HIV estimation using population-based surveys with non-response: A partial identification approach.

HIV estimation using data from the demographic and health surveys (DHS) is limited by the presence of non-response and test refusals. Conventional adjustments such as imputation require the data to be missing at random. Methods that use instrumental variables allow the possibility that prevalence is different between the respondents and non-respondents, but their performance depends critically on the validity of the instrument. Using Manski's partial identification approach, we form instrumental variable bounds for HIV prevalence from a pool of candidate instruments. Our method does not require all candidate instruments to be valid. We use a simulation study to evaluate and compare our method against its competitors. We illustrate the proposed method using DHS data from Zambia, Malawi and Kenya. Our simulations show that imputation leads to seriously biased results even under mild violations of non-random missingness. Using worst case identification bounds that do not make assumptions about the non-response mechanism is robust but not informative. By taking the union of instrumental variable bounds balances informativeness of the bounds and robustness to inclusion of some invalid instruments. Non-response and refusals are ubiquitous in population based HIV data such as those collected under the DHS. Partial identification bounds provide a robust solution to HIV prevalence estimation without strong assumptions. Union bounds are significantly more informative than the worst case bounds without sacrificing credibility.

S1PR1 regulates ovarian cancer cell senescence through the PDK1-LATS1/2-YAP pathway.

Cell senescence deters the activation of various oncogenes. Induction of senescence is, therefore, a potentially effective strategy to interfere with vital processes in tumor cells. Sphingosine-1-phosphate receptor 1 (S1PR1) has been implicated in various cancer types, including ovarian cancer. The mechanism by which S1PR1 regulates ovarian cancer cell senescence is currently elusive. In this study, we demonstrate that S1PR1 was highly expressed in human ovarian cancer tissues and cell lines. S1PR1 deletion inhibited the proliferation and migration of ovarian cancer cells. S1PR1 deletion promoted ovarian cancer cell senescence and sensitized ovarian cancer cells to cisplatin chemotherapy. Exposure of ovarian cancer cells to sphingosine-1-phosphate (S1P) increased the expression of 3-phosphatidylinositol-dependent protein kinase 1 (PDK1), decreased the expression of large tumor suppressor 1/2 (LATS1/2), and induced phosphorylation of Yes-associated protein (p-YAP). Opposite results were obtained in S1PR1 knockout cells following pharmacological inhibition. After silencing LATS1/2 in S1PR1-deficient ovarian cancer cells, senescence was suppressed and S1PR1 expression was increased concomitantly with YAP expression. Transcriptional regulation of S1PR1 by YAP was confirmed by chromatin immunoprecipitation. Accordingly, the S1PR1-PDK1-LATS1/2-YAP pathway regulates ovarian cancer cell senescence and does so through a YAP-mediated feedback loop. S1PR1 constitutes a druggable target for the induction of senescence in ovarian cancer cells. Pharmacological intervention in the S1PR1-PDK1-LATS1/2-YAP signaling axis may augment the efficacy of standard chemotherapy.

Sodium tanshinone IIA sulfonate ameliorates neointima by protecting endothelial progenitor cells in diabetic mice.

BACKGROUND: Endothelial progenitor cells (EPCs) transplantation is one of the effective therapies for neointima associated with endothelial injury. Diabetes impairs the function of EPCs and cumbers neointima prevention of EPC transplantation with an ambiguous mechanism. Sodium Tanshinone IIA Sulfonate (STS) is an endothelium-protective drug but whether STS protects EPCs in diabetes is still unknown. METHODS: EPCs were treated with High Glucose (HG), STS, and Nucleotide-binding Domain-(NOD) like Receptor 3 (NLRP3), caspase-1, the Receptor of Advanced Glycation End products (AGEs) (RAGE) inhibitors, Thioredoxin-Interacting Protein (TXNIP) siRNA, and EPC proliferation, differentiation functions, and senescence were detected. The treated EPCs were transplanted into db/db mice with the wire-injured Common Carotid Artery (CCA), and the CD31 expression and neointima were detected in the CCA inner wall. RESULTS: We found that STS inhibited HG-induced expression of NLRP3, the production of active caspase-1 (p20) and mature IL-1ß, the expression of catalase (CAT) cleavage, γ-H2AX, and p21 in EPCs. STS restored the expression of Ki67, CD31 and von Willebrand Factor (vWF) in EPCs; AGEs were found in the HG-treated EPCs supernatant, and RAGE blocking inhibited the expression of TXNIP and the production of p20, which was mimicked by STS. STS recovered the expression of CD31 in the wire-injured CCA inner wall and the prevention of neointima in diabetic mice with EPCs transplantation. CONCLUSION: STS inhibits the aggravated neointima hyperplasia by protecting the proliferation and differentiation functions of EPC and inhibiting EPC senescence in diabetic mice. The mechanism is related to the preservation of CAT activity by inhibiting the RAGE-TXNIP-NLRP3 inflammasome pathway.

