The analysis aimed to identify the treatment gaps in current fracture liaison services (FLS) and to provide recommendations for best practice establishment of future FLS across the Asia-Pacific ...region. The findings emphasize the unmet need for the implementation of new programs and provide recommendations for the refinement of existing ones. The study’s objectives were to evaluate fracture liaison service (FLS) programs in the Asia-Pacific region and provide recommendations for establishment of future FLS programs. A systematic literature review (SLR) of Medline, PubMed, EMBASE, and Cochrane Library (2000–2017 inclusive) was performed using the following keywords: osteoporosis, fractures, liaison, and service. Inclusion criteria included the following: patients ≥ 50 years with osteoporosis-related fractures; randomized controlled trials or observational studies with control groups (prospective or retrospective), pre–post, cross-sectional and economic evaluation studies. Success of direct or indirect interventions was assessed based on patients’ understanding of risk, bone mineral density assessment, calcium intake, osteoporosis treatment, re-fracture rates, adherence, and mortality, in addition to cost-effectiveness. Overall, 5663 unique citations were identified and the SLR identified 159 publications, reporting 37 studies in Asia-Pacific. These studies revealed the unmet need for public health education, adequate funding, and staff resourcing, along with greater cooperation between departments and physicians. These actions can help to overcome therapeutic inertia with sufficient follow-up to ensure adherence to recommendations and compliance with treatment. The findings also emphasize the importance of primary care physicians continuing to prescribe treatment and ensure service remains convenient. These findings highlight the limited evidence supporting FLS across the Asia-Pacific region, emphasizing the unmet need for new programs and/or refinement of existing ones to improve outcomes. With the continued increase in burden of fractures in Asia-Pacific, establishment of new FLS and assessment of existing services are warranted to determine the impact of FLS for healthcare professionals, patients, family/caregivers, and society.
Matrix metalloproteinase (MMP)-2 plays critical roles in tumor development and in the metastasis of multiple cancers, including human oral cavity squamous cell carcinoma (OCSCC). One of the upstream ...regulators of MMP-2 is FOXM1, which is overexpressed in a microarray dataset of OCSCC. It is interesting that FLJ10540 exhibits similar gene expression profiles with MMP-2 and FOXM1, raising the possibility that these molecules might participate in MMP-2-elicited cancer progression and metastasis of OCSCC. To examine this connection, we first showed that FLJ10540 was significantly overexpressed in OCSCC. A strong FLJ10540 expression was significantly correlated with an advanced tumor node metastasis stage and the cumulative 5-year survival rate. Thus, an elevated FLJ10540 expression is an indicator of poor survival. Functionally, FLJ10540 had the abilities to stimulate cell migration and invasion in oral cancer cells through increased FOXM1 and MMP-2 expressions. Conversely, the depletion of the FLJ10540 expression by small interfering RNAs suppressed the FOXM1 and MMP-2 protein expressions. The suppression of either FLJ10540 or FOXM1 could cause significant inhibition on cell migratory and invasive ability in oral cancer cells. Finally, the immunohistochemical and western blotting analyses of human aggressive OCSCC specimens showed a significant positive correlation among FLJ10540, FOXM1 and MMP-2 expressions. These findings suggest that FLJ10540 is not only an important prognostic factor but also a new therapeutic target in the FLJ10540/FOXM1/MMP-2 pathway for OCSCC treatment.
Ten years since the immune checkpoint inhibitor ipilimumab was approved for advanced melanoma, it is time to reflect on the lessons learned regarding modulation of the immune system to treat cancer ...and on novel approaches to further extend the efficacy of current and emerging immunotherapies. Here, we review the studies that led to our current understanding of the melanoma immune microenvironment in humans and the mechanistic work supporting these observations. We discuss how this information is guiding more precise analyses of the mechanisms of action of immune checkpoint blockade and novel immunotherapeutic approaches. Lastly, we review emerging evidence supporting the negative impact of melanoma metabolic adaptation on anti-tumor immunity and discuss how to counteract such mechanisms for more successful use of immunotherapy.
