Intratympanic Botulinum Toxin Injection as a New Therapeutic Modality for Middle Ear Myoclonic Tinnitus.

OBJECTIVE: Middle ear myoclonic tinnitus (MEMT) is a disease caused by myoclonus or abnormal contractive movement of middle ear muscles (MEMs). This translational study was conducted to propose intratympanic botulinum toxin (IT-BTX) injection as a new therapeutic modality to treat MEMT. STUDY DESIGN: Animal experiment and nonrandomized controlled clinical trial. SETTING: Laboratory and medical center of an academic tertiary medical institution. METHODS: For the animal study, male Sprague-Dawley rats were divided into 4 subgroups according to the sacrificing day after IT-BTX injection. After initial hearing tests, randomly assigned experimental ears were intratympanically injected with 1 unit/100 µL of BTX-A, whereas control ears were injected with normal saline. Changes in the hearing thresholds, morphometry of the cochleae, electron microscopy study, and immunofluorescence analysis of MEMs were evaluated. For the human study, 10 intractable MEMT patients were enrolled. The hearing thresholds and the degree of tinnitus distress were observed for changes after IT-BTX injection. All patients were followed up for 3 months. RESULTS: As for the animal study, there were no significant changes in hearing thresholds and cochlear morphologies in all 4 subgroups of the rats. Significant MEM degenerations and immuno-detection of cleaved synaptosome-associated protein of 25 kDa (cSNAP-25) indicated the efficacy of IT-BTX. MEMT patients enrolled for the pilot clinical trial showed statistically significant improvement in tinnitus after IT-BTX injection. No major complications were noted. CONCLUSION: The new therapeutic modality of IT-BTX injection for the treatment of MEMT seems highly promising with an excellent result.

[The prevalence of HIV, hepatitis C virus and syphilis and related factors among cross-border couples in Mangshi county, Dehong Dai and Jingpo Autonomous Prefecture of Yunnan province from 2017 to 2019].

Objective: To understand the prevalence of HIV, hepatitis C virus (HCV) and syphilis and related factors among cross-border couples in Mangshi county, Dehong autonomous prefecture, Yunnan province. Methods: From May, 2017 to April, 2019, 2 500 couples with 5 000 cross-border marriages were selected by using cluster sampling method. The demographic characteristics, AIDS-related health services, HIV, HCV, syphilis infection and other information were collected through questionnaires and laboratory tests. The influencing factors of HIV, HCV and syphilis infection were analyzed by multivariate logistic regression model. Results: A total of 2 500 couples with cross-border marriage were investigated, among which 2 438 (97.5%) couples were Chinese men with Myanmar women. The average age of 5 000 participants was (34.16±9.00) years. Most of them were minority groups (59.9%), farmers (98.5%), education years ≤6 years (81.4%), marriage years>3 years (80.0%), and from mountainous areas (61.7%). The HIV prevalence of Chinese and Myanmar populations was 1.7% (43/2 500) and 2.0% (49/2 500), respectively. The HCV infection rates were 2.0% (49/2 500) and 1.3% (32/2 500), respectively and the infection rates of syphilis were 0.4% (10/2 500) and 0.2% (4/2 500), respectively. There were no statistically significant differences in the prevalence of three diseases among Chinese and Myanmar populations (P>0.05). The multivariate analysis showed that compared with those aged ≤ 30 years, having lower AIDS awareness, never receiving HIV testing, without HCV and syphilis infection, HIV prevalence was higher among those aged>30 years (OR=3.21, 95%CI: 1.80-5.73), having higher AIDS awareness (OR=17.41, 95%CI: 4.27-70.91), receiving HIV testing (OR=4.93, 95%CI: 2.72-8.92), with HCV infection (OR=5.64, 95%CI: 2.72-11.70) and syphilis infection (OR=8.37, 95%CI: 1.63-43.08). Compared with those aged ≤ 30 years, having marriage years ≤ 3 years, and with HIV negatives, HCV infection rate was higher among those age>30 years (OR=3.02, 95%CI: 1.69-5.38), having marriage years>3 years (OR=2.24, 95%CI: 1.34-3.74), and with HIV positives (OR=6.69, 95%CI: 3.29-13.59). Compared with those having HIV negatives, the syphilis infection rate was relatively higher among participants with HIV positives (OR=9.07, 95%CI: 2.00-41.10). Conclusion: The prevalence of HIV, HCV, and syphilis among cross-border couples in Mangshi county, Dehong autonomous prefecture of Yunnan province is relatively high. Age, AIDS awareness, HIV testing history, and the length of marriage are associated with the HIV, HCV, and syphilis infection.

