Translation of mouse model to human gives insights into periodontitis etiology

To suggest candidate genes involved in periodontitis, we combined gene expression data of periodontal biopsies from Collaborative Cross (CC) mouse lines, with previous reported quantitative trait loci (QTL) in mouse and with human genome-wide association studies (GWAS) associated with periodontitis. Periodontal samples from two susceptible, two resistant and two lines that showed bone formation after periodontal infection were collected during infection and naïve status. Differential expressed genes (DEGs) were analyzed in a case-control and case-only design. After infection, eleven protein-coding genes were significantly stronger expressed in resistant CC lines compared to susceptible ones. Of these, the most upregulated genes were MMP20 (P = 0.001), RSPO4 (P = 0.032), CALB1 (P = 1.06×10-4), and AMTN (P = 0.05). In addition, human orthologous of candidate genes were tested for their association in a case-controls samples of aggressive (AgP) and chronic (CP) periodontitis (5,095 cases, 9,908 controls). In this analysis, variants at two loci, TTLL11/PTGS1 (rs9695213, P = 5.77×10-5) and RNASE2 (rs2771342, P = 2.84×10-5) suggested association with both AgP and CP. In the association analysis with AgP only, the most significant associations were located at the HLA loci HLA-DQH1 (rs9271850, P = 2.52×10-14) and HLA-DPA1 (rs17214512, P = 5.14×10-5). This study demonstrates the utility of the CC RIL populations as a suitable model to investigate the mechanism of periodontal disease

Chronic Subdural Hematoma a Review of 58 Cases

From this short review, immerges a syndrome of the chronic subdural hematoma. The patient is usually an elderly male', with a hisory of moderate or severe trauma to the head incurred about 2 months prionjto admission, with or witout immediate headache which subsides, then recurs lllb6ut two to three weeks prior to admission. The headache becomes severer and the patient may develop a hemiparesis most frequently contralaterally, would become drowsy and may enter coma if not diagnosed and treated early. On examination, he would show dulled mental capacities and possibly papilloedema, with or without a hemiparesis and in one fifth of the cases a peculiar type of disturbance of gait. If there has been waxing and waning of the symptomatology in the past few days. this adds to the completeness of the picture. Although there is a syndrome that caracteriscs cases of subdural hematomas, the picture can be very varied and there is no doubt that the final diagnosis rests with angiography, which shows a typical appearance of an avascular lens shaped area just under tho parietal bone on the AP films or in some cases under the frontal bone in oblique fil

On the production of 52gMn by deuteron irradiation on natural chromium and its radionuclidic purity

The positron emitter 52gMn is used for the Positron Emission Tomography - PET imaging.In this work we investigate the nuclear reactions for production of 52gMn and 54Mn induced by deuteron beams on natural chromium targets at energies up to Ed = 28 MeV using the stacked-foils activation technique. We calculate the thick target yields for 52gMn and for the radionuclidic impurity 54Mn, and we compare the radionuclidic purity of 52gMn with that achievable in proton activation of Cr. The cross-sections of the reactions natCr(d,pxn)51Cr and natCr(d,x)48V are also presented

High‐fat diet and oral infection induced type 2 diabetes and obesity development under different genetic backgrounds

Abstract Background Type 2 diabetes (T2D) is an adult‐onset and obese form of diabetes caused by an interplay between genetic, epigenetic, and environmental components. Here, we have assessed a cohort of 11 genetically different collaborative cross (CC) mouse lines comprised of both sexes for T2D and obesity developments in response to oral infection and high‐fat diet (HFD) challenges. Methods Mice were fed with either the HFD or the standard chow diet (control group) for 12 weeks starting at the age of 8 weeks. At week 5 of the experiment, half of the mice of each diet group were infected with Porphyromonas gingivalis and Fusobacterium nucleatum bacteria strains. Throughout the 12‐week experimental period, body weight (BW) was recorded biweekly, and intraperitoneal glucose tolerance tests were performed at weeks 6 and 12 of the experiment to evaluate the glucose tolerance status of mice. Results Statistical analysis has shown the significance of phenotypic variations between the CC lines, which have different genetic backgrounds and sex effects in different experimental groups. The heritability of the studied phenotypes was estimated and ranged between 0.45 and 0.85. We applied machine learning methods to make an early call for T2D and its prognosis. The results showed that classification with random forest could reach the highest accuracy classification (ACC = 0.91) when all the attributes were used. Conclusion Using sex, diet, infection status, initial BW, and area under the curve (AUC) at week 6, we could classify the final phenotypes/outcomes at the end stage of the experiment (at 12 weeks)

