Nutrition Screening in the Pediatric Intensive Care Unit: Evaluation of an Electronic Medical Record-Based Tool.

Hospitalized, critically ill children are at increased risk of developing malnutrition. While several pediatric nutrition screening tools exist, none have been validated in the pediatric intensive care units (PICU). The Children's Wisconsin Nutrition Screening Tool (CWNST) is a unique nutrition screening tool that includes the Pediatric Nutrition Screening Tool (PNST) and predictive elements from the electronic medical record and was found to be more sensitive than the PNST in acute care units. The aim of this study was to assess the performance of the tool in detecting possible malnutrition in critically ill children. The data analysis, including the results of the current nutrition screening, diagnosis, and nutrition status was performed on all patients admitted to PICUs at Children's Wisconsin in 2019. All 250 patients with ≥1 nutrition assessment by a dietitian were included. The screening elements that were predictive of malnutrition included parenteral nutrition, positive PNST, and BMI-for-age/weight-for-length z-score. The current screen had a sensitivity of 0.985, specificity of 0.06, positive predictive value (PPV) of 0.249, and negative predictive value of 0.929 compared to the PNST alone which had a sensitivity of 0.1, specificity of 0.981, PPV of 0.658, and NPV of 0.749. However, of the 250 included patients, 97.2% (243) had a positive nutrition screen. The CWNST can be easily applied through EMRs and predicts the nutrition risk in PICU patients but needs further improvement to improve specificity.

Histogram analysis of diffusion kurtosis imaging of deep brain nuclei in Parkinson's disease with different motor subtypes.

AIM: To evaluate the diagnostic and differential efficacy of diffusion kurtosis imaging (DKI) histogram analysis for different motor subtypes of Parkinson's disease (PD). MATERIALS AND METHODS: Seventy PD patients including 40 with postural instability and gait disorder (PIGD) and 30 with tremor-dominant (TD) and 36 healthy controls (HC) were enrolled prospectively and underwent MRI examinations. The regions of interest (ROI) in the deep brain nuclei were delineated and features were extracted on the map of mean kurtosis (MK), axial kurtosis (Ka), and radial kurtosis (Kr), respectively. The differences in histogram features between PD patients and HC and between patients with PIGD and TD were compared. The areas under the curve (AUCs) were calculated to evaluate the diagnostic efficacy of all histogram features. The correlations between histogram features and clinical indicators were evaluated. RESULTS: Some DKI histogram features were significantly different between PD patients and HC, and also different between patients with PIGD and TD (all p<0.05). MK of the substantia nigra pars reticulate (SNprkurtosis), Ka of the substantia nigra pars compacta (SNpc) 50 percentile (SNpcP50), and Kr of SNpc 90th percentile showed the highest AUC for distinguishing patients with PIGD from HC. MK-SNpc 10th percentile, Ka-SNpc 25th percentile, and Kr of the head of the caudate nucleus (CN) 90th percentile had the highest AUC for distinguishing patients with TD from HC. MK of the putamen 10th percentile combined with Ka of the bilateral red nucleus RNkurtosis yielded the highest diagnostic performance with an AUC of 0.762 for distinguishing patients with PIGD from TD. Certain DKI histogram features were correlated with Hoehn-Yahr (H&Y) stage, Mini Mental State Examination (MMSE) score, tremor score, and PIGD score (all p<0.05). CONCLUSION: DKI histogram analysis was useful to diagnose and discriminate different motor subtypes of PD. Certain DKI histogram features correlated with clinical indicators.

Evaluation of an electronic medical record-based Paediatric Nutrition Screening Tool.

BACKGROUND: Nutrition screening is recommended to identify children at risk for malnutrition. A unique screening tool was developed based on American Society for Parenteral and Enteral Nutrition (ASPEN) recommendations and embedded in the electronic medical record to assess for nutrition risk. METHODS: The components of the tool included the Paediatric Nutrition Screening Tool (PNST) and other elements recommended by ASPEN. To evaluate the screening tool, retrospective data were analysed on all patients admitted to acute care units of Children's Wisconsin in 2019. Data collected included nutrition screen results, diagnosis and nutrition status. All patients who received at least one full nutrition assessment by a registered dietitian (RD) were included in analysis. RESULTS: One thousand five hundred seventy-five patients were included in analysis. The following screen elements were significantly associated with a diagnosis of malnutrition: any positive screen (p < 0.001), >2 food allergies (p = 0.009), intubation (p < 0.001), parenteral nutrition (p = 0.005), RD-identified risk (p < 0.001), positive risk per the PNST (p < 0.001), BMI-for-age or weight-for-length z-score (p < 0.001), intake <50% for 3 days (p = 0.012) and NPO > 3 days (p = 0.009). The current screen had a sensitivity of 93.9%, specificity of 20.3%, positive predictive value (PPV) of 30.9% and negative predictive value (NPV) of 89.8%. This is compared with the PNST which had a sensitivity of 32%, specificity of 94.2%, PPV of 71% and NPV of 75.8% in this study population. CONCLUSION: This unique screening tool is useful for predicting nutrition risk and has a greater sensitivity than the PNST alone.

