Stool protein mass spectrometry identifies biomarkers for the early detection of diffuse-type gastric cancer.

There is a high unmet need for early detection approaches for diffuse gastric cancer (DGC). We examined whether the stool proteome of mouse models of GC or individuals with hereditary diffuse GC (HDGC) have utility as biomarkers for early detection. Proteomic mass spectrometry of stool from a genetically engineered mouse model driven by oncogenic KrasG12D and loss of p53 and Cdh1 in gastric parietal cells (known as TCON mice) identified differentially abundant proteins compared to littermate controls. Immunoblot assays validated a panel of proteins including actinin alpha 4 (ACTN4), N-acylsphingosine amidohydrolase 2 (ASAH2), dipeptidyl peptidase 4 (DPP4), and valosin-containing protein (VCP) as enriched in TCON stool compared to littermate control stool. Immunofluorescence analysis of these proteins in TCON stomach sections revealed increased protein expression as compared to littermate controls. Proteomic mass spectrometry of stool obtained from HDGC patients with CDH1 mutations identified increased expression of ASAH2, DPP4, VCP, lactotransferrin (LTF), and tropomyosin-2 (TPM2) relative to stool from healthy sex and age-matched donors. Chemical inhibition of ASAH2 using C6-urea ceramide was toxic to GC cell lines and patient derived-GC organoids. This toxicity was reversed by adding downstream products of the S1P synthesis pathway, suggesting a dependency on ASAH2 activity in GC. An exploratory analysis of the HDGC stool microbiome identified features which correlated with patient tumors. Here we provide evidence supporting the potential of analyzing stool biomarkers for the early detection of DGC.

In Vivo Activity of Repurposed Amodiaquine as a Host-Targeting Therapy for the Treatment of Anthrax.

Anthrax is caused by Bacillus anthracis and can result in nearly 100% mortality due in part to anthrax toxin. Antimalarial amodiaquine (AQ) acts as a host-oriented inhibitor of anthrax toxin endocytosis. Here, we determined the pharmacokinetics and safety of AQ in mice, rabbits, and humans as well as the efficacy in the fly, mouse, and rabbit models of anthrax infection. In the therapeutic-intervention studies, AQ nearly doubled the survival of mice infected subcutaneously with a B. anthracis dose lethal to 60% of the animals (LD60). In rabbits challenged with 200 LD50 of aerosolized B. anthracis, AQ as a monotherapy delayed death, doubled the survival rate of infected animals that received a suboptimal amount of antibacterial levofloxacin, and reduced bacteremia and toxemia in tissues. Surprisingly, the anthrax efficacy of AQ relies on an additional host macrophage-directed antibacterial mechanism, which was validated in the toxin-independent Drosophila model of Bacillus infection. Lastly, a systematic literature review of the safety and pharmacokinetics of AQ in humans from over 2 000 published articles revealed that AQ is likely safe when taken as prescribed, and its pharmacokinetics predicts anthrax efficacy in humans. Our results support the future examination of AQ as adjunctive therapy for the prophylactic anthrax treatment.

Direct activation of endothelial cells by SARS-CoV-2 nucleocapsid protein is blocked by Simvastatin

Emerging evidence suggests that endothelial activation plays a central role in the pathogenesis of acute respiratory distress syndrome (ARDS) and multi-organ failure in patients with COVID-19. However, the molecular mechanisms underlying endothelial activation in COVID-19 patients remain unclear. In this study, the SARS-CoV-2 viral proteins that potently activate human endothelial cells were screened to elucidate the molecular mechanisms involved with endothelial activation. It was found that nucleocapsid protein (NP) of SARS-CoV-2 significantly activated human endothelial cells through TLR2/NF-{kappa}B and MAPK signaling pathways. Moreover, by screening a natural microbial compound library containing 154 natural compounds, simvastatin was identified as a potent inhibitor of NP-induced endothelial activation. Remarkablely, though the protein sequences of N proteins from coronaviruses are highly conserved, only NP from SARS-CoV-2 induced endothelial activation. The NPs from other coronaviruses such as SARS-CoV, MERS-CoV, HUB1-CoV and influenza virus H1N1 did not affect endothelial activation. These findings are well consistent with the results from clinical investigations showing broad endotheliitis and organ injury in severe COVID-19 patients. In conclusion, the study provides insights on SARS-CoV-2-induced vasculopathy and coagulopathy, and suggests that simvastatin, an FDA-approved lipid-lowering drug, may benefit to prevent the pathogenesis and improve the outcome of COVID-19 patients.

