Droplet sizes emitted from demonstration electric toothbrushes

The COVID-19 pandemic has drawn attention to microbial transmission risk via aerosols in dental practice. Demonstration electric toothbrushes are used intra-orally for education. The aim of this investigation was to measure the size of droplets emitted by the brush head of two demonstration oscillating-rotating electric toothbrushes. Measurement of droplet production and size was recorded in vitro using three methods: (1) Malvern Spraytec (LASER particle size measurement device with detectable particle size of 0.1–2500 µm) and brushes mounted on a 3D-printed, two-shell form-fit fixture with a supply of tap water; (2) a DustTrak aerosol measurement device and toothpaste slurry, with brushing simulated in the oral cavity of a phantom head; (3) high-speed visualization in a simulated-use situation in the oral cavity of a phantom head, with individual evaluation of tap water, water with detergent, 70% ethanol, glycerin and toothpaste slurry. Both brushes showed the size of emitted droplets was consistently between 200 and 1200 µm, categorized as splatter (dental aerosols are <50 µm diameter). No significant incremental aerosol-sized matter was detected during toothbrush operation. The high-speed video visualization confirmed only splatter-sized droplets during operation. These findings indicate that oscillating-rotating toothbrushes do not produce aerosol-sized particles during simulated use

Identification of the first AHI1 gene mutations in nephronophthisis-associated Joubert syndrome

Joubert syndrome (JBTS) is an autosomal recessive multisystem disease characterized by cerebellar vermis aplasia, mental retardation, muscular hypotonia, an irregular breathing pattern in the neonatal period and abnormal eye movements. Some individuals have progressive renal failure characterized by nephronophthisis (NPHP) and/or retinal dystrophy. Homozygous deletions of NPHP1 on chromosome 2q13 have been identified in individuals with NPHP-associated JBTS. Recently, mutations in AHI1 on chromosome 6q23.3 were found in JBTS patients without NPHP. Here, by direct sequencing, we identify novel truncating mutations within AHI1 in affected patients from two families. One patient had the association of JBTS and NPHP with chronic renal failure. This is the first report of AHI1 mutations causing JBTS associated with NPHP, confirming the clinical and genetic heterogeneity of NPHP.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47827/1/467_2005_Article_2054.pd

Estimated Glomerular Filtration Rates Calculated by New and Old Equations in Children and Adolescents With Type 1 Diabetes-What to Do With the Results?

Background: To apply and evaluate various equations for estimated glomerular filtration rates (eGFR) in a large paediatric type 1 diabetes population and compare the eGFR values with urinary creatinine clearances (UCC) in a subset of patients. Methods: Six eGFR formulae applicable for children and adolescents were used for calculation of eGFR values in 36,782 children/adolescents with type 1 diabetes. Via regression models, factors influencing eGFR values were identified. eGFR values were compared with measured UCC in 549 patients. Spearman correlation coefficients were given to assess the relation of eGFR and UCC values. Bland-Altman-Plots with corresponding linear regression were drawn to evaluate the agreement between eGFR and UCC. Results: eGFR values differed widely depending on the formula used, resulting in a percentage of pathological values <60 mL/min/1.73 m2 up to 8%. Regression models showed age, sex, and duration of diabetes as influencing factors. Microalbuminuria was associated with significantly higher eGFR values for all formulae. In comparison of eGFR with UCC, the highest correlation coefficient was 0.33, the lowest 0.01. Bland-Altman-Plots demonstrated graphically a poor agreement between eGFR and UCC, regardless of the formula used. Conclusions: The broad range of eGFR values indicate that an ideal eGFR formula for children and adolescence with T1D is yet missing. The minimal agreement between measured UCC and eGFR values urges us to be careful in application and interpretation of eGFR values regardless of the formula used

Molecular characterization of HOXA13 polyalanine expansion proteins in hand–foot–genital syndrome How to cite this article: Utsch B, McCabe CD, Galbraith K, Gonzalez R, Born M, DÖtsch J, Ludwig M, Reutter H, Innis JW. 2007. Molecular characterization of HOXA13 polyalanine expansion proteins in hand–foot–genital Syndrome. Am J Med Genet Part A 143A:3161–3168. Boris Utsch and Colleen D. McCabe contributed equally to this work.

