Sustainable Development in the Developing World

NASA Astrophysics Data System (ADS)

Sachs, J. D.

2004-12-01

Meeting the Millennium Development Goals and, ultimately, eradicating extreme poverty, engages experts from many academic disciplines and different parts of society- climatologists, earth engineers, ecologists, economists, public health specialists, social activists, and politicians. We are in the midst of exciting technological and scientific breakthroughs that make it realistic to end extreme poverty by 2025. Indeed, the experiences of China and India in recent years have illustrated that technology can accelerate economic development to impressively high rates. India, which boasts growth rates of nearly 8% over the past decade, may end hunger among its population as early as 2007, thanks in large part to the Green Revolution underway there. The work of agronomists and economists are not unrelated - the science behind soil nutrients, water, and germplasm all fuel sustainable development. Science and technology are important ingredients for growth, and they are improving at an ever-increasing rate. When applied for the sake of human benefit, we have a tool of unprecedented strength. But the developing world has also reached a point of unprecedented environmental stress. Biodiversity faces serious threats, as do water supplies, forests, and the atmosphere. Developing and developed nations continue to grapple with the consequences of greenhouse gas emissions. We must maintain our scientific investigations and analysis while ensuring that development policy addresses long-term environmental needs. The energy sector is one obvious example. Several developing countries, China and India included, harbor vast coal deposits. Fueling development with coal will drastically exacerbate the ongoing spiral of man-made climate change. My presentation will focus on the contributions that 21st century science can make-indeed, must make-to ensure that sustainable development occurs and we meet the Millennium Challenge of cutting extreme poverty in half by 2015.

Incremental development and prototyping in current laboratory software development projects: Preliminary analysis

NASA Technical Reports Server (NTRS)

Griesel, Martha Ann

1988-01-01

Several Laboratory software development projects that followed nonstandard development processes, which were hybrids of incremental development and prototyping, are being studied. Factors in the project environment leading to the decision to use a nonstandard development process and affecting its success are analyzed. A simple characterization of project environment based on this analysis is proposed, together with software development approaches which have been found effective for each category. These approaches include both documentation and review requirements.

Lessons for Staff Developers from an Organization Development Intervention.

ERIC Educational Resources Information Center

Conway, James A.

1990-01-01

A case study of an organization development intervention in a large New York State school district describes to staff developers the complex process of discovering and responding to organizational needs. The discussion focuses on understanding the problem; frameworks for diagnosis and intervention; and implementing the intervention strategy.…

Developing clinical leadership capability.

PubMed

Pintar, Kristi A; Capuano, Terry A; Rosser, Gwendolyn D

2007-01-01

Nursing facilities must be committed to ongoing leadership development and to developing and retaining their staff in the increasingly competitive healthcare market. In this article, the authors share the processes involved in creating a focused small group approach to developing clinical leaders. Programmatic approaches to development, clarity of needs of those targeted for development, individual development plans, external expertise partnerships, and small group session dynamics are discussed. Applications of the process and lessons learned from the program will benefit others in their efforts to enhance organization succession planning, leadership development, group learning, and program administration.

Superconducting power transmission system development. Cable insulation development

NASA Astrophysics Data System (ADS)

1983-09-01

The development of an underground superconducting power transmission system which is economical and technically attractive to the utility industry is discussed. Suitable superconductors and dielectric insulation were developed. Cables several hundred feet long are tested under realistic conditions. Three operating runs of about 2 weeks duration each were accomplished. The 60 Hz steady state performance of the cables under rated conditions was explored. Over voltage endurance tests and emergency level current tests were performed.

Institutionalizing Staff Development.

ERIC Educational Resources Information Center

Shawl, William F.

Three years ago, Golden West College (GWC) decided to make a major commitment to staff development as a means of revitalizing the college. This commitment was evidenced through the creation of the position of Dean of Educational Development, who is responsible solely for serving faculty needs; the Educational Development Center, which houses the…

Women in Development.

ERIC Educational Resources Information Center

Cassara, Beverly Benner

Women in development refers to the needs and problems of women in developing countries and the responsibility of industrialized countries to ensure that aid programs serve the best interests of these women. A concern of adult educators is the relationship between adult education and the challenges facing women in the development of their…

PHOTOGRAPHIC FILM DEVELOPER

DOEpatents

Berry, F.G.

1958-06-24

S>An improved photographic developer is presented having very high energy development fine grain characteristics and a long shelf life. These characteristics are obtained by the use of aminoacetic acid in the developer, the other constituents of which are: sodium sulfite, hydroquinone, sodiunn borate, boric acid and potassium bromide, 1-phenyl-3-pyrazolidone.

Control technology development

NASA Astrophysics Data System (ADS)

Schaechter, D. B.

1982-03-01

The main objectives of the control technology development task are given in the slide below. The first is to develop control design techniques based on flexible structural models, rather than simple rigid-body models. Since large space structures are distributed parameter systems, a new degree of freedom, that of sensor/actuator placement, may be exercised for improving control system performance. Another characteristic of large space structures is numerous oscillatory modes within the control bandwidth. Reduced-order controller design models must be developed which produce stable closed-loop systems when combined with the full-order system. Since the date of an actual large-space-structure flight is rapidly approaching, it is vitally important that theoretical developments are tested in actual hardware. Experimental verification is a vital counterpart of all current theoretical developments.

Developing Strategic Collaborative Partnerships within a Workforce Development Program

ERIC Educational Resources Information Center

Hiscano, Lisa Raudelunas

2010-01-01

Workforce development programs provide training and education to welfare recipients to prepare them to obtain and retain employment in their communities. Federal, state, and local investments are made to develop and implement programs. But, do these programs have relationships with local employers to obtain their input to provide the education and…

Leading Change: An Organizational Development Role for Educational Developers

ERIC Educational Resources Information Center

Weston, Cynthia; Ferris, Jennie; Finkelstein, Adam

2017-01-01

While educational development has long been aligned with organizational development in the literature (Berquist & Phillips, 1975; Gaffe, 1975), in practice this link has faded with time. Schroeder (2011) has recently asserted that given the broad-based changes in teaching and learning that are taking place at universities, it is important that…

Education and Rural Development with Reference to Developing Countries.

ERIC Educational Resources Information Center

Coverdale, G.M.

Seeking full use of the educational resources available to developing countries in the areas of rural education and agricultural training, this paper is concerned with ways in which the efforts of organizations and institutions concerned with rural development might be improved and expanded. A generalized critical analysis of different facets of…

Rural development--national improvement.

PubMed

Malhotra, R C

1984-05-01

Rural development should be viewed as the core of any viable strategy for national development in developing countries where an average 2/3 of the population live in rural areas. Rural development is multisectoral, including economic, sociopolitical, environmental, and cultural aspects of rural life. Initially, the focus is on the provision of basic minimum needs in food, shelter, clothing, health, and education, through optimum use and employment of all available resources, including human labor. The development goal is the total development of the human potential. The hierarchy of goals of development may be shown in the form of an inverted pyramid. At the base are basic minimum needs for subsistence whose fulfillment leads to a higher set of sociopolitical needs and ultimately to the goal of total developmentand the release of creative energies of every individual. If development, as outlined, were to benefit the majority of the people then they would have to participate in decision making which affects their lives. This would require that the people mobilize themselves in the people'ssector. The majority can equitably benefit from development only if they are mobilized effectively. Such mobilization requires raising the consciousness of the people concerning their rights and obligations. All development with the twin objectives of growth with equity could be reduced to restructuring the socioeconomic, and hence political relationships. Desinging and implementing an intergrated approach to rural development is the 1st and fundamental issue of rural development management. The commonly accepted goals and objectives of a target group oriented antipoverty development strategy include: higher productivity and growth in gross national product (GNP); equitable distribution of the benefits of development; provision of basic minimum needs for all; gainful employment; participation in development; self reliance or self sustaining growth and development; maintenance of

Lessons Learned from the Process of Curriculum Developers' and Assessment Developers' Collaboration on the Development of Embedded Formative Assessments

ERIC Educational Resources Information Center

Brandon, Paul R.; Young, Donald B.; Shavelson, Richard J.; Jones, Rachael; Ayala, Carlos C.; Ruiz-Primo, Maria Araceli; Yin, Yue; Tomita, Miki K.; Furtak, Erin Marie

2008-01-01

Our project to embed formative student assessments in the Foundational Approaches in Science Teaching curriculum required a close collaboration between curriculum developers at the Curriculum Research & Development Group (CRDG) and assessment developers at the Stanford Educational Assessment Laboratory (SEAL). This was a new endeavor for each…

Health-promoting ingredients from four selected Azorean macroalgae.