The effectiveness of far-infrared irradiation on foot skin surface temperature and heart rate variability in healthy adults over 50 years of age: A randomized study.

BACKGROUND: Far-infrared irradiation (FIR) is used in the medical field to improve wound healing, hemodialysis with peripheral artery occlusive disease, and osteoarthritis but seldom used in ameliorating poor lower extremity circulation. The purpose of this study was to evaluate the effect of FIR on changes in foot skin surface temperature (FSST) and autonomic nerve system (ANS) activity to evaluate its effectiveness in improving lower limb circulation. METHODS: A randomized controlled study was conducted. Subjects (n = 44), all over the age of 50 years and satisfying the inclusion criteria, were randomly allocated into 2 groups. The intervention group received FIR on a lower limb for 40 minutes and the control group received no intervention. Left big toe (LBT), right big toe (RBT), left foot dorsal (LFD), right foot dorsal (RFD) surface skin temperature, autonomic nervous activity, and blood pressure were assessed. RESULTS: The main results were skin surface temperature at the LBT increased from 30.8 ±â€Š0.4°C to 34.8 ±â€Š0.4°C, at RBT increased from 29.6 ±â€Š0.4°C to 35.3 ±â€Š0.4°C and LFD increased from 31.9 ±â€Š0.3°C to 36.4 ±â€Š0.4°C, RFD increased from 30.7 ±â€Š0.3°C to 37.7 ±â€Š0.2°C. FIR caused a significant increase of the FSST ranging in a 4°C to 7°C increase after 40 minutes irradiation (P < .001). The ANS low-frequency (LF) and high-frequency (HF) activity showed a statistically significant increase in the FIR group (P < .05) but not the LF/HF ratio. CONCLUSION: FIR significantly increased the FSST from between 4°C and 7°C after 40 minutes irradiation, which might improve lower extremity circulation and regulation of ANS activity.

Role of a Small Molecule in the Modulation of Cell Death Signal Transduction Pathways.

Inflammasomes activate caspase-1 in response to molecular signals from pathogens and other dangerous stimuli as a part of the innate immune response. A previous study discovered a small-molecule, 4-fluoro- N'-[1-(2-pyridinyl)ethylidene]benzohydrazide, which we named DN1, that reduces the cytotoxicity of anthrax lethal toxin (LT). We determined that DN1 protected cells irrespectively of LT concentration and reduced the pathogenicity of an additional bacterial exotoxin and several viruses. Using the LT cytotoxicity pathway, we show that DN1 does not prevent LT internalization and catalytic activity or caspase-1 activation. Moreover, DN1 does not affect the proteolytic activity of host cathepsin B, which facilitates the cytoplasmic entry of toxins. PubChem Bioactivities lists two G protein-coupled receptors (GPCR), type-1 angiotensin II receptor and apelin receptor, as targets of DN1. The inhibition of phosphatidylinositol 3-kinase, phospholipase C, and protein kinase B, which are downstream of GPCR signaling, synergized with DN1 in protecting cells from LT. We hypothesize that DN1-mediated antagonism of GPCRs modulates signal transduction pathways to induce a cellular state that reduces LT-induced pyroptosis downstream of caspase-1 activation. DN1 also reduced the susceptibility of Drosophila melanogaster to toxin-associated bacterial infections. Future experiments will aim to further characterize how DN1 modulates signal transduction pathways to inhibit pyroptotic cell death in LT-sensitive macrophages. DN1 represents a novel chemical probe to investigate host cellular mechanisms that mediate cell death in response to pathogenic agents.

Characterization of Novel Piperidine-Based Inhibitor of Cathepsin B-Dependent Bacterial Toxins and Viruses.

