Implementing single-item screening for drug use in a Veterans Health Administration outpatient setting.

BACKGROUND: Unhealthy drug use is a concern in many settings, including military and veteran populations. In 2013, the Veterans Health Administration (VHA) medical center in Bedford, Massachusetts, started requiring routine screening for unhealthy drug use in outpatient primary care and mental health settings, using a validated single question. METHODS: This study used descriptive and multivariable analyses of VHA electronic records for patients eligible for the screening program (N = 16,118). The study assessed first-year rates and predictors of screening and of positive screens, both for drug use and for unhealthy alcohol use, for which screening was already required. RESULTS: During the first year, 70% of patients were screened for unhealthy drug use and 84% were screened for unhealthy alcohol use. In multivariable analyses, screening for drug use was more likely for patients who had 8 or more days with VHA visits or were aged 40 or over. Patients with a prior drug use disorder diagnosis were much less likely to be screened. Three percent of patients screened for unhealthy drug use had a positive screen, and 14% of those screened for unhealthy alcohol use had a positive screen. Strong predictors of a positive drug use screen included a prior-year diagnosis of drug use disorder, any mental health clinic visits, younger age, or being unmarried. CONCLUSIONS: The drug screening initiative was relatively successful in its first-year implementation, having screened 70% of eligible subjects. However, it failed to screen many of those most likely to screen positive, thereby missing many opportunities to address unhealthy drug use. Future refinements should include better training clinicians in how to ask sensitive questions and how to address positive screens.

Inactivation of glycogen synthase kinase-3ß up-regulates ß-catenin and promotes chondrogenesis.

This study aimed to investigate whether inhibition of glycogen synthase kinase-3ß (GSK-3ß) could promote chondrocytes proliferation. The expression pattern of GSK-3ß was firstly determined by immunohistochemistry (IHC) in normal mouse. Tibias were then isolated and cultured for 6 days. The tibias were treated with dimethylsulfoxide (control) or GSK-3 inhibitor SB415286 (SB86). Length of tibias was measured until 6 days after treatment. These bones were either stained with alcian blue/alizarin red or analyzed by IHC. In addition, GSK-3ß and ß-catenin were analyzed by Western blot. Finally, cartilage-specific GSK-3ß deletion mice (KO) were generated. Efficiency of GSK-3ß deletion was determined through Western blot and IHC. After treated by inhibitor SB86, the overall length of growth plate was not changed. However, growth of tibia in SB86 group was increased by 31 %, the length of resting and proliferating was increased 13 % (P < 0.01), whereas the length of hypertrophic was decreased by 57 % (P < 0.01). Besides, the mineralized length was found to be significant longer than the control group (P < 0.05). In KO mice, growth plate and calvaria tissue both exhibit significant reduction of GSK-3ß (P < 0.05) whereas the lengths of tibias in KO were almost same compared with control mice. Finally, an increase amount of ß-catenin protein was observed in SB86 (P < 0.05). In addition, significantly increased ß-catenin was also found in the growth plate of KO mice (P < 0.05). Inhibition of GSK-3 could promote longitudinal growth of bone through increasing bone formation. Besides, the inactivation of GSK-3ß could lead to enhancing ß-catenin, therefore promote chondrocytes proliferation.

Pilot outcomes of a filmmaking intervention designed to enhance treatment entry and social reintegration of veterans.

Military personnel transitioning to civilian life have reported significant challenges in reintegrating into civilian culture. Filmmaking has been used as a therapeutic intervention to enhance the community reintegration of veterans, but there are no published quantitative data documenting its impact. The present study provides outcome data on 40 veterans who participated in the I Was There (IWT) filmmaking workshop. This 3-day (20-hr) group intervention involved veterans working in small teams with a film coach, making short films designed to communicate some aspect of their experience during or after military service, and then creating a screening event to show their films to community members. The sample consisted of community-dwelling veterans who reported at least some mental health symptoms and who were not engaged in mental health treatment for those symptoms. Targeted outcomes included engagement in mental health care, symptoms of posttraumatic stress disorder (PTSD) and depression, and reported perception of community interest in their experience as veterans. Fifty-six percent of participants entered treatment within 4 months of participation. Significant decreases were noted in symptoms of PTSD at 1-month follow-up but not at the 4-month follow-up, while changes in depression were not statistically significant. Participation was related to increased perception of community interest in veterans' experience, and increased interest among community members who viewed the films. These data provide initial support for the conclusion that the IWT film workshop is a potentially effective tool for treatment engagement and for community reintegration among veterans. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Preparation and Characterization of Narrow Size Distribution PMSQ Microspheres for High-Frequency Electronic Packaging.

