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Hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) drive cancer through their respective receptors, MET and VEGF receptor 2 (VEGFR2). VEGFR2 inhibits MET by promoting MET dephosphorylation. However, whether MET conversely regulates VEGFR2 remains unknown. Here we show that MET suppresses VEGFR2 protein by inducing its endoplasmic-reticulum-associated degradation (ERAD), via intracrine VEGF action. HGF–MET signaling in epithelial cancer cells promoted VEGF biosynthesis through PI3-kinase. In turn, VEGF and VEGFR2 associated within the ER, activating inositol-requiring enzyme 1α, and thereby facilitating ERAD-mediated depletion of VEGFR2. MET disruption upregulated VEGFR2, inducing compensatory tumor growth via VEGFR2 and MEK. However, concurrent disruption of MET and either VEGF or MEK circumvented this, enabling more profound tumor inhibition. Our findings uncover unique cross-regulation between MET and VEGFR2—two RTKs that play significant roles in tumor malignancy. Furthermore, these results suggest rational combinatorial strategies for targeting RTK signaling pathways more effectively, which has potentially important implications for cancer therapy.

CCN2/Connective Tissue Growth Factor (CTGF) is a matricellular protein that regulates cell adhesion, migration, and survival. CCN2 is best known for its ability to promote fibrosis by mediating the ability of transforming growth factor β (TGFβ) to induce excess extracellular matrix production. In addition to its role in pathological processes, CCN2 is required for chondrogenesis. CCN2 is also highly expressed during development in endothelial cells, suggesting a role in angiogenesis. The potential role of CCN2 in angiogenesis is unclear, however, as both pro- and anti-angiogenic effects have been reported. Here, through analysis of Ccn2-deficient mice, we show that CCN2 is required for stable association and retention of pericytes by endothelial cells. PDGF signaling and the establishment of the endothelial basement membrane are required for pericytes recruitment and retention. CCN2 induced PDGF-B expression in endothelial cells, and potentiated PDGF-B-mediated Akt signaling in mural (vascular smooth muscle/pericyte) cells. In addition, CCN2 induced the production of endothelial basement membrane components in vitro, and was required for their expression in vivo. Overall, these results highlight CCN2 as an essential mediator of vascular remodeling by regulating endothelial-pericyte interactions. Although most studies of CCN2 function have focused on effects of CCN2 overexpression on the interstitial extracellular matrix, the results presented here show that CCN2 is required for the normal production of vascular basement membranes.

CCN2/Connective Tissue Growth Factor (CTGF) is a matricellular protein that regulates cell adhesion, migration, and survival. CCN2 is best known for its ability to promote fibrosis by mediating the ability of transforming growth factor b (TGFb) to induce excess extracellular matrix production. In addition to its role in pathological processes, CCN2 is required for chondrogenesis. CCN2 is also highly expressed during development in endothelial cells, suggesting a role in angiogenesis. The potential role of CCN2 in angiogenesis is unclear, however, as both pro- and anti-angiogenic effects have been reported. Here, through analysis of Ccn2-deficient mice, we show that CCN2 is required for stable association and retention of pericytes by endothelial cells. PDGF signaling and the establishment of the endothelial basement membrane are required for pericytes recruitment and retention. CCN2 induced PDGF-B expression in endothelial cells, and potentiated PDGF-Bmediated Akt signaling in mural (vascular smooth muscle/pericyte) cells. In addition, CCN2 induced the production of endothelial basement membrane components in vitro, and was required for their expression in vivo. Overall, these results highlight CCN2 as an essential mediator of vascular remodeling by regulating endothelial-pericyte interactions. Although most studies of CCN2 function have focused on effects of CCN2 overexpression on the interstitial extracellular matrix, the results presented here show that CCN2 is required for the normal production of vascular basement membranes. [ABSTRACT FROM AUTHOR]

