Intelligence in childhood, as measured by psychometric cognitive tests, is a strong predictor of many important life outcomes, including educational attainment, income, health and lifespan. Results ...from twin, family and adoption studies are consistent with general intelligence being highly heritable and genetically stable throughout the life course. No robustly associated genetic loci or variants for childhood intelligence have been reported. Here, we report the first genome-wide association study (GWAS) on childhood intelligence (age range 6-18 years) from 17,989 individuals in six discovery and three replication samples. Although no individual single-nucleotide polymorphisms (SNPs) were detected with genome-wide significance, we show that the aggregate effects of common SNPs explain 22-46% of phenotypic variation in childhood intelligence in the three largest cohorts (P=3.9 × 10(-15), 0.014 and 0.028). FNBP1L, previously reported to be the most significantly associated gene for adult intelligence, was also significantly associated with childhood intelligence (P=0.003). Polygenic prediction analyses resulted in a significant correlation between predictor and outcome in all replication cohorts. The proportion of childhood intelligence explained by the predictor reached 1.2% (P=6 × 10(-5)), 3.5% (P=10(-3)) and 0.5% (P=6 × 10(-5)) in three independent validation cohorts. Given the sample sizes, these genetic prediction results are consistent with expectations if the genetic architecture of childhood intelligence is like that of body mass index or height. Our study provides molecular support for the heritability and polygenic nature of childhood intelligence. Larger sample sizes will be required to detect individual variants with genome-wide significance.
Biodegradable fixation systems could reduce or eliminate problems associated with titanium removal of implants in a second operation.
The aim of this study was to compare the long-term (i.e. >5 years ...postoperatively) clinical performance of a titanium and a biodegradable system in oral and maxillofacial surgery.
The present multicenter Randomized Controlled Trial (RCT) was performed in four hospitals in the Netherlands. Patients treated with a bilateral sagittal split osteotomy (BSSO) and/or a Le Fort-I osteotomy, and those treated for fractures of the mandible, maxilla, or zygoma were included from December 2006 to July 2009. The patients were randomly assigned to either a titanium (KLS Martin) or a biodegradable group (Inion CPS).
After >5 years postoperatively, plate removal was performed in 22 of the 134 (16.4%) patients treated with titanium and in 23 of the 87 (26.4%) patients treated with the biodegradable system (P = 0.036, hazard ratio (HR) biodegradable (95% CI) = 2.0 (1.05-3.8), HR titanium = 1). Occlusion, VAS pain scores, and MFIQ showed good and (almost) pain free mandibular function in both groups.
In conclusion, the performance of the Inion CPS biodegradable system was inferior compared to the KLS Martin titanium system regarding plate/screws removal in the abovementioned surgical procedures.
http://controlled-trials.com ISRCTN44212338.
Biodegradable fixation systems could reduce/delete the problems associated with titanium plate removal. This means less surgical discomfort, and a reduction in costs.
The aim of the present study was ...to compare the cost-effectiveness between a biodegradable and a titanium system in Maxillofacial surgery.
This multicenter RCT was performed in the Netherlands from December 2006 to July 2009. Included were 230 patients who underwent a bilateral sagittal split osteotomy (BSSO), a Le Fort-I osteotomy, or a bi-maxillary osteotomy and those treated for fractures of the mandible, maxilla, or zygoma. The patients were randomly assigned to a titanium group (KLS Martin) or to a biodegradable group (Inion CPS). Costs were assessed from a societal perspective. Health outcomes in the incremental cost-effectiveness ratio (ICER) were bone healing (8 weeks) and plate removal (2 years).
In 25 out of the 117 patients who were randomized to the biodegradable group, the maxillofacial surgeon made the decision to switch to the titanium system intra-operatively. This resulted in an Intention-To-Treat (ITT-)analysis and a Treatment-Received (TR-) analysis. Both analyses indicated that operations performed with titanium plates and screws had better health outcomes. In the TR-analysis the costs were lower in the biodegradable group, in the ITT-analysis costs were lower in the titanium group.
The difference in costs between the ITT and the TR analyses can be explained by the intra-operative switches: In the TR-analysis the switches were analysed in the titanium group. In the ITT-analysis they were analysed in the biodegradable group. Considering the cost-effectiveness the titanium system is preferable to the biodegradable system in the regular treatment spectrum of mandibular, Le Fort-I, and zygomatic fractures, and BSSO's, Le Fort-I osteotomies and bimaxillary osteotomies.
Controlled-Trials.com ISRCTN 44212338.