PubMed

Paiva, Lisete; Lima, Elisabete; Neto, Ana Isabel; Marcone, Massimo; Baptista, José

2016-11-01

This study presents, for the first time, the nutritional and health promoting aspects of four selected Azorean macroalgae (Ulva compressa, Ulva rigida, Gelidium microdon and Pterocladiella capillacea) in terms of total lipids, fatty acids (FA) profile, n6/n3 and hypocholesterolemic (h)/hypercholesterolemic (H) FA ratios, minerals, total essential amino acids (AA), anti-ageing and anti-phenylketonuria AA content, coenzyme Q 10 , α-tocopherol, total phenolics, antioxidant properties and energy value, on a dry weight basis. The results revealed low lipid content (1.02-4.32%) but significant PUFA content (29.57-69.22% of total FA), suitable FA ratios (0.48-9.49 for n6/n3 and 1.26-4.22 for h/H), balanced macromineral ratios (0.27-1.91 for Na/K and 0.15-1.07 for Ca/Mg), appreciable amount of essential AA (45.27-58.13% of total AA), high amount of anti-ageing AA, low Phe content, coenzyme Q 10 (1.25-8.27μg/g), α-tocopherol (2.61-9.14mg/100g), high total phenolic content (27.70-55.07mg of gallic acid equivalents/g extract), significant free radical scavenging activity (29.32-47.73%) and valuable energy content (6.80-9.80kJ/g). A regular consumption of these algae either directly or through food supplements may improve human health or may have a protective effect on some diseases and ageing process. They can also be used for producing pharmaceuticals and cosmeceuticals with potential economic value. Copyright © 2016. Published by Elsevier Ltd.

Resolution Mechanism and Characterization of an Ammonium Chloride-Tolerant, High-Thermostable, and Salt-Tolerant Phenylalanine Dehydrogenase from Bacillus halodurans.

PubMed

Jiang, Wei; Wang, Ya-Li; Fang, Bai-Shan

2018-05-09

As phenylalanine dehydrogenase (PheDH) plays an important role in the synthesis of chiral drug intermediates and detection of phenylketonuria, it is significant to obtain a PheDH with specific and high activity. Here, a PheDH gene, pdh, encoding a novel BhPheDH with 61.0% similarity to the known PheDH from Microbacterium sp., was obtained. The BhPheDH showed optimal activity at 60 °C and pH 7.0, and it showed better stability in hot environment (40-70 °C) than the PheDH from Nocardia sp. And its activity and thermostability could be significantly increased by sodium salt. After incubation for 2 h in 3 M NaCl at 60 °C, the residual activity of the BhPheDH was found to be 1.8-fold higher than that of the control group (without NaCl). The BhPheDH could tolerate high concentration of ammonium chloride and its activity could be also enhanced by the high concentration of ammonium salts. These characteristics indicate that the BhPheDH possesses better thermostability, ammonium chloride tolerance, halophilic mechanism, and high salt activation. The mechanism of thermostability and high salt tolerance of the BhPheDH was analyzed by molecular dynamics simulation. These results provide useful information about the enzyme with high-temperature activity, thermostability, halophilic mechanism, tolerance to high concentration of ammonium chloride, higher salt activation and enantio-selectivity, and the application of molecular dynamics simulation in analyzing the mechanism of these distinctive characteristics.

Management Development Study.

ERIC Educational Resources Information Center

Department of Transportation, Washington, DC.

This document reports on a management development study within the Department of Transportation (DOT). The aim of the study was to develop a systematic approach to management development for military and civilian personnel. A variety of methods was used to gather data including having DOT staff members gather the information to be passed on to the…

Input and language development in bilingually developing children.

PubMed

Hoff, Erika; Core, Cynthia

2013-11-01

Language skills in young bilingual children are highly varied as a result of the variability in their language experiences, making it difficult for speech-language pathologists to differentiate language disorder from language difference in bilingual children. Understanding the sources of variability in bilingual contexts and the resulting variability in children's skills will help improve language assessment practices by speech-language pathologists. In this article, we review literature on bilingual first language development for children under 5 years of age. We describe the rate of development in single and total language growth, we describe effects of quantity of input and quality of input on growth, and we describe effects of family composition on language input and language growth in bilingual children. We provide recommendations for language assessment of young bilingual children and consider implications for optimizing children's dual language development. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Vygotsky's Zone of Proximal Development: Instructional Implications and Teachers' Professional Development

ERIC Educational Resources Information Center

Shabani, Karim; Khatib, Mohamad; Ebadi, Saman

2010-01-01

The current paper examines the instructional implications of Vygotsky's (1978) seminal notion of Zone of Proximal Development, originally developed to account for the learning potential of children, and investigates ZPD applications to the concept of teacher professional development. Specific attempt has been made to see how a number of assets at…

Ramathibodi Language Development Questionnaire: A Newly Developed Screening Tool for Detection of Delayed Language Development in Children Aged 18-30 Months.

PubMed

Chuthapisith, Jariya; Wantanakorn, Pornchanok; Roongpraiwan, Rawiwan

2015-08-01

To develop a parental questionnaire for screening children with delayed language development in primary care settings. Ramathibodi Language Development (RLD) questionnaire was developed and completed by groups of 40 typically developing children age 18 to 30 months old and 30 children with delayed language development. The mean score was significantly lower in the delay language group (6.7 ± 1.9), comparing with the typically developing group (9.6 ± 0.7). The optimal ROC curve cut-off score was 8 with corresponding sensitivity and specificity were 98% and 72%, respectively. The corresponding area under the curve was 0.96 (95% CI = 0.92-0.99). The RLD questionnaire was the promising language developmental screening instrument that easily utilized in well-child examination settings.

Career Development in Higher Education. Issues in Career Development

ERIC Educational Resources Information Center

Samide, Jeff L., Ed.; Eliason, Grafton T., Ed.; Patrick, John

2011-01-01

The purpose of Career Development in Higher Education is to provide a broad and in-depth look at the field of career development as it applies to individuals involved in higher education activities, in a variety of educational and vocational training settings. The book will examine some of the field's major themes, approaches and assumptions using…

Using practice development methodology to develop children's centre teams: ideas for the future.

PubMed

Hemingway, Ann; Cowdell, Fiona

2009-09-01

The Children's Centre Programme is a recent development in the UK and brings together multi-agency teams to work with disadvantaged families. Practice development methods enable teams to work together in new ways. Although the term practice development remains relatively poorly defined, its key properties suggest that it embraces engagement, empowerment, evaluation and evolution. This paper introduces the Children's Centre Programme and practice development methods and aims to discuss the relevance of using this method to develop teams in children's centres through considering the findings from an evaluation of a two-year project to develop inter-agency public health teams. The evaluation showed that practice development methods can enable successful team development and showed that through effective facilitation, teams can change their practice to focus on areas of local need. The team came up with their own process to develop a strategy for their locality.

Knowledge Workshop Development

DTIC Science & Technology

1976-01-30

priorities. The mechanism also seems to act as a buffer between developer and user, softening the negative aspects of user frustration while still...structure ’ programming methods. 4) Documentation: Effective documentation methods must be developed and used since undocumented programs are virtually...1-W.,U1..W1 . II I u KNOWLEDGE WORKSHOP DEVELOPMENT Douglas C. Engelbart Stanford Research Institute AD-A022 997 Prepared for: Rome

Business Development Process

DTIC Science & Technology

2001-10-31

832-4736. DISTRIBUTION STATEMENT A Approved for Public Release Distribution Unlimited Attorney Docket No. 83042 BUSINESS DEVELOPMENT PROCESS TO... BUSINESS DEVELOPMENT PROCESS 3 4 STATEMENT OF GOVERNMENT INTEREST 5 The invention described herein may be manufactured and used 6 by or for the...INVENTION 11 (1) Field of the Invention 12 This invention generally relates to a business 13 development process for assessing new business ideas

Talent Development: Potential for Developing Nations.

ERIC Educational Resources Information Center

Harris, Carole Ruth

1993-01-01

A theoretical approach to talent development in emerging nations is proposed, based on principles of curricular intervention derived from qualitative research. Implementation of such a culturally appropriate curriculum in Ebeye, Marshall Islands, illustrates the approach. Adaptations to other cultures are suggested. (Author/DB)

National Profiles of Urinary Calculi: a Comparison Between Developing and Developed Worlds.