Novel Pediatric Height Outlier Detection Methodology for Electronic Health Records via Machine Learning With Monotonic Bayesian Additive Regression Trees.

OBJECTIVE: To create a new methodology that has a single simple rule to identify height outliers in the electronic health records (EHR) of children. METHODS: We constructed 2 independent cohorts of children 2 to 8 years old to train and validate a model predicting heights from age, gender, race and weight with monotonic Bayesian additive regression trees. The training cohort consisted of 1376 children where outliers were unknown. The testing cohort consisted of 318 patients that were manually reviewed retrospectively to identify height outliers. RESULTS: The amount of variation explained in height values by our model, R2 , was 82.2% and 75.3% in the training and testing cohorts, respectively. The discriminatory ability to assess height outliers in the testing cohort as assessed by the area under the receiver operating characteristic curve was excellent, 0.841. Based on a relatively aggressive cutoff of 0.075, the outlier sensitivity is 0.713, the specificity 0.793; the positive predictive value 0.615 and the negative predictive value is 0.856. CONCLUSIONS: We have developed a new reliable, largely automated, outlier detection method which is applicable to the identification of height outliers in the pediatric EHR. This methodology can be applied to assess the veracity of height measurements ensuring reliable indices of body proportionality such as body mass index.

Gadolinium deposition in the brain is related to various contrast agents: a matched case-control study.

AIM: To assess the relationship between gadolinium deposition in the brain and various gadolinium-based contrast agents (GBCAs) and to explore confounding variables. METHODS: The study group included 87 patients with multiple enhanced brain magnetic resonance imaging (MRI) examinations of which 48 patients were in the linear GBCA group (33 patients in gadopentetate dimeglumine group and 15 patients in gadobenate dimeglumine group) and 39 patients in the macrocyclic GBCA group (22 patients in gadobutrol group and 17 patients in gadoterate meglumine group). The control group included 87 normal participants who were matched regarding age, sex, MRI machine and imaging sequences to the study cohort. T1 signal intensity (SI) ratios of the dentate nucleus to the pons (DN/pons) and of the globus pallidus to the frontal white matter (GP/FWM) in both groups were calculated and compared. The relationships between SI ratios and confounding variables were analysed. RESULTS: Significant differences were detected between two linear GBCA groups and control groups in T1 SI ratios of the DN/pons and GP/FWM (all p<0.001). There were no differences for two the macrocyclic GBCA groups compared with matching control groups (all p>0.05). T1 SI ratios of the linear GBCA group were significantly higher than those of the macrocyclic GBCA group (p<0.001). In the linear GBCA group, the T1 SI ratios of the DN/pons correlated moderately positively with the number of GBCA administrations (r=0.643, p<0.001), and MRI machine and sequence used. CONCLUSIONS: Increased T1 SI could be observed after repeated administrations of linear GBCA. T1 SI of the DN correlated with the number of linear GBCA administrations, and detection might be affected by MRI machine and sequence.

LHX6 inhibits the proliferation, invasion and migration of breast cancer cells by modulating the PI3K/Akt/mTOR signaling pathway.

