[Mendelian randomization and its application in periodontitis].

Mendelian randomization is a causal inference method using genetic variations as instrumental variables, which skillfully takes advantages of the distributive randomness and timing priority of genetic variation, effectively avoiding confounding biases and reverse causalities in traditional observational researches. It has become a research hotspot in recent years. As a complex inflammatory disease, periodontitis is associated with many factors, but the cognitions about these associations are mostly based on traditional observational studies, lacking strong evidences to infer the causality. In order to bring up new research ideas in the periodontal field, this article mainly reviewed Mendelian randomization and its research progress in periodontitis.

Relevance of electrical current distribution to the forced flow and grain refinement in solidified Al-Si hypoeutectic alloy.

Significant grain refinement in cast metals can be achieved through the application of electric currents during the solidification process. The present paper investigates the distribution of electric currents on the grain size of solidified Al-7wt.%Si alloy under the application of electric current with constant parameters flowing through two parallel electrodes into the melt within a cylindrical mould. The distribution of electric current was controlled by applying an electrical insulation material coating, boron nitride (NB), to the sidewall of the electrodes. Experimental results showed that the employment of these insulated electrodes can reduce grain size in comparison with the reference case of electrodes without BN coating. Flow measurements were performed in Ga-20wt.%In-12wt.%Sn liquid metal. Higher intensity forced flow occurred when the sidewall of the electrodes was insulated. In order to understand the underlying mechanism behind the stronger forced flow, corresponding numerical simulations were performed to reveal the distributions of the electric current, magnetic field, Lorentz force, and the resultant forced flow. The results achieved indicate that the mechanism of grain refinement driven by electric current is dendrite fragmentation induced by forced flow. In addition, a novel approach to enhance the grain refinement without additional input of current energy was developed.

Acute carbon monoxide poisoning: MR imaging findings with clinical correlation.

PURPOSE: To assess the magnetic resonance imaging (MRI) findings, including diffusion-weighted imaging (DWI) in patients with acute carbon monoxide (CO) poisoning and correlate MRI findings with carboxyhemoglobin levels. MATERIALS AND METHODS: The MRI examinations and medical records of seven men with a mean age of 43±16.0years (SD) (range: 25-63 years) with acute CO poisoning were reviewed. MRI examinations were analyzed with respect to lesion location, imaging presentation on T1- and T2-weighted images, and diffusion characteristics on DWI and apparent diffusion coefficient (ADC) maps. We also evaluated clinical features and laboratory findings including the presenting symptoms and signs, carboxyhemoglobin level, and treatment. RESULTS: All seven patients presented with mental status change. The level of carboxyhemoglobin ranged between 8.3% and 34.8% (normal<1.5%). All seven patients (7/7, 100%) showed restricted diffusion of the lesions on ADC maps and bilateral involvement of globus pallidus. The mean ratios of ADC values was 0.63±0.15 (SD) (range: 0.46-0.92) on bilateral globi pallidi. Cerebral cortex, cerebral white matter, cerebellum, hippocampus, amygdala, splenium of corpus callosum, midbrain and insula were also involved. CONCLUSION: Bilateral globi pallidi with restricted diffusion may be a characteristic MRI feature in patients with acute CO poisoning. However, the relationship was not certain between the carboxyhemoglobin levels and the variety or severity of MRI findings.

Uremic Encephalopathy: MR Imaging Findings and Clinical Correlation.

BACKGROUND AND PURPOSE: Uremic encephalopathy is a metabolic disorder in patients with renal failure. The purpose of this study was to describe the MR imaging findings of uremic encephalopathy. MATERIALS AND METHODS: This study retrospectively reviewed MR imaging findings in 10 patients with clinically proved uremic encephalopathy between May 2005 and December 2014. Parameters evaluated were lesion location and appearance; MR signal intensity of the lesions on T1WI, T2WI, and T2 fluid-attenuated inversion recovery images; the presence or absence of restricted diffusion on diffusion-weighted images and apparent diffusion coefficient maps; and the reversibility of documented signal-intensity abnormalities on follow-up MR imaging. RESULTS: MR imaging abnormalities accompanying marked elevation of serum creatinine (range, 4.3-11.7 mg/dL) were evident in the 10 patients. Nine patients had a history of chronic renal failure with expansile bilateral basal ganglia lesions, and 1 patient with acute renal failure had reversible largely cortical lesions. Two of 6 patients with available arterial blood gas results had metabolic acidosis. All basal ganglia lesions showed expansile high signal intensity (lentiform fork sign) on T2WI. Varied levels of restricted diffusion and a range of signal intensities on DWI were evident and were not correlated with serum Cr levels. All cortical lesions demonstrated high signal intensity on T2WI. Four patients with follow-up MR imaging after hemodialysis showed complete resolution of all lesions. CONCLUSIONS: The lentiform fork sign is reliable in the early diagnosis of uremic encephalopathy, regardless of the presence of metabolic acidosis. Cytotoxic edema and/or vasogenic edema on DWI/ADC maps may be associated with uremic encephalopathy.