PubMed

Alatab, Sudabeh; Pourmand, Gholamreza; El Howairis, Mohammed El Fatih; Buchholz, Noor; Najafi, Iraj; Pourmand, Mohammad Reza; Mashhadi, Rahil; Pourmand, Naghmeh

2016-03-01

The incidence of urolithiasis has increased in both the developed and the developing countries during the past decades. Economically, the increase of urolithiasis contributes to the rise of the healthcare burden everywhere. Moreover, this increase has been associated with a change in the epidemiology of urolithiasis in terms of age and sex distribution, and also the location and type of calculi. We searched the MEDLINE for relevant literature dating back to 1980. This review compared the trends in epidemiological factors affecting urolithiasis in the developed and the developing countries during the past decades. People in the developing countries are more likely to contract kidney calculi at a younger age than in the developed countries. Although calculus disease is still more prevalent in men than in women, the latter are increasingly affected in both worlds. Uric acid calculi are more prevalent in the developing than in industrialized countries. There is a progressive increase in the frequency of calcium oxalate and calcium phosphate calculi in the developing countries where these used to be less frequent. The incidence and prevalence of urinary calculi is increasing globally. Many factors including aging of the population, changes in diet, global warming, and employment of more accurate diagnostic tools seem to be involved in this increase. An increasing affluence and adaptation of Western diet habits in many developing countries seem likely to contribute to the changes.

Competence development for the promotion of gender equality in development cooperation: the case of the Swedish International Development Cooperation Agency (SIDA).

PubMed

Hannan-andersson, C

1997-01-01

The Swedish International Development Cooperation Agency (SIDA) has created an Action Program for Promoting Equality Between Women and Men in Partner Countries that emphasizes competency development as a means of achieving gender equality. Competency development goes beyond formal training and utilizes existing entry points while creating innovative ones. SIDA's partnership approach requires clear delineation of roles for SIDA personnel and partner countries, with SIDA 1) applying a gender perspective to assessments, 2) initiating a constructive dialogue about gender equality if needed, 3) assessing the need for gender equality promoting competency development, 4) studying the local context, and 5) developing effective local networks. In addition, the needs of different groups within SIDA should be met with appropriate competency development inputs while SIDA continues support to competency development in partner countries by developing local capacity for gender training and gender sensitization at the regional and national levels. At SIDA, gender training has evolved since 1989 to its current focus on the practical and concrete challenges facing participants. In addition, departments and divisions conduct sector- and issue-specific training, and gender equality is integrated in all SIDA training activities on every topic. The challenges for future competency development are to 1) increase the number of men involved in provision of competency development inputs, 2) improve competency at embassy and field levels, and 3) improve competency in policy dialogues.

NERVA materials development

NASA Technical Reports Server (NTRS)

Mandell, B.

1970-01-01

Materials development topics include: development of analysis techniques to adjust heterogeneous data; determination of thermal conductivity for AISI 347 stainless steel and elastic moduli and Poisson's ratio for Inconel 718 and Ti 5Al-2.5Sn; embrittlement effects of 1400 psi gaseous hydrogen for alloy 718 and Ti 5Al-2.5Sn; cryogenic radiation damage of Ti 5Al-2.5Sn; and evaluation of prepreg, impregnation, and fabric materials for optimum fibrous graphite properties. Component support topics include: tensile design allowable development of Ti 5Al-2.5Sn for turbopump applications; evaluation of fatigue, fracture toughness, and stress corrosion properties of AA 7039-T63 for pressure vessel applications; development of AISI 347 sheet tensile and creep properties for nozzle applications; evaluation of orbital weld techniques for aluminum line fabrication; material selection of shield materials; development of high load friction and wear properties of hard chrome/gold plate combinations; and evaluation of weld processes for NASS duct coolant channel fabrication.

Development of the larval amphibian growth and development ...

EPA Pesticide Factsheets

The Larval Amphibian Growth and Development Assay (LAGDA) is a Tier II test guideline being developed by the US Environmental Protection Agency under the Endocrine Disruptor Screening Program. The LAGDA was designed to evaluate effects of chronic chemical exposure on growth, thyroid-mediated amphibian metamorphosis and reproductive development. To evaluate the assay’s performance, two model chemicals targeting the hypothalamic-pituitary-gonadal (HPG) axis were tested; a weak estrogen receptor agonist, 4-tert-octylphenol (tOP), and an androgen receptor agonist, 17β-trenbolone (TB). Xenopus laevis embryos were constantly exposed in flow-through conditions to various test concentrations of tOP (nominal: 6.25, 12.5, 25, 50 μg/L) or TB (nominal: 12.5, 25, 50, 100 ng/L) and clean water controls until 8 weeks post-metamorphosis, at which time growth measurements were taken and histopathology assessments were made on gonads, reproductive ducts, liver and kidneys. There were no effects on growth in either study and no signs of overt toxicity, sex reversal or gonad dysgenesis at the concentrations tested. Exposure to tOP caused a treatment-related decrease in circulating thyroxine and an increase in thyroid follicular cell hypertrophy and hyperplasia (25, 50 μg/L). Müllerian duct development was clearly affected following exposure to both chemicals; tOP exposure caused dose-dependent maturation of oviducts in both male and female frogs, whereas TB exposure ca

Child Development: Workshop I.

ERIC Educational Resources Information Center

Ismail, Maznah; And Others

Workshops on child development explored the cognitive development of children, mass media and its effects on children, parenting, the emotional and personality development of children, and educating the exceptional child, including the gifted. The discussion of cognitive development focused on the need to collect information about cognitive…

Information and Rural Development.

ERIC Educational Resources Information Center

Storm, Bonnie L.

1982-01-01

Outlines approaches taken to development in lesser developed countries in the past, discusses the importance of appropriate technology and human development, and summarizes the information needs of the rural poor in developing nations. Information dissemination programs using video- and audiotape technology in Bangladesh, Guatemala, and Peru are…

Built To Last: Using Iterative Development Models for Sustainable Scientific Software Development

NASA Astrophysics Data System (ADS)

Jasiak, M. E.; Truslove, I.; Savoie, M.

2013-12-01

In scientific research, software development exists fundamentally for the results they create. The core research must take focus. It seems natural to researchers, driven by grant deadlines, that every dollar invested in software development should be used to push the boundaries of problem solving. This system of values is frequently misaligned with those of the software being created in a sustainable fashion; short-term optimizations create longer-term sustainability issues. The National Snow and Ice Data Center (NSIDC) has taken bold cultural steps in using agile and lean development and management methodologies to help its researchers meet critical deadlines, while building in the necessary support structure for the code to live far beyond its original milestones. Agile and lean software development and methodologies including Scrum, Kanban, Continuous Delivery and Test-Driven Development have seen widespread adoption within NSIDC. This focus on development methods is combined with an emphasis on explaining to researchers why these methods produce more desirable results for everyone, as well as promoting developers interacting with researchers. This presentation will describe NSIDC's current scientific software development model, how this addresses the short-term versus sustainability dichotomy, the lessons learned and successes realized by transitioning to this agile and lean-influenced model, and the current challenges faced by the organization.

Child development in developing countries: child rights and policy implications.

PubMed

Britto, Pia Rebello; Ulkuer, Nurper

2012-01-01

The Multiple Indicator Cluster Survey was used to provide information on feeding practices, caregiving, discipline and violence, and the home environment for young children across 28 countries. The findings from the series of studies in this Special Section are the first of their kind because they provide information on the most proximal context for development of the youngest children in the majority world using one of the only data sets to study these contexts across countries. Using the framework of the Convention on the Rights of the Child, in particular the Rights to Survival, Development and Protection, findings are explained with implications for international and national-level social policies. Implications are also discussed, with respect to policy makers and the larger international community, who have the obligation to uphold these rights. © 2012 The Authors. Child Development © 2012 Society for Research in Child Development, Inc.

Concentrator Development

NASA Technical Reports Server (NTRS)

Owen, W. A.

1984-01-01

During the years of technology development by the Parabolic Dish program, the problems peculiar to tracking dishes have been explored in depth with particular emphasis on economics. Starting with the Precursor Concentrator, testing techniques and apparatus such as calorimeters and the flux mapper were developed. At the same time, mirrors were developed to have a long operating life as well as high performance. Commercially available equipment was evaluated as well. Building on all these elements, the Test Bed Concentrators were designed and built. With a peak intensity in the focal plane of over 17,500 suns and an average concentrator ratio over 3000 on an eight inch diameter aperture, they have proven to be the work horses of the technology. With a readily adjustable mirror array, they have proved to be an essential tool in the development of dish components, receivers, heat transport systems, instrumentation, controls, engines, and materials - all necessary to cost effective modules and plants. Utilizing the lessons learned from this technology, most cost effective systems were designed. These included Parabolic Dish Number 1 (PDC-1) and PDC-2 currently in final design by Acurex Corporation. Even more advanced concepts are being worked on, such as the Cassegranian systems by BDM Corporation.

