Impacts of Covid-19 interventions on air quality: evidence from Brazilian metropolitan regions.

The Covid-19 pandemic has negatively disrupted the way our economy and society functions. Nonetheless, there have also been some positive externalities of the pandemic on the environment. This paper aims to evaluate the concentration of nitrogen dioxide in Brazilian metropolitan regions after the policies adopted to confront Covid-19. In terms of methodological approach, the study employs cross-sectional quantitative analyses to compare the period of 36 days, i.e., 12 March to 16 April-before (in 2019) and after (in 2020) the pandemic declaration. The data were obtained from the Sentinel 5-P low-Earth polar satellite concerning Brazilian metropolitan regions (n = 24). Thorough spatial and statistical analyses were undertaken to identify the pre- and during pandemic nitrogen dioxide concentrations. Complementarily, Spearman's correlation test was performed with variables that impact air quality. The study results a fall in nitrogen dioxide concentration levels in 21 of the 24 metropolitan regions which was observed. The Spearman's correlation coefficient between the nitrogen dioxide variation and the vehicle density was 0.485, at a significance level of 0.05. With these findings in mind, the paper advocates that while the pandemic has a significant negative consequence on the health of population globally, a series of measures that result in a new social organization directly interfere in the reduction of air pollution that contributes to the quality of the air we breathe.

"LEARN"ing what is important to children and young people with intellectual disabilities when they are in hospital.

BACKGROUND: The need to review health service provision for children and young people (CYP) with disabilities and their families in the United Kingdom has been expressed in multiple reports: the most consistent message being that services need to be tailored to meet their individual needs. Our aim was to understand the hospital-related needs and experiences of CYP with intellectual disabilities. METHOD: An ethnographic study of a neurosciences ward and outpatient department was conducted within a paediatric tertiary hospital setting. RESULTS: Five themes, developed using the acronym LEARN, explained what is important to CYP with intellectual disabilities in hospital: (i) little things make the biggest difference, (ii) eliminate unnecessary waiting, (iii) avoid boredom, (iv) routine and home comforts are key and (v) never assume. CONCLUSIONS: It is imperative that the present authors continue to challenge the idea that it is acceptable to exclude CYP with intellectual disabilities from research because of their inability to participate.

Centre-level variation in outcomes and treatment for otitis media with effusion and hearing loss and the association of hearing loss with developmental outcomes at ages 5 and 7 years in children with non-syndromic unilateral cleft lip and palate: The Cleft Care UK study. Part 2.

OBJECTIVES: To explore centre-level variation in otitis media with effusion (OME), hearing loss and treatments in children in Cleft Care UK (CCUK) and to examine the association between OME, hearing loss and developmental outcomes at 5 and 7 years. SETTING AND SAMPLE POPULATION: Two hundred and sixty-eight 5-year-old British children with non-syndromic unilateral cleft lip and palate (UCLP) recruited to CCUK. MATERIALS AND METHODS: Children had air and bone conduction audiometry at age 5. Information on grommet and hearing aid treatment was obtained from parental questionnaire and medical notes. Hearing loss at age 5 was defined as >20 dB in the better ear and history of OME and hearing loss was determined from past treatment. Children with sensorineural hearing loss were excluded. Associations were examined with speech, behaviour and self-confidence at age 5 and educational attainment at age 7. Centre variation was examined using hierarchical models and associations between hearing variables and developmental outcomes were examined using logistic regression. RESULTS: There was centre-level variation in early grommet placement (variance partition coefficient (VPC) 18%, P=.001) and fitting of hearing aids (VPC 8%, P=.03). A history of OME and hearing loss was associated with poor intelligibility of speech (adjusted odds ratio=2.87, 95% CI 1.42-5.77) and aspects of educational attainment. CONCLUSIONS: Hearing loss is an important determinant of poor speech and treatment variation across centres suggest management of OME and hearing loss could be improved.

Centre-level variation in behaviour and the predictors of behaviour in 5-year-old children with non-syndromic unilateral cleft lip: The Cleft Care UK study. Part 5.