Polymethylsilsesquioxane (PMSQ) has become a kind of widely studied filler used in the electronic circuit board substrates due to its organic-inorganic hybrid structure, low dielectric constant, and good thermal stability, among other factors. Herein, the PMSQ microspheres were prepared by a two-step acid-base-catalyzed sol-gel method; the influences of reaction conditions including the ratio of water/methyltrimethoxysilane (MTMS), reaction temperature, concentration of the catalyst, and stirring time were systematically investigated; and the optimized reaction condition was then obtained towards a narrow particle size distribution and good sphericity. The microstructure of PMSQ microspheres was analyzed by the infrared spectrum and X-ray diffraction (XRD), which indicated that the as-prepared PMSQ had a ladder-dominant structure. The thermogravimetric analysis (TGA) demonstrated an excellent thermal stability of as-prepared PMSQ microspheres. More specifically, the dielectric constants at high frequency (1~20 GHz) of as-prepared PMSQ microspheres were measured to be about 3.7, which turned out a lower dielectric constant compared to SiO2 powder (≈4.0). This study paves the way to further improve the performance of the electronic circuit board substrates for the application of high-frequency electronic packaging.

Referral to Treatment After Positive Screens for Unhealthy Drug Use in an Outpatient Veterans Administration Setting.

OBJECTIVES: To measure the rates and predictors of clinician recommendation for follow-up after a positive screen for unhealthy drug use, in a context of mandatory routine screening. To measure response to clinician recommendations and identification of new drug use diagnoses. METHODS: Data are from a Veterans Health Administration (VHA) medical center that introduced mandatory routine screening for unhealthy drug use in outpatient primary care and mental health settings, using a validated single question. This study analyzed VHA electronic health records data for patients who screened positive for unhealthy drug use (n = 570) and estimated logistic regression models to identify the predictors of receiving a recommendation for any follow-up and for specialty substance use disorder (SUD) treatment. Bivariate tests were used for other analyses. RESULTS: Among patients who screened positive for unhealthy drug use, 66% received no recommendation to return to primary care or another setting from the screening clinician. Further, among the 23% of patients who received a recommendation to visit specialty SUD treatment, only 25% completed the visit within 60 days. Six percent of all positive screens both received a referral to specialty SUD treatment and acted upon it. CONCLUSIONS: In the context of mandatory drug use screening using a single item, rates of clinician action and patient receipt of care appeared low. Improved follow-up will require health systems to provide more supports for clinicians and patients at each of the stages from positive screen to attending the follow-up appointment.

Analysis of influencing factors on soil Zn content using generalized additive model.

Soil zinc (Zn) plays a crucial role in plant growth, but excessive accumulation in the environment may lead to air, water and soil pollution. It is affected by various chemical, environmental and spatial factors. Therefore, it is important to identify the factors influencing Zn content in the landscape. The main motivation for this study is to determine the suitability of a generalized additive model (GAM) to describe change in soil Zn content due to influencing factors. A total of 1497 soil nutrient samples were collected in Fangshan District, Beijing, China. Organic matter (OM), available phosphorus (AP), available potassium (AK), alkali-hydrolyzed nitrogen (AHN) and slowly available potassium (SAK) are considered. The relationship between Zn, nutrients and geographic location (latitude & longitude) is investigated using the GAM. More precisely, the Akaike information criterion (AIC) is used to select influencing factors on Zn content and cross-validated to avoid overfitting of the multivariate model. The results show that Zn content reaches its maximum at latitude 39.8°N and longitude 115.9°E. Zinc content increases as AP increases to 150 mg/kg. When OM content is greater than 90 g/kg, Zinc content decreases with an increase in OM content. Factors that affected Zn content, in descending order of significance derived from deviance explained and adjustment coefficient of determination (Adj.R2) were AP, latitude, AHN, AK and OM. Moreover, the interactions between latitude and longitude, AHN and AP, OM and AK have significant impact on Zn.

