Identifying canonical and replicable multi-scale intrinsic connectivity networks in 100k+ resting-state fMRI datasets.

Despite the known benefits of data-driven approaches, the lack of approaches for identifying functional neuroimaging patterns that capture both individual variations and inter-subject correspondence limits the clinical utility of rsfMRI and its application to single-subject analyses. Here, using rsfMRI data from over 100k individuals across private and public datasets, we identify replicable multi-spatial-scale canonical intrinsic connectivity network (ICN) templates via the use of multi-model-order independent component analysis (ICA). We also study the feasibility of estimating subject-specific ICNs via spatially constrained ICA. The results show that the subject-level ICN estimations vary as a function of the ICN itself, the data length, and the spatial resolution. In general, large-scale ICNs require less data to achieve specific levels of (within- and between-subject) spatial similarity with their templates. Importantly, increasing data length can reduce an ICN's subject-level specificity, suggesting longer scans may not always be desirable. We also find a positive linear relationship between data length and spatial smoothness (possibly due to averaging over intrinsic dynamics), suggesting studies examining optimized data length should consider spatial smoothness. Finally, consistency in spatial similarity between ICNs estimated using the full data and subsets across different data lengths suggests lower within-subject spatial similarity in shorter data is not wholly defined by lower reliability in ICN estimates, but may be an indication of meaningful brain dynamics which average out as data length increases.

The gut microbiota profile in psoriasis: a Brazilian case-control study.

The pathogenesis of psoriasis, an immune-mediated chronic inflammatory skin disease, remains unclear. Studies have shown an association between psoriasis and intestinal inflammation; in this context, the influence of the gut microbiota on the immune response of psoriasis has become a focus of recent research. The present research evaluated the composition and diversity of the gut microbiota of 21 participants with psoriasis from a Brazilian referral dermatology service compared to 24 healthy controls. A stool sample was collected from each participant at the time of inclusion in the study, and the samples were analysed by sequencing the 16S rRNA gene. The recruitment of research participants involved matching between groups by sex, age, body mass index, comorbidities and smoking and the exclusion of several criteria that could potentially influence the gut microbiota and the interpretation of the data. There was an increase in the Dialister genus and Prevotella copri species in patients with psoriasis compared to the control group. A reduction in the Ruminococcus, Lachnospira and Blautia genera, as well as in the Akkermansia muciniphila species, was also verified in the psoriasis group compared to the control group. Furthermore, patients with psoriasis exhibited less gut microbiota diversity than controls.

Sex dimorphism of weight and length at birth: evidence based on disorders of sex development.

BACKGROUND: Males have higher weight and length at birth than females. AIM: To verify the influence of the Y chromosome and the action of intrauterine androgens on weight and length at birth of children with Disorders of Sex Development (DSD). SUBJECTS AND METHODS: A cross-sectional and retrospective study. Patients with Turner syndrome (TS), complete (XX and XY), mixed (45,X/46,XY) and partial (XY) gonadal dysgenesis (GD), complete (CAIS) and partial (PAIS) androgen insensitivity syndromes and XX and XY congenital adrenal hyperplasia (CAH) were included. Weight and length at birth were evaluated. RESULTS: Weight and length at birth were lower in TS and mixed GD when compared to XY and XX DSD cases. In turn, patients with increased androgen action (117 cases) had higher weight and length at birth when compared to those with absent (108 cases) and decreased (68 cases) production/action. In birthweight, there was a negative influence of the 45,X/46,XY karyotype and a positive influence of increased androgen and gestational age. In birth length, there was a negative influence of the 45,X and 45,X/46,XY karyotypes and also a positive influence of increased androgen and gestational age. CONCLUSIONS: The sex dimorphism of weight and length at birth could possibly be influenced by intrauterine androgenic action.

Sodium palatability in male spontaneously hypertensive rats.

