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1.
Heliyon ; 9(8): e18163, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37554832

ABSTRACT

Mechanisms of the length and maximum radius of lotus-type or single pores in ice or nonmetals satisfied by Henry's law at gas-liquid interfaces dissolved by a gas during unidirectional solidification are rigorously investigated and supported by a Table from algebraic predictions involving different dimensionless working parameters. Lotus-type porous materials characterized by directional properties have been often used as functional materials in food, biomedical, and micro- and nano-technologies. Following previous work taking into account solute amount and transport within the pore, and concentration boundary layers on the advancing solid-liquid interface and bubble cap, and the Young-Laplace equation and Henry's law at liquid-gas interfaces, the algebraic study further provides a Table for a quantitative and extensive understanding of different mechanisms of length and maximum radius. Dimensionless parameters include solute transport parameters of Henry's law constant, mass transfer coefficient, partition coefficient, solute gas amount in imposed ambient, and solute transport parameter, and fluid and thermal parameters of solidification rate, imposed gas pressure, hydrostatic pressure, and geometrical parameter of inter-pore spacing. The controlling of the shapes of lotus-type pores is achieved by a good comparison between predicted maximum diameter and inter-pore spacing during freezing of water dissolved by oxygen gas.

2.
Mater Today Bio ; 12: 100129, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34604731

ABSTRACT

This study is the first to assess the applicability of biodegradable poly(1,4-butylene carbonate) (PBC) as a printing ink for fused deposition modeling (FDM). Here, PBC was successfully prepared via the bulk polycondensation of 1,4-butanediol and dimethyl carbonate. PBC was melted above 150°C in the heating chamber of an FDM printer, after which it flowed from the printing nozzle upon applying pressure and solidified at room temperature to create a three-dimensional (3D) scaffold structure. A 3D scaffold exactly matching the program design was obtained by controlling the temperature and pressure of the FDM printer. The compressive moduli of the printed PBC scaffold decreased as a function of implantation time. The printed PBC scaffold exhibited good in vitro biocompatibility, as well as in vivo neotissue formation and little host tissue response, which was proportional to the gradual biodegradation. Collectively, our findings demonstrated the feasibility of PBC as a suitable printing ink candidate for the creation of scaffolds via FDM printing.

3.
Med J Malaysia ; 75(5): 510-513, 2020 09.
Article in English | MEDLINE | ID: mdl-32918418

ABSTRACT

INTRODUCTION: Most of the authors currently agree that congenital talipes equinovarus (CTEV) or idiopathic clubfoot can be effectively treated with the Ponseti method instead of extensive soft tissue surgery. This study was conducted to investigate whether there is a difference in the outcome between starting treatment before one month of age or after that age. METHODS: This is a retrospective study on babies with CTEV treated in University Malaya Medical Centre from 2013 to 2017. The 54 babies (35 boys and 19 girls) were divided into two cohorts, Group 1 that had treatment before the age of one month, and Group 2 that had treatment after one month old. The number of cast changes, rate of full correction, and rate of relapse after treatment were compared between the two groups. RESULTS: Of the 54 babies, with 77 CTEV treated during the period, our outcome showed that the mean number of cast change was 5.9 for Group 1 and 5.7 for Group 2. The difference was not statistically significant. All the affected feet (100%) achieved full correction. One foot in the Group 1 relapsed, while three feet in Group 2 relapsed, but the difference was also not statistically significant. All of the relapsed feet were successfully treated with repeated Ponseti method. CONCLUSIONS: Treating CTEV using Ponseti method starting after one month was not associated with more casting change of higher rate of relapse.