[Analysis of screening results and risk factors of high-risk populations of lung cancer in Nanchang city from 2018 to 2019].

Objective: To collate and analyze the screening results of high-risk lung cancer populations in communities in Nanchang from 2018 to 2019, and to explore the lung-positive nodules and risk factors for lung cancer. Methods: Data of the screening subjects in 8 administrative districts and 15 street health service centers in Nanchang city, Jiangxi province from November 2018 to October 2019 were collected, people at high risk of lung cancer was assessed, clinical screening of high-risk groups of lung cancer was conducted by low-dose helical computed tomography (LDCT), and risk factors for suspected lung cancer and lung-positive nodules were analyzed. Results: Of the 25 871 people participated in screening, 5 220 were at high risk for lung cancer and 15 374 without other malignant tumors were at high risk. There were 2 417 cases participated in clinical LDCT screening, including 193 cases of lung-positive nodules, 67 cases of suspected lung cancer, 912 cases of other lung diseases, the positive rate of lung cancer or lung-positive nodules was 10.76% (260/2 417). Univariate analysis showed that age, coarse grain intake, oil intake, housing heating, passive smoking, alcohol consumption and mental trauma were associated with positive pulmonary nodules or lung cancer (all P<0.05). Multivariate analysis showed that gender, age, housing heating, smoking and drinking were related to the occurrence of lung nodules or lung cancer (all P<0.05). Conclusions: Men are more likely to develop lung cancer or lung-positive nodules than women. The age is an independent risk factor for lung-positive nodules or lung cancer. In a certain range, age will increase the incidence of lung cancer, housing heating may be the protective factor for lung cancer, while smoking and drinking are risk factors.

[Research progression and application of Laennec capsule in liver].

The Laennec capsule of liver was first discovered and reported by French doctor Rene Theophile Hyacinthe Laennec in 1802.However, it has not received enough attention for more than 200 years since then. In recent years, with the rapid development of liver surgery represented by laparoscopic technology, and the deepening of the theory of precise liver surgery, the fine anatomical structure of liver Laennec capsule has returned to the vision of liver surgeons.Recent studies have demonstrated the presence of Laennec capsule in liver histology, covering the whole liver surface, and lining the surface of liver parenchyma around the Glisson pedicle and the main hepatic vein along the inflow and outflow channels of the liver. Based on the Laennec capsule approach, it is expected to unify the current approach of Glisson pedicle and the approach of hepatic vein, and provide a new theoretical basis for the liver surgery, and guide us in the standardization of liver surgeries.

Systemic lupus erythematosus aggravates atherosclerosis by promoting IgG deposition and inflammatory cell imbalance.

BACKGROUND: Systemic lupus erythematosus (SLE) patients experience a premature and more severe presentation of coronary artery disease. The underlying mechanisms of accelerated coronary artery disease in SLE patients remain to be elucidated. METHODS: By using atherosclerosis combining a SLE murine model, we proved that the onset of SLE aggravates atherosclerosis. Although the onset of SLE reduced blood lipids slightly, immune deviation contributed to aggravated atherosclerosis in lupus mice. Lupus atheroma were characterized by inflammatory cell infiltration, such as gathered dendritic cells, macrophages, and IgG deposition. RESULTS: Decreased lymphocytes and magnified dendritic cells in the spleen were also observed in lupus mice. Hydroxychloroquine prevented atherosclerosis progression mainly by reversing immune status abnormality caused by SLE. Serum interferon alfa levels were not changed in lupus mice. CONCLUSION: These findings strongly suggested that anti-inflammatory therapies and hydroxychloroquine provide a new possible strategy for treating SLE patients with atherosclerosis.

The factors associated with natural disease progression from HIV to AIDS in the absence of ART, a propensity score matching analysis.