Exploiting the host endocytic trafficking pathway is a common mechanism by which bacterial exotoxins gain entry to exert virulent effects upon the host cells. A previous study identified a small-molecule, 1-(2,6-dimethyl-1-piperidinyl)-3-[(2-isopropyl-5-methylcyclohexyl)oxy]-2-propanol, that blocks the process of anthrax lethal toxin (LT) cytotoxicity. Here, we report the characterization of the bioactivity of this compound, which we named RC1. We found that RC1 protected host cells independently of LT concentration and also blocked intoxication by other bacterial exotoxins, suggesting that the target of the compound is a host factor. Using the anthrax LT intoxication pathway as a reference, we show that while anthrax toxin is able to bind to cells and establish an endosomal pore in the presence of the drug, the toxin is unable to translocate into the cytosol. We demonstrate that RC1 does not inhibit the toxin directly but rather reduces the enzymatic activity of host cathepsin B that mediates the escape of toxins into the cytoplasm from late endosomes. We demonstrate that the pathogenicity of Human cytomegalovirus and Herpes simplex virus 1, which relies on cathepsin B protease activity, is reduced by RC1. This study reveals the potential of RC1 as a broad-spectrum host-oriented therapy against several aggressive and deadly pathogens.

Antifungal properties of Mimusops elengiseeds against paddy seed-borne fungi and selected pathogenic fungi 152-158

@#Aims:The ever-revolving fungi strains and environmental and health concerns due to current practice of synthetic pesticide in agricultural fields have encourages more ventures into bio-pesticides research. Mimusops elengi, a widely available endogenous plant intropical countries and most parts of this plant have been proven to possess medicinal and antimicrobial potential. In this study, M.elengiseeds crude extracts are tested for their antifungal activities on paddy seed-borne and pathogenic fungi.Methodology and results:The dried and grinded M.elengiseeds are macerated separately using water, methanol, ethyl acetate, dichloromethane and petroleum ether as extraction medium. Crude extract of each solvent wasused on paddy seed surface treatment to determine their antifungal inhibition potential on seed-borne fungi and paddy grain germination. Synthetic fungicide mancozeb and thiram are also tested as comparisons to the performance of plant extracts. Water andmethanol extracts exerted the best fungal inhibiting and grain germination results from the five crude extracts tested and qualitative phytochemical screening reveals both extracts contained the most number of phytoconstituents including saponin, flavonoids, alkaloids, tannins and phenolic. Water extract, methanol extracts and synthetic fungicides are then subjected to in-vitro bioassay to observe their effect on mycelial growth of several fungi strains pathogenic to paddy namely, Fusarium fujikuroi,Curvularia aeria,C.lunata andC.eragrostidis.Water and methanol extracts showed a very similar trend of inhibition on all four fungi strains tested with best percentage of inhibition on mycelia growth of C.eragrostidisfollowed by C. aeria, C. lunataand least effective on F.fujikuroi. Further separation of crude extract need to be done to isolate the specific acting compounds contributing to fungal growth inhibition.Conclusion, significance and impact of study:Both water and methanol extracts of the seeds contain promising antifungal properties on seed borne fungi which is as good as the synthetic fungicides compared in this study. A broad range of active phytochemical properties it possesses may be the contributing factor for the fungal growth inhibition. This preliminary screening could narrow down the potential of this seed extracts as natural antifungal agents and the acting active compounds.

The Effectiveness of Cupping Therapy on Relieving Chronic Neck and Shoulder Pain: A Randomized Controlled Trial.

The research aimed to investigate the effectiveness of cupping therapy (CT) in changes on skin surface temperature (SST) for relieving chronic neck and shoulder pain (NSP) among community residents. A single-blind experimental design constituted of sixty subjects with self-perceived NSP. The subjects were randomly allocated to two groups. The cupping group received CT at SI 15, GB 21, and LI 15 acupuncture points, and the control group received no intervention. Pain was assessed using the SST, visual analog scale (VAS), and blood pressure (BP). The main results were SST of GB 21 acupuncture point raised from 30.6°C to 32.7°C and from 30.7°C to 30.6°C in the control group. Neck pain intensity (NPI) severity scores were reduced from 9.7 to 3.6 in the cupping group and from 9.7 to 9.5 in the control group. The SST and NPI differences between the groups were statistically significant (P < 0.001). One treatment of CT is shown to increase SST. In conjunction with the physiological effect the subjective experience of NSP is reduced in intensity. Further studies are required to improve the understanding and potential long-term effects of CT.

Promotion and guidance of neural network formation on SU-8 photoresist microchannels adjusted with multilayer films.