Recent advances in quinolone hybrids with potential antibacterial activity against drug-resistant bacteria.

Quinolone derivatives, represented by fluoroquinolones, have emerged as the most commonly prescribed antibacterials for the treatment of various bacterial infections. In particular, the combination of a quinolone moiety with other antibacterial pharmacophores has the potential to act on different drug targets, which in turn, overcome drug resistance. Accordingly, quinolone hybrids are useful prototypes for fighting drug-resistant pathogens. The purpose of the present review is to provide an emphasis on the current scenario of quinolone hybrids with potential antibacterial activity against drug-resistant pathogens, covering articles published in the past 10 years. The structure-activity relationships, various aspects of rational design and mechanisms of action are also discussed to facilitate further rational development of more effective candidates.

Utilizing Reusable Catalyst Phosphotungstic Acid for the Synthesis of Thioglycoside from Per-O-acetyl Saccharides with Microwave-Assisted and De-O-acetylation with Methanol.

Traditional methods for synthesizing complex oligosaccharides currently developed are not efficient, requiring a new glycosylation methodology. Herein, using phosphotungstic acid (PTA) as a catalyst has demonstrated to be a simple possibility for carbohydrate synthesis. The methodology is engineered into a PTA-catalyzed thioglycoside preparation under microwave conditions and de-O-acetylation of carbohydrates. These easier operations and convenient protocols display a wide substrate scope. Moreover, both methods can be developed into a one-pot reaction for the efficient synthesis of carbohydrate analogues.

Do Past Experience and Group Heterogeneity Matter to Consumer Preferences? Evidence From a Choice Experiment in Urban China.

This study uses a discrete choice experiment to examine consumers' preferences for Fuji apple product attributes and willingness to pay (WTP) estimates for consumers in six cities in China. We estimated the preference heterogeneity by linking the stated preference choice data with consumers' past experience and socioeconomic characteristics in the latent class model. The empirical results show that, first, the past experience variables are crucial in explaining consumer preferences and WTP. Second, three classes, namely, certification-oriented, price- and origin-oriented, and not interested, are identified. Furthermore, the same type of Fuji apple attribute does not appeal to every respondent. Third, our results indicate the heterogeneity of preferences across different classes of respondents, as well as differences in WTP for Fuji apples.

WISP2 promotes cell proliferation via targeting ERK and YAP in ovarian cancer cells.

BACKGROUND: Wnt-inducible signaling pathway protein 2 (WISP2) is a wnt1-induced signaling pathway protein 2. Although studies indicate that WISP2 may promote the development of various tumors, its role in ovarian cancer remains unclear. The objective of the current study was to analyze the effects of WISP2 on the proliferation and migration of ovarian cancer cells in vitro and in vivo. RESULTS: Immunohistochemistry and western blotting indicated that WISP2 was highly expressed in various ovarian cancer tissues and cell lines, but weakly expressed in normal ovary tissue. WISP2 deletion inhibited cell growth, clone formation, and migration of ovarian cancer cells while promoting cell apoptosis and affecting the cell cycle. This growth inhibitory effect caused by WISP2 loss is due to the inhibition of phosphorylated extracellular signal-related kinase (p-ERK)1/2, as well as CCAAT/enhancer-binding protein α (CEBPα) and CEPBß. In addition, WISP2 deletion also activated the Yes-associated protein (YAP). CONCLUSION: WISP2 deletion inhibits ovarian cancer cell proliferation by affecting ERK signaling pathways.