Flower Development

PubMed Central

Alvarez-Buylla, Elena R.; Benítez, Mariana; Corvera-Poiré, Adriana; Chaos Cador, Álvaro; de Folter, Stefan; Gamboa de Buen, Alicia; Garay-Arroyo, Adriana; García-Ponce, Berenice; Jaimes-Miranda, Fabiola; Pérez-Ruiz, Rigoberto V.; Piñeyro-Nelson, Alma; Sánchez-Corrales, Yara E.

2010-01-01

Flowers are the most complex structures of plants. Studies of Arabidopsis thaliana, which has typical eudicot flowers, have been fundamental in advancing the structural and molecular understanding of flower development. The main processes and stages of Arabidopsis flower development are summarized to provide a framework in which to interpret the detailed molecular genetic studies of genes assigned functions during flower development and is extended to recent genomics studies uncovering the key regulatory modules involved. Computational models have been used to study the concerted action and dynamics of the gene regulatory module that underlies patterning of the Arabidopsis inflorescence meristem and specification of the primordial cell types during early stages of flower development. This includes the gene combinations that specify sepal, petal, stamen and carpel identity, and genes that interact with them. As a dynamic gene regulatory network this module has been shown to converge to stable multigenic profiles that depend upon the overall network topology and are thus robust, which can explain the canalization of flower organ determination and the overall conservation of the basic flower plan among eudicots. Comparative and evolutionary approaches derived from Arabidopsis studies pave the way to studying the molecular basis of diverse floral morphologies. PMID:22303253

Energy Sources and Development.

ERIC Educational Resources Information Center

Crank, Ron

This instructional unit is one of 10 developed by students on various energy-related areas that deals specifically with energy sources and development. Its objective is for the student to be able to discuss energy sources and development related to the historical perspective, biological development, current aspects, and future expectations…

Developing Local Community Leaders.

ERIC Educational Resources Information Center

Dyer, Delwyn A.; Williams, Oscar M.

The successful development of local leaders is the goal of leadership training and community development. Development involves defining and developing leadership. Although leader-centered leadership offers few chances of meeting the maintenance needs of the group as a whole, shared leadership allows the group to join in the decision-making…

Perspectives from the South in Development Education. Development Education Annual 1990/1991.

ERIC Educational Resources Information Center

Kniep, Willard, Ed.; Danant, Joelle, Ed.

This annual publication presents perspectives on development education from developing nations or "Southern" countries. The following articles are included: "Development Education: Education Beyond Labels" (P. Christenson); "Synthesis and Reflections of Annual '90/91" (J. Sommer); "Creating the World in Our Own…

Project-Based Module Development.

ERIC Educational Resources Information Center

Meel, R. M. van

A project management design for modularizing higher education at open universities was developed and tested. Literature in the fields of project management and development of modular curriculum materials was reviewed and used as a basis for developing a project-based approach to the process of developing modules for self-instruction. According to…

Development of Global Change Research in Developing Countries

NASA Astrophysics Data System (ADS)

Sierra, Carlos A.; Yepes, Adriana P.

2010-10-01

Ecosystems and Global Change in the Context of the Neotropics; Medellín, Colombia, 19-20 May 2010; Research in most areas of global environmental change is overwhelmingly produced outside developing countries, which are usually consumers rather than producers of the knowledge associated with their natural resources. While there have been important recent advances in understanding the causes of global-¬scale changes and their consequences to the functioning of tropical ecosystems, there is still an important gap in the understanding of these changes at regional and national levels (where important political decisions are usually made). A symposium was held with the aim of surveying the current state of research activities in a small, developing country such as Colombia. It was jointly organized by the Research Center on Ecosystems and Global Change, Carbono and Bosques; the National University of Colombia at Medellín and the Colombian Ministry of the Environment, Housing, and Regional Development. This 2-¬day symposium gathered Colombian and international scientists involved in different areas of global environmental change, tropical ecosystems, and human societies.

Early Program Development

NASA Image and Video Library

1970-01-01

In 1970, NASA initiated Phase A contracts to study alternate Space Shuttle designs in addition to the two-stage fully-reusable Space Shuttle system already under development. A number of alternate systems were developed to ensure the development of the optimum earth-to-orbit system, including the Stage-and-a-half Chemical Interorbital Shuttle, shown here. The concept would utilize a reusable marned spacecraft with an onboard propulsion system attached to an expendable fuel tank to provide supplementary propellants.

Developing Self-Efficacy: Exploring Preservice Coursework, Student Teaching, and Professional Development Experiences

ERIC Educational Resources Information Center

McKim, Aaron J.; Velez, Jonathan J.

2017-01-01

To extend current understanding of school-based agriculture teacher development, this study explored the relationship between teacher development experiences and the self-efficacy of early career agriculture teachers. Three teacher development experiences were of interest: (a) preservice coursework, (b) student teaching, and (c) professional…

VALIDATION OF A RECENTLY DEVELOPED EPIBENTHIC INDEX DEVELOPED FOR NEW JERSEY ESTUARIES

EPA Science Inventory

An epifaunal index was recently developed for New Jersey estuaries (138 sites). Initial analysis indicated that this index related well to land use gradients from Raritan Bay (more developed) south to Great Bay (less developed). In this study we refined the evaluation by compar...

Development Mobilities: Identity and Authority in an Angolan Development Programme

PubMed Central

Peters, Rebecca Warne

2017-01-01

This ethnographic essay considers how international non-governmental organisations are able to make claims to authoritative knowledge about development work by offering the transnational mobilities of their staff members as evidence. I examine how one professional’s biography—his trajectory from Angola to Britain and back again—was differentially presented to external donors and internal staff members as befitting the institutional needs of an international good governance intervention in Angola. These presentations reflect a commoditisation of the cosmopolitanism of professionals’ histories in the service of development as a regime of mobility. I argue that, in this development regime, a global hierarchy prevents some individual professionals, particularly those from developing nations, from realising the same benefits of their cosmopolitan mobility as professionals from industrialised nations. While one of mobility studies’ many strengths is that it highlights global interconnectedness, social scientists should not read equality in these interconnections but examine how patterns of transnational mobility may produce and reproduce global structures of inequality. PMID:28936113

Cognitive Development Trajectories of Very Preterm and Typically Developing Children.

PubMed

Mangin, Kathryn S; Horwood, L J; Woodward, Lianne J

2017-01-01

Cognitive impairment is common among children born very preterm (VPT), yet little is known about how this risk changes over time. To examine this issue, a regional cohort of 110 VPT (≤ 32 weeks gestation) and 113 full-term (FT) born children was prospectively assessed at ages 4, 6, 9, and 12 years using the Wechsler Preschool and Primary Scale of Intelligence-Revised and then Wechsler Intelligence Scale for Children, 4th ed. At all ages, VPT children obtained lower scores than their FT born peers (p < .001). Growth curve modeling revealed stable cognitive trajectories across both groups. Neonatal white matter abnormalities and family socioeconomic adversity additively predicted cognitive risk. Despite some intraindividual variability, cognitive functioning of typically developing and high-risk VPT children was stable and influenced by early neurological development and family rearing context. © 2016 The Authors. Child Development © 2016 Society for Research in Child Development, Inc.

Human Resource Development Issues in the Implementation of the Western China Development Strategy

ERIC Educational Resources Information Center

Xiao, Mingzheng

2007-01-01

This paper systematically illustrates the value and role of human resource development in the implementation of the Western China development strategy. It analyzes in details some current human resource issues constraining the implementation of the Western China development strategy and those on the sustainable development process of economic…

Improving core outcome set development: qualitative interviews with developers provided pointers to inform guidance.

PubMed

Gargon, Elizabeth; Williamson, Paula R; Young, Bridget

2017-06-01

The objective of the study was to explore core outcome set (COS) developers' experiences of their work to inform methodological guidance on COS development and identify areas for future methodological research. Semistructured, audio-recorded interviews with a purposive sample of 32 COS developers. Analysis of transcribed interviews was informed by the constant comparative method and framework analysis. Developers found COS development to be challenging, particularly in relation to patient participation and accessing funding. Their accounts raised fundamental questions about the status of COS development and whether it is consultation or research. Developers emphasized how the absence of guidance had affected their work and identified areas where guidance or evidence about COS development would be useful including, patient participation, ethics, international development, and implementation. They particularly wanted guidance on systematic reviews, Delphi, and consensus meetings. The findings raise important questions about the funding, status, and process of COS development and indicate ways that it could be strengthened. Guidance could help developers to strengthen their work, but over specification could threaten quality in COS development. Guidance should therefore highlight common issues to consider and encourage tailoring of COS development to the context and circumstances of particular COS. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Artificial heart development program. Volume I. System development. Phase III summary report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1977-01-01