Diffusion MR imaging of hypoglycemic encephalopathy.

BACKGROUND AND PURPOSE: MR imaging features of HE have not been fully established. The purpose of this study was to determine the topographic distribution and DWI findings of HE. MATERIALS AND METHODS: We retrospectively evaluated HE MR imaging (n = 11). The topographic distribution of the lesions was evaluated on routine MR imaging, and DWI SI and ADC values were assessed. The ADC value of involved lesions was compared with the noninvolved subcortical WM area by use of the paired t test. RESULTS: MR images demonstrated bilateral diffusion-restrictive lesions in the posterior limb of the IC (n = 6), cerebral cortex (n = 8), CR (n = 7), CS (n = 9), hippocampus (n = 4), and BG (n = 1). The mean ADC value of lesions was 448.82 +/- 92.34 x 10(-6) mm(2)/s compared with the mean ADC value of noninvolved lesions (837.72 +/- 62.14 x 10(-6) mm(2)/s); this difference was statistically significant (P < .000). The lesions showed complete resolution on follow-up DWI for 6 patients. Three patients with cortical involvement of > or = 2 lobes showed partial recovery or death, but most of the other patients with WM involvement or cortical involvement in only 1 lobe experienced complete recovery. CONCLUSIONS: The topographic localization of the lesions was the posterior limb of the IC, cerebral cortex, CR, CS, hippocampus, and BG. Most HE lesions probably correspond to areas of reversible cytotoxic edema as seen on DWI, which can predict the prognosis of HE according to the degree of lesion extent.

Symptomatic nerve root changes on contrast-enhanced MR imaging after surgery for lumbar disk herniation.

BACKGROUND AND PURPOSE: The significance of postoperative nerve root changes (enhancement, thickening, and displacement) is still a topic of debate. The purpose of this study was to evaluate the association between nerve root changes and residual or recurrent symptoms after lumbar surgery with contrast-enhanced MR imaging. MATERIALS AND METHODS: A total of 120 patients with 140 postoperative lumbar disk lesions causing residual or recurrent pain underwent contrast-enhanced MR imaging. The levels at which diskectomies had been performed were retrospectively evaluated for nerve root enhancement (NRE), thickening, and displacement. Association between nerve root changes and corresponding clinical presentations were statistically assessed. Nerve root changes in recurrent disk herniation (RDH) and postoperative epidural fibrosis (PEF) were also evaluated with clinical symptoms. RESULTS: Ninety-two (65.7%) of the 140 disks demonstrated NRE. Regarding the association with clinical symptoms, the sensitivity was 91.7%, the specificity was 73.2%, the positive predictive value (PPV) was 83.7%, and the negative predictive value was 85.4% (P = .000). Nerve root thickening and displacement were significantly associated with the clinical symptoms, especially when NRE was combined (PPV, 87.7% and 87.2%, respectively). When RDH was combined with all 3 nerve root changes, the PPV was increased up to 94.1%. However, in PEF, the association between nerve root changes and clinical symptoms was not significant unless all 3 nerve root changes were combined. CONCLUSIONS: In patients with residual or recurrent pain after surgery for lumbar disk herniation, nerve root changes on contrast-enhanced MR imaging were well associated with clinical symptoms, of which NRE was the most significant finding.

Emergency department experience of primary diffusion weighted magnetic resonance imaging for the patient with lacunar syndrome.

BACKGROUND: The purpose of this study was to evaluate the usefulness of a particular magnetic resonance imaging technique known as primary diffusion weighted imaging (DWI) for patients with lacunar syndrome in the emergency department (ED). METHODS: Patients with one of five classic lacunar syndromes underwent DWI as primary imaging modality. The DWI findings were classified into groups: (a) having a lesion with high signal intensity, (b) having a lesion with mixed signal intensity, and (c) unremarkable. The final clinical diagnoses were extracted from the patients' medical records, and used as a reference standard. RESULTS: Of 151 DWI images, 120 (79%) were interpreted as high signal lesions, 21 (14%) as mixed signal lesions, and 10 (7%) as unremarkable. All patients with high signal lesions or unremarkable findings were diagnosed with ischaemic stroke. The patients with mixed signal lesions were diagnosed with haemorrhagic stroke with an exception of one ischaemic stroke. CONCLUSION: Primary DWI is a feasible and useful neuroimaging tool for patients with lacunar syndrome in the ED.

C-reactive protein contributes to the hypercoagulable state in coronary artery disease.

