Hnf1b renal expression directed by a distal enhancer responsive to Pax8.

Xenopus provides a simple and efficient model system to study nephrogenesis and explore the mechanisms causing renal developmental defects in human. Hnf1b (hepatocyte nuclear factor 1 homeobox b), a gene whose mutations are the most commonly identified genetic cause of developmental kidney disease, is required for the acquisition of a proximo-intermediate nephron segment in Xenopus as well as in mouse. Genetic networks involved in Hnf1b expression during kidney development remain poorly understood. We decided to explore the transcriptional regulation of Hnf1b in the developing Xenopus pronephros and mammalian renal cells. Using phylogenetic footprinting, we identified an evolutionary conserved sequence (CNS1) located several kilobases (kb) upstream the Hnf1b transcription start and harboring epigenomic marks characteristics of a distal enhancer in embryonic and adult renal cells in mammals. By means of functional expression assays in Xenopus and mammalian renal cell lines we showed that CNS1 displays enhancer activity in renal tissue. Using CRISPR/cas9 editing in Xenopus tropicalis, we demonstrated the in vivo functional relevance of CNS1 in driving hnf1b expression in the pronephros. We further showed the importance of Pax8-CNS1 interaction for CNS1 enhancer activity allowing us to conclude that Hnf1b is a direct target of Pax8. Our work identified for the first time a Hnf1b renal specific enhancer and may open important perspectives into the diagnosis for congenital kidney anomalies in human, as well as modeling HNF1B-related diseases.

Constrained G4 structures unveil topology specificity of known and new G4 binding proteins.

G-quadruplexes (G4) are non-canonical secondary structures consisting in stacked tetrads of hydrogen-bonded guanines bases. An essential feature of G4 is their intrinsic polymorphic nature, which is characterized by the equilibrium between several conformations (also called topologies) and the presence of different types of loops with variable lengths. In cells, G4 functions rely on protein or enzymatic factors that recognize and promote or resolve these structures. In order to characterize new G4-dependent mechanisms, extensive researches aimed at identifying new G4 binding proteins. Using G-rich single-stranded oligonucleotides that adopt non-controlled G4 conformations, a large number of G4-binding proteins have been identified in vitro, but their specificity towards G4 topology remained unknown. Constrained G4 structures are biomolecular objects based on the use of a rigid cyclic peptide scaffold as a template for directing the intramolecular assembly of the anchored oligonucleotides into a single and stabilized G4 topology. Here, using various constrained RNA or DNA G4 as baits in human cell extracts, we establish the topology preference of several well-known G4-interacting factors. Moreover, we identify new G4-interacting proteins such as the NELF complex involved in the RNA-Pol II pausing mechanism, and we show that it impacts the clastogenic effect of the G4-ligand pyridostatin.

Assessment of physicians' resilience level during the COVID-19 pandemic.

We aim to assess physicians' level of resilience and define factors that improve or decrease the resilience level during the COVID-19 pandemic. Physicians from hospitals located in areas with different COVID-19 caseload levels, were invited to participate in a national e-survey between April and May 2020. Study participants were mainly emergency physicians, and anaesthesiologists, infectious disease consultants, and intensive care. The survey assessed participant's characteristics, factors potentially associated with resilience, and resilience using the Connor-Davidson Resilience Scale (RISC-25), with higher scores indicative of greater resilience. Factors associated with the resilience score were assessed using a multivariable linear regression. Of 451 responding physicians involved in the care of COVID-19 patients, 442 were included (98%). Age was 36.1 ± 10.3 years and 51.8% were male; 63% worked in the emergency department (n = 282), 10.4% in anesthesiology (n = 46), 9.9% in infectious disease department (n = 44), 4.8% in intensive care unit (n = 21) or other specialties (n = 49). The median RISC-25 score was at 69 (IQR 62-75). Factors associated with higher RISC scores were anesthesia as a specialty, parenthood, no previous history of anxiety or depression and nor increased anxiety. To conclude, this study is the first to characterize levels of resilience among physicians involved in COVID-19 unit. Our data points to certain protective characteristics and some detrimental factors, such as anxiety or depression, that could be amenable to remediating or preventing strategies to promote resilience and support caregivers in a pandemic.

Otosclerosis surgery under local anesthesia with sedation: Assessment of quality of life and stress.