This study aimed at comparing the factors associated with the natural progression between typical progressors (TPs) and rapid progressors (RPs) in HIV-infected individuals. A retrospective study was conducted on 2095 eligible HIV-infected individuals from 1995 to 2016 in a high-risk area of Henan Province, China. Propensity score matching was used to balance covariates, and the conditional logistic regression analyses were performed to explore the factors of natural disease progression among HIV infectors. A total of 379 pairs of RPs and TPs were matched. The standardised difference values of all covariates were less than 10%. HIV-infected individuals transmitted through sexual transmission (odds ratio (OR) 0.56, 95% confidence interval (CI) 0.36-0.85) were more likely to progress to AIDS compared with those infected through contaminated blood. Older age at diagnosis of HIV-infected individuals (OR 0.72, 95% CI 0.58-0.89) exhibited a faster progression to AIDS. HIV-infected individuals identified through a unique survey (OR 7.01, 95% CI 2.99-16.44) were less likely to progress to AIDS compared with those identified through medical institutions. HIV-infected individuals who had higher baseline CD4+T cell counts (OR 3.37, 95% CI 2.59-4.38) had a slower progression to AIDS. These findings provide evidence for natural disease progression from HIV to AIDS between TPs and RPs.

Identification of antimicrobial metabolites produced by a potential biocontrol Actinomycete strain A217.

AIMS: To extract and identify the metabolites of strain A217 as well as its antifungal spectrum and control effect on various plant pathogens. METHODS AND RESULTS: Strain A217 was identified as a Streptomyces sp. which was most similar to Streptomyces lienomycini. An antimicrobial spectrum test indicated that strain A217 inhibited several plant pathogenic fungi and strong antibacterial effect such as Phytophthora capsici, Botrytis cinerea, Sclerotinia sclerotiorum, Fusarium oxysporum, Pseudomonas syringae and Xanthomonas campestris. An in vivo tissue test demonstrated that the fermentation broth of strain A217 exerted therapeutic and protective effects of 49·47 and 61·60% respectively, on S. sclerotiorum. Additionally, the fermentation broth of A217 exerted control effects on walnut black spot disease in walnut leaves and branches amounting to 79·33 and 81·52% respectively. In a pot experiment, the fermentation broth exhibited a stronger protective and control effect (68·29%), as well as better bacteriostatic and disease control effects on Phytophthora blight of pepper, compared with Metalaxyl. Compounds possessing antifungal and antibacterial activities were obtained from the fermentation broth of strain A217, using column chromatography and HPLC. Chemical and structural analyses conducted using MS and nuclear magnetic resonance confirmed that these compounds were 1H-pyrrole-2-carboxylic acid and 1H-pyrrole-2-carboxamide. The EC50 values of compound 1H-pyrrole-2-carboxylic acid1 for S. sclerotiorum and P. capsici were 20·13 and 50·36 µg ml-1 respectively. Compound 1H-pyrrole-2-carboxamide2 showed significant antibacterial activity against different plant pathogenic bacteria. The MIC values of P. syringae, X. campestris and X. campestris pv. jugiandis were 7·5, 30 and 15·0 µg ml-1 respectively. CONCLUSIONS: Actinomyces A217 fermentation products have a broad spectrum of bacteriostasis, and have good bacteriostasis activity to many plant pathogenic fungi and bacteria. SIGNIFICANCE AND IMPACT OF THE STUDY: The present study revealed a new antimicrobial producing strain of Streptomyces and its potential application as a biological control agent for plant diseases.

Splenic preservation in laparoscopic distal pancreatectomy.

BACKGROUND: Laparoscopic spleen-preserving distal pancreatectomy (LSPDP) is designed principally for the removal of benign and low-grade malignant lesions in the left pancreas. The aims of this study were to compare LSPDP with laparoscopic distal pancreatectomy with splenectomy (LDPS), compare two splenic preservation techniques (splenic vessel preservation and Warshaw technique) and investigate factors that influence splenic preservation. METHODS: Information from patients who underwent laparoscopic distal pancreatectomy between December 2004 and January 2016 at a single institution was reviewed. Data were extracted from a prospectively developed database. Intention-to-treat and propensity score matching analyses were employed. Univariable and multivariable analyses were used to investigate factors affecting splenic preservation. RESULTS: There were 206 patients in total (126 planned LSPDP and 80 planned LDPS procedures), of whom 108 underwent LSPDP and 98 LDPS. In intention-to-treat analysis, the duration of surgery was significantly shorter in the LSPDP group than in the LDPS group (mean 191·0 versus 220·5 min respectively; P < 0·001). Tumour size was an independent risk factor for splenic vessel resection in planned splenic vessel preservation operations, and a cut-off value of 3 cm provided optimal diagnostic accuracy. After a median follow-up of 35·9 months, there were no clinically significant splenic infarctions and no patient developed gastrointestinal bleeding after LSPDP. CONCLUSION: Planned LSPDP had a high splenic preservation rate and was associated with significantly shorter operating time than LDPS. Splenic vessel preservation could be predicted using a tumour cut-off size of 3 cm.