The report documents efforts and results in the development of the power system portions of a calf implantable model of nuclear-powered artificial heart. The primary objective in developing the implantable model was to solve the packaging problems for total system implantation. The power systems portion is physically that portion of the implantable model between the Pu-238 heat sources and the blood pump ventricles. The work performed had two parallel themes. The first of these was the development of an integrated implantable model for bench and animal experiments plus design effort on a more advanced model. The second was research andmore » development on components of the system done in conjunction with the development of the implantable model and to provide technology for incorporation into advanced models plus support to implantations, at the University of Utah, of the systems blood pumping elements when driven by electric motor. The efforts and results of implantable model development are covered, mainly, in the text of the report. The research and development efforts and results are reported, primarily, in the appendices (Vol. 2).« less

Arabidopsis mitochondrial protein slow embryo development1 is essential for embryo development

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ju, Yan; Liu, Chunying; Lu, Wenwen

The plant seeds formation are crucial parts in reproductive process in seed plants as well as food source for humans. Proper embryo development ensure viable seed formation. Here, we showed an Arabidopsis T-DNA insertion mutant slow embryo development1 (sed1) which exhibited retarded embryogenesis, led to aborted seeds. Embryo without SED1 developed slower compared to normal one and could be recognized at early globular stage by its white appearance. In later development stage, storage accumulated poorly with less protein and lipid body production. In vitro culture did not rescue albino embryo. SED1 encoded a protein targeted to mitochondria. Transmission electron microscopic analysismore » revealed that mitochondria developed abnormally, and more strikingly plastid failed to construct grana in time in sed1/sed1 embryo. These data indicated that SED1 is indispensable for embryogenesis in Arabidopsis, and the mitochondria may be involved in the regulation of many aspects of seed development. -- Highlights: •Arabidopsis SED1 is essential for embryo development. •The sed1 embryo accumulates less storage and has abnormal ultrastructure. •SED1 localizes to the mitochondrion.« less

Sociopolitical development.

PubMed

Watts, Roderick J; Williams, Nat Chioke; Jagers, Robert J

2003-03-01

This paper examines theories and concepts relevant to sociopolitical development (SPD). As an emerging theory, SPD expands on empowerment and similar ideas related to social change and activism in community psychology--oppression, liberation, critical consciousness, and culture among them. SPD is the process by which individuals acquire the knowledge, analytical skills, emotional faculties, and the capacity for action in political and social systems necessary to interpret and resist oppression. Equally as important is a vision of liberation that is an alternative to oppressive conditions. All of these concepts have been underemphasized in the social change literature of U.S. community psychology. In our view, sociopolitical development is vital to human development and the creation of a just society. As part of identifying and illustrating concepts and processes relevant to SPD theory, we will draw from the words of young African American activists who were interviewed as part of a research study.

Academic Development and Educational Developers: Perspectives from Different European Higher Education Contexts

ERIC Educational Resources Information Center

Di Napoli, Roberto; Fry, Heather; Frenay, Mariane; Verhesschen, Piet; Verburgh, An

2010-01-01

This paper reports research in five European universities, in four countries between 2004 and 2008. The research explored and compared institutional contexts for academic development and the interpretations and reflections of a number of academic developers on the organizational position and role of academic development, and of…

Population and development.

PubMed

Rao, S V

1992-01-01

A unified approach to development is recommended: one in which the social, economic, and political components are accounted for within a multidimensional process of reorganization and reorientation of structures and attitudes, customs, and beliefs. During the 1970s, development was construed as improvement in employment within a growing economy and elimination of poverty and inequality--a redistribution of growth. Development should increase and widen the distribution of basic life sustaining goods, increase levels of living, and expand economic and social choices and free people from dependence on other people and servitude to ignorance and poverty. Six basic issues linking population growth and development were identified; the interrelationships between economic, social, and demographic variables were explained. The aims of educational development and educational progress as affected by urbanization were discussed. It is inappropriate to isolate economic, social, and demographic concerns as separate entities and as separate from the development process. The population problem of rapid population growth is intertwined with the problem of unmet human needs; problematic are illiteracy, extreme deprivation, insufficient income to purchase essential health services and basic nutrition, and inadequate diets. Improvements have not kept pace with needs. The theories of Malthus are no longer germane, and demographic transition theory is not as effective in achieving or explaining the reduction of birth rates. An approach which attacks poverty and low quality of life would be directed to core motivations. The hidden momentum of population growth and the impact of literacy and age and sex composition are discussed as features of improvement in quality of life and of fertility reduction. Economic and social development are dependent on human resources, not on capital or material resources. The institutional mechanism for developing human potential is the educational system

PERSONNEL TRAINING AND DEVELOPMENT.

DTIC Science & Technology

skills training, supervisory training, training for disadvantaged workers, and management development. It begins by discussing recent developments...and techniques of behavior modification. The most recent developments in training techniques are outlined. Methods for training disadvantaged ...of training and development outcomes are reviewed. The bulk of the empirical literature is concentrated in three areas: laboratory education, programmed instruction, and training the disadvantaged . (Author)

Ed Tech Developer's Guide: A Primer for Software Developers, Startups, and Entrepreneurs

ERIC Educational Resources Information Center

Bienkowski, Marie; Gerard, Sarah Nixon; Rubin, Shawn; Sanford, Cathy; Borrelli-Murray, Dana; Driscoll, Tom; Arora, Jessie; Hruska, Mike; Beck, Katie; Murray, Thomas; Hoekstra, Jason; Gannes, Stuart; Metz, Edward; Midgley, Steve; Castilla, Stephanie; Tomassini, Jason; Madda, Mary Jo; Chase, Zac; Martin, Erik; Noel, Marcus; Styles, Kathleen

2015-01-01

Opportunities abound for software designers and developers to create impactful tools for teachers, school leaders, students, and their families. This guide for developers, startups, and entrepreneurs addresses key questions about the education ecosystem and highlights critical needs and opportunities to develop digital tools and apps for learning.…

Child Development Is Economic Development. A Conversation with Economist Art Rolnick. Perspectives

ERIC Educational Resources Information Center

National Scientific Council on the Developing Child, 2006

2006-01-01

The public dollars spent to stimulate economic development would be more wisely invested in child development programs, according to two different streams of research. Brain research shows the impact of experiences and environments on the developing brain architecture, with weaker architecture leading to increased vulnerability to later problems…

The Universe Adventure - Developers

Science.gov Websites

The Universe Adventure home | help | links | teachers | developers | credits | glossary | feedback Go Developers This page is meant for developers of the Universe Adventure. It contains various design

Instructional Technology Professional Development Evaluation: Developing a High Quality Model

ERIC Educational Resources Information Center

Gaytan, Jorge A.; McEwen, Beryl C.

2010-01-01

Background: The literature contains very few studies that focused on evaluating the impact of professional development activities on student learning. And, many of these studies failed to determine whether the professional development activities met their primary goal--to improve the learning process. Purpose: The purpose of this study was to use…

Economic Development in American Indian Reservations. Development Series No. 1.

ERIC Educational Resources Information Center

Ortiz, Roxanne Dunbar, Ed.

A collection of 13 scholarly articles and essays, this book makes available hard-to-find information and theories about American Indian economic development. Part I, "The Land and the People", emphasizes cultural traditions and beliefs of Indian people and traces the development of the concept of sovereignty and its applicability to…

What Develops in Emotional Development? Emotions, Personality, and Psychotherapy Series.

ERIC Educational Resources Information Center

Mascolo, Michael, F. Ed.; Griffin, Sharon, Ed.

It is difficult to make progress in the study of emotions and emotional development if the meanings assigned to central constructs vary widely across investigators. This book clarifies and synthesizes the different ways in which emotion researchers approach fundamental questions about the nature of emotion and emotional development. Theorist and…

New taxanes in development.

PubMed

Ferlini, Cristiano; Gallo, Daniela; Scambia, Giovanni

2008-03-01

Taxanes are presently widely employed for the medical treatment of cancer. However, despite the huge clinical success, these agents exhibit clinical problems related to poor drug solubility, toxicity and, in particular, drug resistance. To identify the critical points related to the process of development of novel taxanes. Publicly available data on the paclitaxel and docetaxel analogues, which have entered a clinical development phase in the last 2 years have been taken into consideration. The development involved novel formulations of paclitaxel and novel chemical entities. For each agent in each category the development phase is analysed and a synthetic comment for each category is included. Despite all the efforts, until now clinical success with the new development of taxanes has been limited. Moreover, the expected clinical introduction of epothilones could further restrict the space for development of novel taxanes. Despite these facts, some interesting concepts emerged during the process of development and could lead to successful drugs in the forthcoming years.

Acute otitis media guidelines in selected developed and developing countries: uniformity and diversity.