OBJECTIVES: The main study endpoint was tolerance of stapedotomy under local anesthesia with sedation and under general anesthesia using stress and quality of life assessment questionnaires. Secondary endpoints comprised operative time and functional results. MATERIAL AND METHOD: In a consecutive series of stapedotomy patients operated on over a 12-month period, quality of life and perioperative stress were analysed by 3 questionnaires: the Glasgow Benefit Inventory, Cohen's perceived stress scale and the Post-traumatic stress disorder checklist scale. Questionnaire responses and audiometric data were compared between groups treated under local anesthesia with sedation and under general anesthesia. RESULTS: Twenty-two patients were included in the local anesthesia with sedation group and 6 in the general anesthesia group. There was no difference between the groups for quality of life, onset of post-traumatic stress, or perceived pre- and postoperative stress. There was also no difference in operative time. The audiometric data confirmed the reliability of stapedotomy. Stapedotomy under local anesthesia with sedation improved air conduction with≤10dB air-bone gap (ABG), comparable to results under general anesthesia. The rate of ABG≤10dB was 71.4%; no labyrinthisation was observed. CONCLUSION: Under local anesthesia with sedation, stapedotomy was well tolerated without increasing the stress associated with otosclerosis surgery. By correcting hearing loss, the procedure improves quality of life.

Can postoperative calcemia kinetics predict the risk of hypocalcemia for the management of parathyroid adenoma in ambulatory surgery?

INTRODUCTION: The goal of this study was to analyse the kinetics of corrected calcemia levels (Cac) after parathyroid excision and to determine the percentage of variation (ΔCa) in the initial hours after surgery, in order to entertain an early discharge. POPULATION AND METHODS: Were included in this study, patients undergoing operation for parathyroid adenoma responsible for primary hyperparathyroidism (PHP). The Cac was measure preoperatively and four hours after surgery, and then every day until patient discharge. Group A included patients for whom the Cac was inferior to 2.2mmol/L at least once postoperatively while group B included patients for whom the Cac was always equal or superior to 2.2mmol/L. The ΔCa represented the percentage of the fall in postoperative Cac with respect to preoperative Cac. RESULTS: Between 2010 and 2017, 156 patients fulfilled the inclusion criteria (women 80.8%, [sex ratio 1:4], median age 64 years old). Preoperative Cac was statistically significantly lower in group A compared to group B (2.67 vs. 2.82mmol/L; P<0.0001). In total, 9.6% of patients had calcium supplementation for hypocalcemia, symptomatic or not. Postoperative Cac reached its nadir value on postoperative day 2. At four hours postoperative, the risk of postoperative calcelmia falling below 2.2mmol/L appeared when the ΔCa was superior to 6% with a sensitivity of 92.9% and a negative predictive value of 97.4%. CONCLUSION: After excision of a parathyroid adenoma for PHP, the Cac falls rapidly and reaches its nadir value on day 2. If the fall in calcemia is less than 6% four hours after surgery (vs. preoperative level), early discharge within the framework of ambulatory surgery is possible.

Otosclerosis surgery: Assessment of patient comfort.

OBJECTIVES: To evaluate operative comfort and stress in patients undergoing stapedotomy for otosclerosis under local versus general anesthesia. MATERIAL AND METHODS: Consecutive otosclerosis patients managed over a 9-month period responded to 3 validated questionnaires to assess peri- and post-operative comfort: Glasgow Benefit Inventory, Cohen's Perceived Stress Scale and the Posttraumatic Stress Disorder Checklist Scale. These results and audiometric data were compared between local and general anesthesia groups. RESULTS: Twenty-one patients were included in the local anesthesia group and 7 in the general anesthesia group, after exclusion of patients with history of otosclerosis surgery. There was no significant inter-group difference on Glasgow Benefit Inventory (P=0.38) or Posttraumatic Stress Disorder Checklist Scale (P=0.86). Perceived Stress Scale scores were higher in the general anesthesia group (P=0.038). In total, 67% of patients reported no discomfort under local anesthesia, and 86% were ready to undergo the procedure under local anesthesia again. There were no significant differences in postoperative symptoms, or in air-bone gap≤10dB (local anesthesia 81%, general anesthesia 71%; P=0.156). CONCLUSIONS: Local anesthesia in otosclerosis surgery did not increase stress or postoperative symptoms compared to general anesthesia. Audiometric results were not affected by type of anesthesia.