[Study on the properties of felodipine solid dispersions prepared by different technologies].

OBJECTIVE: To prepare felodipine/copovidone solid dispersions, which were made based on different preparation technologies. Insoluble felodipine was selected as the model drug in this research. This drug belonged to Biopharmaceutics Classification System II (BCSII) with insoluble property and good permeability across intestinal mucosa simultaneously. A comparative study was carried out for further investigating their corresponding pharmaceutical properties. METHODS: Felodipine/copovidone solid dispersions were achieved by four methods including spray-drying method, microwave-induced fusion quench cooling method, freeze-drying method and co-precipitation method. These solid dispersions were produced based on corresponding processes that corresponded to these methods. Internal properties of co-povidone solid dispersions were analyzed by various approaches including scanning electron microscope (SEM), differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD). The improvement on insoluble properties of felodipine by solid dispersions produced by different technologies was characterized by dissolution experiments based on dissolution instrument. Crystallization inhibition effect of polymers against drugs was studied by supersaturated experiments through determining the concentration value at different time points. RESULTS: The internal drug was dispersed in amorphous form in solid dispersions produced by spray-drying, microwave method, microwave/quench-cooling method and co-precipitation method. Freeze-drying method resulted in a form of crystal in felodipine/copovidone solid dispersions. Compared with other technologies, microwave-induced quench cooling method could significantly improve the dissolution of insoluble drug felodipine (P<0.05). The dissolution concentration reached approximately 4.65 mg/L at 60 min time point. Copovidone could inhibit or retard the crystallization of felodipine in a supersaturated state. In the solution pre-dissolved with maximum copoyidone polymer, the minimum crystallization rate of supersaturated felodipine was observed at 240 min time point. The value of crystallization rate was 0.19 mg/(L×min). CONCLUSION: The study is helpful to understand and clarify the internal properties of solid dispersions obtained by different technologies. The research also provides beneficial consultation for the choice of technology in practical production of drug-polymer solid dispersions.

microRNA-21 mediates the TGF-ß1-induced migration of keratinocytes via targeting PTEN.

OBJECTIVE: The aim of this study was to investigate the molecular mechanism into the keratinocyte migration, which is promoted by Transforming growth factor-ß1 (TGF-ß1) during wound healing. MATERIALS AND METHODS: In the present study, we investigated the regulation by TGF-ß1 on phosphatase and tensin homolog (PTEN) expression, and microRNA-21 (miR-21) level with real-time quantitative PCR or/and Western blotting, and then examined the regulatory role of miR-21 on the PTEN expression and the mesenchymal transition, with real-time quantitative PCR, western blotting and luciferase reporter assay, and the migration of keratinocytic HaCaT cells with scratch assay. RESULTS: It was demonstrated that miR-21 was upregulated by TGF-ß1 treatment in HaCaT cells; and the upregulated miR-21 targeted the 3' UTR of PTEN gene and downregulated the PTEN expression, along with the Smad3/4 upregulation. Moreover, the miR-21 manipulation with miR-21 mimics or miR-21 inhibitor not only upregulated or downregulated the miR-21 level, but also associated with the mesenchymal transition and the migration of HaCaT cells via promoting or downregulating the FSP1 and Collagen I and the E-cadherin, and via upregulating or downregulating the migration of HaCaT cells. CONCLUSIONS: Our results demonstrate that miR-21 mediates the TGF-ß1-promoted mesenchymal transition and migration of keratinocytes during skin wound healing via targeting PTEN. This study implies that miR-21 might be an important target to promote the skin wound healing.