Objective: This study systematically reviewed and meta-analyzed the differential attrition and utilization of occupational mental health interventions, specifically examining delivery methods (internet-based versus in-person)., Methods: The research, with papers spanning 2010-2024, involved filtering criteria and comprehensive searches across PubMed, Scopus, and Web of Science Core (PROSPERO registration n. CRD42022322394). Of 28 683 titles, 84 records were included in the systematic review, with 75 in meta-analyses. Risk of bias was assessed through the revised Cochrane risk of bias tool for randomized control trials and funnel plots. Differential attrition across studies was meta-analysed through a random-effects model with limited maximum-likelihood estimation for the degree of heterogeneity., Results: Findings reveal higher mean differential attrition in the intervention group, indicating a potential challenge in maintaining participant engagement. The attrition rates were not significantly influenced by the mode of intervention delivery (internet versus in-person). Compensation for participation and year of publication could potentially influence differential attrition from baseline to follow-up measurements., Conclusions: These results suggest a need for cautious consideration of attrition in occupational mental health intervention study designs and emphasize the importance of adapting statistical analyses to mitigate potential bias arising from differential attrition.

Objective: To assess trends in antibiotic prescribing for patients hospitalized with COVID-19 with and without sepsis., Design: Retrospective cohort study using electronic health record (EHR) data., Setting: Five hospitals in eastern Massachusetts., Patients: Adults (≥18 years) hospitalized with community-onset SARS-CoV-2 infections between March 2020 and November 2022., Methods: We assessed quarterly trends in the use of prolonged initial antibiotic therapy (≥4 antibiotic days within one week of admission, including discharge antibiotics) amongst COVID-19 patients with and without sepsis, defined using clinical signs of organ dysfunction before hospital day 3. Poisson regression models were used to adjust for baseline characteristics and severity of illness., Results: Of 431,017 hospitalizations in the study period, 21,563 (5.0%) had community-onset COVID-19. 4,769/21,563 (20.5%) presented with sepsis. Prolonged antibiotics were prescribed in 2,323/4,769 (48.7%) COVID-19 patients with sepsis and 2,866/16,794 (17.1%) without sepsis despite low rates of positive bacterial cultures on admission (15.0% vs 6.3%, respectively). Quarterly rates of prolonged antibiotics declined between the first and second pandemic quarters for both sepsis (66.8% to 43.9%) and no-sepsis (31.8% to 24.4%) groups. However, there was no significant change thereafter through November 2022 in either group (quarterly aORs 1.02, 95% CI 0.99-1.05 and 1.01, 95% CI 0.99-1.03, respectively)., Conclusions: Prolonged antibiotics were common in hospitalized COVID-19 patients with and without sepsis during the first 33 months of the pandemic despite low rates of proven bacterial infection. Decreases in antibiotic utilization occurred primarily between the first and second pandemic quarter with no further reduction thereafter., Competing Interests: Dr Klompas reports personal fees from UpToDate outside the submitted work. Dr Rhee reports personal fees from UpToDate and Cytovale outside the submitted work. No other potential conflicts of interest relevant to the submitted work were reported., (© The Author(s) 2024.)