Lumbar Scoliosis Induction in Juvenile Dogs by Three-dimensional Modulation of Spinal Growth Using Nickel-Titanium Coil Springs.

BACKGROUND: Current treatments for scoliosis have some defects and complications. To study spinal deformities and test novel scoliosis treatments, many animal models of scoliosis have been developed. These models applied a single load to the spine and could not precisely modulate the spinal growth in different dimensions. In this study, we applied posterior tethering in various directions with the application of nickel-titanium (NT) coil springs in dog's spine to modulate spinal growth in the coronal, sagittal, and transverse planes and create a scoliosis model possess curves that mimic adolescent idiopathic scoliosis (AIS) three dimensionally. METHODS: Scoliosis was surgically induced in eight 8-week-old female dogs (weight: 1.95-2.30 kg) using bone screws and NT coil springs. The deformity was induced through the placement of posterior NT coil springs that tethered the spine by bone screw fixation. All dogs were monitored with serial radiographs to document changes in deformities. RESULTS: All experimental animals developed scoliotic curves convex to the left in the lumbar segment. The mean coronal Cobb angle was 18.0° immediately postoperatively and 54.5° at 22 weeks. The mean lordosis increased from 6.2° postoperatively to 35.0° at final follow-up. Apical axial rotation increased from 4.5° postoperatively to 31.2° at 22 weeks. CONCLUSIONS: With the application of NT springs in dogs that allowed posterior tethering in various directions, lumbar spinal deformity was achieved in three planes: coronal, sagittal, and transverse planes. Notably, the lumbar spine in surgically treated dogs developed lordoscoliosis with obvious rotation and the curves mimic AIS three dimensionally well. This method allows lumbar scoliosis to develop without deep dissection of muscle and maintains the essential anatomical elements along the spinal curve. Moreover, the spinal growth modulation technique could yield information that would provide a basis for developing novel early-stage treatments for children with scoliosis.

Pharmacokinetics of oxycodone hydrochloride and three of its metabolites after intravenous administration in Chinese patients with pain.

OBJECTIVES: The aim of this study is to evaluate the pharmacokinetic profile of oxycodone and three of its metabolites, noroxycodone, oxymorphone and noroxymorphone after intravenous administration in Chinese patients with pain. METHODS: Forty-two subjects were assigned to receive intravenous administration of oxycodone hydrochloride of 2.5, 5 or 10 mg. Plasma and urine samples were collected for up to 24 h after intravenous administration of oxycodone hydrochloride. RESULTS: Pharmacokinetic parameters showed that mean values of C(max), AUC(0-t) and AUC(0-∞) of oxycodone were dose dependent, whereas Tmax and t(1/2) were not. The mean AUC(0-t) ratio of noroxycodone to oxycodone ranged from 0.35 to 0.42 over three doses, and those of noroxymorphone, or oxymorphone, to oxycodone were ranging of 0.06-0.08 and 0.007-0.008, respectively. Oxycodone and its three metabolites were excreted from urine. Approximately 10% of unchanged oxycodone was recovered in 24 h. Most adverse events (AEs) reported were mild to moderate. The frequently occurred AEs were dizziness, nausea, vomiting, drowsiness and fatigue. No dose-related AEs were found. CONCLUSION: Our pharmacokinetics of oxycodone injection in Chinese patients with pain strongly support continued development of oxycodone as an effective analgesic drug in China.

[Study of rat lumbar vertebral endplate via micro computed tomography].

