Plasma amyloid beta protein (Abeta42) levels and late onset Alzheimer's disease (LOAD) have been linked to the same region on chromosome 10q. The PLAU gene within this region encodes urokinase-type plasminogen activator, which converts plasminogen to plasmin. Abeta aggregates induce PLAU expression thereby increasing plasmin, which degrades both aggregated and non-aggregated forms of Abeta. We evaluated single nucleotide polymorphisms (SNPs) in PLAU for association with Abeta42 and LOAD. PLAU SNP compound genotypes composed of haplotype pairs showed significant association with AD in three independent case-control series. PLAU SNP haplotypes associated significantly with plasma Abeta42 in 10 extended LOAD families. One of the SNPs analyzed was a missense C/T polymorphism in exon 6 of PLAU (PLAU_1=rs2227564), which causes a proline to leucine change (P141L). We analyzed PLAU_1 for association with AD in six case-control series and 24 extended LOAD families. The CT and TT PLAU_1 genotypes showed association (P=0.05) with an overall estimated odds ratio of 1.2 (1.0-1.5). The CT and TT genotypes of PLAU_1 were also associated with significant age-dependent elevation of plasma Abeta42 in 24 extended LOAD families (P=0.0006). In knockout mice lacking the PLAU gene, plasma--but not brain--Abeta42 as well as Abeta40 was significantly elevated, also in an age-dependent manner. The PLAU_1 associations were independent of the associations we found among plasma Abeta42, LOAD and variants in the IDE or VR22 region. These results provide strong evidence that PLAU or a nearby gene is involved in the development of LOAD. PLAU_1 is a plausible pathogenic mutation that could act by increasing Abeta42, but additional biological experiments are required to show this definitively.

To show that sialoendoscopy is both a safe and effective alternative to traditional treatments for juvenile recurrent parotitis and sialolithiasis.Design: Retrospective medical chart review.Setting: Two major pediatric tertiary care centers. Patients: Eighteen pediatric patients.Interventions: A total of 33 sialendoscopic procedures on 27 glands.Main Outcome Measures: Indications for surgery, age at onset of symptoms, age at procedure, sex, intraopera-tive findings, complications, recurrences, need for additional procedures, and follow-up interval.Results: Juvenile recurrent parotitis was the most common indication for sialendoscopy (12 of 18) followed by sialolithiasis (4 of 18). Ten of 12 patients with juvenile recurrent parotitis were asymptomatic after 1 or 2 sialendoscopies (8 patients and 2 patients, respectively). There were 6 minor complications. Three patients ultimately required gland excision for disease management. Conclusion:Sialoendscopy is safe and effective as a treatment for pediatric salivary gland disorders.

Tracheostomy care requires expertise for all caregivers and is challenging for people without specialized training. Specialized nursing and education protocols are associated with decreased complications of tracheostomy wounds. Children who are discharged directly to home are at higher risk for readmission compared with children discharged to advanced care facilities. Further development of caregiver education protocols is necessary to continue to reduce readmissions and tracheostomy-related complications.

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Objectives The primary purpose of this study was to determine the temporal characteristics of aerodynamic segments in the normal speech of children and adults without cleft palate. A secondary objective was to determine the withinspeaker variability of the segments. Method Speakers consisted of 46 children aged 6 to 8 years, 41 older children aged 11 to 12 years, and 41 adults aged 18 to 37 years (total n = 128) who repeated the word “hamper” during continuous utterances. The pressure-flow method was used to determine the duration of six segments of the oral air pressure and nasal airflow pulses associated with the /mp/ sequence. Descriptive statistics, including coefficients of variation (COV), were computed for each segment as a function of age and sex of the speakers. Analysis of variance (ANOVA) procedures were used to determine the effects of age, sex, or both on the temporal variables. Results ANOVAs indicated statistically significant main effects (p < .008) for age on five of the six temporal measures and for sex on three of the six measures. Five of the six COVs were also statistically significant for age. There were no statistically significant interactions between speaker age and sex for any measure. Conclusions The results indicate distinct patterns of timing for aerodynamic segments of speech produced by children and adults. Overall, adults exhibited less temporal variability than children. The generally longer and more variable segments produced by children suggest diagnostic and treatment implications relative to speakers with velopharyngeal dysfunction.