Importance: Little is known about the degree to which suspected sepsis drives broad-spectrum antibiotic use in hospitals, what proportion of antibiotic courses are unnecessarily broad in retrospect, and whether these patterns are changing over time., Objective: To describe trends in empiric broad-spectrum antibiotic use for suspected community-onset sepsis., Design, Setting, and Participants: This cross-sectional study used clinical data from adults admitted to 241 US hospitals in the PINC AI Healthcare Database. Eligible participants were aged 18 years or more and were admitted between 2017 and 2021 with suspected community-onset sepsis, defined by a blood culture draw, lactate measurement, and intravenous antibiotic administration on admission., Exposures: Empiric anti-methicillin-resistant Staphylococcus aureus (MRSA) and/or antipseudomonal β-lactam agent use., Main Outcomes and Measures: Annual rates of empiric anti-MRSA and/or antipseudomonal β-lactam agent use and the proportion that were likely unnecessary in retrospect based on the absence of β-lactam resistant gram-positive or ceftriaxone-resistant gram-negative pathogens from clinical cultures obtained through hospital day 4. Annual trends were calculated using mixed-effects logistic regression models, adjusting for patient and hospital characteristics., Results: Among 6 272 538 hospitalizations (median [IQR] age, 66 [53-78] years; 443 465 male [49.6%]; 106 095 Black [11.9%], 65 763 Hispanic [7.4%], 653 907 White [73.1%]), 894 724 (14.3%) had suspected community-onset sepsis, of whom 582 585 (65.1%) received either empiric anti-MRSA (379 987 [42.5%]) or antipseudomonal β-lactam therapy (513 811 [57.4%]); 311 213 (34.8%) received both. Patients with suspected community-onset sepsis accounted for 1 573 673 of 3 141 300 (50.1%) of total inpatient anti-MRSA antibiotic days and 2 569 518 of 5 211 745 (49.3%) of total antipseudomonal β-lactam days. Between 2017 and 2021, the proportion of patients with suspected sepsis administered anti-MRSA or antipseudomonal therapy increased from 63.0% (82 731 of 131 275 patients) to 66.7% (101 003 of 151 435 patients) (adjusted OR [aOR] per year, 1.03; 95% CI, 1.03-1.04). However, resistant organisms were isolated in only 65 434 cases (7.3%) (30 617 gram-positive [3.4%], 38 844 gram-negative [4.3%]) and the proportion of patients who had any resistant organism decreased from 9.6% to 7.3% (aOR per year, 0.87; 95% CI, 0.87-0.88). Most patients with suspected sepsis treated with empiric anti-MRSA and/or antipseudomonal therapy had no resistant organisms (527 356 of 582 585 patients [90.5%]); this proportion increased from 88.0% in 2017 to 91.6% in 2021 (aOR per year, 1.12; 95% CI, 1.11-1.13)., Conclusions and Relevance: In this cross-sectional study of adults admitted to 241 US hospitals, empiric broad-spectrum antibiotic use for suspected community-onset sepsis accounted for half of all anti-MRSA or antipseudomonal therapy; the use of these types of antibiotics increased between 2017 and 2021 despite resistant organisms being isolated in less than 10% of patients treated with broad-spectrum agents.

Importance: Efforts to quantify the burden of SARS-CoV-2-associated sepsis have been limited by inconsistent definitions and underrecognition of viral sepsis., Objective: To describe the incidence and outcomes of SARS-CoV-2-associated sepsis vs presumed bacterial sepsis using objective electronic clinical criteria., Design, Setting, and Participants: This retrospective cohort study included adults hospitalized at 5 Massachusetts hospitals between March 2020 and November 2022., Exposures: SARS-CoV-2-associated sepsis was defined as a positive SARS-CoV-2 polymerase chain reaction test and concurrent organ dysfunction (ie, oxygen support above simple nasal cannula, vasopressors, elevated lactate level, rise in creatine or bilirubin level, and/or decline in platelets). Presumed bacterial sepsis was defined by modified US Centers for Disease Control and Prevention adult sepsis event criteria (ie, blood culture order, sustained treatment with antibiotics, and organ dysfunction using identical thresholds as for SARS-CoV-2-associated sepsis)., Main Outcomes and Measures: Trends in the quarterly incidence (ie, proportion of hospitalizations) and in-hospital mortality for SARS-CoV-2-associated and presumed bacterial sepsis were assessed using negative binomial and logistic regression models., Results: This study included 431 017 hospital encounters from 261 595 individuals (mean [SD] age 57.9 [19.8] years, 241 131 (55.9%) females, 286 397 [66.5%] from academic hospital site). Of these encounters, 23 276 (5.4%) were from SARS-CoV-2, 6558 (1.5%) had SARS-CoV-2-associated sepsis, and 30 604 patients (7.1%) had presumed bacterial sepsis without SARS-CoV-2 infection. Crude in-hospital mortality for SARS-CoV-2-associated sepsis declined from 490 of 1469 (33.4%) in the first quarter to 67 of 450 (14.9%) in the last (adjusted odds ratio [aOR], 0.88 [95% CI, 0.85-0.90] per quarter). Crude mortality for presumed bacterial sepsis was 4451 of 30 604 patients (14.5%) and stable across quarters (aOR, 1.00 [95% CI, 0.99-1.01]). Medical record reviews of 200 SARS-CoV-2-positive hospitalizations confirmed electronic health record (EHR)-based SARS-CoV-2-associated sepsis criteria performed well relative to sepsis-3 criteria (90.6% [95% CI, 80.7%-96.5%] sensitivity; 91.2% [95% CI, 85.1%-95.4%] specificity)., Conclusions and Relevance: In this retrospective cohort study of hospitalized adults, SARS-CoV-2 accounted for approximately 1 in 6 cases of sepsis during the first 33 months of the COVID-19 pandemic. In-hospital mortality rates for SARS-CoV-2-associated sepsis were high but declined over time and ultimately were similar to presumed bacterial sepsis. These findings highlight the high burden of SARS-CoV-2-associated sepsis and demonstrate the utility of EHR-based algorithms to conduct surveillance for viral and bacterial sepsis.