OBJECTIVE: To reconstruct the 3-dimensional (3D) models of vertebral endplate and internal canal structure based upon the micro computed tomography (MicroCT) scanning data and clarify the structural characteristics and changes of bone, canals and lumbar vertebral endplates with advancing age in SD rats. METHODS: Lumbar spines from male SD rats aged 3, 9 and 16 months (n = 15 each) were subjected to MicroCT scan. Mimics software was used to reconstruct the 3D models of lumbar vertebral endplate and internal canal structure. The bone volume fraction (BV/TV) of endplate was measured by CTAn software. RESULTS: The rebuilt 3D models of vertebral endplate showed that lumbar endplate was a thin layer of bone and the canals within vertebral endplate formed a ring-shaped canal network after reconstruction. Communicating branches existed between the adjacent canals. Every ring-shaped canal connected with trunk canals lying in the ventral and dorsal portions of endplate. The BV/TV of endplate in the ventral portion was lower than that in dorsal portion (ventral side: 79.9% ± 7.3%; dorsal side: 90.6% ± 6.2%, P < 0.05) and BV/TV increased with advancing age. CONCLUSION: The canals within rat lumbar vertebral endplate are not haphazard, but regularly arrayed to form a ring-shaped network of many circular canals, communicating branches and ventral and dorsal trunk canals. This canal network provides channels for blood vessels within endplate. The ratio of older rat canals decreases in endplate.

Shrinkage empirical likelihood estimator in longitudinal analysis with time-dependent covariates--application to modeling the health of Filipino children.

The method of generalized estimating equations (GEE) is a popular tool for analysing longitudinal (panel) data. Often, the covariates collected are time-dependent in nature, for example, age, relapse status, monthly income. When using GEE to analyse longitudinal data with time-dependent covariates, crucial assumptions about the covariates are necessary for valid inferences to be drawn. When those assumptions do not hold or cannot be verified, Pepe and Anderson (1994, Communications in Statistics, Simulations and Computation 23, 939-951) advocated using an independence working correlation assumption in the GEE model as a robust approach. However, using GEE with the independence correlation assumption may lead to significant efficiency loss (Fitzmaurice, 1995, Biometrics 51, 309-317). In this article, we propose a method that extracts additional information from the estimating equations that are excluded by the independence assumption. The method always includes the estimating equations under the independence assumption and the contribution from the remaining estimating equations is weighted according to the likelihood of each equation being a consistent estimating equation and the information it carries. We apply the method to a longitudinal study of the health of a group of Filipino children.

[Complications of treatment of acromioclavicular joint dislocation and unstable distal clavicular fracture with clavicular hook plate].

OBJECTIVE: To investigate the causes and prevention of the complications about treatment of acromioclavicular joint dislocation (Tossy III) and unstable distal clavicular fracture (Neer II) with clavicular hook plate. METHODS: From January 2001 to December 2011, 246 patients with acromioclavicular joint dislocation (Tossy III) and 222 patients with unstable distal clavicular fracture (Neer II) were treated with acromioclvicular hook plate fixation,including 348 males and 120 females with an average age of 45.4 years old ranging from 21 to 80 years old. The mean time from injury to operation was 30.8 hours (ranged from 1 h to 15 d). All patients had normal shoulder function before injury. According to Karlsson evaluation standard, the cases with excellent and good function of the shoulder joint were regarded as the normal group, and the cases with poor function of shoulder joint as the abnormal group. The comparison of the range of forward flexion,backward stretch, adduction, abduction and elevation of shoulder joints between two groups was performed. The data of impingement, subacromial osteolysis, acromioclavicular arthritis, clavicular stress fracture, downward acromioclavicular joint subluxation, hook cut-out and hook break were summarized. RESULTS: All patients were followed up from 8 to 48 months with an average of 12.5 months. The results were excellent in 308 cases,good in 76,and poor in 84 according to Karlsson evaluation. The excellent and good rate was 82.1%. The difference of the range of forward flexion, backward stretch, adduction, abduction and elevation of shoulder joints between two groups had a statistically significant difference (P < 0.01). Among 84 poor cases, there were 41 (8.76%) in acromial impingement or inadequate place of plate hook, 12 (2.56%) with subacromial osteolysis or/and bursitis, 10 (2.14%) with acromioclavicular arthritis or painful shoulder caused by delayed dirigation,7 (1.50%) with clavicular stress fracture or interal plate upward, 6 (1.28%) with downward acromioclavicular joint subluxation, 5 (1.07%) with hook cut -out and 3 (0.64%) in hook break. CONCLUSION: The clavicular hook plate is useful for the treatment of acromioclavicular joint dislocation (Tossy III) and unstable distal clavicular fracture (Neer II). The correct place and suitable preflex of plate hook,the restoration of fiber structure around the acromioclavicular joint and the advisable dirigation contribute to the modified rate of complications.

