bluuebunny/crossref_metadata_2025 huggingface dataset:
Alcoholic liver disease: Pathogenesis, management, and novel targets for therapy
Authors: Orman Eric S , Odena Gemma , Bataller Ramon
Published: July 2013

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Alcohol use is a leading cause of preventable morbidity and mortality worldwide, with much of its negative impact as the result of alcoholic liver disease (ALD). ALD is a broad term that encompasses a spectrum of phenotypes ranging from simple steatosis to steatohepatitis, progressive fibrosis, cirrhosis, and hepatocellular carcinoma. The mechanisms underlying the development of these different disease stages are incompletely understood. Standard treatment of ALD, which includes abstinence, nutritional support, and corticosteroids, has not changed in the last 40 years despite continued poor outcomes. Novel therapies are therefore urgently needed. The development of such therapies has been hindered by inadequate resources for research and unsuitable animal models. However, recent developments in translational research have allowed for identification of new potential targets for therapy. These targets include: (i) CXC chemokines, (ii) IL‐22/STAT3, (iii) TNF receptor superfamily, (iv) osteopontin, (v) gut microbiota and lipopolysaccharide (LPS), (vi) endocannabinoids, and (vii) inflammasomes. We review the natural history, risk factors, pathogenesis, and current treatments for ALD. We further discuss the findings of recent translational studies and potential therapeutic targets.
Retinoids and their target genes in liver functions and diseases
Authors: Shiota Goshi , Kanki Keita
Published: July 2013

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Retinoids have been reported to prevent several kinds of cancers, including hepatocellular carcinoma (HCC). Retinoic acid (RA) coupled with retinoic acid receptor/retinoid X receptor heterodimer exerts its functions by regulating its target genes. We previously reported that transgenic mice, in which RA signaling is suppressed in a hepatocyte‐specific manner, developed liver cancer at a high rate, and that disruption of RA functions led to the increased oxidative stress via aberrant metabolisms of lipid and iron, indicating that retinoids play an important role in liver pathophysiology. These data suggest that exploring the metabolism of retinoids in liver diseases and their target genes provides us with useful information to understand the liver functions and diseases. Consequently, the altered metabolism of retinoids was observed in liver diseases, including non‐alcoholic fatty liver disease. In this review, we summarize the metabolism of retinoids in the liver, highlight the functions of retinoids in HCC, non‐alcoholic fatty liver disease, and alcoholic liver disease, and discuss the target genes of RA. Investigation of retinoids in the liver will likely help us identify novel therapies and diagnostic modalities for HCC.
Family with sequence similarity 3 gene family and nonalcoholic fatty liver disease
Authors: Yang Jichun , Guan Youfei
Published: July 2013

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Nonalcoholic fatty liver disease (NAFLD) comprises a disease spectrum ranging from simple steatosis (fatty liver) and nonalcoholic steatohepatitis to fibrosis and cirrhosis. NAFLD has become the leading cause of chronic liver diseases as well as liver‐related morbidity and mortality worldwide. NAFLD is also associated with increased risk of cardiovascular diseases, hyperlipidemia, and type2 diabetes. Insulin resistance in adipose tissues and the liver plays crucial roles in the progression of NAFLD. The family with sequence similarity 3 (FAM3) gene family is a cytokine‐like gene family with four members designated FAM3A, FAM3B, FAM3C, and FAM3D, respectively. Increasing evidence suggests that the FAM3 gene family members are involved in the pathogenesis of NAFLD. In particular, FAM3B, also called pancreatic‐derived factor, is an important regulator of glucose and lipid metabolism. In obesity status, increased expression and secretion of FAM3B in pancreatic islets and liver may induce lipid accumulation in the liver via the induction of hepatic insulin resistance and lipogenesis. FAM3A and FAM3D may also participate in the regulation of lipid and energy metabolism. In this brief review, we discussed the latest findings regarding the role of FAM3 gene family members, in particular FAM3B, in the pathogenesis of NAFLD.
Epidemiology of alcoholic and nonalcoholic fatty liver disease in China
Authors: Fan Jian‐Gao
Published: July 2013

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The prevalence of patients presenting with fatty liver disease (FLD) in China has approximately doubled over the past two decades. At present, FLD, which is typically diagnosed by imaging, is highly prevalent (∼27% urban population) in China and is mainly related to obesity and metabolic syndrome (MetS). However, the percentage of alcoholic liver disease (ALD) among patients with chronic liver diseases in clinic is increasing as well, and a synergetic effect exists between heavy alcohol drinking and obesity in ALD. Prevalence figures reveal regional variations, with a median prevalence of ALD and nonalcoholic FLD (NAFLD) of 4.5% and 15.0%, respectively. The prevalence of NAFLD in children is 2.1%, although the prevalence increases to 68.2% among obese children. With the increasing pandemic of obesity and MetS in the general population, China is likely to harbor an increasing reservoir of patients with FLD. The risk factors for FLD resemble to those of Caucasian counterparts, but the ethnic‐specific definitions of obesity and MetS are more useful in assessment of Chinese people. Therefore, FLD/NAFLD has become a most common chronic liver disease in China. Public health interventions are needed to halt the worldwide trend of obesity and alcohol abuse to ameliorate liver injury and to improve metabolic health.
Tumor microenviroment and hepatocellular carcinoma metastasis
Authors: Wang Hongyang , Chen Lei
Published: July 2013