OBJECTIVES: The aims of this study were to describe child behavioural and psychosocial outcomes associated with appearance and speech in the Cleft Care UK (CCUK) study. We also wanted to explore centre-level variation in child outcomes and investigate individual predictors of such outcomes. SETTING AND SAMPLE POPULATION: Two hundred and sixty-eight five-year-old children with non-syndromic unilateral cleft lip and palate (UCLP) recruited to CCUK. MATERIALS AND METHODS: Parents completed the Strengths and Difficulties questionnaire (SDQ) and reported their own perceptions of the child's self-confidence. Child facial appearance and symmetry were assessed using photographs, and intelligibility of speech was derived from audio-visual speech recordings. Centre-level variation in behavioural and psychosocial outcomes was examined using hierarchical models, and associations with clinical outcomes were examined using logit regression models. RESULTS: Children with UCLP had a higher hyperactive difficulty score than the general population. For boys, the average score was 4.5 vs 4.1 (P=.03), and for girls, the average score was 3.8 vs 3.1 (P=.008). There was no evidence of centre-level variation for behaviour or parental perceptions of the child's self-confidence. There is no evidence of associations between self-confidence and SDQ scores and either facial appearance or behaviour. CONCLUSIONS: Children born with UCLP have higher levels of behaviour problems than the general population.

Centre-level variation in speech outcome and interventions, and factors associated with poor speech outcomes in 5-year-old children with non-syndromic unilateral cleft lip and palate: The Cleft Care UK study. Part 4.

OBJECTIVES: To investigate centre-level variation in speech intervention and outcome and factors associated with a speech disorder in children in Cleft Care UK (CCUK). SETTING AND SAMPLE POPULATION: Two hundred and sixty-eight 5-year-old British children with non-syndromic unilateral cleft lip and palate recruited to CCUK. MATERIALS AND METHODS: Centre-based therapists undertook audio-video recordings. Perceptual analysis was undertaken using the CAPS-A tool. Speech outcomes were based on structural and articulation scores, and intelligibility/distinctiveness. Between-centre variation in treatment and outcomes were examined using multilevel models. These models were extended to estimate the association between a range of factors (hearing loss, speech intervention, fistula, secondary speech surgery for velopharyngeal insufficiency, socio-economic status, gender, and parental happiness with speech) and speech outcomes. RESULTS: There was centre-level variation in secondary speech surgery, speech intervention, structure and intelligibility outcomes. Children with a history of speech intervention had a lower odds of poor intelligibility/distinctiveness, 0.1 (95% CI: 0.0-0.4). Parental concern was associated with a higher odds of poor intelligibility/distinctiveness, 13.2 (95% CI: 4.9-35.1). Poor speech outcomes were associated with a fistula, secondary speech surgery and history of hearing loss. CONCLUSIONS: Within the centralized service there is centre-level variation in secondary speech surgery, intervention and speech outcomes. These findings support the importance of early management of fistulae, effective management of velopharyngeal insufficiency and hearing impairment, and most importantly speech intervention in the preschool years. Parental concern about speech is a good indicator of speech status.

Centre-level variation in treatment and outcomes and predictors of outcomes in 5-year-old children with non-syndromic unilateral cleft lip treated within a centralized service: the Cleft Care UK study. Part 6: summary and implications.

OBJECTIVES: To summarize and discuss centre-level variation across a range of treatment and outcome measures and examine individual and ecological determinants of outcome in children in Cleft Care UK (CCUK). SETTING AND SAMPLE POPULATION: Two hundred and sixty-eight 5-year-old British children with non-syndromic unilateral cleft lip and palate (UCLP) recruited to CCUK and treated within a centralized service. MATERIALS AND METHODS: Children had a range of treatment and outcome measures collected at a 5-year audit clinic. These outcomes included dento-alveolar arch relationships from study models, measures of facial appearance from cropped photographs, hearing loss from audiological assessment, speech from speech recordings, self-confidence and strengths and difficulties from parental self-report. Data were collected on educational attainment at age 7 using record linkage. Centre variation was examined using hierarchical regression and associations between variables were examined using logistic or poisson regression. RESULTS: There was centre-level variation for some treatments (early grommet placement, fitting of hearing aids, fluoride treatment, secondary speech surgery and treatment for cleft speech characteristics) and for some outcomes (intelligibility of speech). Hearing loss was associated with a higher risk of poor speech while speech therapy was associated with a lower risk of poor speech. Children had high levels of caries but levels of preventative treatment (fluoride varnish and tablets) were low. CONCLUSIONS: Further improvements to and monitoring of the current centralized model of care are required to ensure the best outcomes for all children with cleft lip and palate.