Spontaneously hypertensive rats (SHRs) ingest more NaCl than normotensive strains. Here we investigated NaCl intake and taste reactivity in adult male SHRs and normotensive Holtzman rats treated or not with AT1 receptor antagonist centrally in euhydrated condition and after fluid depletion. Taste reactivity was measured by the number of orofacial expressions to intra-oral infusions of 0.3 M NaCl. In euhydrated condition, intra-oral infusions of 0.3 M NaCl produced greater number of hedonic responses in SHRs than in normotensive rats, without differences in the number of aversive responses. Compared to euhydrated condition, the treatment with the diuretic furosemide + low dose of captopril (angiotensin converting enzyme blocker) increased the number of hedonic and reduced the number of aversive responses to intra-oral NaCl in normotensive rats, without changing the number of hedonic or aversive responses in SHRs. Losartan (AT1 receptor antagonist, 100 ng/1 µl) injected intracerebroventricularly in SHRs abolished 0.3 M NaCl intake induced by water deprivation + partial rehydration, whereas only transiently (first 30 min of the 60 min test) reduced hedonic responses, without changes in aversive responses to intra-oral NaCl. Losartan intracerebroventricularly also only transiently (first 30 min) reduced the number of hedonic responses to intra-oral NaCl in euhydrated SHRs. The results suggest that NaCl palatability is increased and independent from body fluid balance in SHRs. The results also suggest that central AT1 receptors are part of the mechanisms activated to increase NaCl intake and palatability in SHRs. A partial dissociation between NaCl intake and palatability in SHRs is also suggested.

Tetanus vaccination in pregnant women: a systematic review and meta-analysis of the global literature.

OBJECTIVES: This study aimed to determine the effect of several factors on the uptake of tetanus vaccination in pregnant women. STUDY DESIGN: This is a systematic review and meta-analysis of the global literature. METHODS: The search strategy was carried out in the EMBASE and MEDLINE (Pubmed) databases, without language restrictions. The databases were searched from the beginning until May 2020. Fixed and random effect models were applied according to the methodological heterogeneity between the included studies. The I2 test was performed to assess the magnitude of the heterogeneity. The results were presented as a grouped odds ratio (OR) with a 95% confidence interval (CI) and a significance level of 0.05. RESULTS: The initial search strategy generated 14,349 original articles. In total, 31 studies met all inclusion criteria and 20 articles were included in the meta-analysis. The grouped and subgroup analyses showed a significant association between tetanus vaccination and the following factors: higher number of prenatal visits (OR: 2.00; 95% CI: 1.17-3.42), higher maternal age (OR: 1.24, 95% CI: 1.02-1.50), being single (OR: 1.41; 95% CI: 1.20-1.65), professional vaccine guidance (OR: 9.00; 95% CI: 1.81-44.75) and uptake of influenza vaccine (OR: 5.87; 95% CI: 1.39-24.73). CONCLUSIONS: The uptake of tetanus vaccine in pregnant women is associated with various factors. The identification of these factors is an important step towards the implementation of public health strategies aimed at improving immunisation against tetanus in pregnant women.

8-Hydroxy-2-(1H-1,2,3-triazol-1-yl)-1,4-naphtoquinone derivatives inhibited P2X7 Receptor-Induced dye uptake into murine Macrophages.

Extracellular adenosine 5'-triphosphate (ATP) triggers the P2X7 receptor (P2X7R) ionic channel to stimulate the release of the interleukin-IL-1ß cytokine into macrophages. The current study explored the reaction of six structurally diverse triazole derivatives on P2X7-mediated dye uptake into murine peritoneal macrophages. P2X7R activity determined by ATP-evoked fluorescent dye uptake. Triazole derivatives toxicity measured using dextran rhodamine exclusion based colorimetric assay. A740004 and BBG, both P2X7R antagonist, inhibited ATP-induced dye uptake. In contrast, the derivatives 5a, 5b, 5e, and 5f did not diminish P2X7R activity in concentrations until 100 µM. 5c and 5d analogs caused a potent inhibitory activity on P2X7-induced dye uptake. Dextran Rhodamine exclusion measurements after 24 h of continuous treatment with triazole derivatives indicated a moderated toxicity for all molecules. In conclusion, this study showed that a series of new hybrid 1,2,3-triazolic naphthoquinones reduces P2X7R-induced dye uptake into murine macrophages. In silico analysis indicates a good pharmacokinetic profile and molecular docking results of these analogs indicate the potential to bind into an allosteric site located into the P2X7R pore and juxtaposed with the ATP binding pocket. In this manner, the compounds 5c and 5d may be used as a scaffold for new P2X7R inhibitors with reduced toxicity, and good anti-inflammatory activity.