Evidence of Interleukin 21 Reduction in Osteosarcoma Patients Due to PD-1/PD-L1-Mediated Suppression of Follicular Helper T Cell Functionality.

Interleukin 21 (IL-21) is crucial for the development of a robust CD8+ T cell response and has been shown to promote antitumor immunity. Despite the fact that osteosarcoma presents significant genetic instability with a high immunogenic potential, the antitumor immune response in osteosarcoma is ineffective. We investigated whether this was due to impaired IL-21 responses. We found that the circulating CD4+ T cells, a major source of IL-21, had reduced capacity to express IL-21 in osteosarcoma patients compared to healthy controls. The IL-21 expression in healthy controls was equally shared between Th17 and follicular helper T (Tfh) cells, while in osteosarcoma patients, the Tfh cells presented a severe reduction in IL-21 secretion capacity as well as in proliferation capacity. To explain this loss of Tfh functionality, we found that Tfh cells expressed the highest level of PD-1 among all CD4+ T cell subsets examined. While PD-1 might be crucial for normal Tfh function in healthy individuals, in patients with programmed death ligand 1 (PD-L1)+ tumor, the PD-1/PD-L1 pathway on Tfh cells might be sabotaged to mediate immunosuppression. Indeed, the IL-21 production by Tfh cells was significantly reduced in the presence of PD-L1+ tumor cells and was rescued by the anti-PD-L1 antibody. In healthy individuals, CXCR5+ Tfh cells could enhance the interferon (IFN)-γ secretion, degranulation, and cytotoxicity of CD8+ T cells, but this function of Tfh cells was lost in osteosarcoma patients. Together, this study demonstrated a dysregulated pathway that should be targeted for future immunotherapies in osteosarcoma.

Effects of Angelicae Pubescentis and Loranthi Decotion on repairing knee joint cartilages in rats.

BACKGROUND: Knee osteoarthritis (KOA) is a common orthopedics disease and its pathological changes at early stage are the damage and loss of articular cartilage. Traditional Chinese medicine (TCM) prescription contains multiple components and has the unique advantages of the diversity of targets.We compared the traditional Chinese medical formulae (Angelicae Pubescentis and Loranthi decotion, APLD, or Duhuo Jisheng) with a western medicine (glucosamine sulfate, GS) to treat the rat arthritis models, and tracked the outcomes. METHODS: Thirty-two Wistar rats (weight 180 ± 10 g, 6-week-old) were randomly divided into four groups (eight for each): group A as normal control group (no surgery and no drug treatment), group B as SIA (surgery-induced arthritis) model control without drug treatment, group C as SIA model + APLD, and group D as SIA model + GS. Anterior cruciate ligament in the knee joint of both hind legs from each rat in groups B, C, and D was shown and cut off to establish the SIA model. After 6 weeks of the surgery, rats in group C or D were treated with APLD or GS, respectively, for 8 weeks. Bone X-ray examination, histological images, and determination of genes of collagen II and aggrecan were performed. At week 14, both knee joint gap and bone structure disappeared in rats of group B, but they were visible in rats of groups A, C, and D. RESULTS: Histological images revealed that the structure and composition of the knee joint cartilage were significantly degenerated in group B and improved in group C. Genes of collagen II and aggrecan were significantly increased in both group C and D. CONCLUSION: APLD or GS gavage treatment for knee osteoarthritis (KOA) rat models was effective on the proliferation of cartilage chondrocytes and the damaged knee joint tissue repairing, and the APLD showed slightly superior in general.

Circulating CD4+CXCR5+ T cells contribute to proinflammatory responses in multiple ways in coronary artery disease.