Induction of neural stem/progenitor cells (NSPCs) and establishment of neural network are important issues on neural engineering. In this work, a platform was designed to control and evaluate the differentiation of NSPCs, neurite direction, and to promote the neurite outgrowth. Polyelectrolyte multilayer (PEM) films provide surface properties by and have been used to regulate NSPCs differentiation in our previous study. Herein, a culture platform composed of SU-8 microchannel and PEM films was designed to achieve the goal of promoting NSPCs differentiation and to evaluate the effect of PEM films on the guidance of neural network formation. In this culture platform, NSPCs were induced into functional neurons, and neural network formation was accomplished on ITO glass-PEM films successfully.

Presentation of peptides from Bacillus anthracis protective antigen on Tobacco Mosaic Virus as an epitope targeted anthrax vaccine.

The current anthrax vaccine requires improvements for rapidly invoking longer-lasting neutralizing antibody responses with fewer doses from a well-defined formulation. Designing antigens that target neutralizing antibody epitopes of anthrax protective antigen, a component of anthrax toxin, may offer a solution for achieving a vaccine that can induce strong and long lasting antibody responses with fewer boosters. Here we report implementation of a strategy for developing epitope focused virus nanoparticle vaccines against anthrax by using immunogenic virus particles to present peptides derived from anthrax toxin previously identified in (1) neutralizing antibody epitope mapping studies, (2) toxin crystal structure analyses to identify functional regions, and (3) toxin mutational analyses. We successfully expressed two of three peptide epitopes from anthrax toxin that, in previous reports, bound antibodies that were partially neutralizing against toxin activity, discovered cross-reactivity between vaccine constructs and toxin specific antibodies raised in goats against native toxin and showed that antibodies induced by our vaccine constructs also cross-react with native toxin. While protection against intoxication in cellular and animal studies were not as effective as in previous studies, partial toxin neutralization was observed in animals, demonstrating the feasibility of using plant-virus nanoparticles as a platform for epitope defined anthrax vaccines.

Identification of agents effective against multiple toxins and viruses by host-oriented cell targeting.

A longstanding and still-increasing threat to the effective treatment of infectious diseases is resistance to antimicrobial countermeasures. Potentially, the targeting of host proteins and pathways essential for the detrimental effects of pathogens offers an approach that may discover broad-spectrum anti-pathogen countermeasures and circumvent the effects of pathogen mutations leading to resistance. Here we report implementation of a strategy for discovering broad-spectrum host-oriented therapies against multiple pathogenic agents by multiplex screening of drugs for protection against the detrimental effects of multiple pathogens, identification of host cell pathways inhibited by the drug, and screening for effects of the agent on other pathogens exploiting the same pathway. We show that a clinically used antimalarial drug, Amodiaquine, discovered by this strategy, protects host cells against infection by multiple toxins and viruses by inhibiting host cathepsin B. Our results reveal the practicality of discovering broadly acting anti-pathogen countermeasures that target host proteins exploited by pathogens.

Angiotensin-converting enzyme inhibitors and amyotrophic lateral sclerosis risk: a total population-based case-control study.

IMPORTANCE: Although several studies have shown that use of angiotensin-converting enzyme inhibitors (ACEIs) potentially decreased amyotrophic lateral sclerosis (ALS) risk in animal models, to our knowledge, there has been no human study in the literature discussing this issue. OBJECTIVE: To investigate the association between the use of ACEIs and the risk for developing ALS. DESIGN, SETTING, AND PARTICIPANTS: This case-control study was conducted using the total population of Taiwanese citizens seen in general medical practice; therefore, the findings can be applied to the general population. The case group comprised 729 patients with newly diagnosed ALS and a severely disabling disease certificate between January 1, 2002, and December 31, 2008. These cases were compared with 14,580 sex-, age-, residence-, and insurance premium-matched control individuals. EXPOSURES: Use of ACEIs was analyzed using a conditional logistic regression model that controlled for other antihypertensives, aspirin, steroids, nonsteroidal anti-inflammatory drugs, Charlson Comorbidity Index score, length of hospital stay, and number of outpatient visits. The cumulative defined daily dose (cDDD), which indicates the exposed duration of drug use, was estimated as the sum of dispensed DDD of drug and compared with the risk for ALS. MAIN OUTCOMES AND MEASURES: All patients with ALS fulfilled El Escorial criteria in this study. Medical claim data past 1 to 5 years of ALS first diagnosis date for patients and claim data from their matched control individuals were included in the analysis. RESULTS: There was a dose-dependent inverse association between ACEI use and the risk for developing ALS. When compared with patients who did not use ACEIs, the adjusted odds ratios were 0.83 (95% CI, 0.65-1.07; P = .15) for the group prescribed ACEIs lower than 449.5 of the cDDD and 0.43 cDDD (95% CI, 0.26-0.72; P = .001) for the group with a cumulative ACEI use of greater than 449.5 cDDD. The association was most predominant in men older than 55 years. CONCLUSIONS AND RELEVANCE: Use of ACEIs exhibited a dose-dependent inverse association with ALS. This study demonstrated a 57% risk reduction in the chance for developing ALS in people who used ACEIs greater than 449.5 cDDD in 4 years.