OBJECTIVE: LIM homeobox domain 6 (LHX6) is emerging as a critical regulator in carcinogenesis and tumor progression. The previous study has reported the expression and function of LHX6 in breast cancer (BC). However, its mechanism underlying BC metastasis remains largely unclear. This study aimed to investigate the related mechanisms of the tumor-suppressive role of LHX6 in BC. PATIENTS AND METHODS: Quantitative Real-time PCR (qRT-PCR) and Western blotting were used to determine LHX6 mRNA levels and protein expressions in BC tissues and cell lines. LHX6 protein expression was also analyzed in BC tissues and matched normal breast tissues using immunohistochemistry (IHC). The biologic functions of LHX6 in BC were explored by CCK-8 assay, colony formation assay, and transwell assays in vitro. Finally, we investigated the effect of LHX6 up-regulation on PI3K/AKT/mTOR pathway by Western blot. RESULTS: Our results showed that LHX6 was lowly expressed at the mRNA and protein level in BC cancer tissues and cell lines. Ectopic expression of LHX6 in MDA-MB-231 and T-47D suppressed cell growth, migration, and invasion. Mechanistically, our further investigations revealed that the upregulation of LHX6 inhibited the activation of the PI3K/Akt/mTOR signaling pathway. CONCLUSIONS: We firstly provided evidence that LHX6 exerted its anti-tumor function on BC via suppressing activation of the PI3K/Akt/mTOR signaling, which eventually inhibited the progression of BC.

Multiscale Relaxation Dynamics in Ultrathin Metallic Glass-Forming Films.

The density layering phenomenon originating from a free surface gives rise to the layerlike dynamics and stress heterogeneity in ultrathin Cu-Zr glassy films, which facilitates the occurrence of multistep relaxations in the timescale of computer simulations. Taking advantage of this condition, we trace the relaxation decoupling and evolution with temperature simply via the intermediate scattering function. We show that the ß relaxation hierarchically follows fast and slow modes in films, and there is a ß-relaxation transition as the film is cooled close to the glass transition. We provide the direct observation of particle motions responsible for the ß relaxation and reveal the dominant mechanism varying from the thermal activated to the cooperative jumps across the transition.

Anisotropic stress inhibits crystallization in Cu-Zr glass-forming liquids.

Liquids attain a metastable state without crystallizing by cooling rapidly to a given temperature below the melting point. With increasing supercooling, the nucleation rate would show an increase based on the prediction of the classical nucleation theory. It is generally thought that the nucleation rate will reach the maximum upon approaching the glass transition temperature, Tg, for glass-forming liquids. We report that there exists a supercooled region above Tg in which the crystallization has actually been severely suppressed. Our molecular dynamics simulations show that the growth of embryos in the supercooled Cu60Zr40 melt is subjected to a strong anisotropic stress associated with the dynamic heterogeneity. Its long-range effect drives the embryo to grow into a ramified morphology so that the interface energy dominates over the embryo growth, leading to the suppression of nucleation.

Effects of hTERT antisense oligodeoxynucleotide on cell apoptosis and expression of hTERT and bcl-2 mRNA in keloid fibroblasts.

OBJECTIVE: This study was purposed to investigate the effects of hTERT antisense oligodeoxynucleotide (ASODN) on cell apoptosis and expression of hTERT and bcl-2 mRNA in keloid fibroblasts and to explore its anti-keloid effect. MATERIALS AND METHODS: Primary cultures of dermal fibroblasts derived from 12 keloid samples were established, strains of fibroblasts at passages 3 to 4 were used in this study. After treated by hTERT ASODN the proliferation of the fibroblasts was measured by cell count and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay method, the apoptosis was analyzed by flow cytometry (FCM), and the expression of hTERT and bcl-2 mRNA were observed by semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). The data was analyzed by statistical software (SPSS11.5). RESULTS: The results showed that after sealing hTERT gene with ASODN for 72 h, the fibroblasts growth was repressed and the ability of proliferation decreased as the fibroblasts were treated with 1.0 mol/L ASODN for 72 h, the fibroblasts apoptosis was induced and the expression of hTERT and bcl-2 mRNA was lower than that of controlled group. The result was significantly different between control group and treatment group and was related to the treatment time of ASODN (p<0.01), but the difference was no significant when compared 1.0 µmol/L SODN group with untreated group (p>0.05). CONCLUSIONS: As a negative modutory factor, hTERT-ASODN can suppress growth and proliferation of keloid fibroblasts. Decreasing the telomerase activity of keloid fibroblasts may be one of the most important mechanisms. That hTERT-ASODN inhibited telomerase activity in keloid fibroblasts is an important pathway that may play a key role in the anti- keloid therapy.

[Hydroxyfasudi attenuates lipopolysaccharide induced endothelial dysfunction via suppressing the expression of Rho-associated coiled-coil protein kinase 1, connexin 43 and caveolin 1].