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The cross talk between tumor cells and the surrounding peritumoral stroma has been extensively studied as a dynamic system involving the processes of hepatocarcinogenesis, tumor invasion, and metastasis in recent few decades. Besides hepatocytes, liver tumor microenvironments are generally classified into cellular and noncellular components, including hepatic stellate cells, fibroblasts, immune, endothelial, mesenchymal stem cells, together with growth factors, cytokines, extracellular matrix, hormone as well as viruses et al. The noncellular components manipulate hepatocellular carcinoma invasion and metastasis by facilitating epithelial‐mesenchymal transition, increasing proteolytic activity of matrix metalloproteinases, and regulating antitumor immunity, etc. Because the main cause of death in hepatocellular carcinoma patients is tumor progression with metastasis, a better understanding of the interplay between hepatocytes and their environment during tumor metastasis may be helpful for the discovery of novel molecular targets.
Relationship between xerostomia and salivary flow rates in HIV‐infected individuals
Authors: Nittayananta Wipawee , Chanowanna Nilnara , Pruphetkaew Nannapat , Nauntofte Birgitte
Published: July 2013

Aim

The aim of the present study was to determine the relationship between self‐reported xerostomia and salivary flow rates among HIV‐infected individuals.

Methods

A cross‐sectional study was performed on 173 individuals (81 HIV‐infected individuals, mean age: 32 years, and 92 non‐HIV controls, mean age: 30 years). Subjective complaints of dry mouth, based on a self‐report of xerostomia questions, and dry mouth, based on a visual analogue scale (VAS), were recorded along with measurements of salivary flow rate of both unstimulated and wax‐stimulated whole saliva. The relationship between subjective responses to the xerostomia questions, the VAS of dry mouth, and objective measurements of salivary flow rates were analyzed.

Results

Responses to the questions—Do you carry water or a saliva substitute? and Have you had taste disturbance?—were significantly different between HIV‐infected and non‐HIV individuals (P < 0.05). Individuals' responses to questions concerning dry mouth were significantly correlated with a low unstimulated salivary flow rate. A significant correlation between the VAS of dry mouth and salivary flow rates was observed (P = 0.023).

Conclusions

Responses to self‐reported xerostomia questions reflects low unstimulated salivary flow rates. Thus, questions concerning dry mouth might be useful tools to identify HIV‐infected individuals with hyposalivation, especially at a resting stage.
Mussel‐mimetic, bioadhesive polymers from plant‐derived materials
Authors: Hiraishi Noriko , Kaneko Daisaku , Taira Shu , Wang Siqian , Otsuki Masayuki , Tagami Junji
Published: July 2013

Aim

Mussel‐mimetic, bioadhesive polymers are synthesized from plant‐derived sources. The strong adhesive action is caused by interactions between the catechol groups at the end of the polymer terminal chains and the substrate surface. Here, we present a preliminary study of the adhesion properties and a discussion of the adhesion mechanism.

Methods

Two bioadhesive polymers were synthesized from natural plant‐derived monomers by the transesterification of: (a) caffeic acid (3,4‐dihydroxycinnamic acid; DHCA) and p‐coumaric acid (4‐hydroxycinnamic acid; 4HCA) to produce poly(DHCA‐co‐4HCA); and (b) 4‐dihydroxyhydrocinnamic acid (DHHCA) and 3‐(3‐hydroxyphenyl) propionic acid (3HPPA) to produce poly(DHHCA‐co‐3HPPA). Thermoplastic poly(DHCA‐co‐4HCA) or poly(DHHCA‐co‐3HPPA) was placed between glass, carbon, steel, or bovine dentin substrates, and a lap shear adhesion test was conducted to compare them using conventional cyanoacrylate glue and epoxy resin.

Results

The greatest adhesion for all tested substrates was exhibited by poly(DHHCA‐co‐3HPPA), followed by epoxy resin adhesive, poly(DHCA‐co‐4HCA), and cyanoacrylate adhesive. The adhesive strength of poly(DHHCA‐co‐3HPPA) was greater than 25.6 MPa for glass, 29.6 MPa for carbon, 15.7 MPa for steel, and 16.3 MPA for bovine dentin.

Conclusion

The adhesion of poly(DHHCA‐co‐3HPPA) might be the strongest reported for a mussel‐mimic adhesive system, and could be a feasible alternative to petroleum adhesives.
Are people who still have their natural teeth willing to pay for mandibular two‐implant overdentures?
Authors: Srivastava Akanksha , Feine Jocelyne S. , Esfandiari Shahrokh
Published: July 2013

Aim

Oral health in Canada and most developed and developing countries is funded by private payers, whose acceptance of treatment depends on their valuation of it. This study aims to determine how dentate individuals in Quebec, Canada, would value the benefits of mandibular two‐implant overdentures based on their willingness to pay (WTP) for the treatment, either directly or with insurance/government coverage.

Methods

A total of 39 individuals (23–54 years) completed a Web‐based WTP survey that consisted of three cost scenarios: (a) out‐of‐pocket payment; (b) private dental insurance coverage; and (c) public funding through additional taxes. Variations in WTP amounts were measured using regression models.

Results

Among respondents who were dentate or missing some teeth, average WTP out of pocket for implant overdentures was CAD$5419 for a 90% success rate. They were willing to pay an average CAD$169 as one‐time payment for private dental insurance, with a one in five chance of becoming edentate. WTP amounts increased substantially with the probability of success of implant overdenture therapy. The results of regression analyses were consistent with theoretical predictions for education level and income (P < 0.05).