OBJECTIVES: Elevated plasma C-reactive protein (CRP) levels predict coronary events, but it is unclear whether CRP plays a role in thrombosis associated with these events. We investigated tissue factor (TF) induction by CRP on peripheral blood mononuclear cells (PBMC) from patients with coronary disease. PATIENTS AND METHODS: PBMC from 35 patients with stable angina (SA) in study 1, 10 male patients with SA, 10 with unstable angina (UA) and 10 matched controls in study 2, and 25 patients with inflammatory disorders (ID) and 24 normal controls in study 3 were stimulated with CRP, interferon-gamma (IFN) or lipopolysaccharide (LPS), or their combination. PBMC from additional normal donors were also stimulated with CRP in adherent and non-adherent conditions, and TF activity, antigen and mRNA expression detected. RESULTS: CRP (5-25 microg mL(-1)) dose dependently induced more TF on PBMC from SA patients than 42 contemporary controls (P = 0.001, study 1). Compared with controls, patients with SA or UA had higher basal, and much higher CRP- or CRP/LPS-induced monocyte TF activity although serum CRP levels were similar (study 2). IFN induced monocyte TF activity in patients with angina, but not in controls. Basal or CRP-induced TF levels did not differ between controls and ID, even though ID patients had much higher serum CRP levels (study 3). CRP-induced monocyte TF activity correlated with serum CRP levels in controls (P = 0.005) and ID (P = 0.007) in study 3, but not in patients with angina (P =0.84) in study 2. CRP induced more TF activity, protein and mRNA under adherent than non-adherent conditions implying that it may mainly target macrophages in lymphocyte-rich lesions. CONCLUSIONS: Our results indicate that monocytes from patients with angina are preactivated and express TF but CRP is unlikely to be a major priming factor in vivo. IFN and CRP further increase TF levels that may contribute to the hypercoagulable state in coronary disease.

Expression of TRAIL, DR4, and DR5 in kidney and serum from patients receiving renal transplantation.

Renal transplantation is the best treatment of some end-stage renal diseases. Unfortunately, not every transplant is successful due to the rejection or dysfunction of the transplanted kidney. Many cytokines participate in rejection by inducing inflammation or apoptosis. In this study, the expressions of TRAIL, DR4, and DR5 in rejected renal tissue and of serum soluble TRAIL (sTRAIL) in patients with kidney rejection were investigated by immunohistochemical staining and sandwich enzyme-linked immunosorbent assay, respectively. The results showed that the expression of TRAIL, DR4 and DR5, and serum sTRAIL levels were markedly upregulated among renal transplant patients. Since both membrane and soluble forms of TRAIL can induce apoptosis of DR4/DR5-expressing cells via recruiting FADD and caspase 8, elevated TRAIL and its receptors may participate in renal graft rejection.

Regulation of a recombinant pea nuclear apyrase by calmodulin and casein kinase II.

A cDNA encoding a pea nuclear apyrase was previously cloned. Overexpressions of a full-length and a truncated cDNA have been successfully expressed in Escherichia coli BL21(DE3). The resulting fusion proteins, apyrase and the C-terminus (residues 315-453) of apyrase, were used for calmodulin (CaM) binding and phosphorylation studies. Fusion protein apyrase but not the C-terminus of apyrase can be recognized by polyclonal antibody pc480. This suggested that the motif recognized by pc480 was located in the N-terminal region of apyrase. The recombinant apyrase protein also showed an activity 70 times higher than that of endogenous apyrase using ATP as a substrate. The recombinant apyrase has a preference for ATP more than other nucleoside triphosphate substrates. CaM can bind to recombinant apyrase, but not to the C-terminus of apyrase. This implies that the CaM-binding domain must be in the first 315 amino acids of the N-terminal region of apyrase. We found that one segment from residue 293 to 308 was a good candidate for the CaM-binding domain. This segment 293 FNKCKNTIRKALKLNY 308 has a basic amphiphilic-helical structure, which shows the predominance of basic residues on one side and hydrophobic residues on the other when displayed on a helical wheel plot. Using the gel mobility shift binding assay, this synthetic peptide was shown to bind to CaM, indicating that it is the CaM-binding domain. Both recombinant apyrase and the C-terminus of apyrase can be phosphorylated by a recombinant human protein kinase CKII. Phosphorylation does not affect CaM binding to recombinant apyrase. However, CaM does inhibit CKII phosphorylation of recombinant apyrase and this inhibition can be blocked by 5 mM EGTA.

Heterotopic pancreas in the stomach: CT findings.