Double J stenting evaluation after ureteroscopy for urolithiasis.

OBJECTIVES: During ureteroscopy for urolithiasis, postoperative ureteral drainage with double J stent is frequently used. It may reduce acute postoperative pain and late ureteral stenosis. Double J stent can have negative impact on life quality. After uncomplicated intervention, double J stent is not mandatory. Objective of our study was to evaluate pain and complications after ureteroscopy with or without stent. METHODS: We retrospectively analyzed ureteroscopy performed between May 2014 and January 2017. Interventions were compared regarding ureteral drainage with double J stent or not. Our primary outcome was early postoperative pain evaluated with an oral pain scale form 1 to 10 on day one after intervention. Clinical characteristics, per- and postoperative data were collected. We also looked for risks factors of complications. RESULTS: Three hundred and sixty-six interventions were included, 259 (70.8%) with and 107 (29.2%) without double J stent. Stone burden was higher in stented group (18.3 vs 9.4mm, P<0.0001). Patients without postoperative stents had more ureteral preparation with double J stent (78.5% vs 62.5%, P=0.0032) and had more ambulatory interventions (75.7% vs 52.5%, P<0.0001). Postoperative pain was not different (22% vs 17.75%, P=0.398). Complication rate was similar (29% vs 20.5%, P=0.1181), so was rehospitalization rate (0.8% vs 0.9%, P=1). In multivariate analysis, complications factors were unprepared ureter, experienced surgeons and access sheath. CONCLUSION: Not stenting after ureteroscopy do not increase pain or complications. Stenting should not be used after uncomplicated interventions for centimetric stones. LEVEL OF EVIDENCE: 4.

Association between serum 25-hydroxyvitamin D concentration and severity of first-diagnosed bullous pemphigoid in older adults.

BACKGROUND: Higher vitamin D status has been associated with symptom improvement and decreased risk of various autoimmune disorders. Our objective was to determine whether higher serum 25-hydroxyvitamin D (25OHD) concentration correlated with less severe first-diagnosed bullous pemphigoid (BP) in older inpatients. METHODS: This cross-sectional study was performed from November 2012 to February 2014 among 30 consecutive older inpatients (21 women; mean ± SD, 83 ± 7 years; all Caucasian) with a de novo diagnosis of active BP recruited in the Department of Dermatology of Angers University Hospital, France. The severity of BP was graded clinically on the basis of i) the number of bullae during the first three days of hospitalization (grade 0-4, worse), and ii) the extent of the lesions (grade 0-5, worse). RESULTS: Sixteen participants had ≤ 5 bullae at the time of diagnosis, 8 had 6-20 bullae, 3 had 20-50 bullae, and 3 had >50 bullae. The lesions were spread over 5 cutaneous areas in 5 participants (17%). The median 25OHD concentration was 23 [IQR, 16-42] nmol/L. Serum 25OHD concentration was inversely correlated with the bullae grade (ρ = - 0.38, p = 0.04) and the lesion extension grade (ρ = - 0.50, p = 0.005). CONCLUSIONS: Higher serum 25OHD concentration correlated with less severe BP prior to initiation of treatment among our sample of older inpatients. This result suggests that vitamin D may be involved in the pathophysiology of BP and could serve as prognostic biomarker of BP.

Binding properties of mono- and dimeric pyridine dicarboxamide ligands to human telomeric higher-order G-quadruplex structures.

Here, we report on the in vitro binding properties of the known pyridine dicarboxamide G-quadruplex ligand 360A and a new dimeric analogue (360A)2A to human telomeric DNA higher-order G-quadruplex (G4) structures. This study points to original binding features never reported for G4 ligands, and reveals a greater efficiency for the dimeric ligand to displace RPA (a ssDNA binding protein involved in telomere replication) from telomeric DNA.

Metabolic and genomic adaptations to winter fattening in a primate species, the grey mouse lemur (Microcebus murinus).