Conclusions

The results of this study, within its limitations, suggest that dentate individuals would be willing to pay a significant amount to receive mandibular two‐implant overdentures if and when they become edentate.
Outcomes of Latina Women in CenteringPregnancy Group Prenatal Care Compared With Individual Prenatal Care
Authors: Trudnak Tara E. , Arboleda Elizabeth , Kirby Russell S. , Perrin Karin
Published: July 2013

Introduction

CenteringPregnancy is a client‐centered model of group prenatal care that brings women together into small groups to receive care through assessment, education, and support. As Spanish‐speaking CenteringPregnancy groups become more common, outcomes of Latinas who attend these groups must be assessed. The purpose of this retrospective cohort study was to compare pregnancy outcomes of Latina women who completed CenteringPregnancy in a public health clinic with women who completed individual care in the same clinic during the same time.

Methods

Medical charts were reviewed retrospectively to examine differences in pregnancy outcomes and maternal factors in both prenatal care groups. Latina Spanish‐speaking women who completed CenteringPregnancy were matched with Latina Spanish‐speaking women who completed individual care within the same time frame. Logistic regression analysis was conducted to examine maternal and birth outcomes.

Results

A total of 487 patient charts were obtained for data collection (CenteringPregnancy n = 247, individual n = 240). No differences in low‐birth‐weight or preterm births were observed between the groups. Compared with women in individual care, women in CenteringPregnancy had higher odds of giving birth vaginally (adjusted odds ratio [aOR], 2.57; 95% confidence interval [CI], 1.23‐5.36), attending prenatal care visits (aOR, 11.03; 95% CI, 4.53‐26.83), attending postpartum care visits (aOR, 2.20; 95% CI, 1.20‐4.05), and feeding their infants formula only (aOR, 6.07; 95% CI, 2.57‐14.3). Women in CenteringPregnancy also had lower odds of gaining below the recommended amount of gestational weight (aOR, 0.41; 95% CI, 0.22‐0.78).

Discussion

Women in CenteringPregnancy had higher health care utilization, but there were no differences in preterm birth or low birth weight. Randomized studies are needed to eliminate selection bias.
Effects of CenteringPregnancy Group Prenatal Care on Breastfeeding Outcomes
Authors: Tanner‐Smith Emily E. , Steinka‐Fry Katarzyna T. , Lipsey Mark W.
Published: July 2013

Introduction

The purpose of this study was to examine the effects of CenteringPregnancy group prenatal care on breastfeeding outcomes, relative to traditional prenatal care delivered in an individual format.

Methods

A quasi‐experimental research design was conducted with 794 women receiving prenatal care delivered in a group or individual format at 4 sites in Tennessee. Propensity scores were used to create groups of women statistically matched on background demographics and medical history. Outcomes included breastfeeding at discharge and breastfeeding at postpartum follow‐up.

Results

Compared with the matched comparison group of women receiving prenatal care in an individual format, women in CenteringPregnancy group prenatal care had significantly higher odds of any breastfeeding at discharge (odds ratio [OR], 2.08; 95% confidence interval [CI], 1.32‐3.26; P < .001). Across the 4 sites, there were no consistent differences in the odds of any breastfeeding at follow‐up or exclusive breastfeeding at discharge or postpartum follow‐up.

Discussion

CenteringPregnancy group prenatal care may have beneficial effects on initial rates of breastfeeding relative to individually delivered care. However, there is not sufficient evidence to conclude that CenteringPregnancy group prenatal care has robust effects on exclusive breastfeeding at discharge or postpartum follow‐up.
Successful outcome in a rare case of pregnancy with familial hypercholesterolemia and dilated cardiomyopathy
Authors: Singh Neeta , Goyal Manu , Kumar Sunesh , Roy Kallol Kumar
Published: July 2013

Familial hypercholesterolemia is a rare disorder characterized by high cholesterol levels and early cardiovascular disease. Early detection and treatment with statins and other hypolipidemic agents are effective in heterozygous patients. Low‐density lipoprotein apheresis and liver transplantation are treatment options in homozygous familial hypercholesterolemia. We report a case of a 27‐year‐old pregnant woman with familial hypercholesterolemia who presented with breathlessness and swelling in the joints. She had been taking statins previously, which were stopped and she had been put on low‐lipid and low‐residue diet to reduce the risk of acute coronary event and sudden intrauterine death. She was found to have dilated cardiomyopathy with 25% ejection fraction. At 36 weeks of gestation, we carried out cesarean section in view of poor biophysical profile. Familial hypercholesterolemia is a very rare disorder with only a few cases reported in the published work during pregnancy. Statins are contraindicated during pregnancy and diet modification remains the mainstay of therapy.
Rupture of renal artery aneurysm during the early post‐partum period
Authors: Nakamura Ryo , Koyama Shinsuke , Maeda Munehiro , Kobayashi Masaki , Tanaka Yusuke , Kubota Satoshi , Isobe Masanori , Shiki Yasuhiko
Published: July 2013