We report on a father and daughter with hand–foot–genital syndrome (HFGS) with typical skeletal and genitourinary anomalies due to a 14-residue polyalanine expansion in HOXA13. This is the largest (32 residues) polyalanine tract so far described for any polyalanine mutant protein. Polyalanine expansion results in protein misfolding, cytoplasmic aggregation and degradation; however, HOXA13 polyalanine expansions appear to act as loss of function mutations in contrast to gain of function for HOXD13 polyalanine expansions. To address this paradox we examined the cellular consequences of polyalanine expansions on HOXA13 protein using COS cell transfection and immunocytochemistry. HOXA13 polyalanine expansion proteins form cytoplasmic aggregates, and distribution between cytoplasmic aggregates or the nucleus is polyalanine tract size-dependent. Geldanamycin, an Hsp90 inhibitor, reduces the steady-state abundance of all polyalanine-expanded proteins in transfected cells. We also found that wild-type HOXA13 or HOXD13 proteins are sequestered in HOXA13 polyalanine expansion cytoplasmic aggregates. Thus, the difference between HOXA13 polyalanine expansion loss-of-function and HOXD13 polyalanine expansion dominant-negative effect is not the ability to aggregate wild-type group 13 paralogs but perhaps to variation in activities associated with refolding, aggregation or degradation of the proteins. © 2007 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/57541/1/31967_ftp.pd

Evidence of oligogenic inheritance in nephronophthisis

Nephronophthisis is a recessive cystic renal disease that leads to end-stage renal failure in the first two decades of life. Twenty-five percent of nephronophthisis cases are caused by large homozygous deletions of NPHP1, but six genes responsible for nephronophthisis have been identified. Because oligogenic inheritance has been described for the related Bardet-Biedl syndrome, we evaluated whether mutations in more than one gene may also be detected in cases of nephronophthisis. Because the nephrocystins 1 to 4 are known to interact, we examined patients with nephronophthisis from 94 different families and sequenced all exons of the NPHP1, NPHP2, NPHP3, and NPHP4 genes. In our previous studies involving 44 families, we detected two mutations in one of the NPHP1-4 genes. Here, we detected in six families two mutations in either NPHP1, NPHP3, or NPHP4, and identified a third mutation in one of the other NPHP genes. Furthermore, we found possible digenic disease by detecting one individual who carried one mutation in NPHP2 and a second mutation in NPHP3. Finally, we detected the presence of a single mutation in nine families, suggesting that the second recessive mutation may be in another as yet unidentified NPHP gene. Our findings suggest that oligogenicity may occur in cases of nephronophthisis

Mutational analysis of the NPHP4 gene in 250 patients with nephronophthisis Communicated by JÜrgen Horst Online Citation: Human Mutation , Mutation in Brief #797 (2005) Online http://www3.interscience.wiley.com/homepages/38515/pdf/797.pdf

Nephronophthisis (NPH), a recessive cystic kidney disease, is the most frequent genetic cause for end-stage renal disease in the first two decades of life. Mutations in three genes (NPHP1, 2, and 3) were identified as causative. Extrarenal manifestations are known, such as retinitis pigmentosa (Senior-LØken syndrome, SLS) and ocular motor apraxia type Cogan. Recently, we identified a novel gene (NPHP4) as mutated in NPH. To date, a total of only 13 different NPHP4 mutations have been described. To determine the frequency of NPHP4 mutations, we performed mutational analysis by direct sequencing of all 30 NPHP4 exons in 250 different patients with isolated NPH, SLS, or Cogan syndrome ascertained worldwide over 14 years. We identified 23 novel NPHP4 sequence variants in 26/250 different patients (10%). Interestingly, we detected homozygous or compound heterozygous mutations of NPHP4 in only 6/250 different patients (2.4%), but only one heterozygous NPHP4 sequence variant in 20/250 different patients (8%). In the six patients with two NPHP4 mutations, 5/8 mutations (63%) were likely loss-of-function mutations, whereas in the 20 patients with only one sequence variant, only 1/20 (5%) was a likely loss-of-function (i.e., truncating) mutation. We conclude that: i) two recessive mutations in NPHP4 are a rare cause of nephronophthisis; ii) single heterozygous NPHP4 sequence variants are three times more prevalent than two recessive mutations; iii) there is no genotype/phenotype correlation; iv) there must exist further genes causing nephronophthisis, since in 224/250 (90%) patients, no sequence variants in either of the four NPH genes were detected. © 2005 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/39127/1/9326_ftp.pd

Mutation analysis of NPHP6/CEP290 in patients with Joubert syndrome and Senior-Løken syndrome

BACKGROUND: Nephronophthisis (NPHP) is an autosomal recessive cystic kidney disease that constitutes the most common genetic cause of renal failure in the first three decades of life. Using positional cloning, six genes (NPHP1-6) have been identified as mutated in NPHP. In Joubert syndrome (JBTS), NPHP may be associated with cerebellar vermis aplasia/hypoplasia, retinal degeneration and mental retardation. In Senior-Løken syndrome (SLSN), NPHP is associated with retinal degeneration. Recently, mutations in NPHP6/CEP290 were identified as a new cause of JBTS. METHODS: Mutational analysis was performed on a worldwide cohort of 75 families with SLSN, 99 families with JBTS and 21 families with isolated nephronophthisis. RESULTS: Six novel and six known truncating mutations, one known missense mutation and one novel 3 bp pair in-frame deletion were identified in a total of seven families with JBTS, two families with SLSN and one family with isolated NPHP