Subject(s)
Braces , Clubfoot/therapy , Surgical Procedures, Operative , Female , Humans , Infant, Newborn , Malaysia , Male , Retrospective Studies , Secondary Prevention
4.
Clin Microbiol Infect ; 25(8): 1038.e1-1038.e9, 2019 Aug.
Article in English | MEDLINE | ID: mdl-30590113

ABSTRACT

OBJECTIVE: Despite numerous studies, the clinical value of sputum cultures in the management of pneumonia remains controversial; therefore, understanding the economic value of sputum cultures may help decision makers determine their appropriate use in patient management. METHODS: We developed a decision model to determine the economic and clinical value of using sputum cultures in the treatment of community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP) from the hospital perspective under various conditions. RESULTS: For both CAP and HCAP patients, obtaining sputum cultures resulted in similar costs compared to no culture, even if cultures cost $0. Given current clinical practices, obtaining cultures cost $539-631 more per CAP patient and $13-170 per HCAP patient compared to no culture use. However, cultures saved $8-202 per HCAP patient with a 40% probability the pathogen was the true cause (75% reduction in adverse outcomes, greater length of hospital stay (LOS) increase) to a 70% probability the pathogen was the true cause (25% reduction in outcomes and greater LOS increase and a 75% reduction in outcomes and all LOS increases). Additionally, obtaining sputum cultures had no impact on the number of adverse outcomes (i.e., adverse drug events, Clostridium difficile infection, pneumonia readmissions, additional hospitalization days). When all patients were treated with antibiotics empirically, obtaining cultures saved $4-342. CONCLUSIONS: Overall, obtaining sputum cultures does not provide significant clinical or economic benefits for CAP or HCAP patients; however, it can reduce costs and shorten overall LOS under some circumstances. Clinicians should consider their local conditions when making decisions about sputum culture use.


Subject(s)
Community-Acquired Infections/diagnosis , Community-Acquired Infections/economics , Healthcare-Associated Pneumonia/diagnosis , Healthcare-Associated Pneumonia/economics , Community-Acquired Infections/microbiology , Cross Infection/microbiology , Decision Support Systems, Clinical , Disease Management , Healthcare-Associated Pneumonia/microbiology , Hospitalization , Humans , Length of Stay , Sputum/microbiology
5.
Int J Tuberc Lung Dis ; 22(7): 820-826, 2018 07 01.
Article in English | MEDLINE | ID: mdl-29914609

ABSTRACT

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition that can differ in its clinical manifestation, structural changes and response to treatment. OBJECTIVE: To identify subgroups of COPD with distinct phenotypes, evaluate the distribution of phenotypes in four related regions and calculate the 1-year change in lung function and quality of life according to subgroup. METHODS: Using clinical characteristics, we performed factor analysis and hierarchical cluster analysis in a cohort of 1676 COPD patients from 13 Asian cities. We compared the 1-year change in forced expiratory volume in one second (FEV1), modified Medical Research Council dyspnoea scale score, St George's Respiratory Questionnaire (SGRQ) score and exacerbations according to subgroup derived from cluster analysis. RESULTS: Factor analysis revealed that body mass index, Charlson comorbidity index, SGRQ total score and FEV1 were principal factors. Using these four factors, cluster analysis identified three distinct subgroups with differing disease severity and symptoms. Among the three subgroups, patients in subgroup 2 (severe disease and more symptoms) had the most frequent exacerbations, most rapid FEV1 decline and greatest decline in SGRQ total score. CONCLUSION: Three subgroups with differing severities and symptoms were identified in Asian COPD subjects.


Subject(s)
Dyspnea/epidemiology , Pulmonary Disease, Chronic Obstructive/epidemiology , Quality of Life , Aged , Asia/epidemiology , Cities , Cluster Analysis , Cohort Studies , Dyspnea/etiology , Factor Analysis, Statistical , Female , Follow-Up Studies , Forced Expiratory Volume , Humans , Male , Middle Aged , Phenotype , Pulmonary Disease, Chronic Obstructive/physiopathology , Risk Factors , Severity of Illness Index , Surveys and Questionnaires
6.
Sci Total Environ ; 599-600: 2142-2155, 2017 Dec 01.
Article in English | MEDLINE | ID: mdl-28575929