Previous Emergency Medical Services Use by Victims of Child Homicide.

INTRODUCTION: The medical diagnoses and frequency of emergency department visits made by children who are later given a diagnosis of maltreatment do not differ much from those of nonabused children. However, the type of medical complaints and frequency of emergency medical services (EMS) use by child homicide victims before their death are not known. We compared EMS use between child homicide victims and children who died from natural causes before their death. METHODS: This was a retrospective case-control study of children 0 to 5 years old who died in Houston, Texas, from 2005 to 2010. Cases were child homicide victims. Controls were children who died from natural causes. We reviewed death data and EMS and child protective services (CPS) encounter information before the victim's death. The association between death type (natural vs homicide) and EMS use was assessed using Poisson regression with EMS count adjusted for exposure time. RESULTS: There were 89 child homicides and 183 natural deaths. Age at death was significantly higher for homicides than natural deaths (1.1 vs 0.2 y, P < 0.001). Homicide victims used EMS services (39% vs 14%, P < 0.001) and had previous CPS investigations (55% vs 7%, P < 0.001) significantly more often than children who died from natural causes. Poisson regression, after adjustment for age, revealed that the homicide group had more EMS calls than the natural death group (ß = 0.55; 95% confidence interval, 0.04-1.07; P = 0.03). However, the EMS use frequency and working assessments were not helpful in identifying maltreatment victims. CONCLUSIONS: Child homicide victims use EMS more often and have a higher number of CPS investigations before their death than children who die from natural causes. However, the frequency and nature of EMS medical complaints are not helpful in identifying maltreatment.

Lifelong Maintenance of Oral Tolerance and Immunity Profiles in Mice Depends on Early Exposure to Antigen.

Oral tolerance is defined as a state of systemic hyporesponsiveness to an antigen that has been previously administered by the oral route. Many factors affect oral tolerance induction; some of them related to antigen, and some related to the animal. The age of the animal is one of the most important factors that affect oral tolerance as ageing brings many alterations in immune responses. Herein, we demonstrated that both the oral tolerance and pattern of immune reactivity triggered in early life were kept up to 15 months regarding the magnitude of antibody production, cell proliferation and cytokine profile when compared to immune responses induced in old mice. Therefore, our results corroborate with a promising proposal for prevaccination during childhood and young age, and a booster in older age, to make sure that the primary immunization in early life is not lost in aged individuals.

Fcγ-RI, Fcγ-RII and IL-10 as predictive biomarkers for post-therapeutic cicatrization time in monocytes from cutaneous leishmaniasis patients.

Cutaneous leishmaniasis (CL) treatment is based on therapy with Glucantime® , yet, there are few laboratory methods to monitor its success. In this study, ex vivo and in vitro evaluations of peripheral blood monocytes were performed in a longitudinal study to characterize the impact of Glucantime® on overall phenotypic/functional features of these cells from CL patients to identify predictive biomarkers for post-therapeutic monitoring by flow cytometry. The ex vivo evaluation from CL patients demonstrated a modulatory profile before treatment, with a decrease in TLR-2, FcγRII, HLA-DR, CD86, IFN-γR, TNF, IL-12, NO, and an increase in FcγRIII and IL-10R. Conversely, treatment changes some of these biomarker expressions by decreasing FcγRIII and IL-10R and increasing IFN-γR, IL-12 and NO. Moreover, an in vitro analysis of these patients showed a reduced phagocytic capacity of Leishmania braziliensis and higher levels of IL-10 and TGF-ß modulating functional profile. Regardless of the compromised L. braziliensis phagocytic capacity, treatment re-established the production of IL-12, IL-10, TGF-ß and NO at the basal level. Notably, monocytes from patients with early cicatrization showed enhanced FcγRI and FcγRII expressions and reduced IL-10, which was further corroborated by a baseline fold change analysis. Finally, the logistic regression model emphasized the performance of FcγRI, FcγRII and IL-10 as robust predictive biomarkers for post-therapeutic cicatrization during cutaneous leishmaniasis.

Shortened preprocedural fasting in the pediatric emergency department.