PubMed

Ovnat Tamir, Sharon; Shemesh, Shay; Oron, Yahav; Marom, Tal

2017-05-01

Acute otitis media (AOM) is a common childhood disease, with an enormous economic and healthcare-related burden. Guidelines and consensus papers for AOM diagnosis and management were published in many countries. Our objective was to study the differences and similarities between these protocols in developing and developed countries. The keywords: 'acute otitis media' AND 'children' AND ['treatment' or 'management'] AND ['guideline' or 'consensus'] were used in various electronic databases between 1 January 1989 through 31 December 2015. Overall, 99 sources from 62 countries were retrieved: 53 from 22 developed countries, and 46 from 40 developing countries. Representative guidelines from America (the USA, Argentina), Europe (Italy, Moldova), Africa (South Africa, Tanzania, Ethiopia), Asia (Japan, Afghanistan, Sri Lanka),and Oceania (South Australia, Fiji) were compared. Paediatric societies publish guidelines in most developed countries; in developing countries, the Ministry of Health usually initiates guideline formulation. Most guidelines use the same diagnostic criteria and offer watchful waiting in mild-moderate scenarios. Amoxicillin is the suggested first-line antibiotic, whereas options for second-line and third-line therapies vary. Duration of therapy varies and is usually age dependent: 5-7 days for children <2 years and 10 days for children >2 years in developed countries, while duration and age groups vary greatly in developing countries. Reduction of AOM risk factors is encouraged in developed countries, but rarely in developing countries. Guidelines for AOM from developing and developed countries are similar in many aspects, with variation in specific recommendations, due to local epidemiology and healthcare accessibility. Formulation of regional guidelines may help reduce AOM burden. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Dental Curriculum Development in Developing Countries.

ERIC Educational Resources Information Center

Phantumvanit, Prathip

1996-01-01

Since establishment of formal dental education in Southeast Asia, changes stemming from research and technology have led to dental curriculum changes. Development of the dental curriculum can be divided into three phases: disease oriented; health oriented; and community oriented. Evolution of these phases is traced in the dental curricula of Laos,…

CHP Project Development

EPA Pesticide Factsheets

Access information and tools to support the CHP project development process, including identifying if your facility is a good fit for CHP, the steps involved with CHP project development, and policies and incentives supportive of CHP.

Developing the plan

NASA Technical Reports Server (NTRS)

1975-01-01

The basic sequence in the planning development process is discussed. Alternative ways of satisfying estimated needs, and the selection of an alternative are described along with the development of a plan to implement the selected alternative.

Developing a New Course for Adult Learners. TESOL Language Curriculum Development Series

ERIC Educational Resources Information Center

Snow, Marguerite Ann, Ed.; Kamhi-Stein, Lia, Ed.

2006-01-01

Teachers of English to Speakers of Other Languages, Inc. (TESOL), introduces "Developing a New Course for Adult Learners," edited by Marguerite Ann Snow and Lia Kamhi-Stein. This volume in TESOL's Language Curriculum Development Series presents the stories of teachers, curriculum developers, and administrators from all over the world who…

Developing new minds

NASA Astrophysics Data System (ADS)

2008-12-01

When African leaders met in Lagos, Nigeria, in April 1980 to devise a plan for economic development, they underlined the importance of science and technology with a pledge that each country should spend at least 1% of its GDP on research and development. Nearly 30 years later, the Lagos promise remains largely unfulfilled. Indeed, at a meeting of the African Union in Addis Ababa, Ethiopia, in January last year, the heads of state reiterated the need to increase funding for research and development to 1% by 2010.

Halbach Magnetic Rotor Development

NASA Technical Reports Server (NTRS)

Gallo, Christopher A.

2008-01-01

The NASA John H. Glenn Research Center has a wealth of experience in Halbach array technology through the Fundamental Aeronautics Program. The goals of the program include improving aircraft efficiency, reliability, and safety. The concept of a Halbach magnetically levitated electric aircraft motor will help reduce harmful emissions, reduce the Nation s dependence on fossil fuels, increase efficiency and reliability, reduce maintenance and decrease operating noise levels. Experimental hardware systems were developed in the GRC Engineering Development Division to validate the basic principles described herein and the theoretical work that was performed. A number of Halbach Magnetic rotors have been developed and tested under this program. A separate test hardware setup was developed to characterize each of the rotors. A second hardware setup was developed to test the levitation characteristics of the rotors. Each system focused around a unique Halbach array rotor. Each rotor required original design and fabrication techniques. A 4 in. diameter rotor was developed to test the radial levitation effects for use as a magnetic bearing. To show scalability from the 4 in. rotor, a 1 in. rotor was developed to also test radial levitation effects. The next rotor to be developed was 20 in. in diameter again to show scalability from the 4 in. rotor. An axial rotor was developed to determine the force that could be generated to position the rotor axially while it is rotating. With both radial and axial magnetic bearings, the rotor would be completely suspended magnetically. The purpose of this report is to document the development of a series of Halbach magnetic rotors to be used in testing. The design, fabrication and assembly of the rotors will be discussed as well as the hardware developed to test the rotors.

Promoting Positive Youth Development: The Miami Youth Development Project (YDP)

ERIC Educational Resources Information Center

Kurtines, William M.; Ferrer-Wreder, Laura; Berman, Steven L.; Lorente, Carolyn Cass; Briones, Ervin; Montgomery, Marilyn J.; Albrecht, Richard; Garcia, Arlen J.; Arrufat, Ondina

2008-01-01

The Miami Youth Development Project (YDP) had its beginnings in the early 1990s as a grassroots response to the needs of troubled (multiproblem) young people in the community (Arnett, Kurtines, & Montgomery, 2008, this issue). YDP is an important outcome of efforts to create positive youth development interventions that draw on the strengths…

Neighborhoods in Development: Human Development Index and Self-Organizing Maps

ERIC Educational Resources Information Center

Rende, Sevinc; Donduran, Murat

2013-01-01

The Human Development Index (HDI) has been instrumental in broadening the discussion of economic development beyond money-metric progress, in particular, by ranking a country against other countries in terms of the well being of their citizens. We propose self-organizing maps to explore similarities among countries using the components of the HDI…

Environmental Control Subsystem Development

NASA Technical Reports Server (NTRS)

Laidlaw, Jacob; Zelik, Jonathan

2017-01-01

Kennedy Space Center's Launch Pad 39B, part of Launch Complex 39, is currently undergoing construction to prepare it for NASA's Space Launch System missions. The Environmental Control Subsystem, which provides the vehicle with an air or nitrogen gas environment, required development of its local and remote display screens. The remote displays, developed by NASA contractors and previous interns, were developed without complete functionality; the remote displays were revised, adding functionality to over 90 displays. For the local displays, multiple test procedures were developed to assess the functionality of the screens, as well as verify requirements. One local display screen was also developed.

Development of deployable structures for large space platforms. Volume 2: Design development

NASA Technical Reports Server (NTRS)

Greenberg, H. S.

1983-01-01

Design evolution, test article design, test article mass properties, and structural analysis of deployable platform systems are discussed. Orbit transfer vehicle (OTV) hangar development, OTV hangar concept selection, and manned module development are discussed. Deployable platform systems requirements, material data base, technology development needs, concept selection and deployable volume enclosures are also discussed.

[Adolescent psychosocial development].

PubMed

Gaete, Verónica

2015-01-01

It is increasingly necessary that pediatricians have greater knowledge of adolescent health. To begin with they should be familiar with the psychosocial development of this period, an issue which is imperative for the health care of the age group. With that purpose, this article reviews the normal adolescent psychosocial development. Adolescence is a stage that has been progressively prolonged, during which fast and big changes occur, that lead human beings to become biologically, psychologically and socially mature, and potentially able to live independently. Developmental tasks of this period are the establishment of identity and the achievement of autonomy. Although it is a process of high individual variability in terms of its beginning and end, the progression through stages, the synchrony of development between the various areas, and in other aspects, the psychosocial development of this period usually have common characteristics and a progressive pattern of 3 phases: early, middle and late adolescence. Psychological, cognitive, social, sexual and moral development of young people in each of them are described in this article. Copyright © 2015 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Stereological study of developing glomerular forms during human fetal kidney development.