Contouring has become an increasingly important aspect of radiotherapy due to inverse planning. Several studies have suggested that the clinical implementation of automated contouring tools can reduce inter-observer variation while increasing contouring efficiency, thereby improving the quality of radiotherapy treatment and reducing the time between simulation and treatment. In this study, a novel, commercial automated contouring tool based on machine learning, the AI-Rad Companion Organs RT™ (AI-Rad) software (Version VA31) (Siemens Healthineers, Munich, Germany), was assessed against both manually delineated contours and another commercially available automated contouring software, Varian Smart Segmentation™ (SS) (Version 16.0) (Varian, Palo Alto, CA, United States). The quality of contours generated by AI-Rad in Head and Neck (H&N), Thorax, Breast, Male Pelvis (Pelvis_M), and Female Pelvis (Pevis_F) anatomical areas was evaluated both quantitatively and qualitatively using several metrics. A timing analysis was subsequently performed to explore potential time savings achieved by AI-Rad. Results showed that most automated contours generated by AI-Rad were not only clinically acceptable and required minimal editing, but also superior in quality to contours generated by SS in multiple structures. In addition, timing analysis favored AI-Rad over manual contouring, indicating the largest time saving (753s per patient) in the Thorax area. AI-Rad was concluded to be a promising automated contouring solution that generated clinically acceptable contours and achieved time savings, thereby greatly benefiting the radiotherapy process., (© 2023 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

Background: Electronic Health Record (EHR) data are increasingly being used to monitor population health on account of their timeliness, granularity, and large sample sizes. While EHR data are often sufficient to estimate disease prevalence and trends for large geographic areas, the same accuracy and precision may not carry over for smaller areas that are sparsely represented by non-random samples., Methods: We developed small-area estimation models using a combination of EHR data drawn from MDPHnet, an EHR-based public health surveillance network in Massachusetts, the American Community Survey, and state hospitalization data. We estimated municipality-specific prevalence rates of asthma, diabetes, hypertension, obesity, and smoking in each of the 351 municipalities in Massachusetts in 2016. Models were compared against Behavioral Risk Factor Surveillance System (BRFSS) state and small area estimates for 2016., Results: Integrating progressively more variables into prediction models generally reduced mean absolute error (MAE) relative to municipality-level BRFSS small area estimates: asthma (2.24% MAE crude, 1.02% MAE modeled), diabetes (3.13% MAE crude, 3.48% MAE modeled), hypertension (2.60% MAE crude, 1.48% MAE modeled), obesity (4.92% MAE crude, 4.07% MAE modeled), and smoking (5.33% MAE crude, 2.99% MAE modeled). Correlation between modeled estimates and BRFSS estimates for the 13 municipalities in Massachusetts covered by BRFSS's 500 Cities ranged from 81.9% (obesity) to 96.7% (diabetes)., Conclusions: Small-area estimation using EHR data is feasible and generates estimates comparable to BRFSS state and small-area estimates. Integrating EHR data with survey data can provide timely and accurate disease monitoring tools for areas with sparse data coverage., (© 2022. The Author(s).)