Predicting imminent risk for fracture in patients aged 50 or older with osteoporosis using US claims data.

UNLABELLED: Patient characteristics contributing to imminent risk for fracture, defined as risk of near-term fracture within the next 12 to 24 months, have not been well defined. In patients without recent fracture, we identified factors predicting imminent risk for vertebral/nonvertebral fracture, including falls, age, comorbidities, and other potential fall risk factors. PURPOSE: Several factors contribute to long-term fracture risk in patients with osteoporosis, including age, bone mineral density, and fracture history. Some patients may be at imminent risk for fracture, defined here as a risk of near-term fracture within 12-24 months. Many patient characteristics contributing to imminent risk for fracture have not been well defined. This case-control study used US commercial and Medicare supplemental insured data for women and men without recent fracture to identify factors associated with imminent risk for fracture. METHODS: Patients included were aged ≥50 with osteoporosis, had a vertebral or nonvertebral fracture claim (index date; fracture group) or no fracture claim (control group) from January 1, 2006, to September 30, 2012, continuously enrolled and without fracture in the 24 months before index. Potential risk factors during the period before fracture were assessed. RESULTS: Using data from 12 months before fracture, factors significantly associated with imminent risk for fracture were previous falls, older age, poorer health status, specific comorbidities (psychosis, Alzheimer's disease, central nervous system disease), and other fall risk factors (wheelchair use, psychoactive medication use, mobility impairment). Similar findings were observed with data from 24 months before fracture. CONCLUSIONS: In patients with osteoporosis and no recent fracture, falls, older age, poorer health status, comorbidities, and other potential fall risk factors were predictive of imminent risk for fracture. Identification of factors associated with imminent risk for vertebral/nonvertebral fracture may help identify and risk stratify those patients most in need of immediate and appropriate treatment to decrease fracture risk.

Clinical value of high expression level of CD71 in acute myeloid leukemia.

CD71 (transferrin receptor 1, TfR-1) is a type II membrane glycoprotein and associated closely with tumors. It was recognized as an indication for diagnosing acute erythroid leukemia (AEL). High expression level of CD71 has been identified as a negative prognostic marker for many solid tumors. However, whether CD71 should be identified as an adverse marker in acute myeloid leukemia (AML) remained conflicting. We studied 214 AML patients for analysis of clinical and laboratory data. Taking the CD71 expression level of 60% as a standard, we divided our patients into two groups. We discovered that AML with high expression level of CD71 was prone to linked with severe anemia (P=0.004), thrombocytopenia (P<0.001) and complex karyotype (P=0.024) and had increasing expression level of CD117 (P=0.001). No statistically significant correlations in age, gender, WBC counting, molecular markers between the two groups. And moreover, high expression level of CD71 did not alter the pattern of survival time.

Aggravation of spinal cord compromise following new osteoporotic vertebral compression fracture prevented by teriparatide in patients with surgical contraindications.

Patients with spinal cord deficits following new unstable osteoporotic compression fracture and surgical contraindications were considered to receive conservative treatment. Teriparatide was better than alendronate at improving bone mineral density and bone turnover parameters, as well as preventing aggravation of spinal cord compromise. INTRODUCTION: This study compared the preventive effects of teriparatide and alendronate on aggravation of spinal cord compromise following new unstable osteoporotic vertebral compression fracture (OVCF) in patients with surgical contraindications. METHODS: This was a 12-month, randomized, open-label study of teriparatide versus alendronate in 49 patients with new unstable OVCF and surgical contraindications. Neurological function was evaluated using modified Japanese Orthopedic Association (mJOA) score (11-point scale, the maximum score of 11 implies normalcy). Visual analog scale (VAS) scores, kyphotic angles, anterior-border heights and diameters of the spinal canal of the fractured vertebrae, any incident of new OVCFs (onset of OVCF during follow-up), spine bone mineral density (BMD), and serum markers of bone resorption and bone formation were also examined at baseline and 1, 3, 6, and 12 months after initiation of the medication regimen. RESULTS: At 12 months, mean mJOA score had improved in the teriparatide group and decreased in the alendronate group. Mean concentrations of bone formation and bone resorption biomarkers, mean spine BMD, and mean anterior-border height and spinal canal diameter of the fractured vertebrae were significantly greater in the teriparatide group than in the alendronate group. Mean VAS score, mean kyphotic angle of the fractured vertebrae, and incidence of new OVCFs were significantly smaller in the teriparatide group than in the alendronate group. CONCLUSIONS: In patients with neurological deficits following new unstable OVCF and with surgical contraindications, teriparatide was better than alendronate at improving the BMD and the bone turnover parameters, as well as preventing aggravation of spinal cord compromise.