This review focuses on the development of nanoparticle systems for antimicrobial drug delivery. Numerous antimicrobial drugs have been prescribed to kill or inhibit the growth of microbes such as ...bacteria, fungi and viruses. Even though the therapeutic efficacy of these drugs has been well established, inefficient delivery could result in inadequate therapeutic index and local and systemic side effects including cutaneous irritation, peeling, scaling and gut flora reduction. Nanostructured biomaterials, nanoparticles in particular, have unique physicochemical properties such as ultra small and controllable size, large surface area to mass ratio, high reactivity, and functionalizable structure. These properties can be applied to facilitate the administration of antimicrobial drugs, thereby overcoming some of the limitations in traditional antimicrobial therapeutics. In recent years, encapsulation of antimicrobial drugs in nanoparticle systems has emerged as an innovative and promising alternative that enhances therapeutic effectiveness and minimizes undesirable side effects of the drugs. Here the current progress and challenges in synthesizing nanoparticle platforms for delivering various antimicrobial drugs are reviewed. We also call attention to the need to unite the shared interest between nanoengineers and microbiologists in developing nanotechnology for the treatment of microbial diseases.
Pure CO ice has been irradiated with electrons of energy in the range 150−1000 eV with the Interstellar Energetic-Process System. The main products of irradiation are carbon chains Cn (n = 3, 5, 6, ...8, 9, 10, 11, 12), suboxides, CnO (n = 2, 3, 4, 5, 6, 7), and CnO2 (n = 1, 3, 4, 5, 7) species. CO2 is by far the most abundant reaction product in all the experiments. The destruction cross section of CO peaks at about 250 eV, decreases with the energy of the electrons and is more than one order of magnitude higher than for gas-phase CO ionization. The production cross section of carbon dioxide has been also derived and is characterized by the competition between chemistry and desorption. Desorption of CO and of new species during the radiolysis follows the electron distribution in the ice. Low-energy electrons having short penetration depths induce significant desorption. Finally, as the ice thickness approaches the electron penetration depth the abundance of the products starts to saturate. Implications on the atmospheric photochemistry of cold planets hosting surface CO ices are also discussed.
. Huang C‐N, Huang S‐P, Pao J‐B, Hour T‐C, Chang T‐Y, Lan Y‐H, Lu T‐L, Lee H‐Z, Juang S‐H, Wu P‐P, Huang C‐Y, Hsieh C‐J, Bao B‐Y (Kaohsiung Medical University Hospital, Kaohsiung; Kaohsiung Medical ...University, Kaohsiung; Taipei City Hospital, Taipei; Kaohsiung Medical University, Kaohsiung; China Medical University, Taichung; National Taiwan University Hospital; Oriental Institute of Technology; National Taiwan University, Taipei; China Medical University Hospital, Taichung, Taiwan). Genetic polymorphisms in oestrogen receptor‐binding sites affect clinical outcomes in patients with prostate cancer receiving androgen‐deprivation therapy. J Intern Med 2012; 271: 499–509.
Background. Accumulating evidence indicates that oestrogens have significant direct effects on normal prostate development and carcinogenesis. The majority of the biological activities of oestrogens are mediated through the oestrogen receptor (ER), which functions as a hormone‐inducible transcription factor to regulate target gene expression by binding to oestrogen response elements (EREs) in the regulatory regions of target genes. Sequence variants in EREs might affect the ER–ERE interaction and subsequent physiological activities. Therefore, we tested whether common single‐nucleotide polymorphisms (SNPs) inside EREs are related to the clinical outcomes of androgen‐deprivation therapy (ADT) in men with prostate cancer.
Methods. We systematically evaluated 49 ERE SNPs predicted using a genome‐wide database in a cohort of 601 men with advanced prostate cancer treated with ADT. The prognostic significance of these SNPs on disease progression, prostate cancer‐specific mortality (PCSM) and all‐cause mortality (ACM) after ADT was assessed using Kaplan–Meier analysis and a Cox regression model.
Results. Based on multiple hypothesis testing, BNC2 rs16934641 was found to be associated with disease progression; in addition, TACC2 rs3763763 was associated with PCSM, and ALPK1 rs2051778 and TACC2 rs3763763 were associated with ACM. These SNPs remained significant in multivariate analyses that included known clinicopathological predictors. Moreover, a combined genotype effect on ACM was observed when ALPK1 rs2051778 and TACC2 rs3763763 were analysed in combination. Patients with a greater number of unfavourable genotypes had a shorter time to ACM during ADT (P for trend <0.001).