BACKGROUND: There is no evidence of an association between fasting time and the incidence of adverse events during procedural sedation and analgesia. Pediatric and adult emergency medicine guidelines support avoiding delaying procedures based on fasting time. General pediatric guidelines outside emergent care settings continue to be vague and do not support a set fasting period for urgent and emergent procedures. OBJECTIVE: To describe shortened preprocedural fasting and vomiting event rates during the implementation of a shortened fasting protocol. METHODS: This was a prospective study of patients undergoing procedural sedation and analgesia (PSA) in an urban, tertiary care children's hospital emergency center from March 2010-February 2012. All consecutive patients had documentation of preprocedural fasting time and adverse events recorded on a standardized data collection form. RESULTS: PSA occurred in 2426 patients with fasting data available for 2188 (90.2%); 1472 were fasted ≥6 h for solids and 716 patients were in the shortened fasting group (<6 h). There is no evidence of an association between emesis at any time and shortened fasting time unadjusted (OR = 1.18 (95% CI 0.75-1.84) or adjusted for known risk factors including age >12 years, initial ketamine dose >2.5 mg/kg or total dose >5.0 mg/kg (OR = 1.14 (95% CI 0.74-1.75). CONCLUSION: Analysis of a large prospective cohort study failed to find evidence of an association between emesis and shortened fasting time upon implementation of a shortened fasting protocol for procedural sedation and analgesia.

Impact of rare variants in ARHGAP29 to the etiology of oral clefts: role of loss-of-function vs missense variants.

Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a prevalent, complex congenital malformation. Genome-wide association studies (GWAS) on NSCL/P have consistently identified association for the 1p22 region, in which ARHGAP29 has emerged as the main candidate gene. ARHGAP29 re-sequencing studies in NSCL/P patients have identified rare variants; however, their clinical impact is still unclear. In this study we identified 10 rare variants in ARHGAP29, including five missense, one in-frame deletion, and four loss-of-function (LoF) variants, in a cohort of 188 familial NSCL/P cases. A significant mutational burden was found for LoF (Sequence Kernel Association Test, p = 0.0005) but not for missense variants in ARHGAP29, suggesting that only LoF variants contribute to the etiology of NSCL/P. Penetrance was estimated as 59%, indicating that heterozygous LoF variants in ARHGAP29 confer a moderate risk to NSCL/P. The GWAS hits in IRF6 (rs642961) and 1p22 (rs560426 and rs4147811) do not seem to contribute to the penetrance of the phenotype, based on co-segregation analysis. Our data show that rare variants leading to haploinsufficiency of ARHGAP29 represent an important etiological clefting mechanism, and genetic testing for this gene might be taken into consideration in genetic counseling of familial cases.

Paratuberculosis in Latin America: a systematic review.

Latin America is the definition of the American group, where languages of Latin origin are spoken, including countries in South, Central, and North America. Paratuberculosis is a gastrointestinal contagious chronic disease that affects ruminants, whose etiological agent is the bacilli Mycobacterium avium subsp. paratuberculosis (MAP). Paratuberculosis is characterized by intermittent diarrhea, decreased milk production, dehydration, and progressive weight loss and is possibly involved in Crohn's disease, a human intestinal disease. MAP is resistant to environmental factors, pasteurization, and water disinfection, which coupled with the subclinical-clinical nature of the disease, and makes paratuberculosis a relevant socioeconomic and public health issue, justifying the descriptive review of research on the disease carried out in Latin American countries. A survey of articles, published until September 2016, on the Scopus database, PubMed, Agris, and Science Direct, about detection of the agent and the disease in Latin America, without restrictions to the date of the research was performed. The keywords were as follows: "paratuberculosis," "Mycobacterium avium subsp. paratuberculosis," "cattle," "milk," "wildlife," "goat," "ovine," "dairy," and the name of each country in English. Studies found from nine of the 20 Latin America countries, 31 related to Brazil, 17 to Argentina, 14 to Chile, eight to Colombia, six to Mexico, two to Peru, two to Venezuela, and one to Panama and to Bolivia, each. The agent was detected in cattle, goats, sheep, domesticated water buffalo, and wild animals. Microbiological culture, PCR, and ELISA were the frequent techniques. The small number of studies may result in overestimation or underestimation of the real scenario.

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

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

DAX1 Overexpression in Pediatric Adrenocortical Tumors: A Synergic Role with SF1 in Tumorigenesis.

