Explore the vast range of titles available.

Background Small studies suggest an association of donor-specific anti-human leukocyte antigen (HLA) antibodies (DSAs) with primary graft failure (GF) following haploidentical stem cell transplantation, but primary graft rejection (GR) was not discriminated from primary poor graft function (PGF). In this study, we aimed to determine the association of DSAs with primary GF, including GR and PGF, in patients who underwent unmanipulated haploidentical blood and marrow transplantation. Methods A total of 345 subjects were prospectively recruited and randomly selected as training group ( n  = 173) and validation group ( n  = 172). Patient plasma/serum was screened. For HLA antibody positive samples with a median fluorescent intensity (MFI) >500, DSAs were further tested using a LABScreen Single Antigen Kit (One Lambda). Results A total of 342 patients (99.1 %) achieved sustained myeloid engraftment. The median times to neutrophil engraftment and platelet engraftment were 13 days (range, 8–28 days) and 18 days (range, 6–330 days), respectively. The cumulative incidence of primary GF was 6.4 ± 1.3 % and included GR (0.9 ± 0.5 %) and PGF (5.5 ± 1.2 %). Of the 345 cases tested, 39 (11.3 %) were DSA positive. Multivariate models showed that DSAs (MFI ≥ 10,000) were correlated to primary GR ( P  < 0.001) and that DSAs (MFI ≥ 2000) were strongly associated with primary PGF ( P  = 0.005). All patients were classified into three groups for analysis. Group A included cases that were DSA negative and those with a DSA MFI <2000 ( n  = 316), group B included cases with a 2000 ≤ MFI < 10,000 ( n  = 19), and group C included cases with a MFI ≥10,000 ( n  = 10). The DSAs were associated with an increased incidence of the primary GF (3.2 vs. 31.6 vs. 60 %, for groups A, B, and C, respectively, P  < 0.001), transplant-related mortality (TRM) rate (17.2 vs. 14.7 vs. 33.3 %, for groups A, B, and C, respectively, P  = 0.022), and inferior overall survival (OS, 77.3 vs. 85.3 vs. 44.4 %, for groups A, B, and C, respectively, P  = 0.015). The primary GF was independently associated with a higher incidence of TRM ( P  < 0.001), inferior disease-free survival ( P  < 0.001), and OS ( P  < 0.001). Conclusions The findings confirmed the effect of DSAs on primary GF, including GR and PGF, and survival. Our results suggest incorporating DSAs in the algorithm for haploidentical donor selection.

Tingjie Yin,* Lihui Dong,* Bei Cui, Lei Wang, Lifang Yin, Jianping Zhou, Meirong Huo State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing, People's Republic of China *These authors contributed equally tothis work Abstract: Clinically, paclitaxel (PTX) is one of most commonly prescribed therapies against a wide range of solid neoplasms. Despite its success, the clinical applicability of PTX (Taxol®) is severely hampered by systemic toxicities induced by Cremophor EL. While attempts to bypass the need for Cremophor EL have been developed through platforms such as Abraxane™, nab™ relies heavily on the use of organic solvents, namely, chloroform. The toxicity introduced by residual chloroform poses a potential risk to patient health. To mitigate the toxicities of toxic organic solvent-based manufacture methods, we have designed a method for the formulation of PTX nanosuspensions (PTX-PEG [polyethylene glycol]-HSA [human serum albumin]) that eliminates the dependence on toxic organic solvents. Coined the solid-dispersion technology, this technique permits the dispersion of PTX into PEG skeleton without the use of organic solvents or Cremophor EL as a solubilizer. Once the PTX-PEG dispersion is complete, the dispersion can be formulated with HSA into nanosuspensions suitable for intravenous administration. Additionally, the incorporation of PEG permits the prolonged circulation through the steric stabilization effect. Finally, HSA-mediated targeting permits active receptor-mediated endocytosis for enhanced tumor uptake and reduced side effects. By eliminating the need for both Cremophor EL and organic solvents while simultaneously increasing antitumor efficacy, this method provides a superior alternative to currently accepted methods for PTX delivery. Keywords: human serum albumin, nanosuspension, paclitaxel, polyethylene glycol, solid-dispersion technology

Measures of pain sensitivity have potential relevance for patient care. We previously identified a subgroup of people at risk for ongoing pain characterized by genetic AND psychological factors. Here, we report planned secondary analyses examining the effect of personalized interventions on pain sensitivity outcomes. Two hundred and sixty-one healthy individuals with the COMT SNP rs6269 AA genotype and Pain Catastrophizing Scale scores of 5 or higher received exercise-induced muscle injury, followed by a randomly assigned treatment: (1) general education and placebo; (2) personalized psychological intervention and placebo; (3) general education and propranolol; or (4) personalized psychological intervention and propranolol. Pain sensitivity outcomes (pressure pain thresholds (PPT), suprathreshold heat rating, temporal summation, and conditioned pain modulation efficiency) were compared using a mixed effect model to examine difference among groups, adjusted for age, sex and race. No main effects for group assignment were noted (p > 0.05 for all), when considered as 4 groups or 2 collapsed groups (ie propranolol vs placebo or personalized psychologic vs general education). Interaction terms were then entered into our models in an exploratory fashion. For PPT outcomes interactions were noted for, sex and time, and race and time (p<0.015). For temporal summation outcomes, interactions were noted for sex and group and race and group (p < 0.015). Results indicated no statistically reliable changes in pain sensitivity when considering matched vs unmatched treatment groups. Caution is needed in this interpretation given that the trial was not powered to specifically identify these differences. Exploratory analysis of interactions among ethnic/racial and gender identities by treatment, however, showed the potential for differential effects for specific pain sensitivity measures. Significant interactions across modalities suggest analysis of higher order interactions/intersectionality could be of great interest for testing efficacy of personalized interventions in future trials.