Rupture of renal artery aneurysm associated with pregnancy is an uncommon condition. It is known that almost all previously reported cases have occurred during pregnancy. We experienced a case of rupture of renal artery aneurysm during the early post‐partum period which was diagnosed by computed tomography and treated by angiographic embolization. To our knowledge, only two cases of rupture of renal artery aneurysm during the post‐partum period have been reported in the English‐language published work. An early diagnosis of rupture of renal artery aneurysm during the post‐partum period is very challenging because the clinical symptoms of this condition are acute abdominal, flank or back pain, which are relatively common signs caused by more common post‐partum complications. However, rupture of renal artery aneurysm is a life‐threatening emergency condition requiring prompt diagnosis and treatment. The possibility of a rupture of renal artery aneurysm should be considered in any pregnant women with symptoms of an acute abdomen with hemorrhagic shock.
Time spatial labeling inversion pulse magnetic resonance angiography in pregnancy with adenomyosis
Authors: Yorifuji Takashi , Makino Shintaro , Yamamoto Yuka , Sugimura Motoi , Kuwatsuru Ryohei , Takeda Satoru
Published: July 2013

Time spatial labeling inversion pulse (Time‐SLIP) is a non‐contrast magnetic resonance angiography (MRA) technique. No cases in which this technique was used during pregnancy have been reported. We report herein two cases with adenomyosis of the same size and location that underwent Time‐SLIP MRA during pregnancy. In case 1, the blood flow within the adenomyosis was poor, and the uterine blood flow toward the placenta was normal, resulting in no fetal growth restriction (FGR). In case 2, the blood flow within the adenomyosis was quite rich, and placental blood flow seemed decreased, resulting in severe FGR. As well as the Doppler ultrasonography, Time‐SLIP MRA was useful for evaluating uterine blood flow during pregnancy. This is the first report of the use of Time‐SLIP MRA during pregnancy.
Effect of extracorporeal magnetic energy stimulation on bothersome lower urinary tract symptoms and quality of life in female patients with stress urinary incontinence and overactive bladder
Authors: Lo Tsia‐Shu , Tseng Ling‐Hong , Lin Yi‐Hao , Liang Ching‐Chung , Lu Ching‐Yi , Pue Leng Boi
Published: July 2013

Aims

The aim of this study was to investigate the efficacy of extracorporeal magnetic stimulation (EMS) for the treatment of bothersome and severe symptoms of stress urinary incontinence (SUI) and overactive bladder syndrome (OAB) in female patients.

Material and Methods

A retrospective review was conducted on patients with SUI and OAB who were referred to EMS therapy. Successful treatment for the bothersome symptoms of OAB and SUI was defined as score ≤1 for questions 2 and 3 on the Urodynamic Distress Inventory‐6. The objective cure of SUI and OAB was defined as no urinary leakage during the cough stress test and any urgency, urge incontinence and voiding frequency of less than eight times per 24 h based on the 3‐day bladder diary, after the 9 weeks of treatment, respectively.

Results

Ninety‐three patients with SUI or OAB underwent a 9‐week course of EMS at 20 min twice weekly. Seventy‐two (77%) patients completed EMS treatment. Geographical factor and poor economic status were two main factors for dropout. A total of 94.1% (32 of 34) and 86.8% (33 of 38) of subjects had successful treatment for the bothersome symptoms of OAB and SUI, respectively. In contrast, the cure rate for OAB and SUI was only 61.7% and 42.1%, respectively. There was also a significant improvement in both Urogenital Distress Inventory Short Form (bothersome on lower urinary tract symptoms) and the Incontinence Impact Questionnaire Short Form (quality of life) total score in both groups after EMS.

Conclusions

EMS is a safe and effective alternative method for treating SUI and OAB. Further studies are needed to evaluate the long‐term efficacy.
Acute Ischemic Complications of PCI and CABG: Who Should Cover Whom for Coronary Revascularization?
Authors: COCKBURN JAMES , BLOWS LUCY , COHEN ANDREW , HOLMBERG STEVE , HYDE JONATHAN , LEWIS MICHAEL , TRIVEDI UDAY , HILDICK‐SMITH DAVID , DE BELDER ADAM
Published: July 2013

Introduction

Percutaneous coronary intervention (PCI) has historically required cardiothoracic backup in the event of ischemic complications. However, many complications occurring during PCI can now be effectively treated at the time of the indexed procedure. Equally, ischemic complications, which occur following coronary artery bypass grafting (CABG), which were previously treated medically or with reoperation, may now also be effectively treated by acute PCI.

Aims and Methods

To identify the rate, cause, treatment, and outcomes of ischemic complications from PCI or isolated CABG procedures undertaken from January 2004 to January 2011 where there was immediate crossover from PCI to CABG or vice versa, and to determine from the indexed revascularization procedure, whether or not the ischemic complications were rectified by either CABG with respect to PCI or PCI with respect to CABG.

Results

Three hundred fifty‐six PCI major ischemic complications were identified. Three hundred forty‐seven (97.5%) were rectified percutaneously and 9 (2.5%) required emergency CABG. The commonest reason for emergency CABG was occlusive dissection (n = 7). Of the 9 patients that underwent emergency CABG, 3 patients (33.3%) died. Forty CABG major ischemic complications were identified. Twenty‐seven (67.5%) were treated medically. Thirteen (32.5%) underwent diagnostic angiography. The etiology of the ischemia was found in all cases. Consequently, 2 underwent reoperation, one was treated medically, and 10 underwent acute PCI.