Structure-Activity Relationship of Semicarbazone EGA Furnishes Photoaffinity Inhibitors of Anthrax Toxin Cellular Entry.

EGA, 1, prevents the entry of multiple viruses and bacterial toxins into mammalian cells by inhibiting vesicular trafficking. The cellular target of 1 is unknown, and a structure-activity relationship study was conducted in order to develop a strategy for target identification. A compound with midnanomolar potency was identified (2), and three photoaffinity labels were synthesized (3-5). For this series, the expected photochemistry of the phenyl azide moiety is a more important factor than the IC50 of the photoprobe in obtaining a successful photolabeling event. While 3 was the most effective reversible inhibitor of the series, it provided no protection to cells against anthrax lethal toxin (LT) following UV irradiation. Conversely, 5, which possessed weak bioactivity in the standard assay, conferred robust irreversible protection vs LT to cells upon UV photolysis.

Climatic factors associated with amyotrophic lateral sclerosis: a spatial analysis from Taiwan.

Few studies have assessed the spatial association of amyotrophic lateral sclerosis (ALS) incidence in the world. The aim of this study was to identify the association of climatic factors and ALS incidence in Taiwan. A total of 1,434 subjects with the primary diagnosis of ALS between years 1997 and 2008 were identified in the national health insurance research database. The diagnosis was also verified by the national health insurance programme, which had issued and providing them with "serious disabling disease (SDD) certificates". Local indicators of spatial association were employed to investigate spatial clustering of age-standardised incidence ratios in the townships of the study area. Spatial regression was utilised to reveal any association of annual average climatic factors and ALS incidence for the 12-year study period. The climatic factors included the annual average time of sunlight exposure, average temperature, maximum temperature, minimum temperature, atmospheric pressure, rainfall, relative humidity and wind speed with spatial autocorrelation controlled. Significant correlations were only found for exposure to sunlight and rainfall and it was similar in both genders. The annual average of the former was found to be negatively correlated with ALS, while the latter was positively correlated with ALS incidence. While accepting that ALS is most probably multifactorial, it was concluded that sunlight deprivation and/or rainfall are associated to some degree with ALS incidence in Taiwan.

Selective inhibitor of endosomal trafficking pathways exploited by multiple toxins and viruses.

Pathogenic microorganisms and toxins have evolved a variety of mechanisms to gain access to the host-cell cytosol and thereby exert virulent effects upon the host. One common mechanism of cellular entry requires trafficking to an acidified endosome, which promotes translocation across the host membrane. To identify small-molecule inhibitors that block this process, a library of 30,000 small molecules was screened for inhibitors of anthrax lethal toxin. Here we report that 4-bromobenzaldehyde N-(2,6-dimethylphenyl)semicarbazone, the most active compound identified in the screen, inhibits intoxication by lethal toxin and blocks the entry of multiple other acid-dependent bacterial toxins and viruses into mammalian cells. This compound, which we named EGA, also delays lysosomal targeting and degradation of the EGF receptor, indicating that it targets host-membrane trafficking. In contrast, EGA does not block endosomal recycling of transferrin, retrograde trafficking of ricin, phagolysosomal trafficking, or phagosome permeabilization by Franciscella tularensis. Furthermore, EGA does not neutralize acidic organelles, demonstrating that its mechanism of action is distinct from pH-raising agents such as ammonium chloride and bafilomycin A1. EGA is a powerful tool for the study of membrane trafficking and represents a class of host-targeted compounds for therapeutic development to treat infectious disease.