Objective: To investigate the effect and mechanism of hydroxyfasudi (HF), a specific Rho kinase inhibitor, on lipopolysaccharide(LPS)induced endothelial dysfunction. Methods: A total of 24 male Sprague Dawley rats were randomly divided into control group(n=6), HF group(n=6), LPS group(n=6) and LPS + HF group(n=6) with random number table method. There was no special treatment in control group. HF (30 mg/kg) was injected intraperitoneally in HF group. LPS (1 mg/kg) were injected intravenously in LPS group. In LPS+ HF group, HF (30 mg/kg) was injected intraperitoneally, followed by intravenous LPS injection (1 mg/kg) 30 minutes later. All rats were sacrificed after 8 hours, and aortic tissue was extracted. RT-PCR was performed to detect mRNA levels of Rho-associated coiled-coil protein kinase (ROCK)1, connexin (Cx)43 and caveolin (Cav)1. The protein levers of ROCK1, Cx43 and Cav-1 were assessed by Western blot and immunohistochemical staining respectively. Results: (1) RT-PCR experiments showed that mRNA levels of ROCK1(2.67±0.03 vs. 1.00±0.04), Cx43(1.73±0.03 vs. 1.00±0.08), and Cav1(1.85±0.04 vs. 1.0±0.03) in LPS group were significantly higher than in control group(all P<0.05). mRNA levels of ROCK1(0.38±0.02), Cx43(0.58±0.02), and Cav1(0.27±0.01) in LPS + HF group were significantly lower than in LPS group(all P<0.05). (2)Western blot analysis showed that protein levels of ROCK1(3.46±0.82 vs. 2.19±0.56), Cx43(0.33±0.09 vs.0.11±0.06), and Cav1(3.45±0.74 vs. 2.25±0.91) in LPS group were significantly higher than in control group(all P<0.05). Protein levels of ROCK1(1.09±0.52), Cx43(0.01±0.06), and Cav1(2.06±0.40) in LPS + HF group were significantly lower than in LPS group(all P<0.05). (3) Immunohistochemical staining showed that protein levels of ROCK1(84.1±0.953.7±2.9), Cx43(99.1±2.1 vs. 46.2±0.8), and Cav1(167.0±6.4 vs. 84.9±1.0) in LPS group were significantly higher than in control group(all P<0.05). Protein levels of ROCK1(30.4±0.6), Cx43(21.4±1.3), and Cav1(55.8±2.8) in LPS + HF group were significantly lower than in LPS group(all P<0.05). Conclusion: HF attenuates LPS induced endothelial dysfunction probably via suppressing the expression of ROCK1, Cx43 and Cav1.

[The clinical characteristics of stroke in young patients with cardiac myxoma].

Objective: To investigate the clinical characteristics of stroke in young patients with cardiac myxoma. Methods: Medical records of young patients (aged between 18-44 years) diagnosed with cardiac myxoma in Beijing Anzhen Hospital affiliated to Capital Medical University from January 2005 to March 2016 were retrospective reviewed. Results: A total of 117 cases were included (85 female and 32 male)with the average age (36±7)years old. Most myxomas (83.8%) were located in the left atrium, 7.7% were in the right atrium, 3.5% were in the both atriums, 2.6% were in the left ventricle, and a few were in the left atrium plus left ventricle and in the right ventricle. Of all the patients, 24 (20.5%) (16 women and 8 men) were complicated with cerebral infarction. Among them, 3 patients were with lower extremity arterial embolisms. Two patients were with cerebral hemorrhage. The cerebral infarction mainly involved in the distribution area of the internal carotid artery. Infarctions involving 2 or more cerebral vessels were found in 4 cases. Most subjects (58.3%) manifested with hemiplegia, and some (18.2%) with syncope. The proportion of the left atrial myxoma in patients with cerebral infarction (100.0%) was significantly higher than those in patients without cerebral infarction (85.1%, P=0.044). Subjects with tumor diameter less than 3 cm were more frequently complicated with cerebral infarction (37.5% vs 13.8%, P= 0.009). A logistic analysis showed that the odds ratio of myxoma with tumor diameter less than 3 cm for cerebral infarction was 3.750(95%CI 1.343-10.470). Conclusions: Cardiac myxoma is more common in young women, and often complicated with cerebral infarction. The infarctions are mainly distributed in internal carotid artery system, and some are involved in multiple vascular systems. The incidence of stroke is associated with the position of the myxoma. Smail-size myxoma cannot be ignored for its risk of stroke.

Novel polymeric nanoparticles targeting the lipopolysaccharides of Pseudomonas aeruginosa.