ABSTRACT

Mitigating for the negative impacts of stormwater runoff is becoming a concern due to increased land development. Understanding how land development influences stormwater runoff is essential for sustainably managing water resources. In recent years, aggregate low impact development-best management practices (LID-BMPs) have been implemented to reduce the negative impacts of stormwater runoff on receiving water bodies. This study used an integrated approach to determine the influence of land development and assess the ecological benefits of four aggregate LID-BMPs in stormwater runoff from a mixed land use and land cover (LULC) catchment with ongoing land development. It used data from 2011 to 2015 that monitored 41 storm events and monthly LULC, and a Personalized Computer Storm Water Management Model (PCSWMM). The four aggregate LID-BMPs are: ecological (S1), utilizing pervious covers (S2), and multi-control (S3) and (S4). These LID-BMPs were designed and distributed in the study area based on catchment characteristics, cost, and effectiveness. PCSWMM was used to simulate the monitored storm events from 2014 (calibration: R2 and NSE>0.5; RMSE <11) and 2015 (validation: R2 and NSE>0.5; RMSE <12). For continuous simulation and analyzing LID-BMPs scenarios, the five-year (2011 to 2015) stormwater runoff data and LULC change patterns (only 2015 for LID-BMPs) were used. Results show that the expansion of bare land and impervious cover, soil alteration, and high amount of precipitation influenced the stormwater runoff variability during different phases of land development. The four aggregate LID-BMPs reduced runoff volume (34%-61%), peak flow (6%-19%), and pollutant concentrations (53%-83%). The results of this study, in addition to supporting local LULC planning and land development activities, also could be applied to input data for empirical modeling, and designing sustainable stormwater management guidelines and monitoring strategies.

7.
Pediatr Obes ; 12(3): e20-e23, 2017 06.
Article in English | MEDLINE | ID: mdl-27060703

ABSTRACT

BACKGROUND: Research on the types of interventions needed for population-level prevention of childhood obesity in complex societal systems can benefit from greater use of systems-science concepts and tools. OBJECTIVES: We report outcomes of a funding programme promoting incorporation of systems-science approaches into studies of imminent policy or environmental changes potentially impacting childhood obesity. METHODS: Seven funding cycles over 3 years yielded 172 initial submissions from 29 US states and 25 other countries were analyzed. RESULTS: Submissions focused primarily on aspects of school or child-care settings, parks and recreational settings, or access to healthy food; about half reflected attention to systems perspectives. CONCLUSIONS: Analysis of initial submissions as well as the 15 funded projects showed some success in motivating use of systems concepts and tools but suggested the need for a more focused effort to educate and prepare the childhood obesity prevention research community for this potentially crucial type of research.


Subject(s)
Financial Management/methods , Health Policy , Pediatric Obesity/prevention & control , Child , Humans , Motivation , Research/economics
8.
Clin Microbiol Infect ; 23(1): 48.e9-48.e16, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27642178

ABSTRACT

OBJECTIVES: The Centers for Disease Control and Prevention considers carbapenem-resistant Enterobacteriaceae (CRE) an urgent public health threat; however, its economic burden is unknown. METHODS: We developed a CRE clinical and economics outcomes model to determine the cost of CRE infection from the hospital, third-party payer, and societal, perspectives and to evaluate the health and economic burden of CRE to the USA. RESULTS: Depending on the infection type, the median cost of a single CRE infection can range from $22 484 to $66 031 for hospitals, $10 440 to $31 621 for third-party payers, and $37 778 to $83 512 for society. An infection incidence of 2.93 per 100 000 population in the USA (9418 infections) would cost hospitals $275 million (95% CR $217-334 million), third-party payers $147 million (95% CR $129-172 million), and society $553 million (95% CR $303-1593 million) with a 25% attributable mortality, and would result in the loss of 8841 (95% CR 5805-12 420) quality-adjusted life years. An incidence of 15 per 100 000 (48 213 infections) would cost hospitals $1.4 billion (95% CR $1.1-1.7 billion), third-party payers $0.8 billion (95% CR $0.6-0.8 billion), and society $2.8 billion (95% CR $1.6-8.2 billion), and result in the loss of 45 261 quality-adjusted life years. CONCLUSIONS: The cost of CRE is higher than the annual cost of many chronic diseases and of many acute diseases. Costs rise proportionally with the incidence of CRE, increasing by 2.0 times, 3.4 times, and 5.1 times for incidence rates of 6, 10, and 15 per 100 000 persons.