Oral leukoplakia is the most common oral potentially malignant disorder with a malignant transformation rate into oral squamous cell carcinoma of 1-3% annually. The presence and grade of World Health ...Organization defined dysplasia is an important histological marker to assess the risk for malignant transformation, but is not sufficiently accurate to personalize treatment and surveillance. Differentiated dysplasia, known from differentiated vulvar intraepithelial neoplasia, is hitherto not used in oral dysplasia grading. We hypothesized that assessing differentiated dysplasia besides World Health Organization defined (classic) dysplasia will improve risk assessment of malignant transformation of oral leukoplakia. We investigated a retrospective cohort consisting of 84 oral leukoplakia patients. Biopsies were assessed for dysplasia presence and grade, and the expression of keratins 13 (CK13) and 17, known to be dysregulated in dysplastic vulvar mucosa. In dysplastic oral lesions, differentiated dysplasia is as common as classic dysplasia. In 25 out of 84 (30%) patients, squamous cell carcinoma of the upper aerodigestive tract developed during follow-up. Considering only classic dysplasia, 11 out of 56 (20%) patients with nondysplastic lesions progressed. With the incorporation of differentiated dysplasia, only 2 out of 30 (7%) patients with nondysplastic lesions progressed. The risk of progression increased from 3.26 (Hazard ratio, p = 0.002) when only classic dysplasia is considered to 7.43 (Hazard ratio, p = 0.001) when classic and differentiated dysplasia are combined. Loss of CK13, combined with presence of dysplasia, is associated with greater risk of malignant progression (p = 0.006). This study demonstrates that differentiated dysplasia should be recognized as a separate type of dysplasia in the oral mucosa and that its distinction from classic dysplasia is of pathological and clinical significance since it is a strong (co)prognostic histopathological marker for oral malignant transformation. In oral lesions without dysplasia and retained CK13 staining the risk for progression is very low.
Objectives
Evaluate whether regular follow‐up of oral leukoplakia (OL) resulted in early detection of malignant transformation (MT).
Method
Two hundred and twenty‐two consecutive patients with OL ...(147 females, 75 males); median follow‐up period of 64 months (range: 12–300). Three groups were distinguished: group A (n = 92) follow‐up at the hospital; group B (n = 84) follow‐up by their dentist; group C (n = 46) lost to follow‐up.
Results
OLs in group B compared to group A, were smaller in size (<2 cm; p < 0.001), showed more hyperkeratosis (p < 0.001) and less moderate/severe dysplasia (p < 0.001). MT occurred in 45 (20%) patients: 32 (35%) in group A, five (6%) in group B and eight (17%) in group C. There was no significant difference in clinical tumour size between group A (median: 15 mm, range: 1–40) and group B (median: 10 mm, range: 3–25; p = 0.496). Tumour size was smaller for patients in groups A and B (median: 10 mm, range 1–40) compared to group C (median: 33 mm, range: 3–100; p = 0.003). There was a positive correlation between tumour size and interval between the last visit in all patients (p = 0.022).
Conclusion
Regular follow‐up of OL resulted in early detection of MT. If properly selected, follow‐up of OL performed by the dentist seems feasible.
Objectives
To identify possible associations between patients’ demographics and habits and the clinical aspects and histopathological characteristics of oral leukoplakia (OL) at patients’ first ...visit.
Method
A total of 140 consecutive patients with OL at a single institute between 1997 and 2019. All biopsies were microscopically examined for classic dysplasia (CD) (WHO definition oral epithelial dysplasia) and differentiated dysplasia (DD) known from differentiated vulvar intraepithelial neoplasia. Clinical characteristics were correlated to histopathological diagnosis and odds ratios (OR) were calculated.
Results
A total of 96 females and 44 males, mean age 58 years, were presented. OLs were found mainly on the tongue (41%) and floor of mouth (FOM) (18%). Homogeneous OLs (58%) were associated with smoking, FOM and size <2cm and non‐homogeneous OLs (42%) with non‐smokers. No dysplasia was present in 40% and any dysplasia (AD) in 60%. Tongue OLs were correlated with AD (OR:6.0) and CD (OR:5.7). FOM OLs were correlated with CD (OR:4.5). DD was correlated with non‐homogeneous OLs (OR:2.6).
Conclusions
CD was most frequently observed in tongue and FOM OLs, while DD was associated with non‐homogeneous OLs. In this series of patients, there was no consistent reliable association between the clinical and histopathological features and clinical characteristics can therefore not substitute microscopic examination of biopsies.
Abstract
Objectives
A classification and staging system for oral leukoplakia (OL) was introduced to promote uniform reporting. In this system, size and the histopathologic diagnosis are assessed and ...combined in a staging system. The various stages could be predictive for malignant transformation of OL. Differentiated dysplasia (DD) was recently recognized as an important architectural pattern of dysplasia and is highly associated with malignant transformation (MT) of OL. In the present study, DD was incorporated in the OL‐system. The aim of the present study was to test the adapted system on a cohort of patients with OL.