[The prevalence and risk factors of kidney disease in type 2 diabetic patients in rural Shanghai].

OBJECTIVE: To identify the prevalence and etiology of kidney disease and the related risk factors in type 2 diabetic patients in rural Shanghai. METHODS: A cross-sectional study in type 2 diabetic patients was conducted in a community of Shanghai. Questionnaire, clinical examination and laboratory tests were completed to collect the information about sociodemographic and healthcare characteristics. RESULTS: A total of 1421 eligible patients with complete information were screened from 1487 type 2 diabetic patients between November 2008 and March 2009. Of them, 40.75% were men, 59.25% were women, aged 37 - 86 (61.33 ± 9.65) years old, with diabetic duration of 0.25 - 43.92 (7.85 ± 6.34) years. Among them, 43.42% had diabetic retinopathy, 21.18% had neuropathy; 69.95% met the screening definition for hypertension, 76.07% for hyperlipidemia, 15.55% for hyperuricemia and 23.65% for cardiovascular disease. The control rates of fasting blood glucose, glycosylated hemoglobin, blood pressure and serum cholesterol were 57.71%, 33.99%, 14.22% and 2.46%, respectively. The prevalence of kidney disease, diabetic nephropathy and non-diabetic renal disease was 41.31%, 18.51% and 13.44%, respectively; and 9.36% were diagnosed as renal insufficiency of unknown reasons. Age, diabetic duration, hyperuricemia, diabetic retinopathy and poor control of blood pressure were independently associated with kidney disease; age and poor control of blood pressure were independently associated with diabetic nephropathy; age and hyperuricemia were independent risk factors of renal insufficiency in patients with diabetic nephropathy. CONCLUSIONS: Although the diabetic duration of these subjects is relatively short, the prevalence of complications including diabetic nephropathy is high. The high prevalence of non-diabetic renal disease shows the importance of further screening and diagnoses for prevention. Strict control of blood glucose, blood pressure, serum cholesterol and serum uric acid are key points of cutting down the prevalence of diabetic nephropathy and chronic kidney disease.

Circuit-based method for synthesizing of coupled-resonators bandpass photonic crystal filters.

A method for synthesizing bandpass photonic crystal filters for wavelength division multiplexing (WDM) systems is presented. The proposed method permits the calculation of the physical dimensions of the crystalline structures given the desired frequency response of the filter in terms of bandwidth, in-band ripple, minimum out-of-band attenuation, and central frequency. The method, explained in detail for Chebyshev frequency responses, is equivalent circuit based. The resulting devices are very compact, have a high out-of-band attenuation, and are suitable for high density photonic integrated circuits. The validity of the proposed method is confirmed through contrasting the simulation concluded from the finite-difference time-domain (FDTD) method by the design of a third-order Chebyshev filter having a center frequency of 1 THz, a flat bandwidth of 4 GHz, and ripples of 0.5 dB in the passband.

[Study on fat-soluble components in different parts of miao ethnomedicine Pileostegia viburnoides by the herbal blitzkrieg extractor].

OBJECTIVE: To study the fat-soluble components in different parts of Pileostegia viburnoides. METHODS: The fat-soluble components in different parts of Pileostegia viburnoides were extracted by Herbal Blitzkrieg Extractor (HBE), and its constituents were analyzed by GC-MS. RESULTS: 37 compounds from the stems, 14 compounds from the leaves were separated and identified. The ratios of identification of total compounds were 90. 63% and 81.61%, respectively. CONCLUSION: This result provides the scientific basis for ex-ploiting resources of Miao ethnomedicine Pileostegia viburnoides.

Amelioration of dementia induced by Aß 22-35 through rectal delivery of undecapeptide-hEGF to mouse brain.

