Variation in LPA Is Associated with Lp(a) Levels in Three Populations from the Third National Health and Nutrition Examination Survey

The distribution of lipoprotein(a) [Lp(a)] levels can differ dramatically across diverse racial/ethnic populations. The extent to which genetic variation in LPA can explain these differences is not fully understood. To explore this, 19 LPA tagSNPs were genotyped in 7,159 participants from the Third National Health and Nutrition Examination Survey (NHANES III). NHANES III is a diverse population-based survey with DNA samples linked to hundreds of quantitative traits, including serum Lp(a). Tests of association between LPA variants and transformed Lp(a) levels were performed across the three different NHANES subpopulations (non-Hispanic whites, non-Hispanic blacks, and Mexican Americans). At a significance threshold of p<0.0001, 15 of the 19 SNPs tested were strongly associated with Lp(a) levels in at least one subpopulation, six in at least two subpopulations, and none in all three subpopulations. In non-Hispanic whites, three variants were associated with Lp(a) levels, including previously known rs6919246 (p = 1.18×10−30). Additionally, 12 and 6 variants had significant associations in non-Hispanic blacks and Mexican Americans, respectively. The additive effects of these associated alleles explained up to 11% of the variance observed for Lp(a) levels in the different racial/ethnic populations. The findings reported here replicate previous candidate gene and genome-wide association studies for Lp(a) levels in European-descent populations and extend these findings to other populations. While we demonstrate that LPA is an important contributor to Lp(a) levels regardless of race/ethnicity, the lack of generalization of associations across all subpopulations suggests that specific LPA variants may be contributing to the observed Lp(a) between-population variance

Ultrasound-guided fine-needle aspiration cytology as a diagnostic tool in comparison to ultrasound and MRI for staging in oral- and oropharyngeal squamous cell tumors

The aim of this retrospective study was to test the diagnostic performance of ultrasound guided fine needle aspiration cytology (USFNAC) in comparison to ultrasound (US) and magnetic resonance imaging (MRI) for detecting lymph node metastases in patients with squamous cell carcinoma of the oral and oropharyngeal region. 143 patients with oral cavity and oropharyngeal squamous cell carcinoma were included in the study. US, USFNAC and MRI were routinely performed prior to neck dissection. The results of the imaging studies were compared to histopathology. The sensitivity of MRI was highest at 83%, followed by USFNAC and US at 81% and 73%, respectively. The specificity was highest for FNAC at 100%, followed by MRI and US at 76% and 45%, respectively. Positive predictive value was highest for USFNAC 100%, US 57%, MRI 75% and negative predictive value was 77%, 69% and 84%, respectively. In our patient group with oral and oropharyngeal carcinoma, MRI had a higher sensitivity than USFNAC and US alone. USFNAC provided additional staging information. Especially in an uncertain lymph node situation it can facilitate and optimize preoperative planning with a specificity of 100% regarding tissue entity of cervical lymph nodes

Cranioplasty with Customized Titanium and PEEK Implants in a Mechanical Stress Model

Large skull defects as a result of craniectomies due to cerebral insults, trauma, or tumors create functional and aesthetic disturbances for the patient. Cranioplasty with implants in these cases are an alternative to autogenous bone transplantation. In our clinic, customized titanium or optima poly-ether-ether ketone (PEEK) implants are used to reconstruct craniectomy defects. To compare the two materials we investigated the structural changes of the implants fixed to a sintered polyamide skull model under mechanical stress in four simplified models. In a standard testing machine, the models were subjected to a load under a quasi-static loading rate of 1.925 mm/min. Fractures of the PEEK implants occurred at a force of 24.2 and 24.5kN with a displacement of 8.4 and 8 mm. The titanium implants showed no deformation, but extensive damage was seen in the polyamide skull models. The highest pressures achieved were 45.8 and 50.9 kN. In a simplified model with quasi-static loading, both implants withstood forces that were higher than those capable of causing skull fractures. It seems that the mechanical properties of PEEK could provide better protection when used for cranioplasty in patients after craniectomy if reconstruction with autogenous bone is not possible

Investigation and Functional Characterization of Rare Genetic Variants in the Adipose Triglyceride Lipase in a Large Healthy Working Population

Recent studies demonstrated a strong influence of rare genetic variants on several lipid-related traits. However, their impact on free fatty acid (FFA) plasma concentrations, as well as the role of rare variants in a general population, has not yet been thoroughly addressed. The adipose triglyceride lipase (ATGL) is encoded by the PNPLA2 gene and catalyzes the rate-limiting step of lipolysis. It represents a prominent candidate gene affecting FFA concentrations. We therefore screened the full genomic region of ATGL for mutations in 1,473 randomly selected individuals from the SAPHIR (Salzburg Atherosclerosis Prevention program in subjects at High Individual Risk) Study using a combined Ecotilling and sequencing approach and functionally investigated all detected protein variants by in-vitro studies. We observed 55 novel mostly rare genetic variants in this general population sample. Biochemical evaluation of all non-synonymous variants demonstrated the presence of several mutated but mostly still functional ATGL alleles with largely varying residual lipolytic activity. About one-quarter (3 out of 13) of the investigated variants presented a marked decrease or total loss of catalytic function. Genetic association studies using both continuous and dichotomous approaches showed a shift towards lower plasma FFA concentrations for rare variant carriers and an accumulation of variants in the lower 10%-quantile of the FFA distribution. However, the generally rather small effects suggest either only a secondary role of rare ATGL variants on the FFA levels in the SAPHIR population or a recessive action of ATGL variants. In contrast to these rather small effects, we describe here also the first patient with "neutral lipid storage disease with myopathy" (NLSDM) with a point mutation in the catalytic dyad, but otherwise intact protein