DAX1 transcription factor is a key determinant of adrenogonadal development, acting as a repressor of SF1 targets in steroidogenesis. It was recently demonstrated that DAX1 regulates pluripotency and differentiation in murine embryonic stem cells. In this study, we investigated DAX1 expression in adrenocortical tumors (ACTs) and correlated it with SF1 expression and clinical parameters. DAX1 and SF1 protein expression were assessed in 104 ACTs from 34 children (25 clinically benign and 9 malignant) and 70 adults (40 adenomas and 30 carcinomas). DAX1 gene expression was studied in 49 ACTs by quantitative real-time PCR. A strong DAX1 protein expression was demonstrated in 74% (25 out of 34) and 24% (17 out of 70) of pediatric and adult ACTs, respectively (χ(2)=10.1, p=0.002). In the pediatric group, ACTs with a strong DAX1 expression were diagnosed at earlier ages than ACTs with weak expression [median 1.2 (range, 0.5-4.5) vs. 2.2 (0.9-9.4), p=0.038]. DAX1 expression was not associated with functional status in ACTs. Interestingly, a positive correlation was observed between DAX1 and SF1 protein expression in both pediatric and adult ACTs (r=0.55 for each group separately; p<0.0001). In addition, DAX1 gene expression was significantly correlated with SF1 gene expression (p<0.0001, r=0.54). In conclusion, DAX1 strong protein expression was more frequent in pediatric than in adult ACTs. Additionally, DAX1 and SF1 expression positively correlated in ACTs, suggesting that these transcription factors might cooperate in adrenocortical tumorigenesis.

Prevalence of Leptospira antibodies in wild boars (Sus scrofa) from Northern Portugal: risk factor analysis.

Leptospirosis is a zoonosis of worldwide distribution, caused by infection with pathogenic spirochaetes of the genus Leptospira. The wild boar (Sus scrofa), an important hunting species in Europe, seems to play a significant role in the epidemiological cycle of leptospirosis. A total of 101 serum samples from wild boar hunted in Northern Portugal were analysed for leptospiral antibodies detection by microscopic agglutination test. Sera were collected during hunting seasons (2011-2013) and tested with 17 different pathogenic serovars of Leptospira. Antibodies against nine serovars were detected in 66 (65·4%) of these sera. Serovars Tarassovi and Altodouro exhibited the highest seroreactivity rates (23·8% and 16·8%, respectively), followed by Autumnalis (7·9%) and Bratislava (6·9%). Age and district of origin were found to be risk factors for the presence of leptospiral antibodies in contrast to gender. From a One Health perspective, this study revealed that wild boar should be considered as a potential source of leptospirosis dissemination for humans and animal species (domestic and wild) in shared environments, particularly in the Trás-os-Montes region.

[Multiple intracranial epidermoid cysts: Case report].

Epidermoid cyst is a benign and rare tumor, that evolves slowly. We describe the case of a 55 years-old woman, who came to our consultation for atypical trigeminal neuralgia of left V1 and V2 nerves. Brain MRI found two tumors: T1W hypointense with no appreciable enhancement after gadolinium injection and T2W and diffusion hyperintense. This last feature was in favour of an epidermoid cyst, but the multiplicity of cerebral lesions was definitely not in favor of such a diagnos­tic. They were located behind the right eye and in the left Meckel's cave (trigeminal cave). The surgical strategy consis­ted in removal the retro orbital tumor witch was the most acces­si­ble of both the diagnostic of epidermoid cyst was retaned thanks to the anatomopathology report. As these lesions had the exact same characteristics, we concluded that they were simi­lar. The second epidermoid cyst was not removed because of surgical risk, its benign nature and low evolutionary potential.

Short communication: Viable Mycobacterium avium subspecies paratuberculosis in retail artisanal Coalho cheese from Northeastern Brazil.