PURPOSE: To describe the computed tomographic (CT) findings of heterotopic pancreas in the stomach. MATERIALS AND METHODS: CT findings in 12 patients with heterotopic pancreas in the stomach were reviewed. Surgical resection (n = 11) or endoscopic excision (n = 1) was performed in cases of symptomatic heterotopic pancreas (n = 4), suspected submucosal tumors (n = 7), and gastric carcinoma (n = 1). Seven patients underwent helical CT with water as an oral contrast agent; five underwent nonhelical CT with water-soluble contrast material. RESULTS: Nine heterotopic pancreata were in the antrum and one each was in the body, fundus, and perigastric fat. Seven lesions were on the greater curvature aspect; five, on the lesser curvature aspect. Common CT findings were well-defined oval or round masses with smooth or serrated margins in the gastric antral wall. Four of the seven lesions in which helical CT was performed enhanced similarly to normal pancreas. Preoperatively, CT depicted 11 of the 12 lesions, but CT findings were interpreted correctly as heterotopic pancreas in only two; the remaining 10 were misinterpreted as other lesions. Atypical findings were cystic dilatation of heterotopic pancreatic duct in two, unusual location in the fundus or perigastric fat in two, and malignant transformation in one. CONCLUSION: CT findings of heterotopic pancreas in the stomach appear to be nonspecific for diagnosis, except for location.

MR imaging and histologic features of subinsular bright spots on T2-weighted MR images: Virchow-Robin spaces of the extreme capsule and insular cortex.

PURPOSE: To determine the cause and frequency of high-signal-intensity foci detected in the insular cortex and extreme capsule on thin-section, high-spatial-resolution, coronal, T2-weighted magnetic resonance (MR) images. MATERIALS AND METHODS: The authors assessed high-signal-intensity areas in the insular cortex and extreme capsule on coronal MR images obtained in 56 patients with seizure and five control subjects. Images were obtained with thin-section, high-spatial-resolution, T2-weighted, fast spin-echo; three-dimensional, spoiled gradient-recalled-echo; and fluid-attenuated inversion-recovery sequences. In two formalin-fixed brain specimens, MR imaging findings were correlated with gross anatomic and histologic findings. RESULTS: Subinsular bright spots were found in 53 of the 56 (95%) patients (96 of 112 [86%] hemispheres) and all five control subjects. The spots were elliptical in 30 patients, round in 14 patients, linear in 22 patients, and dotlike in seven patients and often had a featherlike configuration. The spots were isointense to cerebrospinal fluid on T2-weighted, fast SE images and were located in the anterior extreme capsule white matter and insular cortex. MR imaging of brain specimens revealed bilateral elliptical areas of high signal intensity that corresponded to small multiple cavities at gross anatomic inspection. At microscopic examination, these cavities were perivascular spaces of mostly arteriolar origin. CONCLUSION: High-signal-intensity subinsular foci at MR imaging are due to enlarged perivascular spaces. In most cases, these foci can be visualized on thin-section, high-spatial-resolution, coronal T2-weighted images; they should not be mistaken for pathologic conditions when they occur unilaterally.

Detection and characterization of hepatocellular carcinoma: value of dynamic CT during the arterial dominant phase with uniphasic contrast medium injection.

OBJECTIVE: Our goal was to assess the effect of dynamic CT during the arterial dominant phase with uniphasic injection of intravenous contrast material (5 ml/s) in the detection and characterization of hepatocellular carcinomas (HCCs). MATERIALS AND METHODS: Three-phase incremental dynamic CT was performed in 66 patients with 84 HCCs diagnosed by pathologic findings, characteristic angiographic findings, and clinical manifestations. One hundred fifty milliliters of nonionic contrast medium was administered intravenously by using a power injector at a flow rate of 5 ml/s for 30 s, and three-phase images were obtained at 20-45 s (arterial dominant phase), 55-80 s (portal venous phase), and 2-4 min (equilibrium phase) after the start of uniphasic intravenous injection. Three-phase images in 66 patients were compared and assessed for the detectability and enhancement pattern of the tumors. RESULTS: The arterial dominant phase images of dynamic CT showed a moderate to marked hyperattenuation in 73 (87%) of the 84 HCCs, isoattenuation in 6 (7%), and hypoattenuation in 5 (6%). The portal venous phase images showed hyperattenuation in 6 (7%), isoattenuation in 45 (54%), and hypoattenuation in 33 (39%). In the equilibrium phase, CT findings showed hypoattenuation in 67 (80%) and isoattenuation in 17 (20%). The detectability of HCCs in the arterial dominant, portal venous, and equilibrium phase was 93, 46, and 80%, respectively. The detectability of HCCs in the arterial dominant phase was significantly (p < 0.0001) superior to that in both the portal venous phase and the equilibrium phase. CONCLUSION: Dynamic CT during the arterial dominant phase with uniphasic injection of intravenous contrast medium (5 ml/s) is a useful method in the detection and characterization of HCCs.