Dietary supplementation is the most feasible method to improve oocyte function and developmental potential in vivo . During three experiments, oocytes were collected from maturing, dominant follicles of older mares to determine whether short-term dietary supplements can alter oocyte metabolic function, lipid composition, and developmental potential. Over approximately 8 weeks, control mares were fed hay (CON) or hay and grain products (COB). Treated mares received supplements designed for equine wellness and gastrointestinal health, flaxseed oil, and a proprietary blend of fatty acid and antioxidant support (reproductive support supplement (RSS)) intended to increase antioxidant activity and lipid oxidation. RSS was modified for individual experiments with additional antioxidants or altered concentrations of n-3 to n-6 fatty acids. Oocytes from mares supplemented with RSS when compared to COB had higher basal oxygen consumption, indicative of higher aerobic metabolism, and proportionately more aerobic to anaerobic metabolism. In the second experiment, oocytes collected from the same mares prior to (CON) and after approximately 8 weeks of RSS supplementation had significantly reduced oocyte lipid abundance. In the final experiment, COB was compared to RSS supplementation, including RSS modified to proportionately reduce n-3 fatty acids and increase n-6 fatty acids. The ability of sperm-injected oocytes to develop into blastocysts was higher for RSS, regardless of fatty acid content, than for COB. We demonstrated that short-term diet supplementation can directly affect oocyte function in older mares, resulting in oocytes with increased metabolic activity, reduced lipid content, and increased developmental potential., (© The authors.)

Introduction: The outbreak of the coronavirus disease 2019 (COVID-19) poses an unprecedented challenge to healthcare workers (HCWs) globally. This study investigated potential factors related to depression, anxiety, and stress in a sample of Chinese HCWs during the peak of the COVID-19 epidemic., Methods: An online survey was distributed to Chinese HCWs using respondent-driven sampling. Data were collected between February 13th and February 20th, 2020, immediately following the COVID-19 contagion peak in Hubei. A total of 1208 respondents were eligible for analysis. Mental health problems and social support were measured by the Depression Anxiety Stress Scales-21 (DASS-21) and the Perceived Social Support Scale (PSS)., Results: The prevalence rates of depression, (DASS-depression > 9) anxiety (DASS-anxiety > 7) and stress (DASS-stress > 14) were 37.8%, 43.0% and 38.5%, respectively. Multivariate logistic regressions revealed that stress, anxiety, and depression were positively related to lower levels of social support, longer working hours, discrimination experience and workplace violence. The scarcity of medical equipment was correlated with increased stress and depression. Chinese HCWs working at COVID 19 designated hospitals were more likely to report anxiety. Additionally, volunteering to work in the frontline health facilities was inversely associated with depression., Conclusion: Mental health problems among Chinese HCWs were alarming during the peak of the COVID-19 epidemic. Health facilities require appropriate and standing services that address the mental health of healthcare workers, particularly during epidemic outbreaks., Competing Interests: The authors declare no conflicts of interest., (© 2021 Yang et al.)

Background: China and other developing countries in Asia follow similar economic growth patterns described by the flying geese (FG) model, which explains the "catching-up" process of industrialization in latecomer economies. Japan, newly industrialized economies, and China have followed this path, with similar economic development trajectories. Based on the FG model, we postulated a "flying S" hypothesis stating that if a country is located within an FG region and its energy matrix is relatively constant, its per capita CO 2 emission curve will mirror that of "leading geese" countries in the same FG group., Method: Historical CO 2 emissions data were obtained from literature review and national reports and were calculated using bottom-up methods. A sigmoid-shaped, non-linear mixed effect model was applied to examine ex post data with 1000 simulated predictions to construct 95% empirical bands from these fits. By multiplying by estimated population, we predicted total emissions of selected FG countries., Results: Per capita CO 2 emissions from the same FG group mirror each other, especially among second and third industrial sectors. We estimated an annual 18,252.24 million tons of CO 2 emissions (MtCO 2 ) (95% CI = 9458.88-23,972.88) in China and 8281.76 MtCO2 (95% CI = 2765.68-14,959.12) in India in 2030., Conclusion: This study bridges the macroeconomic FG paradigm to study climate change and proposes a "flying S" hypothesis to predict greenhouse gas emissions in East Asia. By applying our theory to empirical data, we provide an alternative framework to predict CO 2 emissions in 2030 and beyond., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