Coronary artery disease (CAD) is a common subtype of cardiovascular disease. The major contributing event is atherosclerosis, which is a progressive inflammatory condition resulting in the thickening of the arterial wall and the formation of atheromatous plaques. Recent evidence suggests that circulating CD4+CXCR5+ T cells can contribute to inflammatory reactions. In this study, the frequency, phenotype, and function of circulating CD4+CXCR5+ T cells in CAD patients were examined. Data showed that circulating CD4+CXCR5+ T cells in CAD patients were enriched with a PD-1+CCR7- subset, which was previously identified as the most potent in B cell help. The CD4+CXCR5+ T cells in CAD patients also secreted significantly higher levels of IFN-γ, IL-17A, and IL-21 than those from healthy controls. Depleting the PD-1+ population significantly reduced the cytokine secretion. Interestingly, the CD4+CXCR5+PD-1- T cells significantly upregulated PD-1 following anti-CD3/CD28 or SEB stimulation. CD4+CXCR5+ T cells from CAD patients also demonstrated more potent capacity to stimulate B cell inflammation than those from healthy individuals. The phosphorylation of STAT1 and STAT3 were significantly higher in B cells incubated with CD4+CXCR5+ T cells from CAD than controls. The IL-6 and IFN-γ expression were also significantly higher in B cells incubated with CD4+CXCR5+ T cells from CAD. Together, this study demonstrated that CAD patients presented a highly activated CD4+CXCR5+ T cell subset that could contribute to proinflammatory responses in multiple ways. The possibility of using CD4+CXCR5+ T cells as a therapeutic target should therefore be examined in CAD patients.

Tim3+ Foxp3 + Treg Cells Are Potent Inhibitors of Effector T Cells and Are Suppressed in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disorder. Earlier studies have demonstrated that regulatory T (Treg) cells, the main cell type mediating immune tolerance, appeared to be enriched in the inflamed synovial tissues. It is still unclear why the Treg cells in RA patients are unable to limit exacerbated inflammation. Here, we found that the frequency of Tim3+Foxp3+ Treg cells, which were potent suppressors of proinflammatory responses, was downregulated in RA patients. Reduction in Tim3+Foxp3+ Treg frequency was correlated with increased RA disease activity. Furthermore, we observed that Tim3+Foxp3+ Tregs were expressed more interleukin (IL)-10 than Tim3-Foxp3+ Tregs. CD4+CD25+Tim3+ T cells had higher capability of inhibiting interferon (IFN)-γ and tumor necrosis factor (TNF)-α secretion from T cells and peripheral blood mononuclear cells (PBMCs) than CD4+CD25+Tim3- T cells. Compared to that in healthy individuals, CD4+CD25+ T cells in RA patients were less potent in suppressing IFN-γ and TNF-α production from PBMCs. Blocking Tim3 on CD4+CD25+ T cells from healthy controls resulted in an elevation of IFN-γ and TNF-α production from PBMCs, suggesting that Tim3 expression on CD4+CD25+ T cells was required for optimal Treg function. However, this phenomenon was not observed in RA patients. In conclusion, our study suggested that the CD4+CD25+Foxp3+ Treg cells from RA patients demonstrated a reduction of Tim3 and were less functional than Treg cells from healthy controls in a Tim3-related manner.

Inhibition of translation by consecutive rare leucine codons in E. coli: absence of effect of varying mRNA stability.

Consecutive homologous codons that are rarely used in E. coli are known to inhibit translation to varying degrees. As few as two consecutive rare arginine codons exhibit a profound inhibition of translation when they are located in the 5' portion of a gene in E. coli. We have previously shown that nine consecutive rare CUA leucine codons cause almost complete inhibition of translation when they are placed after the 13th codon of a test message (although they do not inhibit translation when they are placed in the middle of the message). In the present work, we report that five consecutive rare CUA leucine codons exhibit approximately a threefold inhibition of translation when they are similarly placed after the 13th codon of a test message, compared to five consecutive common CUG leucine codons, in a T7 RNA polymerase-driven system. Further, by removing RNase III processing sites at the 3' ends of the mRNAs, we have manipulated the stability of the mRNAs encoding the test and control messages to see if decreasing mRNA stability might have an effect on the extent of translation inhibition by the rare leucine codons. However, the inhibition with the less stable mRNAs was similar to that with the stable mRNAs, approximately 3.4-fold, indicating that mRNA stability per se does not have a major influence on the effects of rare codons in this system.