Conclusion

Acute coronary ischemia remains a small but significant complication of both PCI and CABG. Resolution of ischemia requires prompt diagnosis and early discussion between cardiothoracic surgeon and cardiac interventionalist to determine the safest and therefore most appropriate way to resolve the problem.
Serum albumin levels and 10‐year tooth loss in a 70‐year‐old population
Authors: Yoshihara A. , Iwasaki M. , Ogawa H. , Miyazaki H.
Published: July 2013

Serum albumin levels are a practical marker of general health status in the elderly and have been used to determine the severity of underlying diseases and the risk for death. This longitudinal study evaluated the relationship between serum albumin concentrations and tooth loss over 10 years in elderly subjects, after controlling for confounding factors. A sample of 554 dentate subjects among enrolled subjects (n = 600) was involved in this planned longitudinal study with follow‐up examinations after 5 and 10 years. At the 5‐year follow‐up, 373 (67·3%), subjects were available for re‐examination. In addition, 331 (59·7%) were available at the 10‐year follow‐up. Multiple Poisson regression analysis was conducted to evaluate the relationship between the number of missing teeth over 5 or 10 years and serum albumin levels at baseline after adjusting for 10 variables: gender, serum markers levels at baseline, dental status, smoking habits and educational years and oral health behaviour. The number of missing teeth over 5 or 10 years was significantly negatively associated with serum albumin levels at baseline [incidence rate ratios (IRR) = 0·373, P < 0·0001 for 5 years; IRR = 0·570, P < 0·0001 for 10 years]. We conclude that elderly subjects with hypoalbuminemia are at high risk for 5‐ and 10‐year tooth loss.
Financing Higher Education in a Mobile World
Authors: DEMANGE GABRIELLE , FENGE ROBERT , UEBELMESSER SILKE
Published: July 2013

This paper analyzes how integrated labor markets affect the financing of higher education. For this, we employ a general‐equilibrium model with overlapping generations and individuals who differ in their abilities. At the first stage, governments can choose the quality of education and the financing system. At the second stage, individuals make their education and migration decisions given the governmental framework for higher education and the mobility assumptions. In a closed economy and in the presence of imperfect credit markets, a mix of tax‐ and fee‐financing is optimal. In integrated labor markets, countries have an incentive to attract skilled workers and to free‐ride on education provided by other countries. When only skilled workers are mobile, there is a suboptimal shift from taxes to fees and the number of students is too low. When also students can migrate, there is a countervailing force such that maintaining the optimal financial mix becomes possible.
Antitumour and free radical scavenging effects of γ-mangostin isolated from Garcinia mangostana pericarps against hepatocellular carcinoma cell
Authors: Chang Hui-Fang , Wu Chih-Hsiung , Yang Ling-Ling
Published: July 2013

Objectives

Liver cancer is one of the highest rate diseases in southeastern Asia. Recently, many of functional foods and alternative medicines are very popularly utilized to prevent chronic diseases and cancer in Taiwan. In this study, we wanted to select and develop some of novel effectual agents or phytochemicals of γ-mangostin for clinical management or prevent hepatocellular carcinoma cell (HCC).

Methods

Lipid peroxidation (LPO) is an autocatalytic mechanism which induced tissue injure and carcinogenesis. In this study, the inhibitory activity of γ-mangostin on oxidative damage induced rat mitochondria LPO, the free radical scavenging of γ-mangostin and the apoptotic effects of γ-mangostin on HepG2 cells were investigated.

Key findings

γ-Mangostin processed activity to inhibit LPO and scavenge 2,2-diphenyl-1-picrylhydrazyl. γ-Mangostin showed antiproliferative activity and induced nuclear condensation and apoptotic bodies appearance under Giemsa staining by microscopic observation. In addition, γ-mangostin showed increases of hypodiploid cells via propidium iodide, 2′7′-dichlorofluorescein diacetate, and 3,3′-dihexyloxacarbocyanine iodide staining by flow cytometry analysis in HepG2 cells.

Conclusions

γ-Mangostin has demonstrated free radical scavenging activity, and antiproliferative and apoptotic activity in HepG2 cells. The proof suggests that γ-mangostin is a lead compound candidate for clinical management or prevent HCC.
Are relatively rare antelope narrowly selective feeders? A sable antelope and zebra comparison
Authors: Owen‐Smith N. , Le Roux E. , Macandza V.
Published: July 2013

Animals that are relatively rare in local species assemblages are commonly assumed to be narrowly selective in their habitat or dietary requirements, with the latter generally assessed in terms of the range of food types consumed. We investigated whether a narrow dietary range might help explain the restricted distribution and low local densities attained by sable antelope Hippotragus niger compared with other grazing ungulates. Selection by sable antelope for grass species, its relation to species availability and the resulting evenness of the diet were compared with these measures for zebra Equus quagga, which are assumed to be generalist feeders owing to their hindgut fermentation system, under dry season conditions when food was most limiting. Both grazers exhibited a clear distinction between highly favoured and infrequently accepted or rejected grass species in the same region, and both favoured mostly the same common grass species, but sable showed greater acceptance of several less common grass species than did zebra. Distinctions were evident among individual sable herds in favoured grass species, dependent on local availability. Dietary evenness was similar for sable and zebra herds overall, although seasonal trends differed depending on whether animals concentrated their diet more narrowly on a few grass species or broadened it during more extremely dry conditions. Hence, although sable were more narrowly selective for green leaf content than zebra, the dietary acceptance range of these two grazers at grass species level did not differ fundamentally. In particular, sable readily consumed tall grass species rated as having low to moderate forage value. This dietary tolerance enables sable antelope to occupy savannah woodlands associated with relatively infertile soils where the risk of predation is reduced due to the relatively low abundance of other prey. Accordingly, the causes of local rarity may lie in the restricted availability of food in the places to which these species are restricted by other factors.
FtsEX is required for CwlO peptidoglycan hydrolase activity during cell wall elongation in Bacillus subtilis
Authors: Meisner Jeffrey , Montero Llopis Paula , Sham Lok‐To , Garner Ethan , Bernhardt Thomas G. , Rudner David Z.
Published: July 2013