This paper presents the development of a multi-sensor platform capable of simultaneous measurement of dissolved oxygen (DO) concentration, glucose and lactate concentrations in a micro-chamber for real-time evaluation of metabolic flux in bovine embryos. A micro-chamber containing all three sensors (DO, glucose, and lactate) was made to evaluate metabolic flux of single oocytes or embryos at different stages of development in ≤ 120 µL of respiration buffer. The ability of the sensor to detect a metabolic shift from oxidative phosphorylation (OXPHOS) to glycolysis was demonstrated in embryos by an ablation of oxygen consumption and an increase in lactate production following addition of oligomycin, an inhibitor of mitochondrial adenosine triphosphate (ATP) synthesis. An increased reliance upon glycolysis relative to OXPHOS was demonstrated in embryos as they developed from morula to hatched blastocysts by a progressive increase in the lactate/oxygen flux ratio, consistent with isolated metabolic assessments reported previously. These studies highlight the utility of a metabolic multi-sensor for integrative real-time monitoring of aerobic and anaerobic energy metabolism in bovine embryos, with potential applications in the study of metabolic processes in oocyte and early embryonic development., (Published by Elsevier B.V.)

Background: Exposure to ambient particulate matter generated from coal-fired power plants induces long-term health consequences. However, epidemiologic studies have not yet focused on attributing these health burdens specifically to energy consumption, impeding targeted intervention policies. We hypothesize that the generating capacity of coal-fired power plants may be associated with lung cancer incidence at the national level., Methods: Age- and sex-adjusted lung cancer incidence from every country with electrical plants using coal as primary energy supply were followed from 2000 to 2016. We applied a Poisson regression longitudinal model, fitted using generalized estimating equations, to estimate the association between lung cancer incidence and per capita coal capacity, adjusting for various behavioral and demographic determinants and lag periods., Results: The average coal capacity increased by 1.43 times from 16.01 gigawatts (GW) (2000~2004) to 22.82 GW (2010~2016). With 1 kW (KW) increase of coal capacity per person in a country, the relative risk of lung cancer increases by a factor of 59% (95% CI = 7.0%~ 135%) among males and 85% (95% CI = 22%~ 182%) among females. Based on the model, we estimate a total of 1.37 (range = 1.34 ~ 1.40) million standardized incident cases from lung cancer will be associated with coal-fired power plants in 2025., Conclusions: These analyses suggest an association between lung cancer incidence and increased reliance on coal for energy generation. Such data may be helpful in addressing a key policy question about the externality costs and estimates of the global disease burden from preventable lung cancer attributable to coal-fired power plants at the national level.

The ability to view biological events in real time has contributed significantly to research in the life sciences. While video capture of real time changes in anatomical relationships is important, it is equally important to visualize real time changes in the chemical communications that drive cell behaviors. This paper describes an electrochemical imaging system capable of capturing changes in chemical gradients in live tissue slices. The system consists of a CMOS microchip with 8192 configurable Pt surface electrodes, on-chip potentiostat, on-chip control logic, and a microfluidic device designed to interface with the CMOS chip to support ex vivo tissue experimentation. All data processing and visualization methods, sensor calibrations, microfluidics fabrication, and tissue preparation and handling procedures are described. Using norepinephrine as a target analyte for proof of concept, the system is capable of differentiating concentrations of norepinephrine as low as 8 µM and up to 1024 µM with a linear response and a spatial resolution of 25.5 µm × 30.4 µm. Electrochemical imaging was tested using murine adrenal tissue as a biological model and successfully showed caffeine-stimulated release of catecholamines from live slices of adrenal tissue with temporal sensitivity. This system successfully demonstrates the use of a high-density microelectrode array for electrochemical analysis with high spatiotemporal resolution to gather chemical gradient information in parallel with optical microscopy recordings., (Copyright © 2018. Published by Elsevier B.V.)