Centre-level variation of treatment and outcome in 5-year-old children with non-syndromic unilateral cleft lip and palate: The Cleft Care UK study. Part 1: Methodology and results for dento-facial outcomes.

OBJECTIVES: Outline methods used to describe centre-level variation in treatment and outcome in children in the Cleft Care UK (CCUK) study. Report centre-level variation in dento-facial outcomes. SETTING AND SAMPLE POPULATION: Two hundred and sixty-eight five-year-old British children with non-syndromic unilateral cleft lip and palate (UCLP). MATERIALS AND METHODS: Between January 2011 and December 2012, data were collected on a comprehensive range of outcomes. Child facial appearance and symmetry were assessed using photographic pictures. Dental arch relationships were assessed from standardized dental study models. Hierarchical statistical models were used to predict overall means and the variance partition coefficient (VPC)-a measure of amount of variation in treatment or outcome explained by the centre. RESULTS: Data on dento-alveolar arch relationships and facial appearance were available on 197 and 252 children, respectively. The median age of the children was 5.5 years, and 68% were boys. Variation was described across 13 centres. There was no evidence of centre-level variation in good or poor dento-alveolar arch relationships with a VPC of 4% and 3%, respectively. Similarly, there was no evidence of centre-level variation in good or poor facial appearance with a VPC of 2% and 5%, respectively. CONCLUSIONS: There was no evidence of centre-level variation for dento-facial outcomes although this study only had the power to detect large variation between sites.

Identifying research priorities with nurses at a tertiary children's hospital in the United Kingdom.

AIM: The objective of this study was to undertake a research priority setting exercise with the aim of maximizing efficiency and impact in research activity undertaken by nurses at one children's tertiary healthcare institution by ensuring the clinical staff directly shaped a coherent, transparent and consensus driven nurse-led research agenda. BACKGROUND: In Round 1, the research topics of 147 nurses were elicited using a modified nominal group technique as the consensus method. The number of participants in the 24 separate discussions ranged from 3 to 21, generating lists of between 6 and 23 topics. In Round 2, nurses from the clinical areas ranked topics of importance resulting in a set of four to five priorities. In Round 3, the divisional heads of nursing consulted with staff in all of their clinical areas to each finalize their five divisional priorities. The Nursing Research Working Group discussed and refined the divisions' priorities and voted on the final list to agree the top five research priorities for the organization. RESULTS: A total of 269 research topics were initially generated. Following three rounds of ranking and prioritizing, five priorities were agreed at Divisional level, and from these, the five top organizational priorities were selected. These were (i) understanding and improving all aspects of the patient journey through the hospital system; (ii) play; (iii) staff wellbeing, patient care and productivity; (iv) team work - linking to a more efficient service; and (v) supporting parents/parent pathway. CONCLUSIONS: Divisional priorities have been disseminated widely to clinical teams to inform a patient-specific nurse-led research agenda. Organizational priorities agreed upon have been disseminated through management structures and processes to ensure engagement at all levels. A subgroup of the Nursing Research Working Group has been delegated to take this work forward so that the agreed priorities continue to contribute towards shaping nurse-led research activity, thereby going some way to inform and embed an evidence-based culture of inquiry.

Effect of chronic hypoxia on RAGE and its soluble forms in lungs and plasma of mice.