AIM: To understand the mechanisms underlying the development of metabolic changes leading to obesity remains a major world health issue. Among such mechanisms, seasonality is quite underestimated although it corresponds to the manifestation of extreme metabolic flexibility in response to a changing environment. Nevertheless, the changes induced by such flexibility are far to be understood, especially at the level of insulin signaling, genomic stability or inflammation. METHODS: Here, we investigated the metabolic regulations displayed by a seasonal primate species, the grey mouse lemur (Microcebus murinus) that exhibits pronounced changes in body mass during the 6-month winter season: a fattening period followed by a spontaneous fat loss, without ever reaching pathological stages. RESULTS: Such body weight modulations result from a combination of behavioral (food intake) and physiological (endocrine changes, switch between carb and lipid oxidation) adjustments that spontaneously operate during winter. Conversely to classical models of obesity, insulin sensitivity is paradoxically preserved during the obesogenic phase. Fat loss is associated with increased metabolic activity, especially in brown adipose tissue, and induced increased oxidative stress associated with telomere length dynamic. Furthermore, liver gene expression analysis revealed regulations in metabolic homeostasis (beta-oxidation, insulin signaling, cholesterol and lipid metabolism) but not for genes involved in inflammatory process (for example, Ifng, Tnf, Nfkb1). CONCLUSION: Altogether, these results show that mouse lemurs undergo deep physiological and genomic seasonal changes, without ever reaching a pathological stage. Further investigation is needed to decipher the underlying mechanisms, which may well be highly relevant for human therapeutic strategies.

[Study of the reproducibility of the sterilization process and proposal of an sterilizer requalification protocol]. / Étude de la reproductibilité du procédé de stérilisation et proposition d'un protocole de requalification des stérilisateurs.

Unlike EN 554, and since the publication of ISO 17665-1 standard, the user of autoclaves may use methods other than those indicated in the guidelines. Outsourcing the requalification of sterilizers by an external service provider and after observing from the previous requalification reports that the thermometric data seemed reproducible, we decided to propose and validate a validation method for the reproducibility of the sterilization process. This is to exempt from the study of the repeatability of the EN 554 standard in future requalifications. Reproducibility was studied with the sensors of the sterilization service and from the production cycles. This study was carried out in three parts. First, we checked whether our sensors were reliable. Then we evaluated the sterilization process fidelity of each sterilizer. Finally, we compared our measurements performed by the service sensors with the measurements performed by the service provider during the requalifications of the previous years. This work leads us to describe a new protocol of requalification of our sterilizers.

Hospitalization of HIV positive patients: Significant demand affecting all hospital sectors.

BACKGROUND: In a context of the evolution of severe morbidities in patients living with HIV (PLWH), the aim of this study was to describe reasons for hospitalization and the mode of care for the patients requiring hospitalization. METHODS: All admissions (≥24h) of PLWH to 10 hospitals in the south of Paris (COREVIH Ile-de-France Sud) between 1/1/2011 and 12/31/2011 were identified. The hospital database and the file of patients followed in the HIV referral department of each hospital were matched. Detailed clinical and biological data were collected, by returning to the individual medical records, for a random sample (65% of hospitalized patients). RESULTS: A total of 3013 hospitalizations (1489 patients) were recorded in 2011. The estimated rate of hospitalized patients was about 8% among the 10105 PLWH routinely managed in COREVIH Ile-de-France Sud in 2011. The majority (58.5%) of these hospitalizations occurred in a unit other than the HIV referral unit. Non-AIDS-defining infections were the main reason for admission (16.4%), followed by HIV-related diseases (15.6%), hepatic/gastrointestinal diseases (12.0%), and cardiovascular diseases (10.3%). The median length of stay was 5 days overall (IQR: 2-11), it was longer among patients admitted to a referral HIV care unit than to another ward. HIV infection had been diagnosed >10 years previously in 61.4% of these hospitalized patients. They often had associated comorbidities (coinfection HCV/HVB 40.5%, smoking 45.8%; hypertension 33.4%, dyslipidemia 28.8%, diabetes 14.8%). Subjects over 60 years old accounted for 15% of hospitalized patients, most of them were virologically controlled under HIV treatment, and cardiovascular diseases were their leading reason for admission. CONCLUSION: Needs for hospitalization among PLWH remain important, with a wide variety in causes of admission, involving all hospital departments. It is essential to prevent comorbidities to reduce these hospitalizations, and to maintain a link between the management of PLWH, that becomes rightly, increasing ambulatory, and recourse to specialized inpatient services.

Spontaneous nano-emulsification: Process optimization and modeling for the prediction of the nanoemulsion's size and polydispersity.