Considering outburst of various infectious diseases globally, nanoparticle assisted targeted drug delivery has emerged as a promising strategy that can enhance the therapeutic efficacy and minimize the undesirable side effects of an antimicrobial agents. Molecular imprinting is a newly developed strategy that can synthesize a drug carrier with highly stable ligand-like 'cavity', may serve as a new platform of ligand-free targeted drug delivery systems. In this study, we use the amphiphilic lipopolysaccharides, derived from Pseudomonas aeruginosa as imprinting template and obtained an evenly distributed sub-40 nm polymeric nanoparticles by using inverse emulsion method. These molecularly imprinted nanoparticles (MIPNPs) showed specific binding to the lipopolysaccharide as determined by fluorescence polarization and microscale thermophoresis. MIPNPs showed selective recognition of target bacteria as detected by flow cytometry. Additionally, MIPNPs exhibited the in vivo targeting capabilities in both the keratitis model and meningitis model. Moreover, the photosensitizer methylene blue-loaded MIPNPs presented significantly strong inhibition of bacterial Growth, compared to non-imprinted controls for in vitro model of the photodynamic therapy. Our study shows an attempt to design a magic bullet by molecular imprinting that may provide a novel approach to generate synthetic carrier for targeting pathogen and treatment for a variety of infectious human diseases.

Familial hypercholesterolaemia with tuberous and tendinous xanthomas: case report and mutation analysis.

Xanthomas are important clinical manifestations of disordered lipid metabolism, which are mostly found in patients with familial hypercholesterolaemia (FH), an inherited disorder that is predominantly caused by mutations in the low-density lipoprotein receptor gene (LDLR). Tuberous and tendinous xanthomas with wide distribution and large size are rare; however, they may indicate the severity of FH, and tend to be found in homozygous FH. In this study, we investigated the clinical and genetic aspects of a young patient with FH presenting with multiple large masses in various locations. The lesions on the elbows and buttocks were locally excised and subsequently confirmed by biopsy to be xanthomas. Genetic analysis further confirmed that the patient was compound heterozygous for two mutations in both alleles of the LDLR gene. This rare case of compound heterozygous FH presenting with multiple large and widely distributed xanthomas provides a better understanding of FH and xanthomas.

Hydrogen sulfide accelerates cell cycle progression in oral squamous cell carcinoma cell lines.

OBJECTIVE: To investigate the cell cycle regulator role of the third gaseous transmitter hydrogen sulfide (H2 S) in three oral SCC cell lines by using NaHS, a donor of H2 S. METHODS: The synchronized oral squamous cell carcinoma cell lines (Cal27, GNM, and WSU-HN6) were treated with different concentrations of NaHS and then subjected to cell proliferation, cell cycle, and Western blot analyses. RESULTS: The CCK-8 assay results showed that the exogenously administered H2 S donor, NaHS, induced CAL-27, and GNM cell proliferation in a concentration-dependent manner, and the cell cycle analysis indicated that NaHS accelerated cell cycle progression of the synchronized CAL-27, GNM, and WSU-HN6 cells. Western blot analysis revealed that the cell cycle regulatory genes RPA70 and RB1 were significantly down-regulated and that proliferating cell nuclear antigen (PCNA) and CDK4 were markedly up-regulated by NaHS at specific time points in the cell cycle. In addition, our results indicated that the phosphorylation of Akt and Erk1/2 was involved in exogenous H2 S-induced oral SCC cell proliferation. CONCLUSIONS: H2 S is a potential pro-proliferative factor of human oral SCC cells that accelerates the progression of the SCC cell cycle; thus, H2 S plays a deleterious role in oral SCC cancer development.

Infection of Plasmodiophora brassicae in Chinese cabbage.

Brassica crops infected by Plasmodiophora brassicae can produce root galls (clubroots) and be prevented from growing normally. To understand the series of changes that occur in the host root during root gall production, the resistance character of 21 Chinese cabbage lines were identified and then resistant and susceptible lines were used for infection observation. Hydroponic technology system was used for plants growing, and the infection process of P. brassicae in the roots of resistant and susceptible Chinese cabbage was examined based on morphology and microscopic characteristics using micoscope. In susceptible Chinese cabbage, the root hair infection stage occurred over approximately 7 days after inoculation, the cortical infection happened over approximatly 14 days after inoculation, and clubroots formed in approximately 30 days after inoculation. However, in resistant Chinese cabbage, the pathogen could be prevented and maintained in the root hair infection stage. This research provides a foundation for the subsequent studies of cabbage resistance of P. brassicae.