The receptor for advanced glycation end products (RAGE) is a multi-ligand receptor. Alternative splicing and enzymatic shedding produce soluble forms that protect against damage by ligands including Advanced Glycation End products (AGEs). A link between RAGE and oxygen levels is evident from studies showing RAGE-mediated injury following hyperoxia. The effect of hypoxia on pulmonary RAGE expression and circulating sRAGE levels is however unknown. Therefore mice were exposed to chronic hypoxia for 21 d and expression of RAGE, sheddases in lungs and circulating sRAGE were determined. In addition, accumulation of AGEs in lungs and expression of the AGE detoxifying enzyme GLO1 and receptors were evaluated. In lung tissue gene expression of total RAGE, variants 1 and 3 were elevated in mice exposed to hypoxia, whereas mRAGE and sRAGE protein levels were decreased. In the hypoxic group plasma sRAGE levels were enhanced. Although the levels of pro-ADAM10 were elevated in lungs of hypoxia exposed mice, the relative amount of the active form was decreased and gelatinase activity unaffected. In the lungs, the RAGE ligand HMGB1 was decreased and of the AGEs, only LW-1 was increased by chronic hypoxia. Gene expression of AGE receptors 2 and 3 was significantly upregulated. Chronic hypoxia is associated with downregulation of pulmonary RAGE protein levels, but a relative increase in sRAGE. These alterations might be part of the adaptive and protective response mechanism to chronic hypoxia and are not associated with AGE formation except for the fluorophore LW-1 which emerges as a novel marker of tissue hypoxia.

Assent for children's participation in research: why it matters and making it meaningful.

BACKGROUND: There are gaps in the existing evidence base about assent, with conflicting and unhelpful views prevalent. We contend that appropriate assent is a valuable process that has important consequences for children's/young people's participation in research. Furthermore, there is a need for a model to support researchers in making decisions about who to assent and how to do this is a meaningful way. METHODS: We undertook a scoping review of the literature to assess the body of opinion on assent in research with children/young people. An anonymous online survey was conducted to gather views from the wider community undertaking research with children/young people. We also sought to gather examples of current and effective practice that could be shared beyond the level of a single institution and our own experience. Survey participants included 48 health professionals with varied levels of experience, all actively involved in research with children. RESULTS: Published work, the findings from the online survey and our knowledge as experienced researchers in the field have confirmed four domains that should be considered in order for assent to be meaningful and individualized: child-related factors, family dynamics, study design and complexity and researcher and organizational factors. Mapping these domains onto the three paradigm cases for decision-making around children and young people's assent/consent as recommended by the Nuffield Council on Bioethics has resulted in a model that will aid researchers in understanding the relationship between assent and consent and help them make decisions about when assent is appropriate. CONCLUSIONS: The debate about assent needs to move away from terminology, definition and legal issues. It should focus instead on practical ways of supporting researchers to work in partnership with children, thus ensuring a more informed, voluntary and more robust and longer lasting commitment to research.

The Cleft Care UK study. Part 4: perceptual speech outcomes.

OBJECTIVES: To describe the perceptual speech outcomes from the Cleft Care UK (CCUK) study and compare them to the 1998 Clinical Standards Advisory Group (CSAG) audit. SETTING AND SAMPLE POPULATION: A cross-sectional study of 248 children born with complete unilateral cleft lip and palate, between 1 April 2005 and 31 March 2007 who underwent speech assessment. MATERIALS AND METHODS: Centre-based specialist speech and language therapists (SLT) took speech audio-video recordings according to nationally agreed guidelines. Two independent listeners undertook the perceptual analysis using the CAPS-A Audit tool. Intra- and inter-rater reliability were tested. RESULTS: For each speech parameter of intelligibility/distinctiveness, hypernasality, palatal/palatalization, backed to velar/uvular, glottal, weak and nasalized consonants, and nasal realizations, there was strong evidence that speech outcomes were better in the CCUK children compared to CSAG children. The parameters which did not show improvement were nasal emission, nasal turbulence, hyponasality and lateral/lateralization. CONCLUSION: These results suggest that centralization of cleft care into high volume centres has resulted in improvements in UK speech outcomes in five-year-olds with unilateral cleft lip and palate. This may be associated with the development of a specialized workforce. Nevertheless, there still remains a group of children with significant difficulties at school entry.

A cross-sectional survey of 5-year-old children with non-syndromic unilateral cleft lip and palate: the Cleft Care UK study. Part 1: background and methodology.