The aim of the present study was to optimize the size and polydispersity of a lipid nanoemulsion as a function of the oil (Labrafac® WL1349), surfactant (Kolliphor® HS 15) and cosurfactant (Span® 80) phase composition and temperature. The nanoemulsions were prepared using a low-energy self-emulsification method. The Z-average diameter and the polydispersity index (PDI) were modeled with mixture experiments. Nanoemulsions from 20nm to 120nm with PDI<0.2 were obtained at the three different tested temperatures (30°C, 50°C and 90°C). The nanoemulsion size was able to be controlled with the oil, surfactant and cosurfactant concentrations. Interestingly, the smallest PDIs were obtained at 30°C, and the cosurfactant concentration was able to be adjusted to optimize the formulation and to obtain nanoemulsions in the 20-120nm range with a PDI smaller than 0.14. These nanoemulsions have shown a good stability at 4°C in storage conditions and at 37°C in diluted conditions.

[Development and validation of an analytical method to quantify residues of cleaning products able to inactivate prion]. / Développement et validation d'une méthode de dosage des traces de détergents inactivants totaux du prion.

OBJECTIVES: In this study, a novel analytical method to quantify prion inactivating detergent in rinsing waters coming from the washer-disinfector of a hospital sterilization unit has been developed. The final aim was to obtain an easy and functional method in a routine hospital process which does not need the cleaning product manufacturer services. METHODS: An ICP-MS method based on the potassium dosage of the washer-disinfector's rinsing waters was developed. Potassium hydroxide is present on the composition of the three prion inactivating detergent currently on the French market. The detergent used in this study was the Actanios LDI(®) (Anios laboratories). A Passing and Bablok regression compares concentrations measured with this developed method and with the HPLC-UV manufacturer method. RESULTS: According to results obtained, the developed method is easy to use in a routine hospital process. The Passing and Bablok regression showed that there is no statistical difference between the two analytical methods during the second rinsing step. Besides, both methods were linear on the third rinsing step, with a 1.5ppm difference between the concentrations measured for each method. CONCLUSIONS: This study shows that the ICP-MS method developed is nonspecific for the detergent, but specific for the potassium element which is present in all prion inactivating detergent currently on the French market. This method should be functional for all the prion inactivating detergent containing potassium, if the sensibility of the method is sufficient when the potassium concentration is very low in the prion inactivating detergent formulation.

Hepatitis C virus seroprevalence in adults in Africa: a systematic review and meta-analysis.

With the introduction of more efficient treatments for hepatitis C virus (HCV), improved epidemiological information is required at the country level to allow evidence-based policymaking for elaboration of national strategies and HCV resources planning. We present a systematic review with meta-analysis of HCV seroprevalence data in adults in African countries. We conducted a systematic review of all HCV seroprevalence estimates reported in African countries from 2000 to 2014 in MEDLINE, AJOL and grey literature. We assessed studies performed in the general population and among blood donors, pregnant women and HIV-positive patients. A meta-regression analysis was used to provide adjusted estimates of HCV seroprevalence in the general adult population in each country, accounting for the heterogeneity in sample age structure and population types in the included studies. We identified 775 national-level estimations, among which 184 were included. Estimates of HCV seroprevalence were produced for 38 countries, in addition to the results from nationwide representative surveys available in Egypt and Libya. Next to Egypt, which clearly stands out, the highest levels of seroprevalence were found in Middle Africa (e.g. Cameroon, Gabon and Angola) and some West African countries (e.g. Burkina Faso, Benin), and the largest absolute numbers of infected adults were found in Nigeria, Ethiopia and Democratic Republic of Congo. This study exposes the diversity of HCV epidemiology among African countries. Egypt and several countries of West and Middle Africa present a HCV burden that will require strong governmental commitment to promote efficient preventive and curative interventions.

Improvements in phenotype studies of hemoglobin disorders brought by advances in reversed-phase chromatography of globin chains.