Genetic Evidence For Plasminogen As A Shared Genetic Risk Factor Of Coronary Artery Disease And Periodontitis

Background-Genetic studies demonstrated the presence of risk alleles in the genes ANRIL and CAMTA1/VAMP3 that are shared between coronary artery disease (CAD) and periodontitis. We aimed to identify further shared genetic risk factors to better understand conjoint disease mechanisms. Methods and Results-In-depth genotyping of 46 published CAD risk loci of genome-wide significance in the worldwide largest case-control sample of the severe early-onset phenotype aggressive periodontitis (AgP) with the Illumina Immunochip (600 German AgP cases, 1448 controls) and the Affymetrix 500K array set (283 German AgP cases and 972 controls) highlighted ANRIL as the major risk gene and revealed further associations with AgP for the gene PLASMINOGEN (PLG; rs4252120: P=5.9x10(-5); odds ratio, 1.27; 95% confidence interval, 1.3-1.4 [adjusted for smoking and sex]; 818 cases; 5309 controls). Subsequent combined analyses of several genome-wide data sets of CAD and AgP suggested TGFBRAP1 to be associated with AgP (rs2679895: P=0.0016; odds ratio, 1.27 [95% confidence interval, 1.1-1.5]; 703 cases; 2.143 controls) and CAD (P=0.0003; odds ratio, 0.84 [95% confidence interval, 0.8-0.9]; n=4117 cases; 5824 controls). The study further provides evidence that in addition to PLG, the currently known shared susceptibility loci of CAD and periodontitis, ANRIL and CAMTA1/VAMP3, are subjected to transforming growth factor-beta regulation. Conclusions-PLG is the third replicated shared genetic risk factor of atherosclerosis and periodontitis. All known shared risk genes of CAD and periodontitis are members of transforming growth factor-beta signaling.WoSScopu

Chronic coronary syndromes without standard modifiable cardiovascular risk factors and outcomes: the CLARIFY registry

Background and Aims: It has been reported that patients without standard modifiable cardiovascular (CV) risk factors (SMuRFs—diabetes, dyslipidaemia, hypertension, and smoking) presenting with first myocardial infarction (MI), especially women, have a higher in-hospital mortality than patients with risk factors, and possibly a lower long-term risk provided they survive the post-infarct period. This study aims to explore the long-term outcomes of SMuRF-less patients with stable coronary artery disease (CAD). Methods: CLARIFY is an observational cohort of 32 703 outpatients with stable CAD enrolled between 2009 and 2010 in 45 countries. The baseline characteristics and clinical outcomes of patients with and without SMuRFs were compared. The primary outcome was a composite of 5-year CV death or non-fatal MI. Secondary outcomes were 5-year all-cause mortality and major adverse cardiovascular events (MACE—CV death, non-fatal MI, or non-fatal stroke). Results: Among 22 132 patients with complete risk factor and outcome information, 977 (4.4%) were SMuRF-less. Age, sex, and time since CAD diagnosis were similar across groups. SMuRF-less patients had a lower 5-year rate of CV death or non-fatal MI (5.43% [95% CI 4.08–7.19] vs. 7.68% [95% CI 7.30–8.08], P = 0.012), all-cause mortality, and MACE. Similar results were found after adjustments. Clinical event rates increased steadily with the number of SMuRFs. The benefit of SMuRF-less status was particularly pronounced in women. Conclusions: SMuRF-less patients with stable CAD have a substantial but significantly lower 5-year rate of CV death or non-fatal MI than patients with risk factors. The risk of CV outcomes increases steadily with the number of risk factors