Meta-analysis of the TNF-α-308G/A polymorphism and vitiligo risk.

Several case-control studies have been conducted to investigate the association between the tumor necrosis factor-α (TNF-α)-308G/A polymorphism and vitiligo risk. However, the results of these studies are inconsistent; therefore, we attempted to comprehensively evaluate the association between TNF-α-308G/A polymorphism and vitiligo risk via a meta-analysis. Studies reporting the association between TNF-α-308G/A polymorphism and vitiligo risk were retrieved from PubMed and EmBase databases. Data were extracted from these studies and the pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the association. Six case-control studies including 1391 vitiligo cases and 2455 control subjects were included in this meta-analysis. The overall results showed the lack of a significant difference in TNF-α-308G/A genotype distribution between the patients and controls when the G allele and GG, GG + GA, GG, and GG genotypes were compared against the A allele and the GA + AA, AA, AA, and GA genotypes, respectively (ORs = 0.65, 0.53, 0.63, 0.41, 0.55; 95%CI = 0.35-1.23, 0.24-1.18, 0.10-4.09, 0.08-1.97, 0.25-1.21; P = 0.188, 0.121, 0.627, 0.264, 0.135, respectively). This meta-analysis suggests that the TNF-α-308G/A polymorphism may not be associated with vitiligo risk. As few studies are available in this field and current evidence remains limited, these results must be corroborated with well-designed and larger studies in the future.

Association between MTHFR 677C/T polymorphism and psoriasis risk: a meta-analysis.

Previous studies investigating the association between methylenetetrahydrofolate reductase (MTHFR) 677C/T polymorphisms and psoriasis risk have reported inconsistent results. The present meta-analysis aimed to comprehensively evaluate the association between MTHFR 677C/T polymorphism and psoriasis risk. The studies regarding the association between MTHFR 677C/T polymorphism and psoriasis risk were retrieved from the PubMed, Embase, Web of Science, Chinese National Knowledge Infrastructure, and Chinese Biomedical databases. Data were extracted and statistical analysis was performed with the program STATA 12.0. A total of seven studies involving 1290 psoriasis cases and 1068 healthy controls were retrieved. Combined analysis showed that there was no significant difference in MTHFR 677C/T genotype distribution between psoriasis and control subjects in the comparisons C vs T, CC vs CT + TT, CC + CT vs TT, CC vs TT, and CC vs CT [respectively: odds ratio (OR) = 0.98, 95% confidence interval (CI) = 0.76-1.26, P = 0.882; OR = 1.11, 95%CI = 0.81-1.51, P = 0.526; OR = 0.79, 95%CI = 0.53-1.19, P = 0.261; OR = 0.88, 95%CI = 0.51-1.52, P = 0.648; OR = 1.19, 95%CI = 0.90-1.58, P = 0.217]. Subgroup analysis by ethnicity also showed no significant association between MTHFR 677C/T polymorphism and psoriasis risk in both Asian and Caucasian populations. In conclusion, this meta-analysis indicates that MTHFR 677C/T polymorphism may not be associated with psoriasis risk.

Teriparatide treatment patterns in osteoporosis and subsequent fracture events: a US claims analysis.