Construction, expression, and characterization of recombinant hirudin in Escherichia coli.

The mutant gene of HV2-K47 was obtained by polymerase chain reaction-directed mutagenesis and expressed in Escherichia coli. Many elements that could affect its expression level were compared. The product was purified to homogeneity via three chromatographic steps--ion exchange, gel filtration, and reverse phase chromatography--on the AKTA Explorer System. The anti-thrombin activity of HV2-K47 is much higher than that of recombinant HV2. Some properties and expression conditions were investigated systematically, which would be useful for further studies of hirudin and other small proteins.

[Study on the specificity of complement C5 for the postmortem diagnosis of myocardial infarction].

In order to explore the specificity of complement C5 in the postmortem diagnosis of myocardial infarction, changes of C5 staining in normal, infarcted and other non-infarcted myocardia with direct or indirect myocardial injuries (myocarditis, mechanical asphyxia, electrocution, hemorrhagic shock, cardiac contusion and organophosphate poisoning) were studied with immunohistochemistry and image analysis. The results showed that positive C5 staining could be observed in groups of myocardial infarction and myocarditis, but not in groups of mechanical asphyxia, electrocution, hemorrhagic shock, cardiac contusion, and organophosphate poisoning. It is indicated that positive reaction of C5 could only be affected by myocarditis, which means that it was more specific for the diagnosis of myocardial infarction.

Re-design of Smith predictor systems for performance enhancement

In this paper, a new design for Smith Predictor systems is presented. It employs a deliberately mismatched model to enhance performance over a perfectly matched system while using a simple primary controller. The design methodology is formulated in the frequency domain as an optimization problem and it turns out that an approximate solution can be obtained using the linear least squares method. To improve the performance further, a modified Smith Predictor system structure is also proposed, and it reduces the system into one involving second-order dynamics for the primary controller design. Illustrative simulation of several typical processes are included.

[Changes of leukocyte rheologic characteristics and cell adhesion molecules in patients with multiple organ failure after severe trauma].

OBJECTIVE: To explore the changes of leukocyte rheologic characteristics and of cell adhesion molecule in patients with multiple organ failure (MOF) after severe trauma. METHODS: By using the erythrocyte deformability apparatus, platelet and thrombus adhesion dual-purpose apparatus and enzyme-linked immunosorbent assay (ELISA), We measured the leukocyte deformability (LD), leukocyte adhesion function (LAF), leukocyte CD18 expression, soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule (sVCAM-1) concentration in 36 MOF patients, 31 trauma patients, and 35 to be controls. RESULTS: The leukocyte filtration index (LFI), leukocyte adhesion rate (LAR), leukocyte CD18 expression, and sICAM-1 and sVCAM-1 concentration were significantly higher in MOF patients than in controls and trauma patients (F = 68.45 - 116.20, q = 12.161 - 21.374, P < 0.00), and the changes of these indicators in MOF deaths were more obvious than those in MOF survivors (t = 6.920 - 11. 665, P < 0.00). The LFI and LAR in MOF patients were positively related to leukocyte CD18 expression, sICAM-1, and sVCAM-1 concentration (r = 0.691 - 0.844, P < 0.001); LFI was positively related to LAR (r = 0.711, P < 0.001). CONCLUSION: The abnormalities of leukocyte rheologic characteristics and CAMs might be closely related to the occurrence of MOF and the severity of pathologic changes.

Presenilin mutations associated with Alzheimer disease cause defective intracellular trafficking of beta-catenin, a component of the presenilin protein complex.

The presenilin proteins are components of high-molecular-weight protein complexes in the endoplasmic reticulum and Golgi apparatus that also contain beta-catenin. We report here that presenilin mutations associated with familial Alzheimer disease (but not the non-pathogenic Glu318Gly polymorphism) alter the intracellular trafficking of beta-catenin after activation of the Wnt/beta-catenin signal transduction pathway. As with their effect on betaAPP processing, the effect of PS1 mutations on trafficking of beta-catenin arises from a dominant 'gain of aberrant function' activity. These results indicate that mistrafficking of selected presenilin ligands is a candidate mechanism for the genesis of Alzheimer disease associated with presenilin mutations, and that dysfunction in the presenilin-beta-catenin protein complexes is central to this process.