INTRODUCTION: Phenotype studies still occupy a key position in the diagnosis of hemoglobin (Hb) disorders. MATERIAL AND METHODS: In addition to the conventional methods for diagnosis of Hb disorders which are mostly based on differences in charge of the Hb molecules, some progresses have been brought by studying other properties of the globin chains. Among those, difference in hydrophobicity that may be investigated by reversed-phase HPLC (RP-HPLC) discriminates between variants displaying identical charges. RESULTS: In this study, we show how an update of this method allows to recognize an α-chain variant from a γ-chain variant, a problem frequently during neonatal screening. We illustrate that RP-HPLC may also unravel unclear phenotypes which are modified by the presence of an additional variant not detected by the conventional methods, and help to characterize rare mutants. Also we show that it allows a clear distinction between variants with identical electrophoretical charges as exemplified by Hb Lepore Boston-Washington and Lepore Baltimore. CONCLUSIONS: In view of our results, RP-HPLC is a technique that needs to be used as a second step in the general strategy for a correct characterization of Hb variants.

The two-year outcome of the I-Stop TOMS™ transobturator sling in the treatment of male stress urinary incontinence in a single centre and prediction of outcome.

PURPOSE: The aim of this study was to present the results of the 2 year outcome of I-Stop TOMS™ transobturator sling for post-prostatectomy (UIPP) minor to moderate male urinary incontinence treatment. MATERIALS AND METHODS: A prospective, single center study, including 26 patients with minor to moderate IUPP and operated on using a suburethral sling (MS) TOMS™ (four arms) was performed. UIPP assessment was made preoperatively and 1 year postoperatively, using validated questionnaires (SF36 and ICIQ), number of pads daily, and the 24 hours Pad-test (LPT). Telephone follow-up evaluation was performed in 21 patients over a 2 years period following surgery. RESULTS: Radical prostatectomy was performed 48.4 months earlier and average patient age was 67.3 years. Preoperatively, the mean number of pads used daily was 2.3 with an average weight loss of 207.1grams at LPT. At 1 year, ICIQ and SF36 scores significantly improved. Weight loss in the LPT as well as the number of pads significantly decreased (P<0.05). At 1 year, 13 patients were cured, 12 were improved, one reached improvement criteria, and 96.2% using a pad daily maximum. With more than a 2 year follow-up, 10/21 patients were dry, nine improved and two failed, and 90.5% using 0 to 1 pad per day. CONCLUSIONS: The transobturator TOMS™ male sling is a simple and well-tolerated procedure permitting a significant improvement of UIPP, with 50% of patients achieving complete continence at 1 year postoperatively, these good results continued beyond 2 years. LEVEL OF EVIDENCE: 4.

[Senescence and cellular immortality]. / Sénescence et immortalité cellulaire.

Senescence was originally described from the observation of the limited ability of normal cells to grow in culture, and may be generated by telomere erosion, accumulation of DNA damages, oxidative stress and modulation of oncogenes or tumor suppressor genes. Senescence corresponds to a cellular response aiming to control tumor progression by limiting cell proliferation and thus constitutes an anticancer barrier. Senescence is observed in pre-malignant tumor stages and disappears from malignant tumors. Agents used in standard chemotherapy also have the potential to induce senescence, which may partly explain their therapeutic activities. It is possible to restore senescence in tumors using targeted therapies that triggers telomere dysfunction or reactivates suppressor genes functions, which are essential for the onset of senescence.

Neonatal screening for sickle cell disease in France.

BACKGROUND: As a result of population growth in African-Caribbean regions of overseas France, and now immigration essentially from North and sub-Saharan Africa to mainland France, neonatal screening for sickle cell disease (SCD) has been performed in France since 1985 in Guadalupe and dependencies, as a universal test. After several pilot studies, screening was gradually extended to mainland France in 1996. Since 2000, the test has been performed at national level for all newborns defined as being "at risk" for SCD based on ethnic origin. METHODS: A dry blood sample is obtained by heel stick and analysed by isoelectric focusing as a first-line method, followed by either high-performance liquid chromatography or acid agar electrophoresis for confirmation, whenever a variant haemoglobin is observed on isoelectric focusing. RESULTS: In 2007, 28.45% of all newborns in mainland France were screened for SCD. Since 1996, a total of 3,890 newborns have been found to have SCD, and they have been followed up by reference paediatricians. CONCLUSION: Although screening for SCD at birth in France is not universal, it appears that missed babies are relatively infrequent. Despite obvious sociological problems inherent to the at-risk population, the follow-up of SCD babies is rather successful. Due to the birth prevalence of SCD in France, especially in comparison with other common genetic diseases, screening all newborns regardless of ethnic origin is an issue that is being addressed.