Subject(s)
Anti-Bacterial Agents/economics , Carbapenems/pharmacology , Drug Resistance, Bacterial , Enterobacteriaceae Infections/economics , Enterobacteriaceae Infections/therapy , Enterobacteriaceae/drug effects , Anti-Bacterial Agents/therapeutic use , Computer Simulation , Cost of Illness , Enterobacteriaceae Infections/epidemiology , Humans , Models, Economic , Monte Carlo Method , Risk Factors , United States/epidemiology
9.
Genet Mol Res ; 15(2)2016 Apr 28.
Article in English | MEDLINE | ID: mdl-27173282

ABSTRACT

Abies koreana is an endemic and rare species from Korea and is classified as endangered by the International Union for Conservation of Nature. Although the genetic diversity assessment for current population of A. koreana needs to be performed urgently, no microsatellite markers have been developed for this species. In the present study, we developed 22 novel polymorphic microsatellite loci and the characteristics of these loci were determined in A. koreana as well as in Abies nephrolepis, the most closely related species, and these loci were compared with previously reported microsatellite markers developed for the Abies genus. Genomic sequence (161 Mbp; 325,776 reads) was obtained from one individual of A. koreana using Roche 454 GS-FLX Titanium sequencing and 19,258 repeat motifs were identified from it. A total of 288 primer pairs with high copy numbers of di-repeat motifs were evaluated for amplification in A. koreana and A. nephrolepis. A total of 71 primer pairs successfully amplified fragments, of which 22 showed polymorphisms in A. koreana and A. nephrolepis. The average expected diversity was 0.767 and 0.717 in A. koreana and A. nephrolepis, respectively; these heterozygosity levels were moderate compared to the previously reported microsatellite loci from Abies species. This is the first set of microsatellite markers developed for A. koreana as well as A. nephrolepis and further population genetic studies of both species and genetic delimitation can be carried out for the species conservation and management.


Subject(s)
Abies/genetics , Microsatellite Repeats , Polymorphism, Genetic , Endangered Species
10.
J Fish Biol ; 88(3): 1249-56, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26822496

ABSTRACT

In this study, whole Hox gene clusters in the self-fertilizing mangrove killifish Kryptolebias marmoratus (Cyprinodontiformes; Rivulidae), a unique hermaphroditic vertebrate in which both sex organs are functional at the same time, were identified from whole genome and transcriptome sequences. The aim was to increase the understanding of the evolutionary status of conservation of this Hox gene cluster across fish species.


Subject(s)
Cyprinodontiformes/genetics , Genes, Homeobox , Multigene Family , Animals , Biological Evolution , Cyprinodontiformes/classification , Cyprinodontiformes/physiology , Genome , Phylogeny , Self-Fertilization , Sequence Alignment/methods
11.
Chem Commun (Camb) ; 52(8): 1586-9, 2016 Jan 28.
Article in English | MEDLINE | ID: mdl-26660677

ABSTRACT

2-Naphthyl-methyl ethers as permanent protecting groups are readily removed under acidic conditions and are key to the synthesis of complex glycosylphosphatidylinositol anchors containing unsaturated lipids. The total synthesis of the GPI pseudo-disaccharide core found on the surface of the Trypanosoma cruzi parasite serves to illustrate the power of the strategy.


Subject(s)
Glycolipids/chemistry , Glycosylphosphatidylinositols/chemistry
12.
Br J Cancer ; 112(8): 1340-8, 2015 Apr 14.
Article in English | MEDLINE | ID: mdl-25867259