OBJECTIVES: We describe the methodology for a major study investigating the impact of reconfigured cleft care in the United Kingdom (UK) 15 years after an initial survey, detailed in the Clinical Standards Advisory Group (CSAG) report in 1998, had informed government recommendations on centralization. SETTING AND SAMPLE POPULATION: This is a UK multicentre cross-sectional study of 5-year-olds born with non-syndromic unilateral cleft lip and palate. Children born between 1 April 2005 and 31 March 2007 were seen in cleft centre audit clinics. MATERIALS AND METHODS: Consent was obtained for the collection of routine clinical measures (speech recordings, hearing, photographs, models, oral health, psychosocial factors) and anthropometric measures (height, weight, head circumference). The methodology for each clinical measure followed those of the earlier survey as closely as possible. RESULTS: We identified 359 eligible children and recruited 268 (74.7%) to the study. Eleven separate records for each child were collected at the audit clinics. In total, 2666 (90.4%) were collected from a potential 2948 records. The response rates for the self-reported questionnaires, completed at home, were 52.6% for the Health and Lifestyle Questionnaire and 52.2% for the Satisfaction with Service Questionnaire. CONCLUSIONS: Response rates and measures were similar to those achieved in the previous survey. There are practical, administrative and methodological challenges in repeating cross-sectional surveys 15 years apart and producing comparable data.

Centralization of cleft care in the UK. Part 6: a tale of two studies.

OBJECTIVES: We summarize and critique the methodology and outcomes from a substantial study which has investigated the impact of reconfigured cleft care in the United Kingdom (UK) 15 years after the UK government started to implement the centralization of cleft care in response to an earlier survey in 1998, the Clinical Standards Advisory Group (CSAG). SETTING AND SAMPLE POPULATION: A UK multicentre cross-sectional study of 5-year-olds born with non-syndromic unilateral cleft lip and palate. Data were collected from children born in the UK with a unilateral cleft lip and palate between 1 April 2005 and 31 March 2007. MATERIALS AND METHODS: We discuss and contextualize the outcomes from speech recordings, hearing, photographs, models, oral health and psychosocial factors in the current study. We refer to the earlier survey and other relevant studies. RESULTS: We present arguments for centralization of cleft care in healthcare systems, and we evidence this with improvements seen over a period of 15 years in the UK. We also make recommendations on how future audit and research may configure. CONCLUSIONS: Outcomes for children with a unilateral cleft lip and palate have improved after the introduction of a centralized multidisciplinary service, and other countries may benefit from this model. Predictors of early outcomes are still needed, and repeated cross-sectional studies, larger longitudinal studies and adequately powered trials are required to create a research-led evidence-based (centralized) service.

Palate lengthening by buccinator myomucosal flaps for velopharyngeal insufficiency.

OBJECTIVE : To assess the outcome of palate lengthening by myomucosal buccinator flaps for velopharyngeal insufficiency both in terms of speech and changes in palate length. DESIGN : Thirty-two consecutive patients who underwent the buccinator flap procedure were reviewed retrospectively. Palate length and the presence or absence of a velopharyngeal gap were assessed on pre- and postoperative videofluoroscopic recordings using a calibrated image analysis system. Hypernasality, nasal emission, nasal turbulence, and passive cleft type articulation errors were evaluated blindly by a speech-language pathologist external to the team using pre- and postoperative speech recordings. SETTING : Multidisciplinary cleft team based in a tertiary referral center. Results : In 81% of patients, speech outcome was such that no further velopharyngeal surgery was considered necessary at the time of follow-up. The buccinator flap procedure resulted in a mean palate lengthening of 7.5 mm (±5.5 SD). After the operation, there was a complete elimination of the velopharyngeal gap on lateral videofluoroscopy in 77% of patients. There were significant decreases in hypernasality ratings and passive cleft type articulation errors postoperatively. CONCLUSION: Palatal lengthening with myomucosal buccinator flaps in patients with velopharyngeal insufficiency is effective and safe. It has become one of our routinely practiced procedures for velopharyngeal insufficiency.

Liver parenchymal cell injury. 8. Lesions of membranous cellular components following iodoform.