This paper presents a label-free affinity-based capacitive biosensor using interdigitated electrodes. Using an optimized process of DNA probe preparation to minimize the effect of contaminants in commercial thiolated DNA probe, the electrode surface was functionalized with the 24-nucleotide DNA probes based on the West Nile virus sequence (Kunjin strain). The biosensor has the ability to detect complementary DNA fragments with a detection limit down to 20 DNA target molecules (1.5aM range), making it suitable for a practical point-of-care (POC) platform for low target count clinical applications without the need for amplification. The reproducibility of the biosensor detection was improved with efficient covalent immobilization of purified single-stranded DNA probe oligomers on cleaned gold microelectrodes. In addition to the low detection limit, the biosensor showed a dynamic range of detection from 1µL -1 to 10 5 µL -1 target molecules (20 to 2 million targets), making it suitable for sample analysis in a typical clinical application environment. The binding results presented in this paper were validated using fluorescent oligomers., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Total body irradiation (TBI) treatments are mainly used in a preparative regimen for hematopoietic stem cell (or bone marrow) transplantation. Our standard clinical regimen is a 12 Gy/6 fraction bi-daily technique using 6MV X-rays at a large extended source to surface distance (SSD). This work investigates and quantifies the dose build-up characteristics and thus the requirements for bolus used for in vivo dosimetry for TBI applications. Percentage dose build-up characteristics of photon beams have been investigated at large extended SSDs using ionization chambers and Gafchromic film. Open field measurements at different field sizes and with differing scatter conditions such as the introduction of standard Perspex scattering plates at different distances to the measurement point were made in an effort to determine the required bolus/build-up material required for accurate determination of applied dose. Percentage surface dose values measured for open fields at 300 cm SSD were found to range from 20% up to 65.5% for fields 5 cm × 5 cm to 40 cm × 40 cm, respectively. With the introduction of 1 cm Perspex scattering plates used in TBI treatments, the surface dose values increased up to 83-90% (93-97% at 1 mm depth), depending on the position of the Perspex scattering plate compared to the measurement point. Our work showed that at least 5 mm water equivalent bolus/scatter material should be placed over the EBT3 film for accurate dose assessment for TBI treatments. Results also show that a small but measurable decrease in measured dose occurred with 5 mm water equivalent thick bolus material of areas '3 cm(2). As such, we recommend that 3 cm × 3 cm × 5 mm bolus build-up is the smallest size that should be placed over EBT3 Gafchromic film when used for accurate in vivo dosimetry for TBI applications.

Background: The ultrasonically activated scalpel has been introduced as an alternative to conventional methods of hemostasis in surgical procedures. The present study investigated the benefits of using the Harmonic FOCUS (HF) scalpel in breast-conserving surgery (BCS) and in axillary staging surgery., Methods: All early-stage breast cancer patients who underwent BCS and axillary staging surgery between January 2009 and December 2010 were retrospectively identified. Those patients treated with the HF scalpel were defined as the HF group, while patients whose surgery involved the electrocautery and the clamp-and-tie technique were designated as the conventional method (CM) group. Both groups were subsequently divided into the axillary lymph node dissection (ALND) and sentinel lymph node biopsy (SLNB) subgroups, respectively., Results: A total of 89 patients were included in the study, with 41 patients in the HF group and 48 in the CM group. There were 13 patients in the SLNB subgroup and 28 were in the ALND subgroup of the HF group, and 21 patients were in the SLNB subgroup and 27 in the ALND subgroup of the CM group. Multiple linear regression analysis revealed that the length of surgery was significantly reduced in the ALND subgroup of the HF group (β = -16.70, p < 0.001). The incidence of axillary numbness was significantly decreased in the ALND subgroup of the HF group, with the results measured by multiple logistic regression analysis (OR = 0.27, p = 0.044). No statistically significant differences were identified concerning intraoperative blood loss, postoperative drainage, and seroma between the HF and CM groups., Conclusion: Using the Harmonic FOCUS scalpel in breast conserving surgery and axillary lymph mode dissection significantly reduced the length of surgery and decreased the axillary numbness rate as compared to conventional methods., (Copyright © 2012. Published by Elsevier B.V.)

Ilicicolin H is a polyketide-nonribosomal peptide synthase (NRPS)-natural product isolated from Gliocadium roseum, which exhibits potent and broad spectrum antifungal activity, with sub-μg/mL MICs against Candida spp., Aspergillus fumigatus, and Cryptococcus spp. It showed a novel mode of action, potent inhibition (IC50 = 2-3 ng/mL) of the mitochondrial cytochrome bc1 reductase, and over 1000-fold selectivity relative to rat liver cytochrome bc1 reductase. Ilicicolin H exhibited in vivo efficacy in murine models of Candida albicans and Cryptococcus neoformans infections, but efficacy may have been limited by high plasma protein binding. Systematic structural modification of ilicicolin H was undertaken to understand the structural requirement for the antifungal activity. The details of the biological activity of ilicicolin H and structural modification of some of the key parts of the molecule and resulting activity of the derivatives are discussed. These data suggest that the β-keto group is critical for the antifungal activity.