In this study, quasi-three-dimensional (3D) microwell patterns were fabricated with poly (l-lactic acid) for the development of cell-based assays, targeting voltage-gated calcium channels (VGCCs). SH-SY5Y human neuroblastoma cells were interfaced with the microwell patterns and found to grow as two dimensional (2D), 3D, and near two dimensional (N2D), categorized on the basis of the cells' location in the pattern. The capability of the microwell patterns to support 3D cell growth was evaluated in terms of the percentage of the cells in each growth category. Cell spreading was analyzed in terms of projection areas under light microscopy. SH-SY5Y cells' VGCC responsiveness was evaluated with confocal microscopy and a calcium fluorescent indicator, Calcium Green™-1. The expression of L-type calcium channels was evaluated using immunofluorescence staining with DM-BODIPY. It was found that cells within the microwells, either N2D or 3D, showed more rounded shapes and less projection areas than 2D cells on flat poly (l-lactic acid) substrates. Also, cells in microwells showed a significantly lower VGCC responsiveness than cells on flat substrates, in terms of both response magnitudes and percentages of responsive cells, upon depolarization with 50 mM K(+). This lower VGCC responsiveness could not be explained by the difference in L-type calcium channel expression. For the two patterns addressed in this study, N2D cells consistently exhibited an intermediate value of either projection areas or VGCC responsiveness between those for 2D and 3D cells, suggesting a correlative relation between cell morphology and VGCC responsiveness. These results suggest that the pattern structure and therefore the cell growth characteristics were critical factors in determining cell VGCC responsiveness and thus provide an approach for engineering cell functionality in cell-based assay systems and tissue engineering scaffolds.

The Southern African Customs Union (SACU) is the oldest customs union in the world, with significant opportunities ahead for creating higher economic growth and increased welfare benefits to the people of the region, by fulfilling its vision to become an economic community with a common market and monetary union. This volume describes policy options to address the barriers to equitable and sustainable development in the region and outlines a plan for deeper regional integration.

AbstractThis study reviewed the incidence of heterotopic ossification and the functional limitations in a cohort of consecutive patients with prior stroke who underwent primary total hip arthroplasty (THA). Thirty-one primary THAs were performed in 22 patients who had a cerebrovascular accident prior to THA. Mean follow-up was 35 months. The overall incidence of heterotopic ossification was 36%, with significant Brooker class III and IV heterotopic ossification reported in 22% of patients. The data suggest that prior cerebrovascular accident may pose an increased risk of significant heterotopic ossification following primary THA. Consideration of prophylaxis in this subset of patients may be warranted.

Bovine bone morphogenetic protein (bBMP) induces differentiation of mesenchymal-type cells into cartilage and bone. bBMP has an apparent Mrof 18,500 ± 500 and represents <0.001% of the wet weight of bone tissue. A Mr34,000 protein resembling osteonectin is separated by extraction with Triton X-100. A Mr24,000 protein and about half of a Mr22,000 protein are disassociated from bBMP by precipitation in 1.5 M guanidine hydrochloride. Aggregates of bBMP and a Mr14,000 protein are insoluble in aqueous media; the bBMP becomes soluble when the Mr14,000 protein is disassociated in 6 M urea and removed from the solution by ultrafiltration. Three separate molecular species with apparent Mrs 18,500, 17,500, and 17,000 are eluted at 0.10, 0.15, and 0.20 M phosphate ion concentrations, respectively, from a hydroxy-apatite column. The Mr18,500 protein has the amino acid composition of acidic polypeptide and includes four halfcystine residues; the pI is 4.9-5.1. The Mr22,000 component is a chromoprotein resembling ferritin. The NH2-terminal amino acid sequence of the Mr17,500 protein simulates histone H2B. The Mr17,000 protein may possess calmodulin activity. Aggregates of the Mr18,500 and other proteins induce formation of large deposits of bone; the Mr18,500 protein alone is rapidly absorbed and induces formation of small deposits. None of the other proteins induces bone formation.

Frontier economies are receiving increasing attention from policymakers, investors, and academics. Compared with other low-income countries they have experienced rapid growth over the last two decades, giving rise to speculation as to whether they will become the next generation of emerging markets. This book looks at the growing importance of the countries that make up frontier and developing Asia from different angles, including achieving inclusive growth, financial sector deepening, and strengthening policy frameworks.

Despite its vast oil wealth, central Africa still struggles to sustain strong, inclusive economic growth or to generate sufficient employment opportunities, particularly for its fast-growing youth population. Drawing on new research, Oil Wealth in Central Africa lays out the macroeconomic and growth challenges facing the region; examines oil wealth management and its implications for poverty reduction; and includes four case studies that exemplify lessons learned.

China has reached a stage where further financial sector reforms appear essential. As the reform process progresses and macrofinancial linkages deepen, the preservation of financial stability will become a major policy preoccupation. China is already working toward enhancing its surveillance and monitoring capabilities and is actively determining ways to undertake a series of reforms that would lay the foundation for a strong, sustained, and balanced growth. \"China's Road to Economic Stability\" focuses on the key financial policy issues facing China today. The volume draws upon contributions from senior Chinese authorities and academics, as well as staff from the IMF to discuss the financial policy context within China, macroeconomic factors affecting financial stability, and the critical role of financial system oversight. It seeks to improve the understanding of the financial sector policy processes underway and the shifts taking place among China's economic priorities. The book also covers issues such as the financial stability framework, systemic linkages, liquidity management, risk and vulnerability analysis, and sequencing financial reforms. The book is a must read for academics, researchers, and stakeholders interested in China and the shifts taking place in the manner in which China views its financial sector policies and oversees the stability of the financial system.