Conclusion. The incorporation of ERE SNPs into models with known predictors might improve outcome prediction in patients with prostate cancer receiving ADT.
Postprocedural infections by Mycobacterium abscessus complex are increasing worldwide, and the source and route of transmission are infrequently identified. Here the extension of a previous ...clustering of paediatric patients with surgical site infections due to a single strain of the subspecies M. massiliense is reported. The investigation was conducted at a 2200-bed teaching hospital in Taiwan and included microbial surveillance of the environment (water, air, equipment and supplies) and a case–control study. We performed molecular identification and typing of the isolates by a trilocus sequencing scheme, confirmed by multilocus sequencing typing and pulsed-field gel electrophoresis. We investigated 40 patients who developed postprocedure soft tissue or bloodstream infections by M. massiliense (TPE101) during a 3-year period. Thirty-eight patients were identified at hospital A, and one newborn and her mother were identified at hospital B (185 km from hospital A). A case–control study identified the association of invasive procedures (adjusted odds ratio, 9.13) and ultrasonography (adjusted odds ratio, 2.97) (both p <0.05) with acquiring the outbreak strain. Isolates from the cases and unopened bottles of ultrasound transmission gel were all of strain ST48 and indistinguishable or closely related by pulsed-field gel electrophoresis. After replacement of contaminated gel, no new cases were detected during 18 months' follow-up. This investigation identified the use of contaminated gel as the common source causing an outbreak on a larger scale than had been recognized. Our findings halted production by the manufacturer and prompted revision of hospital guidelines.
Blended learning combines online digital resources with traditional classroom activities and enables students to attain higher learning performance through well-defined interactive strategies ...involving online and traditional learning activities. Learning analytics is a conceptual framework and as a part of our Precision education used to analyze and predict students' performance and provide timely interventions based on student learning profiles. This study applied learning analytics and educational big data approaches for the early prediction of students' final academic performance in a blended Calculus course. Real data with 21 variables were collected from the proposed course, consisting of video-viewing behaviors, out-of-class practice behaviors, homework and quiz scores, and after-school tutoring. This study applied principal component regression to predict students' final academic performance. The experimental results show that students' final academic performance could be predicted when only one-third of the semester had elapsed. In addition, we identified seven critical factors that affect students' academic performance, consisting of four online factors and three traditional factors. The results showed that the blended data set combining online and traditional critical factors had the highest predictive performance.
Not only is Asia the most populous region in the world, but inappropriate therapy, including seif-medication with over-the-counter antimicrobial agents, is a common response to infectious diseases. ...The high antibiotic selective pressure among the overcrowded inhabitants creates an environment that is suitable for the rapid development and efficient spread of numerous multidrug-resistant pathogens. Indeed, Asia is among the regions with the highest prevalence rates of healthcare-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) and community-associated methicillin-resistant S. aureus (CA-MRSA) in the world. Most hospitals in Asia are endemic for multidrug-resistant methicillin-resistant S. aureus (MRSA), with an estimated proportion from 28% (in Hong Kong and Indonesia) to >70% (in Korea) among all clinical S. aureus isolates in the early 2010s. Isolates with reduced susceptibility or a high level of resistance to glycopeptides have also been increasingly identified in the past few years. In contrast, the proportion of MRSA among community-associated S. aureus infections in Asian countries varies markedly, from <5% to >35%. Two pandemic HA-MRSA clones, namely multilocus sequence type (ST) 239 and ST5, are disseminated internationally in Asia, whereas the molecular epidemiology of CA-MRSA in Asia is characterized by clonal heterogeneity, similar to that in Europe. In this review, the epidemiology of S. aureus in both healthcare facilities and communities in Asia is addressed, with an emphasis on the prevalence, clonal structure and antibiotic resistant profiles of the MRSA strains. The novel MRSA strains from livestock animals have been considered to constitute a public health threat in western countries. The emerging livestock-associated MRSA strains in Asia are also included in this review.
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