Long-term outcome of patients with aortic aneurysms taking low-dose aspirin: a population-based cohort study.

BACKGROUND: Limited studies evaluated the association between low-dose aspirin use and abdominal aortic aneurysm (AAA), thoracoabdominal aortic aneurysm (TAAA), and thoracic aortic aneurysm (TAA) treatment. We conducted this study to investigative the association of low-dose aspirin in terms of preventing death and exacerbation of different aortic aneurysms. METHODS: This retrospective study identified aortic aneurysm cases between 1999 and 2006 from the National Health Insurance Research Database and used time-dependent methods to determine whether the use of low-dose aspirin reduced the risk of outcomes. Primary outcomes, including a composite outcome of death, aortic dissection, a rupture event, an unruptured event, or surgical repair, and secondary outcomes, the composite end point of death and readmission for aortic aneurysm events, were estimated separately. RESULTS: Two hundred eighty-seven cases were identified. The hazard ratio for the primary outcome in patients taking low-dose aspirin in AAA/TAAA patients at each 90-day interval based on the time-dependent analysis was 1.000 (95% confidence interval [CI], 0.994-1.005), and in TAA patients 1.010 (95% CI, 0.994-1.026) compared with those with no exposure. In terms of the secondary outcomes, the hazard ratio for all-cause mortality was 0.995 (95% CI, 0.988-1.003) for AAA/TAAA patients and 1.008 (95% CI, 0.991-1.026) for TAA patients. CONCLUSIONS: From a national population database, we did not find an association between low-dose aspirin exposure and mortality or exacerbation in different aortic aneurysms by using time-dependent analysis. However, adjustments for aneurysms size and smoking status could not be made, which may limit the validity of the study.

Epidemiology and disease burden of ischemic stroke in Taiwan.

BACKGROUND: The incidence and prevalence of ischemic stroke (IS) are increasing in Asian countries. We conducted this retrospective database research to investigate epidemiology and disease burden of IS in Taiwan. METHODS: We identified cases from the National Health Insurance Research Database during period from 2000 to 2005 to calculate prevalence and mortality. We analyzed the relationship between disease burden and gender in Taiwan during the period from 2000 to 2005 using Dismod II. RESULTS: From study period, stroke mortality increased from 50 to 2300 per 100 000 among individuals aged 50-90 years, with a higher prevalence among females than males. The highest prevalence was observed among men aged 80-84 years, but prevalence among women was highest in patients aged >85 years. The burden of stroke during the period per 1000 population was estimated as follows: the sum of the years of life lost as a result of premature mortality of 55-80 years, years lost as a result of disability of 11-19 years, and disability-adjusted life years (DALYs) of 70-80 years. Most of the DALYs of stroke occurred among those aged 65-69 years. The DALY value was higher among women than among men before 2005; there was no clear trend in 2005. CONCLUSIONS: Stroke is a significant health concern in Taiwan. The associated disease burden was found to increase each year, especially among individuals aged 65-69 years. Overall, the DALY value increased from 2000 to 2005, which suggests that the associated disease burden will continue to increase over time.

Extended acute toxicity study of (188) Re-liposome in rats.

Liposomes can selectively target cancer sites and carry payloads, thereby improving diagnostic and therapeutic effectiveness as well as reducing toxicity. To evaluate therapeutic strategies, it is essential to use animal models reflecting important safety aspects before clinical application. As our previous study found that a high dosage (185 of MBq) of (188) Re-N,N-bis (2-mercaptoethyl)-N',N'-diethylethylenediamine-labeled pegylated liposomes ((188) Re-liposome) induced a decrease in white blood cell (WBC) count in Sprague-Dawley rats 7 days postinjection, the objective of the present study was to investigate extended acute radiotoxicity of (188) Re-liposome. Rats were administered via intravenous (i.v.) injection with (188) Re-liposome (185, 55.5 and 18.5 MBq), normal saline as a blank control or non-radioactive liposome as a vehicle control. Mortality, clinical signs, food consumption, body weights, urinary, biochemical and hematological analyzes were examined. In addition, gross necropsy and histopathological examinations were also performed at the end of the follow-up period. None of the rats died and no clinical sign was observed during the 28-day study period. Only male rats receiving (188) Re-liposome at a high dosage (185 MBq) displayed a slight weight loss compared with the control rats. In both male and female rats, the WBC counts of both high-dose and medium-dose (55.5 MBq) groups reduced significantly 7 days postinjection, but recovered to the normal range on Study Day 29. There was no significant difference in urinary analyzes, biochemical parameters and histopathological assessments between the (188) Re-liposome-treated and control groups. The information generated from the present study on extended acute toxicity of (188) Re-liposome will serve as a safety reference for radiopharmaceuticals in early-phase clinical trials.