Background: Magnetic resonance cholangiopancreatography (MRCP) is a popular modality for evaluation of the biliary tract, yet there is no data on the normal common bile duct (CBD) size of the average Taiwanese adult. This study attempts to establish a reference range for CBD diameter for the Taiwanese population., Methods: Over a 2-year period, all adults who underwent abdominal magnetic resonance imaging for health screening were recruited into the study. Patients with a prior history of hepatobiliary surgery and other significant morbidity were not included. Patients who were found to have abnormal liver function test results or abnormal imaging findings were also excluded from the study. After the patients fasted for a minimum of 8 hours, MR imaging was performed with a 1.5 T MR imager using a phased-array coil. Breath-hold thick slab single-shot turbo spin echo (ssTSE BH) projections were obtained, and these were used for CBD and portal vein diameter (PVD) measurement by workstation software. Initial recruitment included 265 patients, of which 66 were excluded due to abnormal liver function tests, seven more were excluded due to excess imaging artifacts or incomplete CBD visualization, and five were excluded due to other abnormal blood tests. This yielded a final study group of 187 patients between the ages of 21 and 78 years, which comprised 69 women and 118 men., Results: The mean CBD diameter is 4.6 mm, with a range from 1.76 to 10.49 mm. CBD diameters are significantly different in patients both younger and older than 65 years of age (p < 0.05), and are not significantly related to gender, serum glucose level, cholesterol level, hepatitis status and PVD., Conclusion: Our study showed that the average CBD diameter for an asymptomatic Taiwanese adult is 4.6 mm, with an upper limit of 10.49 mm. CBD diameter is only significantly correlated with age. This is a useful reference in today's clinical setting where MRCP are commonly performed for evaluation of suspected biliary tract disease., (Copyright © 2012. Published by Elsevier B.V.)

Background/purpose: The use and cost of computed tomography (CT) and magnetic resonance imaging (MRI) are both very high. The purpose of this study was to evaluate the relation between physicians' characteristics and the CT and MRI repeated within 90 days, using a nationwide population-based data set from Taiwan's National Health Insurance system., Methods: All physicians who ordered CT and MRI examinations in 2004-2005 were identified. We analyzed the total number of CT and MRI scans, the number of repeat scans, and the repeat scan rate, according to physician characteristics (specialty, age, sex, and type of practice hospital). A multivariate logistic regression analysis was performed to explore the adjusted relationship between physician characteristics and their rate of ordering repeat CT and MRI., Results: A total of 16,307 physicians were responsible for a total of 2,152,292 CT and MRI scans during 2004-2005 in Taiwan. The repeat scans accounted for 21.5% of the total scans. Male physicians and physicians aged 41-50 years ordered more repeat scans. Internal medicine physicians ordered 44.3% of all scans and 50.6% of all repeat scans. Surgeons ordered 40.4% of the total scans and 38.5% of repeat scans. Internal medicine physicians were the most frequent users of CT/MRI scans. Family doctors, obstetricians/gynecologists, and pediatricians ranked last among the specialists. Physicians who practiced in medical centers ordered the most CT/MRI scans., Conclusion: Our study shows that repeat use of CT and MRI scans is related to physicians' characteristics. We recommend that different monitoring standards should be set for CT and MRI repeat use by physicians of different specialties and in hospitals of different accreditation levels., (Copyright © 2011. Published by Elsevier B.V.)

A 56-year-old woman was maintained on continuous ambulatory peritoneal dialysis (PD) for 12 years. The patient presented to our hospital with chief complaints of intermittent abdominal pain and frequent loose stool. Plain radiograph of abdomen revealed extensive peritoneal calcification. Computed tomography confirmed the extensive peritoneal calcification and revealed a large right ovarian cyst. Torsion of the right ovarian cyst was suspected. Right oophorectomy was performed. Small intestinal perforation developed 37 days after the operation. The patient expired because of peritonitis and sepsis. Extensive peritoneal calcification is a rare and serious complication after long-term PD. Intestinal perforation is a rare complication of PD. Pathognomic signs of imaging studies can be important in early diagnosis and treatment., (Copyright © 2011 Elsevier Taiwan LLC. All rights reserved.)