Patient and methods
The group consisted of 140 patients. The size, absence or presence and degree of classic dysplasia (CD) and DD were incorporated into the OL‐system.
Results
In 31/140 patients, MT occurred. Size was not statistically significant with MT (
p
= 0.422). The presence of dysplasia was predictive for MT (
p
= 0.003), whereby severe CD and DD were highly statistically significant for MT (
p
= 0.008). Stage IV was statistically significant for MT (
p
= 0.011).
Conclusions
The present study emphasizes the value of the slightly modified OL‐system with incorporation of DD in uniform reporting of OL and the value in predicting MT.
Salivary stones (sialoliths) are calcified structures located in the ductal system of the major salivary glands. Their exact cause is not clear but in general they are characterized by concentric ...inorganic (hydroxyapatite) layers. The formation is a slow intermittent process which may result in enlargement of the sialolith causing obstruction of saliva secretion resulting in mealtime related pain and swelling of the affected salivary gland. Various studies reported the presence of organic material such as proteins and lipids in the core of sialoliths. In the present study the protein composition of twenty submandibular sialoliths was analyzed. It was found that proteins contributed on average 5% to the dry weight of submandibular stones whereby small salivary stones contained more extractable proteins than large salivary stones. Using a combination of SDS-PAGE gel electrophoresis and Western blotting, we identified α-amylase (in all stones; 100%), lysozyme (95%), lactoferrin (85%), secretory-IgA (75%), MUC7 (60%), complement C4 (60%) and C-reactive protein (35%). The presence, and the combinations, of lactoferrin, lysozyme, s-IgA and α-amylase in sialoliths was confirmed by ELISA. The gradually increasing size of a sialolith might provoke a local inflammatory response in the duct of the submandibular gland whereby the relatively low concentrations of lactoferrin and lysozyme may originate from neutrophils. The interaction of lactoferrin with s-IgA could contribute to the accumulation of lactoferrin in sialoliths. In summary, these results suggest a new pathophysiological role for lactoferrin, in the formation of sialoliths.
There has been an increasing trend in oral squamous cell carcinoma (OSCC) in patients under 45 years of age. The aim of this study was to evaluate the burden of OSCC in the Netherlands between 1989 ...and 2018 among young adults (age 20–34 years) when compared to adults (age 35–44 years), and to describe the burden in older groups as well, utilizing cancer registry data to characterize incidence patterns by age, sex, and risk factors. A total of 18,963 cases of OSCC were reported. The overall incidence rate, as measured by annual percentage change (APC), increased significantly from 1989 to 2010 by 1.3% per year (95% confidence interval (CI) 0.9–1.7%) but decreased thereafter by −0.9% (95% CI −2.5% to 0.7%). Annual incidence increased significantly by 2.4% (95% CI 1.1–3.8%) for patients aged 20–34 years, while it decreased for those aged 35–44 years by −0.9% (95% CI −1.7% to 0.0%). In patients older than 60 years, incidence rates increased overall (60–74 years: APC 1.8%, 95% CI 1.5–2.1%; ≥75 years: APC 1.5%, 95% CI 1.2–1.9%). Overall, 66.5% of patients were smokers and 65.3% were alcohol consumers. The marked differences in incidence within the young age subgroups warrants further investigation to elucidate any likely disparity in biological process and clinical outcomes in these populations.
Oral leukoplakia is the most common oral potentially malignant disorder with an annual malignant transformation rate of 1% to 5%. Consequently, oral leukoplakia patients have a 30% to 50% lifetime ...risk to develop oral squamous cell carcinoma. Although risk factors for malignant transformation of oral leukoplakia have been investigated, no definitive risk stratification model has been proposed. Next-generation sequencing can elucidate the genetic landscape of oral leukoplakia, which may be used to predict the risk for malignant transformation.
We investigated a retrospective cohort of 89 oral leukoplakia patients, and analyzed their oral leukoplakia lesions for the presence of genomic copy-number alterations and mutations in genes associated with oral squamous cell carcinoma.
In 25 of 89 (28%) patients, oral squamous cell carcinoma developed during follow-up. Seventy-nine of 89 (89%) oral leukoplakias harbored at least one genetic event. Copy-number alterations were present in 61 of 89 (69%) oral leukoplakias, most commonly gains of chromosome regions 8q24 (46%) and 20p11 (20%) and loss of 13q12 (19%). Mutations were present in 59 of 89 (66%) oral leukoplakias, most commonly in TP53 (28%), FAT1 (20%), and NOTCH1 (13%). Genetic data were combined with the presence of dysplasia to generate a prediction model, identifying three groups with a distinct risk for malignant transformation.
We provide an extensive description of genetic alterations in oral leukoplakia and its relation to malignant transformation. On the basis of our data we provide a model for the prediction of malignant transformation of oral leukoplakia using dysplasia and genetic markers.
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