UNLABELLED: The objective of this study was to describe the risk of fragility-related fractures in the 2 years following teriparatide initiation. In an administrative claims analysis of over 11,407 patients, approximately one in eight patients had a new or recurrent fragility-related fracture in the 2 years following teriparatide initiation. INTRODUCTION: The objective of this study was to describe the risk of fragility-related fractures in the 2 years following the initiation of teriparatide in a real-world setting. METHODS: This retrospective study used data from the 2002 to 2011 MarketScan® Commercial and Medicare Supplemental Databases to identify patients 50 years and older with a diagnosis of osteoporosis (ICD-9-CM code 733.0x) who were initiating teriparatide. Patients were required to have continuous medical and pharmacy benefit coverage for the 12 months prior to and 24 months following teriparatide initiation (index event). Teriparatide treatment patterns (persistence and adherence) were described, as was the use of antiresorptive therapy. The primary study outcome was the presence of a new or recurring fragility fracture following the initiation of teriparatide. RESULTS: A total of 11,407 patients met the study criteria (mean age = 69.5, standard deviation = 10.6 years; 92.0% female). One in four (25.6%) patients had fragility fracture claims in the year prior to teriparatide initiation, of which 64.0% were on existing antiresorptive therapy. Overall, 13.4% (n = 1527) of patients had a new or recurrent fracture during the 2-year follow-up period. Forty-eight percent of patients on teriparatide treatment were considered persistent; fragility fractures were more common among patients nonpersistent with teriparatide (15.2%) than among those persistent with teriparatide (11.4%). A higher fracture rate (35.7%) was observed in the cohort with previous fragility fracture then those without pre-index fractures (24%). CONCLUSION: More than 13.4% of patients had new or recurrent fragility-related fractures during the 2 years following the initiation of teriparatide; these fractures were more in common in patients with pre-existing fractures and the patients who were nonpersistent with teriparatide.

Dose-dependent effects of selenite (Se(4+)) on arsenite (As(3+))-induced apoptosis and differentiation in acute promyelocytic leukemia cells.

To enhance the therapeutic effects and decrease the adverse effects of arsenic on the treatment of acute promyelocytic leukemia, we investigated the co-effects of selenite (Se(4+)) and arsenite (As(3+)) on the apoptosis and differentiation of NB4 cells and primary APL cells. A 1.0-µM concentration of Se(4+) prevented the cells from undergoing As(3+)-induced apoptosis by inhibiting As(3+) uptake, eliminating As(3+)-generated reactive oxygen species, and repressing the mitochondria-mediated intrinsic apoptosis pathway. However, 4.0 µM Se(4+) exerted synergistic effects with As(3+) on cell apoptosis by promoting As(3+) uptake, downregulating nuclear factor-кB, and activating caspase-3. In addition to apoptosis, 1.0 and 3.2 µM Se(4+) showed contrasting effects on As(3+)-induced differentiation in NB4 cells and primary APL cells. The 3.2 µM Se(4+) enhanced As(3+)-induced differentiation by promoting the degradation of promyelocytic leukemia protein-retinoic acid receptor-α (PML-RARα) oncoprotein, but 1.0 µM Se(4+) did not have this effect. Based on mechanistic studies, Se(4+), which is similar to As(3+), might bind directly to Zn(2+)-binding sites of the PML RING domain, thus controlling the fate of PML-RARα oncoprotein.

First measurement of time evolution of electron temperature profiles with Nd:YAG Thomson scattering system on Heliotron J.

A Nd:YAG Thomson scattering system has been developed for Heliotron J. The system consists of two 550 mJ 50 Hz lasers, large collection optics, and 25 radial channel (∼1 cm spatial resolution) interference polychromators. This measurement system achieves a S/N ratio of ∼50 for low-density plasma (ne ∼ 0.5 × 10(19) m(-3)). A time evolution of electron temperature profiles was measured with this system for a high-intensity gas-puff (HIGP) fueling neutral-beam-injection plasma. The peripheral temperature of the higher-density phase after HIGP recovers to the low-density pre-HIGP level, suggesting that improving particle transport in the HIGP plasma may be possible.

Highly time-resolved evaluation technique of instantaneous amplitude and phase difference using analytic signals for multi-channel diagnostics.

A fluctuation analysis technique using analytic signals is proposed. Analytic signals are suitable to characterize a single mode with time-dependent amplitude and frequency, such as an MHD mode observed in fusion plasmas since the technique can evaluate amplitude and frequency at a specific moment without limitations of temporal and frequency resolutions, which is problematic in Fourier-based analyses. Moreover, a concept of instantaneous phase difference is newly introduced, and error of the evaluated phase difference and its error reduction techniques using conditional/ensemble averaging are discussed. These techniques are applied to experimental data of the beam emission spectroscopic measurement in the Heliotron J device, which demonstrates that the technique can describe nonlinear evolution of MHD instabilities. This technique is widely applicable to other diagnostics having necessity to evaluate phase difference.