ABSTRACT

BACKGROUND: Docetaxel improves symptoms and survival in metastatic castration-resistant prostate cancer (CRPC). However, ∼50% of patients are chemoresistant. This study examined whether changes in cytokine levels predict for docetaxel resistance in vitro and in a clinical cohort. METHODS: PC3 cells or their docetaxel-resistant subline (PC3Rx) were co-cultured with U937 monocytes, with and without docetaxel treatment, and cytokine levels were measured. The circulating levels of 28 cytokines were measured pre-/post cycle 1 of docetaxel from 55 men with CRPC, and compared with prostate-specific antigen (PSA) response. RESULTS: PC3Rx-U937 co-culture expressed more cytokines, chiefly markers of alternative macrophage differentiation, compared with PC3-U937 co-culture. Docetaxel treatment enhanced cytokine production by PC3Rx-U937 co-culture, while reducing cytokine levels in PC3-U937. In patients, changes in the levels of seven circulating cytokines (macrophage inhibitory cytokine 1 (MIC1), interleukin (IL)-1ra, IL-1ß, IL-4, IL-6, IL-12 and IFNγ) after cycle 1 of docetaxel were associated with progressive disease (all P<0.05). The combination of changes in MIC1, IL-4 and IL-6 most strongly predicted PSA response (P=0.002). CONCLUSIONS: In vitro studies suggest docetaxel resistance is mediated, at least in part, by cytokines induced by the interaction between the docetaxel-resistant tumour cells and macrophages. Early changes in circulating cytokine levels were associated with docetaxel resistance in CRPC patients. When considered together, these data suggest a significant role for the inflammatory response and macrophages in the development of docetaxel resistance in CRPC.


Subject(s)
Cytokines/blood , Drug Resistance, Neoplasm , Kallikreins/blood , Macrophages/metabolism , Prostate-Specific Antigen/blood , Prostatic Neoplasms, Castration-Resistant/metabolism , Aged , Aged, 80 and over , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Coculture Techniques , Docetaxel , Humans , Male , Middle Aged , Prostatic Neoplasms, Castration-Resistant/drug therapy , Taxoids/pharmacology
13.
J Vet Pharmacol Ther ; 38(2): 199-202, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25131428

ABSTRACT

Ondansetron is a potent antiemetic drug that has been commonly used to treat acute and chemotherapy-induced nausea and vomiting (CINV) in dogs. The aim of this study was to perform a pharmacokinetic analysis of ondansetron in dogs following oral administration of a single dose. A single 8-mg oral dose of ondansetron (Zofran(®) ) was administered to beagles (n = 18), and the plasma concentrations of ondansetron were measured by liquid chromatography-tandem mass spectrometry. The data were analyzed by modeling approaches using ADAPT5, and model discrimination was determined by the likelihood-ratio test. The peak plasma concentration (Cmax ) was 11.5 ± 10.0 ng/mL at 1.1 ± 0.8 h. The area under the plasma concentration vs. time curve from time zero to the last measurable concentration was 15.9 ± 14.7 ng·h/mL, and the half-life calculated from the terminal phase was 1.3 ± 0.7 h. The interindividual variability of the pharmacokinetic parameters was high (coefficient of variation > 44.1%), and the one-compartment model described the pharmacokinetics of ondansetron well. The estimated plasma concentration range of the usual empirical dose from the Monte Carlo simulation was 0.1-13.2 ng/mL. These findings will facilitate determination of the optimal dose regimen for dogs with CINV.


Subject(s)
Antiemetics/pharmacokinetics , Dogs/metabolism , Ondansetron/pharmacokinetics , Administration, Oral , Animals , Antiemetics/administration & dosage , Antiemetics/blood , Area Under Curve , Dogs/blood , Half-Life , Models, Biological , Monte Carlo Method , Ondansetron/administration & dosage , Ondansetron/blood
14.
Water Sci Technol ; 70(2): 218-25, 2014.
Article in English | MEDLINE | ID: mdl-25051467

ABSTRACT

Stormwater runoff quality is sensitive to land use and land cover (LULC) change. It is difficult to understand their relationship in predicting the pollution potential and developing watershed management practices to eliminate or reduce the pollution risk. In this study, the relationship between LULC change and stormwater runoff quality in two separate monitoring sites comprising a construction area (Site 1) and mixed land use (Site 2) was analyzed using geographic information system (GIS), event mean concentration (EMC), and correlation analysis. It was detected that bare land area increased, while other land use areas such as agriculture, commercial, forest, grassland, parking lot, residential, and road reduced. Based on the analyses performed, high maximum range and average EMCs were found in Site 2 for most of the water pollutants. Also, urban areas and increased conversion of LULC into bare land corresponded to degradation of stormwater quality. Correlation analysis between LULC and stormwater quality showed the influence of different factors such as farming practices, geographical location, and amount of precipitation, vegetation loss, and anthropogenic activities in monitoring sites. This research found that GIS application was an efficient tool for monthly monitoring, validation and statistical analysis of LULC change in the study area.