Mycobacterium avium ssp. paratuberculosis (MAP) is the etiologic agent of paratuberculosis and it potentially plays a role in Crohn's disease. In humans, the main route of transmission of MAP might be the intake of contaminated milk and dairy products. Considering that MAP has already been detected in many types of cheese in different counties, and that Coalho cheese is an important dairy product in northeastern Brazil, the aim of this study was to report the first detection of MAP in retail Coalho cheese in Brazil by PCR and culture. Of 30 retail Coalho cheese samples, 3 (10%) amplified fragments of a similar size to that expected (626 bp) were obtained and viable MAP was recovered by culture from 1 (3.3%) sample. The DNA from the positive culture sample was sequenced and showed 99% identity with the insertion sequence IS900 deposited in GenBank. It was possible to identify the presence of MAP-specific DNA in the analyzed samples for the first time in Brazil, and to recover viable cells from retail Coalho cheese.

Critical swimming speeds of wild-caught sand-smelt Atherina presbyter larvae.

Swimming abilities of wild-caught sand-smelt Atherina presbyter larvae were assessed as critical swimming speed (Ucrit ) throughout ontogeny. The mean Ucrit increased with size, ranging from 3·6 to 18·7 cm s(-1) , over the size range of 6·6-21·0 mm LT . This indicates that at hatching A. presbyter larvae, far from being passive floaters, are already capable of active behaviours, which may influence their dispersal patterns.

Clinical Correlates of the PET-based Braak Staging Framework in Alzheimer's Disease.

In vivo Alzheimer's disease diagnosis and staging is traditionally based on clinical features. However, the agreement between clinical and pathological Alzheimer's disease diagnosis, whose diagnosis assessment includes amyloid and Braak histopathological tau staging, is not completely convergent. The development of positron emission tomography (PET) tracers targeting neurofibrillary tangles offers prospects for advancing the staging of Alzheimer's disease from both biological and clinical perspectives. Recent advances in radiochemistry made it possible to apply the postmortem Braak staging framework to tau-PET images obtained in vivo. Here, our aim is to provide a narrative review of the current literature on the relationship between Alzheimer's disease clinical features and the PET-based Braak staging framework. Overall, the available studies support the stepwise increase in disease severity following the advance of PET-based Braak stages, with later stages being associated with worse cognitive and clinical symptoms. In line with this, there is a trend for unimpaired cognition, mild cognitive impairment, and Alzheimer's disease dementia to be compatible with early, intermediate, and late patterns of tau deposition based on PET-based Braak stages. Moreover, neuropsychiatric symptom severity seems to be linked to the extent of tau-PET signal across Braak areas. In sum, this framework seems to correspond well with the clinical progression of Alzheimer's disease, which is an indication of its potential utility in research and clinical practice, especially for detecting preclinical tau levels in individuals without symptoms. However, further research is needed to improve the generalizability of these findings and to better understand the applications of this staging framework.

Dietary practices in pyridoxine non-responsive homocystinuria: a European survey.

BACKGROUND: Within Europe, the management of pyridoxine (B6) non-responsive homocystinuria (HCU) may vary but there is limited knowledge about treatment practice. AIM: A comparison of dietetic management practices of patients with B6 non-responsive HCU in European centres. METHODS: A cross-sectional audit by questionnaire was completed by 29 inherited metabolic disorder (IMD) centres: (14 UK, 5 Germany, 3 Netherlands, 2 Switzerland, 2 Portugal, 1 France, 1 Norway, 1 Belgium). RESULTS: 181 patients (73% >16 years of age) with HCU were identified. The majority (66%; n=119) were on dietary treatment (1-10 years, 90%; 11-16 years, 82%; and >16 years, 58%) with or without betaine and 34% (n=62) were on betaine alone. The median natural protein intake (g/day) on diet only was, by age: 1-10 years, 12 g; 11-16 years, 11 g; and >16 years, 45 g. With diet and betaine, median natural protein intake (g/day) by age was: 1-10 years, 13 g; 11-16 years, 20 g; and >16 years, 38 g. Fifty-two percent (n=15) of centres allocated natural protein by calculating methionine rather than a protein exchange system. A methionine-free l-amino acid supplement was prescribed for 86% of diet treated patients. Fifty-two percent of centres recommended cystine supplements for low plasma concentrations. Target treatment concentrations for homocystine/homocysteine (free/total) and frequency of biochemical monitoring varied. CONCLUSION: In B6 non-responsive HCU the prescription of dietary restriction by IMD centres declined with age, potentially associated with poor adherence in older patients. Inconsistencies in biochemical monitoring and treatment indicate the need for international consensus guidelines.