A group of growth factors have been shown to play important roles in amelioration of the malfunction of the neurodegenerative diseases. However, the proteins or polypeptides passing across the blood-brain barrier (BBB) to access the brain parenchyma are relatively few so that it hinders the therapies in clinic. Here a genetically reconstructed fusion peptide of human epidermal growth factor (hEGF) with an undecapeptide YGRKKRRQRRR (P11) was used to investigate the permeability between the cell membrane and the BBB via rectal administration. The efficiency to rescue the Aß 22-35-induced dementia in mice was assessed after administration of P11-hEGF per rectal. Our results showed that P11-hEGF permeates across not only the 3T3 cell membrane in vitro, but also the endothelia of vessels after intravenous injection (IV), and the mucosa of the rectum after per rectal administration. Further results showed that the circulating P11-hEGF allowed penetrating through the blood-brain barrier and then getting into the brain manifesting biological responses. In the animal experiments, treatment with P11-hEGF not only ameliorated the dementia induced by Aß 22-35 but also rescued the dementia of the aged mice, no matter how it was administrated (IV or per rectal). These results suggest that the rectal non-invasive delivery of the P11 polypeptide-conjugated growth factor is an efficient way for BBB transduction, thus raises the hope of real therapeutic progress against neurodegenerative diseases.

Single-dose safety, pharmacokinetics, and food effects studies of compound naphthoquine phosphate tablets in healthy volunteers.

The compound naphthoquine phosphate is a novel antimalaria drug tablet containing a fixed-dose combination of naphthoquine phosphate and artemisinin in a 1:2.5 ratio. A randomized, open study on the safety and tolerability was conducted in 28 healthy male volunteers using a single oral dose of 350 mg, 700 mg, 1400 mg, or 2100 mg of artemisinin-naphthoquine phosphate. Pharmacokinetics at the last 3 doses were examined in 30 volunteers. Food effects were also determined. Serial blood samples up to 216 hours after single oral dose administration were analyzed for plasma concentrations using a validated high-performance liquid chromatography-tandem mass spectrometry assay. The compound was well tolerated at single doses up to 2100 mg. Increased exposure to naphthoquine phosphate and artemisinin was less than dose proportional and linear. The half-life of naphthoquine phosphate was approximately 255 hours. The combination increased the AUC(0-t) and C(max) of both artemisinin (by 71% and 49%) and naphthoquine phosphate (by 135% and 104%) compared with monotherapy. Food intake greatly increased the AUC(0-t) of artemisinin with a ratio of 77% and reduced that of naphthoquine phosphate from 955 ± 352 µg·h/L under the fasted state to 446 ± 231 µg·h/L in the fed condition. The pharmacokinetics and safety profile of the drug support its continued investigation in future clinical studies.

Changes of autologous neural stem cells in the hippocampi of aging mice.

Although there is possibility of cognitive disturbance in aging people, many of them live for long life and enjoy well-functioning brain during the whole life-span. The biological basis of longevity is unknown. In this study, we investigated the influence of aging on hippocampal neural stem cells (NSCs), and the correlations between hippocampal neurogenesis and cognitive function. The result showed that the protein production and mRNA expression of nestin, and the number of BrdU(+) cells in dentate gyrus (DG) of the aged non-dementia mice were clearly higher than that in the aged dementia mice and the young adult mice. We also found that the number of NeuN(+) (neuron-specific nuclear antigen) cells in DG and CA1, choline O-acetyltransferase (ChAT, EC 2.3.1.6) production and mRNA expression in hippocampi of the aged-dementia mice were significantly reduced as compared to that of the young adult mice and the aged non-dementia mice, whereas the number of NeuN(+) cells, ChAT production and mRNA expression of the aged non-dementia mice has no difference with that of the young adult mice. Glial fibrillary acidic protein (GFAP) expression in the hippocampi of aged dementia mice significantly higher than that of the young adult mice and the aged non-dementia mice. Our results suggest that aging sometimes does not cause changing of the number of neurons and the hippocampal neurogenesis. Increment of DNA replication and neuron replacement, promotion of differentiation of neural stem cells, enhancement of neuronal proliferation, facilitation of synaptic plasticity of neurons may all benefit to the maintenance of the normal cognitive ability in the aged mice.