The peptidoglycan (PG) sacculus, a meshwork of polysaccharide strands cross‐linked by short peptides, protects bacterial cells against osmotic lysis. To enlarge this covalently closed macromolecule, PG hydrolases must break peptide cross‐links in the meshwork to allow insertion of new glycan strands between the existing ones. In the rod‐shaped bacterium Bacillus subtilis, cell wall elongation requires two redundant endopeptidases, CwlO and LytE. However, it is not known how these potentially autolytic enzymes are regulated to prevent lethal breaches in the cell wall. Here, we show that the ATP‐binding cassette transporter‐like FtsEX complex is required for CwlO activity. In Escherichia coli, FtsEX is thought to harness ATP hydrolysis to activate unrelated PG hydrolases during cell division. Consistent with this regulatory scheme, B. subtilis FtsE mutants that are unable to bind or hydrolyse ATP cannot activate CwlO. Finally, we show that in cells depleted of both CwlO and LytE, the PG synthetic machinery continues moving circumferentially until cell lysis, suggesting that cross‐link cleavage is not required for glycan strand polymerization. Overall, our data support a model in which the FtsEX complex is a remarkably flexible regulatory module capable of controlling a diverse set of PG hydrolases during growth and division in different organisms.
Proteomic identification of potential target proteins regulated by the SCFFbp1‐mediated proteolysis pathway in Fusarium oxysporum
Authors: Miguel‐Rojas Cristina , Hera Concepcion
Published: July 2013

F‐box proteins function in the recruitment of proteins for SCF ubiquitination and proteasome degradation. Here, we studied the role of Fbp1, a nonessential F‐box protein of the tomato pathogen Fusarium oxysporum f. sp. lycopersici. The Δfbp1 mutant showed a significant delay in the production of wilt symptoms on tomato plants and was impaired in invasive growth on cellophane membranes and on living plant tissue. To search for target proteins recruited by Fbp1, a combination of sodium dodecylsulphate‐polyacrylamide gel electrophoresis (SDS‐PAGE) and matrix‐assisted laser desorption/ionization time‐of‐flight/time‐of‐flight (MALDI‐TOF/TOF) was used to compare proteins in mycelia of the wild‐type and Δfbp1 mutant. The proteomic approach identified 41 proteins differing significantly in abundance between the two strains, 17 of which were more abundant in the Δfbp1 mutant, suggesting a possible regulation by proteasome degradation. Interestingly, several of the identified proteins were related to vesicle trafficking. Microscopic analysis revealed an impairment of the Δfbp1 strain in directional growth and in the structure of the Spitzenkörper, suggesting a role of Fbp1 in hyphal orientation. Our results indicate that Fbp1 regulates protein turnover and pathogenicity in F. oxysporum.
Effectiveness of an electronic inpatient medication record in reducing medication errors in Singapore
Authors: Choo Janet , Johnston Linda , Manias Elizabeth
Published: July 2013

This study examined the effectiveness of an inpatient electronic medication record system in reducing medication errors in Singaporean hospitals. This pre‐ and post‐intervention study involving a control group was undertaken in two Singaporean acute care hospitals. In one hospital the inpatient electronic medication record system was implemented while in another hospital the paper‐based medication record system was used. The mean incidence difference in medication errors of 0.06 between pre‐intervention (0.72 per 1000 patient days) and post‐intervention (0.78 per 1000 patient days) for the two hospitals was not statistically significant (95%, CI: [0.26, 0.20]). The mean incidence differences in medication errors relating to prescription, dispensing, and administration were also not statistically different. Common system failures involved a lack of medication knowledge by health professionals and a lack of a systematic approach in identifying correct dosages. There was no difference in the incidence of medication errors following the introduction of the electronic medication record system. More work is needed on how this system can reduce medication error rates and improve medication safety.
Development of boceprevir: a first‐in‐class direct antiviral treatment for chronic hepatitis C infection
Authors: Hazuda Daria J. , Burroughs Margaret , Howe Anita Y.M. , Wahl Janice , Venkatraman Srikanth
Published: July 2013

The identification of hepatitis C virus (HCV) as the causative agent of non‐A and non‐B hepatitis, over 20 years ago, fueled an intensive effort to develop direct‐acting antivirals targeting the viral polymerase and protease, two key proteins critical for HCV replication. However, it took more than two decades for these efforts to be realized with boceprevir, one of the two HCV protease inhibitors approved for treatment of HCV infection in 2011. The development of boceprevir is a major advancement in the ability to treat HCV infection and a significant step toward the long‐term goal of eradicating chronic HCV infection. Both as a first‐in‐class agent and an entirely new modality for treating HCV infection, many challenges were encountered during the discovery and development of this compound. The lessons learned in overcoming these obstacles offer insights and pave the way for the newly emerging field of HCV antiviral therapeutics. This paper will describe the discovery and development of a first‐in‐class direct antiviral treatment for chronic hepatitis C infection, boceprevir, marketed around the world as VictrelisTM.
Auswirkungen der Hartz-Reformen auf den Arbeitsmarkt und auf die Bundesagentur für Arbeit
Authors: Weise Frank-J.
Published: July 2013