Epidemiology and Disease Burden of Ulcerative Colitis in Taiwan: A Nationwide Population-Based Study.

OBJECTIVES: A rising trend of incidence and prevalence of ulcerative colitis (UC) had been noticed in Asian countries. We conducted this study to investigate the epidemiology and medical burden of UC in Taiwan. METHODS: In this 10-year retrospective database study, we identified cases of patients with UC during 1998 to 2008 from the Taiwan National Health Insurance Research Database. Patients who had a catastrophic illness certificate were included in epidemiology and medical burden calculation. RESULTS: There were 1522 cases identified in our study period. The incidence increased twofold from 0.37 per 100,000 in 1998 to 0.78 per 100,000 in 2008. The incidence and prevalence had an increasing trend in our population. The cases onset age was 45.0 years on average. In our survey, most of the top 20 coexisting diseases were gastrointestinally relevant diseases, anemia (9.99%), and hypertension (7.69%). There were more than 70% patients using mesalamine, and the medical expenditure on mesalamine occupied the highest position in patients with UC. The average medical expenditure of patients with UC had a decreasing trend after 2001. CONCLUSIONS: This study had the largest sample and the longest study period for the epidemiology and medical burden estimation of UC in Taiwan. The incidence rates and medicine use of patients with UC had a definite rising trend across the years in Taiwan. Patients with anemia or choric diseases were observed in our population. More surveillance of UC-related diseases and health care costs need to be conducted in the future.

Rupture of symptomatic blood blister-like aneurysm of the internal carotid artery: clinical experience and management outcome.

BACKGROUND: Aneurysms at nonbranching sites in the supraclinoid internal carotid artery (ICA), known as blood blister-like aneurysms (BBAs), are rare entities and differ from saccular aneurysms. In this study, we attempt to describe our clinical experience and the outcome of treatments for BBAs. METHOD: Thirteen of 745 patients with aneurysmal subarachnoid hemorrhage (SAH) who visited our institution between March 2005 and July 2010, and were confirmed to have BBAs at nonbranching sites of the supraclinoid ICA by digital subtraction angiography (DSA) or computed tomography angiography, were followed-up. In these patients, several therapeutic managements were provided depending on their clinical condition. Data analyzed included patient age, sex, World Federation of Neurologic Surgeons (WFNS) scale, time interval from first DSA to second DSA, treatment of aneurysms, and the modified Rankin scale score at follow-up, 6 months after SAH. RESULT: Of these 13 patients, 5 underwent rapid configuration change from blood blister-like aneurysm to saccular-shaped. Different therapeutic managements were provided, including clipping on wrapping material in 2 patients, ICA trapping without extracranial-intracranial (EC-IC) bypass in 3 patients, EC-IC bypass and ICA trapping in 3 patients, transarterial endovascular therapy in 3 patients, direct clipping in 1 patient, and external ventricular drainage in 1 patient. Good clinical outcome was achieved in 4 patients, whereas the other 9 patients had moderate to severe disability due to rebleeding of aneurysms, large cerebral infarction, or severe cerebral vasospasm. CONCLUSIONS: BBAs of the supraclinoid ICA have special neuroradiological and clinicopathological characteristics. Direct clipping or endovascular coil embolization along may not be sufficient and sometimes have undesirable results. ICA trapping or ligation including the lesion segment can be considered an alternative choice if the balloon occlusion test (BOT) is successful. However, if the patient does not tolerate the BOT, EC-IC bypass surgery with ICA ligation or trapping is another option.