Overrepresentation of Th1- and Th17-like Follicular Helper T Cells in Coronary Artery Disease.

T cells and B cells play substantial roles in the process of coronary artery disease (CAD). Here, we examined the role of circulating follicular helper T (Tfh) cells in CAD. Compared to non-CAD controls, CAD patients had increased levels of circulating Tfh. Also, circulating Tfh in CAD patients exhibited increased frequencies of Th1- and Th17-like phenotypes and aberrant cytokine expressions. Coculture experiments with B cells showed that Tfh from CAD patients were more potent at inducing antibody production from B cells, enhancing plasmablast differentiation and suppressing B10 cell differentiation. Importantly, we found that the skewing of circulating Tfh toward the Th1/Th17-like cells was directly correlated with B cell inflammation and low density lipoprotein level in CAD patients. Together, our data demonstrated a skewing of blood Tfh composition in CAD patients, which resulted in significant changes in B cell inflammation.

Identification of the protein disulfide isomerase family member PDIp in experimental Parkinson's disease and Lewy body pathology.

Parkinson's disease (PD) is a slowly progressing neurodegenerative disorder with no clear etiology. Pathological hallmarks of the disease include the loss of dopaminergic neurons from the substantia nigra (SN) and the presence of Lewy bodies (LBs) (alpha-synuclein and ubiquitin-positive, eosinophilic, cytoplasmic inclusions) in many of the surviving neurons. Experimental modeling of PD neurodegeneration using the neurotoxins 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenyl-pyridinium (MPP(+)) has identified changes in gene expression of different endoplasmic reticulum (ER) stress proteins associated with MPTP- and PD-related neurodegeneration. We show that the protein disulfide isomerase (PDI) family member pancreatic protein disulfide isomerase (PDIp), previously considered exclusively expressed in pancreatic tissue, is uniquely upregulated among PDI family members within 24 h following exposure of retinoic acid (RA)-differentiated SH-SY5Y human neuroblastoma cells to either 1 mM MPP(+) or 10 microM of the highly specific proteasome inhibitor lactacystin. RT-PCR confirms PDIp expression in brain of post-mortem human PD subjects and immunohistochemical studies demonstrate PDIp immunoreactivity in LBs. Collectively, these findings suggest that increased PDIp expression in dopaminergic (DA) neurons might contribute to LB formation and neurodegeneration, and that this increased PDIp expression may be the result of proteasome impairment.

Insulin degrading enzyme is expressed in the human cerebrovascular endothelium and in cultured human cerebrovascular endothelial cells.

Insulin degrading enzyme (IDE) is found in the cytosol, peroxisomes and plasma membrane of many cells. Although it preferentially cleaves insulin it can also cleave many other small proteins with diverse sequences including the monomeric form of the amyloid beta peptide (A beta). In the brain, IDE has been reported to be expressed predominantly in neurons. In this study, IDE expression was detected in cultured human cerebrovascular endothelial cells. Using laser capture microdissection followed by PCR analysis, it was found that IDE mRNA is expressed in human brain blood vessels. Using immunofluorescence and multiphoton microscopy IDE was localized to the endothelium of the cerebrovascular blood vessels in human.

Effect of serum interleukin 21 on the development of coronary artery disease.