Iodoform, a relatively water-insoluble yellow solid, chemically reactive in free-radical reactions, produces early hepatocellular injury qualitatively similar to that of carbon tetrachloride. 2 hr after administration of radioactively labeled iodoform, nonvolatile (14)C is preferentially recovered in microsomal lipid and protein. By 30 min microsomal properties are profoundly affected: oxidative demethylation decreases abruptly; increased lipoperoxide decomposition products are detected; and amino acid incorporation into liver protein is depressed. By 1 hr glucose-6-phosphatase is suppressed centrolobularly and increased stainable calcium is present in the midzone. Increased cell sap RNA contents are observed by 2 hr. Morphologically, the biochemical and histochemical changes are associated with progressive dispersion, vacuolation, and degranulation of the granular endoplasmic reticulum. Calcium-associated masses accumulate within the mitochondrial matrix, and mitochondria become progressively pleomorphic. Golgi components dilate and disperse. Membranous components of the cytoplasm of parenchymal cells conglomerate into labyrinthine tubular aggregates. Lipid accumulates in cytoplasmic droplets. Ultimately, centrolobular necrosis ensues. The close cytochemical and morphological similarities between the cellular injury produced in the liver by iodoform and that produced by carbon tetrachloride suggest common pathogenetic mechanisms associated with damage to membranes.

Cleft audit protocol for speech (CAPS-A): a comprehensive training package for speech analysis.

BACKGROUND: The previous literature has largely focused on speech analysis systems and ignored process issues, such as the nature of adequate speech samples, data acquisition, recording and playback. Although there has been recognition of the need for training on tools used in speech analysis associated with cleft palate, little attention has been paid to this issue. AIMS: To design, execute, and evaluate a training programme for speech and language therapists on the systematic and reliable use of the Cleft Audit Protocol for Speech-Augmented (CAPS-A), addressing issues of standardized speech samples, data acquisition, recording, playback, and listening guidelines. METHODS & PROCEDURES: Thirty-six specialist speech and language therapists undertook the training programme over four days. This consisted of two days' training on the CAPS-A tool followed by a third day, making independent ratings and transcriptions on ten new cases which had been previously recorded during routine audit data collection. This task was repeated on day 4, a minimum of one month later. Ratings were made using the CAPS-A record form with the CAPS-A definition table. An analysis was made of the speech and language therapists' CAPS-A ratings at occasion 1 and occasion 2 and the intra- and inter-rater reliability calculated. OUTCOMES & RESULTS: Trained therapists showed consistency in individual judgements on specific sections of the tool. Intraclass correlation coefficients were calculated for each section with good agreement on eight of 13 sections. There were only fair levels of agreement on anterior oral cleft speech characteristics, non-cleft errors/immaturities and voice. This was explained, at least in part, by their low prevalence which affects the calculation of the intraclass correlation coefficient statistic. CONCLUSIONS & IMPLICATIONS: Speech and language therapists benefited from training on the CAPS-A, focusing on specific aspects of speech using definitions of parameters and scalar points, in order to apply the tool systematically and reliably. Ratings are enhanced by ensuring a high degree of attention to the nature of the data, standardizing the speech sample, data acquisition, the listening process together with the use of high-quality recording and playback equipment. In addition, a method is proposed for maintaining listening skills following training as part of an individual's continuing education.

Disruption of FOXF2 as a Likely Cause of Absent Uvula in an Egyptian Family.

This study investigated the genetic basis of an unusual autosomal dominant phenotype characterized by familial absent uvula, with a short posterior border of the soft palate, abnormal tonsillar pillars, and velopharyngeal insufficiency. Cytogenetic analysis and single-nucleotide polymorphism-based linkage analysis were investigated in a 4-generation family with 8 affected individuals. Whole exome sequencing data were overlaid, and segregation analysis identified a single missense variant, p.Q433P in the FOXF2 transcription factor, that fully segregated with the phenotype. This was found to be in linkage disequilibrium with a small 6p25.3 tandem duplication affecting FOXC1 and GMDS. Notably, the copy number imbalances of this region are commonly associated with pathologies that are not present in this family. Bioinformatic predictions with luciferase reporter studies of the FOXF2 missense variant indicated a negative impact, affecting both protein stability and transcriptional activation. Foxf 2 is expressed in the posterior mouse palate, and knockout animals develop an overt cleft palate. Since mice naturally lack the structural equivalent of the uvula, we demonstrated FOXF2 expression in the developing human uvula. Decipher also records 2 individuals with hypoplastic or bifid uvulae with copy number variants affecting FOXF2. Nevertheless, given cosegregation with the 6p25.3 duplications, we cannot rule out a combined effect of these gains and the missense variant on FOXF2 function, which may account for the rare palate phenotype observed.