Subject(s)
Agriculture , Environmental Monitoring/methods , Rain , Water Movements , Water Pollutants, Chemical/chemistry , Geographic Information Systems , Republic of Korea
15.
Br J Cancer ; 110(10): 2462-71, 2014 May 13.
Article in English | MEDLINE | ID: mdl-24714754

ABSTRACT

BACKGROUND: Docetaxel is the first-line chemotherapy for castration-resistant prostate cancer (CRPC). However, response rates are ∼50% and determined quite late in the treatment schedule, thus non-responders are subjected to unnecessary toxicity. The potential of circulating microRNAs as early biomarkers of docetaxel response in CRPC patients was investigated in this study. METHODS: Global microRNA profiling was performed on docetaxel-resistant and sensitive cell lines to identify candidate circulating microRNA biomarkers. Custom Taqman Array MicroRNA cards were used to measure the levels of 46 candidate microRNAs in plasma/serum samples, collected before and after docetaxel treatment, from 97 CRPC patients. RESULTS: Fourteen microRNAs were associated with serum prostate-specific antigen (PSA) response or overall survival, according to Mann-Whitney U or log-rank tests. Non-responders to docetaxel and patients with shorter survival generally had high pre-docetaxel levels of miR-200 family members or decreased/unchanged post-docetaxel levels of miR-17 family members. Multivariate Cox regression with bootstrapping validation showed that pre-docetaxel miR-200b levels, post-docetaxel change in miR-20a levels, pre-docetaxel haemoglobin levels and visceral metastasis were independent predictors of overall survival when modelled together. CONCLUSIONS: Our study suggests that circulating microRNAs are potential early predictors of docetaxel chemotherapy outcome, and warrant further investigation in clinical trials.


Subject(s)
Adenocarcinoma/drug therapy , Androgen Antagonists/therapeutic use , Antineoplastic Agents, Hormonal/therapeutic use , Antineoplastic Agents, Phytogenic/therapeutic use , Biomarkers, Tumor/blood , Drug Resistance, Neoplasm/genetics , MicroRNAs/blood , Prostatic Neoplasms/drug therapy , RNA, Neoplasm/blood , Taxoids/therapeutic use , Adenocarcinoma/genetics , Adenocarcinoma/pathology , Adenocarcinoma/secondary , Adenocarcinoma/surgery , Aged , Aged, 80 and over , Antineoplastic Agents, Phytogenic/pharmacology , Cell Line, Tumor/drug effects , Docetaxel , Gene Expression Profiling , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Proportional Hazards Models , Prostate-Specific Antigen/blood , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology , ROC Curve , Risk Factors , Taxoids/pharmacology , Treatment Outcome
16.
Cell Death Dis ; 5: e1112, 2014 Mar 13.
Article in English | MEDLINE | ID: mdl-24625971

ABSTRACT

Although curcumin suppresses the growth of a variety of cancer cells, its poor absorption and low systemic bioavailability have limited its translation into clinics as an anticancer agent. In this study, we show that dimethoxycurcumin (DMC), a methylated, more stable analog of curcumin, is significantly more potent than curcumin in inducing cell death and reducing the clonogenicity of malignant breast cancer cells. Furthermore, DMC reduces the tumor growth of xenografted MDA-MB 435S cells more strongly than curcumin. We found that DMC induces paraptosis accompanied by excessive dilation of mitochondria and the endoplasmic reticulum (ER); this is similar to curcumin, but a much lower concentration of DMC is required to induce this process. DMC inhibits the proteasomal activity more strongly than curcumin, possibly causing severe ER stress and contributing to the observed dilation. DMC treatment upregulates the protein levels of CCAAT-enhancer-binding protein homologous protein (CHOP) and Noxa, and the small interfering RNA-mediated suppression of CHOP, but not Noxa, markedly attenuates DMC-induced ER dilation and cell death. Interestingly, DMC does not affect the viability, proteasomal activity or CHOP protein levels of human mammary epithelial cells, suggesting that DMC effectively induces paraptosis selectively in breast cancer cells, while sparing normal cells. Taken together, these results suggest that DMC triggers a stronger proteasome inhibition and higher induction of CHOP compared with curcumin, giving it more potent anticancer effects on malignant breast cancer cells.


Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Breast Neoplasms/drug therapy , Curcumin/analogs & derivatives , Proteasome Endopeptidase Complex/drug effects , Proteasome Inhibitors/pharmacology , Transcription Factor CHOP/metabolism , Animals , Breast Neoplasms/enzymology , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Cell Proliferation/drug effects , Cell Survival/drug effects , Curcumin/pharmacology , Dose-Response Relationship, Drug , Female , Humans , MCF-7 Cells , Male , Mice , Mice, Inbred BALB C , Mice, Nude , Proteasome Endopeptidase Complex/metabolism , Proto-Oncogene Proteins c-bcl-2/genetics , Proto-Oncogene Proteins c-bcl-2/metabolism , RNA Interference , Time Factors , Transcription Factor CHOP/genetics , Transfection , Tumor Burden/drug effects , Up-Regulation , Xenograft Model Antitumor Assays
17.
Eur J Clin Microbiol Infect Dis ; 33(6): 1053-61, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24500598

ABSTRACT

Our objective was to model the cost-effectiveness and economic value of routine peri-operative Staphylococcus aureus screening and decolonization of lung and heart-lung transplant recipients from hospital and third-party payer perspectives. We used clinical data from 596 lung and heart-lung transplant recipients to develop a model in TreeAge Pro 2009 (Williamsport, MA, USA). Sensitivity analyses varied S. aureus colonization rate (5-15 %), probability of infection if colonized (10-30 %), and decolonization efficacy (25-90 %). Data were collected from the Cardiothoracic Transplant Program at the University of Pittsburgh Medical Center. Consecutive lung and heart-lung transplant recipients from January 2006 to December 2010 were enrolled retrospectively. Baseline rates of S. aureus colonization, infection and decolonization efficacy were 9.6 %, 36.7 %, and 31.9 %, respectively. Screening and decolonization was economically dominant for all scenarios tested, providing more cost savings and health benefits than no screening. Savings per case averted (2012 $US) ranged from $73,567 to $133,157 (hospital perspective) and $10,748 to $16,723 (third party payer perspective), varying with the probability of colonization, infection, and decolonization efficacy. Using our clinical data, screening and decolonization led to cost savings per case averted of $240,602 (hospital perspective) and averted 6.7 S. aureus infections (4.3 MRSA and 2.4 MSSA); 89 patients needed to be screened to prevent one S. aureus infection. Our data support routine S. aureus screening and decolonization of lung and heart-lung transplant patients. The economic value of screening and decolonization was greater than in previous models of other surgical populations.


Subject(s)
Carrier State/diagnosis , Carrier State/drug therapy , Mass Screening/economics , Staphylococcal Infections/diagnosis , Staphylococcal Infections/drug therapy , Staphylococcus aureus/isolation & purification , Transplant Recipients , Academic Medical Centers , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Cohort Studies , Computer Simulation , Cost-Benefit Analysis , Female , Heart Transplantation , Humans , Infant , Lung Transplantation , Male , Mass Screening/methods , Middle Aged , Pennsylvania , Retrospective Studies , Young Adult
18.
Cytogenet Genome Res ; 142(2): 79-86, 2014.
Article in English | MEDLINE | ID: mdl-24434812

ABSTRACT

Infertile men with azoospermia commonly have associated microdeletions in the azoospermia factor (AZF) region of the Y chromosome, sex chromosome mosaicism, or sex chromosome rearrangements. In this study, we describe an unusual 46,XX and 45,X mosaicism with a rare Y chromosome rearrangement in a phenotypically normal male patient. The patient's karyotype was 46,XX[50]/45,X[25]/46,X,der(Y)(pter→q11.222::p11.2→pter)[25]. The derivative Y chromosome had a deletion at Yq11.222 and was duplicated at Yp11.2. Two copies of the SRY gene were confirmed by fluorescence in situ hybridization analysis, and complete deletion of the AZFb and AZFc regions was shown by multiplex-PCR for microdeletion analysis. Both X chromosomes of the predominant mosaic cell line (46,XX) were isodisomic and derived from the maternal gamete, as determined by examination of short tandem repeat markers. We postulate that the derivative Y chromosome might have been generated during paternal meiosis or early embryogenesis. Also, we suggest that the very rare mosaicism of isodisomic X chromosomes might be formed during maternal meiosis II or during postzygotic division derived from the 46,X,der(Y)/ 45,X lineage because of the instability of the derivative Y chromosome. To our knowledge, this is the first confirmatory study to verify the origin of a sex chromosome mosaicism with a Y chromosome rearrangement.