There has been more and more evidence to confirm the essential role of inflammatory processes in the development of coronary artery disease (CAD). Interleukin-21 (IL-21), the most recently discovered CD132-dependent cytokine, plays a key role in regulating inflammation. The aim of the study was to understand the effect of peripheral IL-21 on the pathogenesis and progression of CAD. Serum level of IL-21 in 92 CAD patients and 73 controls was measured by the enzyme-linked immunosorbent assay. Data showed that IL-21 expression was significantly increased in CAD than in controls (p < 0.001). Interestingly, when comparing IL-21 level with different genders, male subjects revealed higher IL-21 than female subjects (p = 0.024). Also, we observed that patients with hypertension had upregulated level of serum IL-21 (p = 0.002). Moreover, serum level of IL-21 was positively correlated with total cholesterol level (p = 0.015) or low-density lipoprotein cholesterol (p = 0.0009) of CAD cases. In addition, we analyzed IL-21 level with the severity of CAD, and identified that cases with 3-vessel affected had significantly elevated level of IL-21 than those with 1-vessel or 2-vessel affected. These data suggested that serum level of IL-21 may be closely associated with the development and progression of CAD.

Effect of interleukin-2 level and genetic variants on coronary artery disease.

Inflammation plays important roles in the development of atherosclerosis and coronary artery disease (CAD). Interleukin-2 (IL-2) is a proinflammatory cytokine and induces proliferation of T cells. The aim of the study was to understand the effect of IL-2 on the development of CAD from genetic polymorphism perspective and serum level perspective. IL-2 -330T/G and +114T/G polymorphisms were tested in 692 CAD cases and 723 healthy controls. IL-2 expression of these two polymorphisms was compared. Serum level of IL-2 in CAD patients and controls was analyzed. Data showed that prevalence of IL-2 -330GG genotype was significantly increased in CAD than in controls (p = 5.1 × 10(-6)). Function analysis revealed that subjects carrying IL-2 -330GG genotype had higher serum level of IL-2 than those with TG or TT genotypes (p < 0.01). Serum level of IL-2 in the study subjects was further analyzed, and results showed that CAD patients had significantly increased IL-2 level than healthy controls (p < 0.01). Also, cases with three vessels affected were observed to have higher IL-2 level than cases with one vessel affected (p < 0.05). These data suggested IL-2 polymorphism could affect the susceptibility to CAD by elevating protein expression, and serum level of IL-2 may be closed correlated with the development and progression of this disease.

Cytotoxic T-lymphocyte antigen-4 genetic variants and risk of Ewing's sarcoma.

Despite the knowledge of many genetic alterations present in Ewing's sarcoma (ES), the complexity of this disease precludes placing its biology into a simple conceptual framework. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) can decrease T-cell activation and attenuate antitumor responses. Polymorphisms in the CTLA-4 gene have been shown to be associated with different diseases. Here, we investigated the association of four CTLA-4 gene polymorphisms, -1661A/G (rs4553808), -318C/T (rs5742909), +49G/A (rs231775), and CT60A/G (rs3087243), with ES in the Chinese population. A total of 308 ES cases and 362 healthy controls were recruited and CTLA-4 polymorphisms were tested by polymerase chain reaction-restriction fragment length polymorphism. Results showed that frequencies of the CTLA-4 gene +49AA genotype, +49A allele, and GTAG haplotype were significantly increased in ES patients compared to healthy controls (odds ratio [OR]=2.42, 95% confidence interval [CI] 1.43-4.09, p<0.001; OR 1.38, 95% CI 1.11-1.73, p=0.005, and OR=1.46, 95% CI 1.06-2.02, p=0.020, respectively). We further compared CTLA-4 polymorphisms in ES patients based on different clinical parameters and data revealed that ES patients with metastasis had higher numbers of the +49AA genotype than those without metastasis (p=0.004). These results indicated that the CTLA-4 polymorphism could be a risk factor for ES and suggested a potential role of CTLA-4 in the metastasis of this malignancy.

[A preliminary report of open reduction and Numelock II polyaxial system fixation for type C fracture of distal radius].