PubMed

Dakovic Bjelakovic, Marija; Vlajkovic, Slobodan; Petrovic, Aleksandar; Bjelakovic, Marko; Antic, Milorad

2018-05-01

Human fetal kidney development is a complex and stepwise process. The number, shape, size and distribution of glomeruli provide important information on kidney organization. The aim of this study was to quantify glomerular developing forms during human fetal kidney development using stereological methods. Kidney tissue specimens of 40 human fetuses with gestational ages ranging from 9 to 40 weeks were analyzed. Specimens were divided into eight groups based on gestational age, each corresponding to 1 lunar month. Stereological methods were used at the light microscopy level to estimate volume, surface and numerical density of the glomerular developing forms. During gestation, nephrogenesis continually advanced, and the number of nephrons increased. Volume, surface and numerical densities of vesicular forms and S-shaped bodies decreased gradually in parallel with gradual increases in estimated stereological parameters for vascularized glomeruli. Volume density and surface density of vascularized glomeruli increased gradually during fetal kidney development, and numerical density increased until the seventh lunar month. A relative decrease in vascularized glomeruli per unit volume of cortex occurred during the last 3 lunar months. Nephrogenesis began to taper off by 32 weeks and was completed by 36 weeks of gestation. The last sample in which we observed vesicles was from a fetus aged 32 weeks, and the last sample with S-shaped bodies was from a fetus aged 36 weeks. The present study is one of few quantitative studies conducted on human kidney development. Knowledge of normal human kidney morphogenesis during development could be important for future medical practice. Events occurring during fetal life may have significant consequences later in life.

NASA DEVELOP students

NASA Image and Video Library

2008-07-08

NASA DEVELOP students at Stennis Space Center recently held a midterm review with George Crozier, who serves as a science adviser to the team. The team also was joined by Jamie Favors of the Mobile (Ala.) County Health Department DEVELOP Team; Cheri Miller, the team's NASA adviser; and Kenton Ross, a team science adviser. Students participating in the meeting included: Lauren Childs, Jason Jones, Maddie Brozen, Matt Batina, Jenn Frey, Angie Maki and Aaron Brooks. The primary purpose of the meeting was to update Crozier on the status of the team's work for the summer 2008 term and discuss plans for the fiscal year 2009 project proposal. This included discussion of a possible project to study the effects of hurricanes on the Florida panhandle. DEVELOP is a NASA-sponsored, student-led, student-run program focused on developing projects to help communities.

Disasters and development: Part 2: understanding and exploiting disaster-development linkages.

PubMed

Stephenson, Rob S; DuFrane, Charles

2002-01-01

Disasters can impede the effectiveness of development resource allocation. The damage sustained from an event can be classified into four categories: (1) Loss of resources; (2) Interruption of programs and switching of crucial resources to other, shorter-term needs; (3) Negative impacts upon investment climates; and/or (4) Disruption of the non-formal sector (local businesses). Disasters have a particularly destructive economic impact in areas in which there are few alternatives for assets that are destroyed or in areas in which the resources already are at critical levels. Development processes can both increase and/or decrease the vulnerability of a society to hazards. There are dearly established linkages between poverty, marginalization, over-population, and vulnerability. To a large extent, vulnerability derives from poverty. The poor are more likely to live in vulnerable areas (slopes prone to landslides, flood plains, marginal agricultural land), have difficulty accessing education and information, have fewer assets to invest in resources to reduce vulnerability, and are more prone to become malnourished and have chronic illnesses that predispose them to injury and death. Development may be associated with the production of new hazards accepted by a society because the perceived benefits of the development project far exceed the relative risk associated with the project. Therefore, risk assessments must be part of any program planning and evaluation. Training and education are of critical importance in preventing increased vulnerability as a result of development strategies. Development also can progress in a manner that will result in mitigation of the impacts of an event on a given society (increase absorbing capacity and/or buffering capacity, elimination of hazards or the risk of them producing a disaster). Such mitigation measures can be either structural or nonstructural. There exists a wide range of options for incorporating mitigation measures in

Future NTP Development Synergy Leveraged from Current J-2X Engine Development

NASA Astrophysics Data System (ADS)

Ballard, Richard O.

2008-01-01

This paper is a discussion of how the many long-lead development elements required for the realization of a future nuclear thermal propulsion (NTP) system can be effectively leveraged from the ongoing work being conducted on the J-2X engine program for the Constellation Program. Development studies conducted to date for NTP forward planning have identified a number of technical areas that will require advancement to acceptable technology readiness levels (TRLs) before they can be utilized in NTP system development. These include high-temperature, high-area ratio nozzle extension; long-life, low-NPSP turbomachinery; and low-boiloff propellant management, and a qualified nuclear fuel element. The current J-2X program is working many of these areas that can be leveraged to support NTP development in a highly compatible and synergistic fashion. In addition to supporting technical development, there are other programmatic issues being worked in the J-2X program that can be leveraged by a future NTP development program. These include compliance with recently-evolved space system requirements such as human-rating, fault tolerance and fracture control. These and other similar mandatory system requirements have been adopted by NASA and can result in a significant technical impact beyond elevation of the root technologies required by NTP. Finally, the exploitation of experience, methodologies, and procedures developed by the J-2X program in the areas of verification, qualification, certification, altitude simulation testing, and facility definition will be especially applicable to a future NTP system. The similarities in system mission (in-space propulsion) and operational environment (vacuum, zero-gee) between J-2X and NTP make this highly synergistic. Thus, it can be shown that the collective benefit of leveraging experience and technologies developed during the J-2X program can result in significant savings in development cost and schedule for NTP.

Future NTP Development Synergy Leveraged from Current J-2X Engine Development

NASA Technical Reports Server (NTRS)

Ballard, Richard O.

2008-01-01

This paper is a discussion of how the many long-lead development elements required for the realization of a future nuclear thermal propulsion (NTP) system can be effectively leveraged from the ongoing work being conducted on the J-2X engine program for the Constellation Program. Development studies conducted to date for NTP forward planning have identified a number of technical areas that will require advancement to acceptable technology readiness levels (TRLs) before they can be utilized in NTP system development. These include high-temperature, high-area ratio nozzle extension; long-life, low-NPSP. turbomachinery; and low-boiloff propellant management; and a qualified nuclear fuel element. The current J-2X program is working many of these areas that can be leveraged to support NTP development in a highly compatible and synergistic fashion. In addition to supporting technical development, there are other programmatic issues being worked in the J-2X program that can be leveraged by a future NTP development program. These include compliance with recently-evolved space system requirements such as human-rating, fault tolerance and fracture control. These and other similar mandatory system requirements have been adopted by NASA and can result in a significant technical impact beyond elevation of the root technologies required by NTP. Finally, the exploitation of experience, methodologies, and procedures developed by the J-2X program in the areas of verification, qualification, certification, altitude simulation testing, and facility definition will be especially applicable to a future NTP system. The similarities in system mission (in-space propulsion) and operational environment (vacuum, zero-gee) between J-2X and NTP make this highly synergistic. Thus, it can be $hown that the collective benefit of leveraging experience and technologies developed during the J-2X program can result in significant savings in development cost and schedule for NTP.

Human pancreas development.

PubMed

Jennings, Rachel E; Berry, Andrew A; Strutt, James P; Gerrard, David T; Hanley, Neil A

2015-09-15

A wealth of data and comprehensive reviews exist on pancreas development in mammals, primarily mice, and other vertebrates. By contrast, human pancreatic development has been less comprehensively reviewed. Here, we draw together those studies conducted directly in human embryonic and fetal tissue to provide an overview of what is known about human pancreatic development. We discuss the relevance of this work to manufacturing insulin-secreting β-cells from pluripotent stem cells and to different aspects of diabetes, especially permanent neonatal diabetes, and its underlying causes. © 2015. Published by The Company of Biologists Ltd.

FPG Child Development Institute

MedlinePlus

... Development, Teaching, and Learning The Frank Porter Graham Child Development Institute will partner with Zero to Three to ... Center October 6, 2017 More Frank Porter Graham Child Development Institute The University of North Carolina at Chapel ...

Drug Development Process

MedlinePlus

... Home Food Drugs Medical Devices Radiation-Emitting Products Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products For Patients Home For Patients Learn About Drug and Device Approvals The Drug Development Process The Drug Development Process Share Tweet Linkedin Pin ...

Women, Work and Early Childhood: The Nexus in Developed and Developing Countries.

ERIC Educational Resources Information Center

United Nations Educational, Scientific, and Cultural Organization, Paris (France). Early Childhood and Family Education Unit.