End-stage renal disease and diabetes catalyze the formation of a pentose-derived crosslink from aging human collagen.

Structure elucidation of a specific fluorophore from the aging extracellular matrix revealed the presence of a protein crosslink formed through nonenzymatic glycosylation of lysine and arginine residues. The unexpected finding that a pentose instead of a hexose is involved in the crosslinking process suggested that the crosslink, named pentosidine, might provide insight into abnormalities of pentose metabolism in aging and disease. This hypothesis was investigated by quantitating pentosidine in hydrolysates of 103 human skin specimens obtained randomly at autopsy. Pentosidine level was found to increase exponentially from 5 to 75 pmol/mg collagen over lifespan (r = 0.86, P less than 0.001). A three- to tenfold increase was noted in insulin-dependent diabetic and nondiabetic subjects with severe end-stage renal disease requiring hemodialysis (P less than 0.001). Moderately elevated levels were also noted in some very old subjects, some subjects with non-insulin dependent diabetes, and two subjects with cystic fibrosis and diabetes. The cause of the abnormal pentose metabolism in these conditions is unknown but may relate to hemolysis, impaired pentose excretion, cellular stress, and accelerated breakdown of ribonucleotides. Thus, pentosidine emerges as a useful tool for assessment of previously unrecognized disorders of pentose metabolism in aging and disease. Its presence in red blood cells and plasma proteins suggests that it might be used as a measure of integrated pentosemia in analogy to glycohemoglobin for the assessment of cumulative glycemia.

SISL (ScreeningsInstrument Schisis Leuven): assessment of cleft palate speech, resonance and myofunction.

This paper presents an assessment protocol for the evaluation and description of speech, resonance and myofunctional characteristics commonly associated with cleft palate and/or velopharyngeal dysfunction. The protocol is partly based on the GOS.SP.ASS'98 and adapted to Flemish. It focuses on the relevant aspects of cleft type speech necessary to facilitate assessment, adequate diagnosis and management planning in a multi-disciplinary setting of cleft team care.

Chromatographic quantitation of plasma and erythrocyte pentosidine in diabetic and uremic subjects.

Pentosidine is a fluorescent advanced Maillard/glycosylation product and protein cross-link present in elevated amounts in skin from diabetic and uremic subjects. A high-performance liquid chromatographic (HPLC) assay was developed to quantitate pentosidine in plasma and erythrocytes and other tissue proteins with low levels of pentosidine. High protein content and presence of basic amino acids and O2 during acid hydrolysis led to the formation of fluorescent artifacts that could be separated from true pentosidine through combined reverse-phase ion-exchange HPLC. No true pentosidine was formed during acid hydrolysis of ribated protein, suggesting that Amadori products do not generate artifactual pentosidine during hydrolysis. With the combined reverse-phase ion-exchange chromatographic assay, we found a 2.5-fold (P less than 0.001) and a 23-fold (P less than 0.001) elevation of mean +/- SD plasma protein pentosidine in diabetic (2.4 +/- 1.2 pmol/mg) and uremic (21.5 +/- 10.8 pmol/mg) subjects compared with healthy (0.95 +/- 0.33 pmol/mg) subjects. Pentosidine in hemolysate was normal in diabetes but dramatically elevated in uremia (0.6 +/- 0.4 pmol/mg hemoglobin, P less than 0.001). Although the precise nature of the pentosidine precursor sugar is unknown, plasma pentosidine may be a useful marker for monitoring the biochemical efficacy of trials with aminoguanidine or other treatment modalities. Furthermore, pentosidine in plasma proteins may act as a signal for advanced glycosylation end product-mediated receptor uptake by macrophages and other cells and contribute to accelerated atherosclerosis in diabetes and uremia.