Subject(s)
Azoospermia/genetics , Chromosomes, Human, X/genetics , Chromosomes, Human, Y/genetics , Mosaicism , Sex Chromosome Aberrations , Adult , Chromosome Deletion , Humans , Karyotype , Male , Meiosis/genetics , Sex-Determining Region Y Protein/genetics
19.
J Hosp Infect ; 85(4): 297-302, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24358509

ABSTRACT

BACKGROUND: The efficacy of antibiotics in preventing surgical site infections (SSIs) depends on the timing of administration relative to the start of surgery. However, currently, both the timing of and recommendations for administration vary substantially. AIM: To determine how the economic value from the hospital perspective of preoperative antibiotics varies with the timing of administration for orthopaedic procedures. METHODS: Computational decision and operational models were developed from the hospital perspective. Baseline analyses looked at current timing of administration, while additional analyses varied the timing of administration, compliance with recommended guidelines, and the goal time-interval. FINDINGS: Beginning antibiotic administration within 0-30 min prior to surgery resulted in the lowest costs and SSIs. Operationally, linking to a pre-surgical activity, administering antibiotics prior to incision but after anaesthesia-ready time was optimal, as 92.1% of the time, antibiotics were administered in the optimal time-interval (0-30 min prior to incision). Improving administration compliance from 80% to 90% for this pre-surgical activity results in cost savings of $447 per year for a hospital performing 100 orthopaedic operations a year. CONCLUSION: This study quantifies the potential cost-savings when antibiotic administration timing is improved, which in turn can guide the amount hospitals should invest to address this issue.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/economics , Antibiotic Prophylaxis/economics , Antibiotic Prophylaxis/methods , Orthopedic Procedures/methods , Preoperative Care/methods , Surgical Wound Infection/prevention & control , Costs and Cost Analysis , Humans , Time Factors
20.
Clin Microbiol Infect ; 19(11): 1014-22, 2013 Nov.
Article in English | MEDLINE | ID: mdl-23800220

ABSTRACT

During the 2009 H1N1 pandemic, decision-makers had access to mathematical and computational models that were not available in previous pandemics in 1918, 1957, and 1968. How did models contribute to policy and action during the 2009 H1N1 pandemic? Modelling encountered six primary challenges: (i) expectations of modelling were not clearly defined; (ii) appropriate real-time data were not readily available; (iii) modelling results were not generated, shared, or disseminated in time; (iv) decision-makers could not always decipher the structure and assumptions of the models; (v) modelling studies varied in intervention representations and reported results; and (vi) modelling studies did not always present the results or outcomes that are useful to decision-makers. However, there were also seven general successes: (i) modelling characterized the role of social distancing measures such as school closure; (ii) modelling helped to guide data collection; (iii) modelling helped to justify the value of the vaccination programme; (iv) modelling helped to prioritize target populations for vaccination; (v) modelling addressed the use of antiviral medications; (vi) modelling helped with health system preparedness planning; and (vii) modellers and decision-makers gained a better understanding of how to work with each other. In many ways, the 2009 pandemic served as practice and a learning opportunity for both modellers and decision-makers. Modellers can continue working with decision-makers and other stakeholders to help overcome these challenges, to be better prepared when the next emergency inevitably arrives.


Subject(s)
Decision Support Techniques , Epidemiological Monitoring , Influenza A Virus, H1N1 Subtype/isolation & purification , Influenza, Human/epidemiology , Influenza, Human/transmission , Models, Theoretical , Pandemics , Humans , Influenza, Human/virology
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