OBJECTIVE: To study the clinical outcomes of Numelock II polyaxial system in treatment of type C fractures of the distal radius. METHODS: From March 2006 to June 2007, 12 cases of type C distal radial fractures (6 males and 6 females) were treated with open reduction and internal fixation. The mean age of the patients was 48.2 years (34-64 years). The locations were left wrist in 5 cases and right wrist in 7 cases, including 1 case of old fracture and 11 cases of fresh fractures. All fractures were closed. The mean course of disease was 9 days and 7 hours (4 hours to 60 days). According to AO/ASIF classification, there were 4 cases of C1 type, 5 cases of C2 type and 3 cases of C3 type. Preoperatively, the palmar tilt angle was -30 degrees to 30 degrees (- 5 degrees on average), and the radial inclination angle was 5 degrees to 13 degrees (7.7 degrees on average), and the radial shortening was 5 mm to 15 mm (9 mm on average). One case combined with dislocation of elbow joint and 2 cases combined with multiple injuries. RESULTS: All incision healed by first intention. Postoperative follow-up ranged from 14 months to 29 months (15.6 months on average). The X-ray films showed that the union of fractures was achieved 6-8 weeks (6.6 weeks on average). No screws breakage occurred. The articular facets were smooth in 11 of 12 patients. After operation, the palmar tilt angle was 0 degrees to 15 degrees (6.7 degrees on average), and the radial inclination angle was 5 degrees to 15 degrees (10.2 degrees on average), showing significant differences when compared with those before operation (P < 0.05). All the radial shortening was corrected. The ROM of the wrist was 55%-100% of the normal side. The grip strength was 55%-90% of the normal side. The results were excellent in 9 cases, good in 2 cases, and poor in 1 cases by X-ray film and wrist function assessment, the excellent and good rate was 91.7%. CONCLUSION: Numelock II polyaxial system fixation is an ideal method to treat type C fractures of the distal radius. Numelock II polyaxial mechanism may provide the free adjustability of screw trajectories and a higher degree of overall stability compared to monoaxial locking plates.

Insulin degrading enzyme is localized predominantly at the cell surface of polarized and unpolarized human cerebrovascular endothelial cell cultures.

Insulin degrading enzyme (IDE) is expressed in the brain and may play an important role there in the degradation of the amyloid beta peptide (Abeta). Our results show that cultured human cerebrovascular endothelial cells (HCECs), a primary component of the blood-brain barrier, express IDE and may respond to exposure to low levels of Abeta by upregulating its expression. When radiolabeled Abeta is introduced to the medium of cultured HCECs, it is rapidly degraded to smaller fragments. We believe that this degradation is largely the result of the action of IDE, as it can be substantially blocked by the presence of insulin in the medium, a competitive substrate of IDE. No inhibition is seen when an inhibitor of neprilysin, another protease that may degrade Abeta, is present in the medium. Our evidence suggests that the action of IDE occurs outside the cell, as inhibitors of internalization fail to affect the rate of the observed degradation. Further, our evidence suggests that degradation by IDE occurs on the plasma membrane, as much of the IDE present in HCECs was biotin-labeled by a plasma membrane impermeable reagent. This activity seems to be polarity dependent, as measurement of Abeta degradation by each surface of differentiated HCECs shows greater degradation on the basolateral (brain-facing) surface. Thus, IDE could be an important therapeutic target to decrease the amount of Abeta in the cerebrovasculature.

Specific up-regulation of GADD153/CHOP in 1-methyl-4-phenyl-pyridinium-treated SH-SY5Y cells.

Growth arrest DNA damage-inducible 153 (GADD153) expression was increased in 1-methyl-4-phenyl-pyridinium (MPP(+))-treated human SH-SY5Y neuroblastoma cells as determined by gene microarray analysis. GADD153 expression increased after 24 hr of MPP(+) (1 mM) exposure and preceded activation of caspase 3. Comparison of GADD153 expression among cultures treated with other toxins whose primary mode of action is either via mitochondrial impairment (rotenone) or via oxidative stress (6-hydroxydopamine or hydrogen peroxide) showed that GADD153 was uniquely up-regulated by MPP(+). Together these data suggest that a cellular mechanism distinct from mitochondrial impairment or oxidative stress contributes significantly to the up-regulation of GADD153 by MPP(+) and that GADD153 may function as an inducer of apoptosis following MPP(+) exposure. Published 2002 Wiley-Liss, Inc.