Starting in 2003, the labour market in Germany underwent major reforms. They introduced new types of employment, reshaped the benefit system, and remodelled active labour market policies. Over the 10 following years, unemployment fell dramatically and participation hit record levels, while rising non-standard employment and wage inequality became causes for concern. The Bundesagentur für Arbeit has developed into a modern service provider whose programmes are scientifically evaluated. Anticipating future trends on the labour market, the Bundesagentur has recently devised a strategy to cope with them. Overall, the German experience with labour market reforms points to the benefits of evidence-based policies.
ATP release and Ca2+ signalling by human bronchial epithelial cells following Alternaria aeroallergen exposure
Authors: O'Grady Scott M. , Patil Nandadavi , Melkamu Tamene , Maniak Peter J. , Lancto Cheryl , Kita Hirohito
Published: July 2013

Key points

Exposure of human bronchial epithelial (HBE) cells to fungal aeroallergens derived from Alternaria alternata stimulates Ca2+‐dependent and Ca2+‐independent ATP release across the apical membrane.

The Ca2+‐dependent component was blocked by inhibitors of both ATP uptake and transport of exocytotic vesicles to the plasma membrane.

Treatment with inhibitors that target cysteine proteases significantly blocked Ca2+‐dependent ATP release evoked by Alternaria in normal HBE cells, but not in cells derived from asthmatic patients.

The magnitude of ATP release and associated intracellular Ca2+ mobilization was significantly greater in bronchial epithelial cells obtained from patients with asthma.

These findings establish a novel role for ATP release as a mechanism underlying Alternaria aeroallergen activation of airway mucosal immunity and that cells derived from patients with asthma exhibit greater responsiveness to these allergens.

Abstract  Exposure of human bronchial epithelial (HBE) cells from normal and asthmatic subjects to extracts from Alternaria alternata evoked a rapid and sustained release of ATP with greater efficacy observed in epithelial cells from asthmatic patients. Previously, Alternaria allergens were shown to produce a sustained increase in intracellular Ca2+ concentration ([Ca2+]i) that was dependent on the coordinated activation of specific purinergic receptor (P2Y2 and P2X7) subtypes. In the present study, pretreatment with a cell‐permeable Ca2+‐chelating compound (BAPTA‐AM) significantly inhibited ATP release, indicating dependency on [Ca2+]i. Alternaria‐evoked ATP release exhibited a greater peak response and a slightly lower EC50 value in cells obtained from asthmatic donors compared to normal control cells. Furthermore, the maximum increase in [Ca2+]i resulting from Alternaria treatment was greater in cells from asthmatic patients compared to normal subjects. The vesicle transport inhibitor brefeldin A and BAPTA‐AM significantly blocked Alternaria‐stimulated incorporation of fluorescent lipid (FM1‐43)‐labelled vesicles into the plasma membrane and ATP release. In addition, inhibiting uptake of ATP into exocytotic vesicles with bafilomycin also reduced ATP release comparable to the effects of brefeldin A and BAPTA‐AM. These results indicate that an important mechanism for Alternaria‐induced ATP release is Ca2+ dependent and involves exocytosis of ATP. Serine and cysteine protease inhibitors also reduced Alternaria‐induced ATP release; however, the sustained increase in [Ca2+]i typically observed following Alternaria exposure appeared to be independent of protease‐activated receptor (PAR2) stimulation.
Brief history of arrhythmia in the WPW syndrome – the contribution of George Ralph Mines
Authors: Boukens Bas J. , Janse Michiel J.
Published: July 2013

Abstract  George Ralph Mines studied the basic principles of reentry and published his data in The Journal of Physiology in 1913. Exactly 100 years later we discuss his first electrophysiological experiments and how his results lead to the insight that was the basis for the treatment of the clinical arrhythmias seen in Wolff–Parkinson–White syndrome.
Reconfiguration Manipulability Analyses for Redundant Robots
Authors: Zhang Tongxiao , Minami Mamoru , Yasukura Osami , Song Wei
Published: July 2013

This paper is concerned with a concept of reconfiguration manipulability inspired from manipulability. The reconfiguration manipulability represents a shape-changeability of each intermediate link when a prior end-effector task is given. Through analyses of reconfiguration matrices, we propose a method to judge whether the plural shape-changing subtasks can be executed simultaneously or not. Then the sufficient conditions guaranteeing sustainability of reconfiguration manipulability space are presented, which are the conditions for keeping the reconfiguration manipulability as high as possible under the prior end-effector task. Further, we confirm the proposed analyses can be useful practically for evaluating the realistic manipulator's configurations and structures.
Optimization of Heliostat Aim Point Selection for Central Receiver Systems Based on the Ant Colony Optimization Metaheuristic
Authors: Belhomme Boris , Pitz-Paal Robert , Schwarzbözl Peter
Published: July 2013

The optimization of the selection of heliostat aim points in a solar power tower plant with the objective of an increased overall efficiency represents a NP-hard optimization problem of high dimension. This paper presents a universal procedure for the purpose of aim point optimization based on the ant colony optimization metaheuristic that uses the principles of swarm intelligence. The applicability of the developed aim point optimization procedure to central receiver systems is demonstrated on a test case, for which the electrical power of a concentrated photovoltaic (CPV) receiver is maximized for a selected operating point. The example of a CPV receiver was chosen due to its nonlinear and nonmonotonous dependency of efficiency and flux density. It is shown that the optimization result is very close to the theoretical maximum.
Magnetic Heating of Nanoparticles: The Importance of Particle Clustering to Achieve Therapeutic Temperatures
Authors: Pearce John , Giustini Andrew , Stigliano Robert , Jack Hoopes P.
Published: July 2013