Most female workers in developing countries do not have wage jobs. However, the preponderance of female workers in non-wage jobs is not consistent across all developing countries. It is highly likely that the proportion of non-wage female workers in developing countries is greater than is suggested by the statistics. Consequently, mothers in the…

Telemedicine for Developing Countries

PubMed Central

Combi, Carlo; Pozzani, Gabriele

2016-01-01

Summary Background Developing countries need telemedicine applications that help in many situations, when physicians are a small number with respect to the population, when specialized physicians are not available, when patients and physicians in rural villages need assistance in the delivery of health care. Moreover, the requirements of telemedicine applications for developing countries are somewhat more demanding than for developed countries. Indeed, further social, organizational, and technical aspects need to be considered for successful telemedicine applications in developing countries. Objective We consider all the major projects in telemedicine, devoted to developing countries, as described by the proper scientific literature. On the basis of such literature, we want to define a specific taxonomy that allows a proper classification and a fast overview of telemedicine projects in developing countries. Moreover, by considering both the literature and some recent direct experiences, we want to complete such overview by discussing some design issues to be taken into consideration when developing telemedicine software systems. Methods We considered and reviewed the major conferences and journals in depth, and looked for reports on the telemedicine projects. Results We provide the reader with a survey of the main projects and systems, from which we derived a taxonomy of features of telemedicine systems for developing countries. We also propose and discuss some classification criteria for design issues, based on the lessons learned in this research area. Conclusions We highlight some challenges and recommendations to be considered when designing a telemedicine system for developing countries. PMID:27803948

Another Approach to Measuring Human Development: The Composite Dynamic Human Development Index

ERIC Educational Resources Information Center

Bilbao-Ubillos, Javier

2013-01-01

This paper seeks mainly to contribute to the debate on how the relative degree of development of a country should be measured by proposing an indicator to build on the valuable starting point provided by the Human Development Index (HDI). The indicator proposed is called the "Composite, Dynamic Human Development Index". It incorporates in a simple…

Toddler Growth and Development

MedlinePlus

... to Raise Concerns about a Child’s Speech and Language Development: Do’s and Don’ts How to Share Books ... Old Language Delays in Toddlers: Information for Parents Language Development: 1 Year Olds Language Development: 2 Year Olds ...

Liga developer apparatus system

DOEpatents

Boehme, Dale R.; Bankert, Michelle A.; Christenson, Todd R.

2003-01-01

A system to fabricate precise, high aspect ratio polymeric molds by photolithograpic process is described. The molds for producing micro-scale parts from engineering materials by the LIGA process. The invention is a developer system for developing a PMMA photoresist having exposed patterns comprising features having both very small sizes, and very high aspect ratios. The developer system of the present invention comprises a developer tank, an intermediate rinse tank and a final rinse tank, each tank having a source of high frequency sonic agitation, temperature control, and continuous filtration. It has been found that by moving a patterned wafer, through a specific sequence of developer/rinse solutions, where an intermediate rinse solution completes development of those portions of the exposed resist left undeveloped after the development solution, by agitating the solutions with a source of high frequency sonic vibration, and by adjusting and closely controlling the temperatures and continuously filtering and recirculating these solutions, it is possible to maintain the kinetic dissolution of the exposed PMMA polymer as the rate limiting step.

Nursing leadership in academic nursing: The wisdom of development and the development of wisdom.

PubMed

Pesut, Daniel J; Thompson, Sarah A

The purpose of this article is to discuss insights derived from adult cognitive developmental theories and relate the insights to vertical leadership development in academic nursing contexts. Equipped with developmental understanding, academic leaders are in a better position to support the vertical leadership development of one's self, faculty, peers, and colleagues. From a cognitive developmental perspective, the authors' reason as leaders develop, grow, and evolve, sense making becomes more sophisticated and nuanced resulting in the development of wisdom. Leadership wisdom is a function of horizontal (acquisition of information, skills, and competencies) and vertical development (the development of more complex and sophisticated ways of thinking). Ways to enhance vertical development, and sense making to cultivate wisdom are discussed. Principles and practices that promote vertical development in self and others deepens performance expectations of those in the academy and supports personal professional development and organizational success. Copyright © 2017 Elsevier Inc. All rights reserved.

Development of a framework for transit-oriented development (TOD) : research summary.

DOT National Transportation Integrated Search

2013-12-01

Transit-oriented development is a type of development that encourages public : transit and a transit-friendly urban environment. In general TOD provides an : environment where residents live within walking distance of one or more major : transit stat...

Energy demand, energy substitution and economic growth : Evidence from developed and developing countries

NASA Astrophysics Data System (ADS)

Abd Aziz, Azlina

This thesis contributes to the literature on energy demand in three ways. Firstly, it examines the major determinants of energy demand using a panel of 23 developed countries and 16 developing countries during 1978 to 2003. Secondly, it examines the demand for energy in the industrial sector and the extent of inter-fuel substitution, as well as substitution between energy and non-energy inputs, using data from 5 advanced countries and 5 energy producer's developing countries. Third, the thesis investigates empirically the relationship between energy consumption and economic growth for these groups of countries over a 26-year period. The empirical results of this study confirm the majority of the findings in energy demand analysis. Income and price have shown to be important determinants for energy consumption in both developed and developing countries. Moreover, both economic structure and technical progress appear to exert significant impacts on energy consumption. Income has a positive impact on energy demand and the effect is larger in developing countries. In both developed and developing countries, price has a negative impact but these effects are larger in developed countries than in developing countries. The share of industry in GDP is positive and has a greater impact on energy demand in developing countries, whereas technological progress is found to be energy using in developed countries and energy saving in developing countries. With respect to the analysis of inter-factor and inter-fuel substitution in industrial energy demand, the results provide evidence for substitution possibilities between factor inputs and fuels. Substitutability is observed between capital and energy, capital and labour and labour and energy. These findings confirm previous evidence that production technologies in these countries allow flexibility in the capital-energy, capital-labour and labour-energy mix. In the energy sub-model, the elasticities of substitution show that large

Managing Ada development

NASA Technical Reports Server (NTRS)

Green, James R.

1986-01-01

The Ada programming language was developed under the sponsorship of the Department of Defense to address the soaring costs associated with software development and maintenance. Ada is powerful, and yet to take full advantage of its power, it is sufficiently complex and different from current programming approaches that there is considerable risk associated with committing a program to be done in Ada. There are also few programs of any substantial size that have been implemented using Ada that may be studied to determine those management methods that resulted in a successful Ada project. The items presented are the author's opinions which have been formed as a result of going through an experience software development. The difficulties faced, risks assumed, management methods applied, and lessons learned, and most importantly, the techniques that were successful are all valuable sources of management information for those managers ready to assume major Ada developments projects.

Inequality, poverty and development.

PubMed

Ahluwalia, M S

1976-12-01

Dicussion explores the nature of the relationship between the distribution of income and the process of development on the basis of cross country data on income inequality. The results presented are based on a sample of 60 countries, including 40 developing countries, 14 developed countries, and 6 socialist countries. The approach adopted is essentially exploratory. Multivariate regression analysis was used to estimate cross country relationships between the income shares of different percentile groups and selected variables reflecting aspects of the development process which are likely to influence income inequality. The estimated equations are then used as a basis for broad generalizations about the relationship between income distribution and development. There was strong support for the proposition that relative inequaltiy increases substantially in the early stages of development, with a reversal of this tendency in the later stages. The propositions held whether the sample was restricted to developing countries or expanded to include developed and socialist countries. The process was most prolonged for the poorest group. There were a number of processes occurring "pari passu" with development which were correlated with income inequality and which can plausibly be interpreted as causal. These were intersectoral shifts in the structure of production, expansion in education attainment and skill level of the labor force; and reduction in the growth of population. The operation of these processes appeared to explain some of the improvement in income distribution observed in the later stages of development, but they did not serve to explain the marked deterioration observed in the earlier stages. The cross section results failed to support the stronger hypothesis that the deterioration in relative inequality reflected a prolonged absolute impoverishment of large sections of the population in the course of development. The cross country pattern showed average

Imperial Valley's proposal to develop a guide for geothermal development within its county

NASA Technical Reports Server (NTRS)

Pierson, D. E.

1974-01-01

A plan to develop the geothermal resources of the Imperial Valley of California is presented. The plan consists of development policies and includes text and graphics setting forth the objectives, principles, standards, and proposals. The plan allows developers to know the goals of the surrounding community and provides a method for decision making to be used by county representatives. A summary impact statement for the geothermal development aspects is provided.

Textile technology development

NASA Technical Reports Server (NTRS)

Shah, Bharat M.

1995-01-01

The objectives of this report were to evaluate and select resin systems for Resin Transfer Molding (RTM) and Powder Towpreg Material, to develop and evaluate advanced textile processes by comparing 2-D and 3-D braiding for fuselage frame applications and develop window belt and side panel structural design concepts, to evaluate textile material properties, and to develop low cost manufacturing and tooling processes for the automated manufacturing of fuselage primary structures. This research was in support of the NASA and Langley Research Center (LaRc) Advanced Composite Structural Concepts and Materials Technologies for Primary Aircraft Structures program.

Value Contestations in Development Intervention: Community Development and Sustainable Livelihoods Approaches.

ERIC Educational Resources Information Center

Arce, Alberto

2003-01-01

Both community development and sustainable livelihood approaches ignore value contestations that underlie people's interests and experiences. A case from Bolivia demonstrates that local values, social relations, actions, and language strategies must underlie policy and method in development. (Contains 28 references.) (SK)