Hyperthermia therapy for cancer treatment seeks to destroy tumors through heating alone or combined with other therapies at elevated temperatures between 41.8 and 48 °C. Various forms of cell death including apoptosis and necrosis occur depending on temperature and heating time. Effective tumoricidal effects can also be produced by inducing damage to the tissue vasculature and stroma; however, surrounding normal tissue must be spared to a large extent. Magnetic nanoparticles have been under experimental investigation in recent years as a means to provide a favorable therapeutic ratio for local hyperthermia; however, practical numerical models that can be used to study the underlying mechanisms in realistic geometries have not previously appeared to our knowledge. Useful numerical modeling of these experiments is made extremely difficult by the many orders of magnitude in the geometries: from nanometers to centimeters. What has been missing is a practical numerical modeling approach that can be used to more deeply understand the experiments. We develop and present numerical models that reveal the extent and dominance of the local heat transfer boundary conditions, and provide a new approach that may simplify the numerical problem sufficiently to make ordinary computing machinery capable of generating useful predictions. The objectives of this paper are to place the discussion in a convenient interchangeable classical electromagnetic formulation, and to develop useful engineering approximations to the larger multiscale numerical modeling problem that can potentially be used in experiment evaluation; and eventually, may prove useful in treatment planning. We cast the basic heating mechanisms in the framework of classical electromagnetic field theory and provide calibrating analytical calculations and preliminary experimental results on BNF-Starch® nanoparticles in a mouse tumor model for perspective.
An Unpowered Mechanical Magnetic Field Sensor to Improve MRI Safety
Authors: Kopp Keith A. , DeMent H. Duane
Published: July 2013

Medical equipment that is used in the MRI room, such as infusion pumps, contrast injectors, patient monitors, anesthesia machines may malfunction and potentially injure the patient if not kept outside of a specific magnetic field strength. In addition, some equipment can degrade the MR image quality because of electromagnetic interference if this equipment is brought too close to the magnet.
Workspace and Force Capabilities of a Miniature Multi-Functional Surgical Robot
Authors: Strabala Kyle W. , McCormick Ryan M. , Wortman Tyler D. , Lehman Amy C. , Farritor Shane M. , Oleynikov Dmitry
Published: July 2013

This paper describes the capabilities of a miniature multi-functional in vivo robot designed and developed for Laparoendoscopic Single-Site Surgery (LESS). The paper outlines several competing design criteria including robot size, workspace volume, endpoint speeds, and endpoint forces. In this paper, the robot is evaluated according to these criteria. The workspace is described and the maximum no-load endpoint speeds and maximum attainable endpoint forces are presented. Finally, the robot capabilities are discussed, related to medical applications, and demonstrated in an animal surgery.
Connected Healthcare Solution Using Cell Phone
Authors: Osman Mohammed , Nasor Mohamed , Imran Ahmed
Published: July 2013

Recent developments in device technology and widespread use of cell phone and wireless technology globally have provided an unprecedented opportunity for enhanced healthcare delivery. This study presents development of a cell phone based electronic healthcare system for remote monitoring and control of patients. The system comprises of two modules, each connected to a cell phone for communication of data or instructions. The first module allows real-time data acquisition and analysis from several devices that may be connected to the patient. By calling the cell phone for this module, data can be accessed or any of the connected devices be controlled remotely. Any observed abnormality is reported in real-time by calling a pre-set cell phone. This module allows interactive communication utilizing machine generated voice. Also, this module calls the second module at regular time intervals to transfer the patient’s data over phone. The second module thus receives the data for storage in a central location. All of these features of the system were tested successfully on simulated patient devices. For data and device security, ID and password verifications are required.
Advancing Medical Technology Using FPGAs
Authors: Olson Zach
Published: July 2013

Field Programmable Gate Arrays (FPGAs) have dramatically changed the design of medical devices in the past decade. FPGAs offer the flexibility of writing software on a standard microprocessor and the reliability and performance of dedicated hardware. In the design of medical devices that previously required the rigorous design of custom circuits or ASIC design, FPGAs are providing a good alternative at a much lower cost for low to mid-volume medical device design. In this session, we will explore how FPGAs relate to medical device technology including real-time processing of data, high performance image processing, precise control, and code reuse from prototype to deployed device. We will explore how this technology was applied to two devices that improve the success of high-risk surgeries. In the first, FPGA technology is used to monitor blood glucose levels in patients during open-heart surgery. The second example is a device that simulates electrical signals from the human nervous system to train neurophysiologists for events that may happen during surgery. We will explore the impact FPGAs have on design cycles, briefly explore the design process, and compare different programming methodologies including C, VHDL, and LabVIEW. Finally, we will discuss the impact of FPGAs with respect to the 510k process.
Development of an Endoscopic Fiber Optic Shape Tracker
Authors: Eisenstein Jessica , Wong Peter Y. , Cao Caroline G. L.
Published: July 2013

Colon cancer is estimated to be the third leading cause of cancer-related death in the US [1], with the cost of colorectal cancer treatment reaching $8.4 billion annually [2]. Though colonoscopy is the current standard for colon cancer screening and diagnosis, the procedure has disadvantages due from the near-blind navigation process used. During the procedure, endoscopists frequently lose sight of landmarks in the colon, losing track of their locations within the colon and becoming disoriented.